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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Limited Benzodiazepine Policy | Experimental | Policy of no routine use of any intraoperative benzodiazepines. |
|
| Liberal Benzodiazepine Policy | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Limited Intraoperative Benzodiazepine | Other | policy for limited use of intraoperative benzodiazepine |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
- Hospital does not meet inclusion criteria
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| Name | Affiliation | Role |
|---|---|---|
| Jessica Spence, MD FRCPC | Population Health Research Institute | Principal Investigator |
| Eric Jacobsohn, MBChB MPHE | University of Manitoba | Principal Investigator |
| Stuart Connolly, MD FRCPC | Population Health Research Institute | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110-1010 | United States | ||
| Weill Cornell Medicine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39878960 | Derived | Spence J, Devereaux PJ, Lee SF, D'Aragon F, Avidan MS, Whitlock RP, Mazer CD, Rousseau-Saine N, Rajamohan RR, Pryor KO, Klein R, Tan E, Cameron MJ, Di Sante E, DeBorba E, Mustard ME, Couture EJ, Zamper RPC, Law MWY, Djaiani G, Saha T, Choi S, Hedlin P, Pikaluk DR, Lam W, Deschamps A, Ramasundarahettige CF, Vincent J, McIntyre WF, Oczkowski SJW, Dulong BJ, Beaver C, Kloppenburg SA, Lamy A, Jacobsohn E, Belley-Cote EP; B-Free Investigators and the Canadian Perioperative Anesthesia Clinical Trials Group. Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium: A Cluster Randomized Crossover Trial. JAMA Surg. 2025 Mar 1;160(3):286-294. doi: 10.1001/jamasurg.2024.6602. | |
| 37744662 |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Aug 20, 2025 | |
| Unrelease | Aug 21, 2025 | |
| Release | Sep 2, 2025 |
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Multicenter, cluster-randomized, crossover trial
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| Liberal Intraoperative Benzodiazepine | Other | policy for liberal use of intraoperative benzodiazepine |
|
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 |
| New York |
| New York |
| 10065 |
| United States |
| Mazankowski Alberta Heart Institute | Edmonton | Alberta | T6G 2B7 | Canada |
| Royal Columbian Hospital | New Westminster | British Columbia | V3L 3W7 | Canada |
| Vancouver General Hospital | Vancouver | British Columbia | V5Z 1M9 | Canada |
| St. Paul's Hospital | Vancouver | British Columbia | V6Z 1Y6 | Canada |
| St. Boniface General Hospital | Winnipeg | Manitoba | R2H 2A6 | Canada |
| Queen Elizabeth II Health Sciences Centre | Halifax | Nova Scotia | B3H 3A7 | Canada |
| Hamilton Health Sciences, Hamilton General Hospital | Hamilton | Ontario | L8L 2X2 | Canada |
| Kingston General Hospital | Kingston | Ontario | K7L 2V7 | Canada |
| London Health Sciences Centre | London | Ontario | N6A 5W9 | Canada |
| Sunnybrook Health Sciences Centre | Toronto | Ontario | M4N 3M5 | Canada |
| St. Michael's Hospital | Toronto | Ontario | M5B 1W8 | Canada |
| Toronto General Hospital | Toronto | Ontario | M5G 2C4 | Canada |
| Montreal Heart Institute | Montreal | Quebec | H1T 1C8 | Canada |
| Jewish General Hospital | Montreal | Quebec | H3T 1E2 | Canada |
| Hôpital Laval | Québec | Quebec | G1V 4G5 | Canada |
| Centre Hospitalier Universitaire de Sherbrooke | Sherbrooke | Quebec | J1H 4C6 | Canada |
| Regina General Hospital | Regina | Saskatchewan | S4P 0W5 | Canada |
| Royal University Hospital | Saskatoon | Saskatchewan | S7N OW8 | Canada |
| Derived |
| Spence J, Belley-Cote E, Jacobsohn E, Lee SF, D'Aragon F, Avidan M, Mazer CD, Rousseau-Saine N, Rajamohan R, Pryor K, Klein R, Tan EC, Cameron M, Di Sante E, DeBorba E, Mustard M, Couture E, Zamper R, Law M, Djaiani G, Saha T, Choi S, Hedlin P, Pikaluk R, Lam WY, Deschamps A, Whitlock R, Dulong B, Devereaux PJ, Beaver C, Kloppenburg S, Oczkowski S, McIntyre WF, McFarling M, Lamy A, Vincent J, Connolly S; B-Free Investigators. 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. doi: 10.1016/j.cjco.2023.06.001. eCollection 2023 Sep. |
| 33721875 | Derived | 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. |
| Reset | Sep 18, 2025 |
| Release | Oct 15, 2025 |
| Reset | Nov 4, 2025 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Aug 20, 2025 | Aug 21, 2025 | |||
| Sep 2, 2025 | Sep 18, 2025 | |||
| Oct 15, 2025 | Nov 4, 2025 |
| ID | Term |
|---|---|
| D003693 | Delirium |
| ID | Term |
|---|---|
| D003221 | Confusion |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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