Benzodiazepine-free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free)

B-FREE is a pragmatic, multicentre, cluster crossover trial evaluating whether a policy limiting the use of intra-operative benzodiazepine reduces post-operative delirium when compared with a policy of 'ad libitum' administration. The knowledge generated by this study will provide the basis for cardiac anesthesia practice guidelines.

Study Overview

• Status: Active, not recruiting
• Conditions: Delirium; Post-cardiac Surgery
• Intervention / Treatment: Other: Limited Intraoperative Benzodiazepine; Other: Liberal Intraoperative Benzodiazepine

Detailed Description

Delirium, an acute state of confusion, occurs in approximately 1 in 5 adults after open heart surgery. Even though it is a temporary state, patients who experience delirium are at increased risk of serious problems that last after the delirium has resolved. These problems include decreases in thinking, mobility, self-care, and the ability to live independently in a community setting. Patients who experience delirium have longer stays in hospital, are more likely to be discharged to a nursing home, and are more likely to die. Benzodiazepines are a sedative and amnestic medication that may be associated with delirium. As such, benzodiazepines are rarely used for sedation in the intensive care unit after cardiac surgery. However, benzodiazepines continue to be used frequently in the operating room by anesthesiologists during open heart surgery because of their amnestic effects and limited impact on blood pressure. Nevertheless, practice is divided among cardiac anesthesiologists, with some never using benzodiazepines and others using them for nearly all patients.

Because the best approach (routine benzodiazepines or restricted benzodiazepines) remains uncertain, we will compare the effect of a hospital policy of intraoperative medication use that includes benzodiazepines to a policy that uses alternative medications and no benzodiazepines on the incidence of delirium after open heart surgery. The findings of the study have the potential to improve the outcomes of tens of thousands of patients around the world and will provide the basis for cardiac anesthesiology practice guidelines.

• Study Type: Interventional
• Enrollment (Estimated): 15886
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: B-Free Study Coordinator; Phone Number: 905212100; Email: B-FREE@phri.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Mazankowski Alberta Heart Institute
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3W7
      • Royal Columbian Hospital
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St. Boniface General Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Queen Elizabeth II Health Sciences Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences, Hamilton General Hospital
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston General Hospital
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
  • Quebec
    • Montréal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montréal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
    • Québec, Quebec, Canada, G1V 4G5
      • Hôpital Laval
    • Sherbrooke, Quebec, Canada, J1H 4C6
      • Centre Hospitalier Universitaire de Sherbrooke
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4P 0W5
      • Regina General Hospital
    • Saskatoon, Saskatchewan, Canada, S7N OW8
      • Royal University Hospital
• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1010
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Hospital is a major surgical center with a minimum of 250 cases of cardiac surgery per year.
• Equipoise by the hospital physicians regarding the use of benzodiazepines during surgery (≥ 95% of hospital cardiac anesthesia group agrees to manage adult patients (age >18 years) as per the benzodiazepine policy in place during a given crossover period).
• Hospital routinely assesses patients (age >18 years) for postoperative delirium at least once every 12 hours during the initial 72 hours after cardiac surgery as a part of routine clinical care using either the Confusion Assessment Method-ICU (CAM-ICU) or the Intensive Care Delirium Screening Checklist (ICDSC).

Exclusion Criteria:

- Hospital does not meet inclusion criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Limited Benzodiazepine Policy; Policy of no routine use of any intraoperative benzodiazepines.	Other: Limited Intraoperative Benzodiazepine; policy for limited use of intraoperative benzodiazepine
Active Comparator: Liberal Benzodiazepine Policy; Policy for the administration of benzodiazepine as per clinical guidelines but no lower than 0.03 mg/kg (ideal body weight midazolam equivalent) to all patients undergoing cardiac surgery. Any benzodiazepine may be used.	Other: Liberal Intraoperative Benzodiazepine; policy for liberal use of intraoperative benzodiazepine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Delirium	Delirium assessed up to 72 hours after surgery using standardized and validated delirium scales	up to 72 hours post cardiac surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Days in ICU after Cardiac Surgery	Length of Stay (LOS) in Intensive Care Unit after Cardiac Surgery	through study completion, approximately 37 months
Number of Days in Hospital after Cardiac Surgery	Length of Stay (LOS) in Hospital after Cardiac Surgery	through study completion, approximately 37 months
Incidence of In-hospital Mortality	Death from any cause after index cardiac surgery and during the index hospitalization	through study completion, approximately 37 months

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Investigators: Principal Investigator: Jessica Spence, MD FRCPC, Population Health Research Institute; Principal Investigator: Eric Jacobsohn, MBChB MPHE, University of Manitoba; Study Chair: Stuart Connolly, MD FRCPC, Population Health Research Institute

Publications and helpful links

General Publications

• Wang ML, Min J, Sands LP, Leung JM; the Perioperative Medicine Research Group. Midazolam Premedication Immediately Before Surgery Is Not Associated With Early Postoperative Delirium. Anesth Analg. 2021 Sep 1;133(3):765-771. doi: 10.1213/ANE.0000000000005482.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2019
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: April 18, 2019
• First Submitted That Met QC Criteria: April 24, 2019
• First Posted (Actual): April 26, 2019

Study Record Updates

• Last Update Posted (Actual): December 27, 2023
• Last Update Submitted That Met QC Criteria: December 23, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Emergence Delirium
• Other Study ID Numbers: B-Free.2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No