Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free): A Protocol for a Multi-centre Randomized Cluster Crossover Trial
Jessica Spence, MD, PhD,
Emilie Belley-Côté, MD, PhD,
Eric Jacobsohn, MBChB, MPHE,
Shun Fu Lee, PhD,
Frederick D’Aragon, MD, MSc, FRCPC,
Michael Avidan, MBBCh,
C. David Mazer, MD,
Nicolas Rousseau-Saine, MD,
Raja Rajamohan, MD,
Kane Pryor, MD,
Rael Klein, MBBCh,
Edmund (Chong-How) Tan, MD,
Matthew Cameron, MDCM, MPH,
Emily Di Sante, MA,
Erin DeBorba, MSc,
Mary Mustard, BScN, MN,
Etienne Couture, MD,
Raffael Zamper, MD, PhD,
Michael Law, MD,
George Djaiani, MD,
Tarit Saha, MBBS,
Stephen Choi, MD, MSc,
Peter Hedlin, MD, PhD,
Ryan Pikaluk, MD,
Wing Ying Lam, MD, MPH,
Alain Deschamps, MD, PhD,
Richard Whitlock, MD, PhD,
Braden Dulong, MD,
P.J. Devereaux, MD, PhD,
Chris Beaver, P.Eng,
Shelley Kloppenburg, BSW,
Simon Oczkowski, MD, MHSc,
William Finlay McIntyre, MD, PhD,
Matthew McFarling, MD,
Andre Lamy, MD, MHSc,
Jessica Vincent, MSc,
Stuart Connolly, MD, MSc
Affiliations
Jessica Spence, MD, PhD
Departments of Anesthesia and Critical Care and Health Research Methods, Evaluation, and Impact, McMaster University; and Perioperative Research Division, Population Health Research Institute, Hamilton, Ontario, Canada; Corresponding author: Dr Jessica Spence, Department of Anesthesia and Critical Care, Perioperative Research Division, Population Health Research Institute, McMaster University, C2-DBCVSRI, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.
Emilie Belley-Côté, MD, PhD
Departments of Medicine (Cardiology and Critical Care), and Health Research Methods, Evaluation, and Impact, McMaster University, and Perioperative Research Division, Population Health Research Institute, Hamilton, Ontario, Canada
Eric Jacobsohn, MBChB, MPHE
Departments of Anesthesia and Perioperative Medicine and Medicine (Critical Care), University of Manitoba, Winnipeg, Manitoba, Canada
Shun Fu Lee, PhD
Department of Health Research Methods, Evaluation, and Impact, McMaster University, and Population Health Research Institute, Hamilton, Ontario, Canada
Frederick D’Aragon, MD, MSc, FRCPC
Département d'anesthésiologie, Université de Sherbrooke, Sherbrooke, Quebec, Canada
Michael Avidan, MBBCh
Department of Anesthesia, Washington University at St. Louis, St. Louis, Missouri, USA
C. David Mazer, MD
Department of Anesthesia and Li Ka Shing Knowledge Institute, St. Michael’s Hospital, and Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, Canada
Nicolas Rousseau-Saine, MD
Département d'anesthésiologie, Université de Montréal, Montréal, Quebec, Canada
Raja Rajamohan, MD
Department of Anesthesia, University of British Columbia, Vancouver, British Columbia, Canada
Kane Pryor, MD
Department of Anesthesiology, Weill Cornell Medical College, New York, New York, USA
Rael Klein, MBBCh
Department of Anesthesia, University of British Columbia, Vancouver, British Columbia, Canada
Edmund (Chong-How) Tan, MD
Department of Anesthesia, Dalhousie University, Halifax, Nova Scotia, Canada
Matthew Cameron, MDCM, MPH
Department of Anesthesia, McGill University, Montreal, Quebec, Canada
Emily Di Sante, MA
Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
Erin DeBorba, MSc
Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
Mary Mustard, BScN, MN
St. Michael's Hospital, Toronto, Ontario, Canada
Etienne Couture, MD
Département d'anesthésiologie, Université Laval, Quebec City, Quebec, Canada
Raffael Zamper, MD, PhD
Department of Anesthesia, University of Western Ontario, London, Ontario, Canada
Michael Law, MD
Department of Anesthesia, University of British Columbia, Vancouver, British Columbia, Canada
George Djaiani, MD
Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, Canada
Tarit Saha, MBBS
Department of Anesthesia, Queen's University, Kingston, Ontario, Canada
Stephen Choi, MD, MSc
Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, Canada
Peter Hedlin, MD, PhD
Department of Anesthesia, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Ryan Pikaluk, MD
Department of Anesthesia, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Wing Ying Lam, MD, MPH
Department of Anesthesia, University of Alberta, Edmonton, Alberta, Canada
Alain Deschamps, MD, PhD
Département d'anesthésiologie, Université de Montréal, Montréal, Quebec, Canada
Richard Whitlock, MD, PhD
Departments of Surgery (Cardiac Surgery) and Health Research Methods, Evaluation, and Impact, McMaster University, and Perioperative Research Division, Population Health Research Institute, Hamilton, Ontario, Canada
Braden Dulong, MD
Department of Anesthesia, Dalhousie University, Halifax, Nova Scotia, Canada
P.J. Devereaux, MD, PhD
Departments of Medicine (Cardiology and Critical Care), and Health Research Methods, Evaluation, and Impact, McMaster University, and Perioperative Research Division, Population Health Research Institute, Hamilton, Ontario, Canada
Chris Beaver, P.Eng
Sheridan College, Brampton, Ontario, Canada
Shelley Kloppenburg, BSW
Population Health Research Institute, Hamilton, Ontario, Canada
Simon Oczkowski, MD, MHSc
Department of Medicine (Critical Care), McMaster University, Hamilton, Ontario, Canada
William Finlay McIntyre, MD, PhD
Department of Medicine (Cardiology), McMaster University, and Perioperative Research Division, Population Health Research Institute, Hamilton, Ontario, Canada
Matthew McFarling, MD
Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada
Andre Lamy, MD, MHSc
Departments of Surgery (Cardiac Surgery) and Health Research Methods, Evaluation, and Impact, McMaster University, Perioperative Research Division, Population Health Research Institute, Hamilton, Ontario, Canada
Jessica Vincent, MSc
Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
Stuart Connolly, MD, MSc
Department of Medicine (Cardiology), McMaster University, and Population Health Research Institute, Hamilton, Ontario, Canada
Delirium is common after cardiac surgery and is associated with adverse outcomes. Administration of benzodiazepines before and after cardiac surgery is associated with delirium; guidelines recommend minimizing their use. Benzodiazepine administration during cardiac surgery remains common because of its recognized benefits. The Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free) trial is a randomized cluster crossover trial evaluating whether an institutional policy of restricting intraoperative benzodiazepine administration (ie, ≥ 90% of patients do not receive benzodiazepines during cardiac surgery), as compared with a policy of liberal intraoperative benzodiazepine administration (ie, ≥ 90% of patients receive ≥ 0.03 mg/kg midazolam equivalent), reduces delirium. Hospitals performing ≥ 250 cardiac surgeries a year are included if their cardiac anesthesia group agrees to apply both benzodiazepine policies per their randomization, and patients are assessed for postoperative delirium every 12 hours in routine clinical care. Hospitals apply the restricted or liberal benzodiazepine policy during 12 to 18 crossover periods of 4 weeks each. Randomization for all periods takes place in advance of site startup; sites are notified of their allocated policy during the last week of each crossover period. Policies are applied to all patients undergoing cardiac surgery during the trial period. The primary outcome is the incidence of delirium at up to 72 hours after surgery. The B-Free trial will enroll ≥ 18,000 patients undergoing cardiac surgery at 20 hospitals across North America. Delirium is common after cardiac surgery, and benzodiazepines are associated with the occurrence of delirium. The B-Free trial will determine whether an institutional policy restricting the administration of benzodiazepines during cardiac surgery reduces the incidence of delirium after cardiac surgery.Clinicaltrials.gov registration number: NCT03928236 (First registered April 26, 2019). Résumé: L’état confusionnel est fréquent après une chirurgie cardiaque et il est associé à des complications. L’administration de benzodiazépines avant et après une chirurgie cardiaque est associée à l’état confusionnel; dans les lignes directrices, on recommande de réduire leur utilisation au minimum. L’administration de benzodiazépines pendant une chirurgie cardiaque demeure fréquente, en raison des leurs bienfaits reconnus. L’essai B-Free (Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium ou l’anesthésie sans benzodiazépine en contexte de chirurgie cardiaque pour la réduction de l’état confusionnel postopératoire) est un essai à répartition aléatoire par grappes et avec permutation, visant à évaluer si une politique institutionnelle de restriction de l’administration peropératoire de benzodiazépines (c.-à-d. que ≥ 90 % des patients ne reçoivent pas de benzodiazépines durant une chirurgie cardiaque) réduit l’état confusionnel, comparativement à une politique d’administration peropératoire libérale de benzodiazépines (c.-à-d. que ≥ 90 % des patients reçoivent ≥ 0,03 mg/kg d’équivalent du midazolam). Des hôpitaux effectuant au moins 250 chirurgies cardiaques par année sont inclus dans l’essai si leurs équipes d’anesthésie cardiaque acceptent d’appliquer les deux politiques relatives aux benzodiazépines en vertu de la répartition aléatoire et si les patients sont évalués toutes les 12 heures, en ce qui a trait à l’état confusionnel postopératoire, dans le cadre des soins cliniques habituels. Les hôpitaux mettent en œuvre la politique d’administration restreinte ou libérale de benzodiazépines durant 12 à 18 périodes de permutation de 4 semaines chacune. La répartition aléatoire de l’ensemble des périodes a lieu avant le début de l’essai à l’hôpital; les établissements sont avisés de la politique qui leur est attribuée au cours de la dernière semaine de chaque période de permutation. Les politiques sont appliquées à tous les patients qui subissent une chirurgie cardiaque durant la période de l’essai. Le critère d’évaluation principal est l’incidence de l’état confusionnel dans les 72 heures suivant l’intervention chirurgicale. L’étude B-Free inclura au moins 18 000 patients qui subiront une chirurgie cardiaque dans 20 hôpitaux en l’Amérique du Nord. L’état confusionnel est fréquent après une chirurgie cardiaque, et les benzodiazépines sont associées à la survenue de l’état confusionnel. L’essai B-Free permettra de déterminer si une politique institutionnelle de restriction de l’administration de benzodiazépines durant une chirurgie cardiaque réduit l’incidence de l’état confusionnel après une telle chirurgie.Clinicaltrials.gov registration number: NCT03928236 (First registered April 26, 2019).
