Clinical trial NCT03928236: Benzodiazepine-free Cardiac Anesthesia for Reduction of Postoperative Delirium
Official title: Benzodiazepine-free Cardiac Anesthesia for Reduction of Postoperative Delirium
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Delirium
Post-cardiac Surgery
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
First posted: 2019-04-26
Enrollment: 15886
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Multicenter, cluster-randomized, crossover trial
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Delirium
timeFrame: up to 72 hours post cardiac surgery
Secondary outcomes:
measure: Number of Days in ICU after Cardiac Surgery
timeFrame: through study completion, approximately 37 months
measure: Number of Days in Hospital after Cardiac Surgery
timeFrame: through study completion, approximately 37 months
measure: Incidence of In-hospital Mortality
timeFrame: through study completion, approximately 37 months
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Edmonton
country: Canada
facility: Mazankowski Alberta Heart Institute
state: Alberta
city: New Westminster
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences, Hamilton General Hospital
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montréal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Québec
country: Canada
facility: Hôpital Laval
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
city: Regina
country: Canada
facility: Regina General Hospital
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
Study officials:
affiliation: Population Health Research Institute
name: Jessica Spence, MD FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Manitoba
name: Eric Jacobsohn, MBChB MPHE
role: PRINCIPAL_INVESTIGATOR
affiliation: Population Health Research Institute
name: Stuart Connolly, MD FRCPC
role: STUDY_CHAIR
References:
citation: 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.