Benzodiazepine-free Cardiac Anesthesia for Reduction of Postoperative Delirium

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Benzodiazepine-free Cardiac Anesthesia for Reduction of Postoperative Delirium

Conditions
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Delirium, Post-cardiac Surgery

Intervention / Treatment
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* Other: Limited Intraoperative Benzodiazepine
* Other: Liberal Intraoperative Benzodiazepine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Multicenter, cluster-randomized, crossover trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Limited Benzodiazepine Policy<br>Policy of no routine use of any intraoperative benzodiazepines. | Other: Limited Intraoperative Benzodiazepine<br>* policy for limited use of intraoperative benzodiazepine<br>|
| Active Comparator: Liberal Benzodiazepine Policy<br>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<br>* policy for liberal use of intraoperative benzodiazepine<br>|

What is the study measuring?
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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 |