Study Evaluating Whether the Bispectral Index Prevents Patients at Higher Risk From Being Awake During Surgery and Anesthesia

Study Overview
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Brief Summary
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The overall purpose of this study is to see if a Bispectral Index (BIS) monitor, a Food and Drug Administration (FDA) approved brain monitoring device, will help to reduce the risk of patients remembering being awake during surgery. The BIS monitor may be able to measure how asleep a patient is during surgery. Using the BIS monitor to guide anesthesia will be compared with using the concentration of anesthetic gas to guide anesthesia.

Detailed Description
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The incidence of anesthesia awareness (AA) is 0.1-0.2% and may result in post traumatic stress disorders. For some patients, owing to illness, medications, substance misuse or surgery, the risk approaches 1%. The B-AWARE Study by Myles et al. suggested that the bispectral index (BIS) monitor, which reportedly reflects anesthetic depth, may decrease the incidence of AA in higher risk patients by 82%. The American Society of Anesthesiologists has published a practice advisory on AA, which does not recommend the routine use of cerebral function monitors. We propose to test the hypothesis that an anesthetic protocol based on BIS decreases the incidence of AA among higher risk patients compared with an anesthetic protocol based on the end-tidal anesthetic gas (ETAG) concentration. We have completed a randomized, single-blinded prospective feasibility study (The B-Unaware Trial) which enrolled 2000 patients at higher risk for AA. Four patients (0.21%; 95% CI=0.06% to 0.57%) had definite AA, of whom two were in the BIS-guided group and two in the ETAG-guided group. Nine patients (0.46%; 95% CI=0.22% to 0.91%) had definite or possible AA, of whom six were in the BIS-guided group and three in the ETAG-guided group. The BAG RECALL study will be a multi-center, prospective, single-blinded, randomized study enrolling 6000 patients at higher risk for AA. The BAG RECALL study is adequately powered and rigorously designed to answer with a reasonable degree of scientific probability whether BIS guidance results in clinically relevant reduction in anesthesia awareness among higher risk patients undergoing general anesthesia. At the University of Michigan, a parallel study will be conducted - Michigan Awareness Control Study, MACS (NCT00689091) - enrolling 30,000 patients to assess whether the BIS monitor decreases the likelihood of anesthesia awareness among all patients undergoing general anesthesia, regardless of their risk profile. The investigators of this study and the BAG-RECALL study have collaborated in designing these studies and are pre-specifying that common outcome measures will be examined collaboratively including data from both studies.

Official Title
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BAG-RECALL Study: BIS or Anesthesia Gas to Reduce Explicit Recall

Conditions
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Explicit Recall of Intra-Operative Events

Intervention / Treatment
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* Behavioral: Bispectral index protocol
* Behavioral: End tidal anesthetic gas-guided


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MUST HAVE: General Anesthesia with volatile anesthetic PATIENT CHARACTERISTICS Major Criteria (Must have any 1 of the following:) Planned open heart surgery Medications - anticonvulsants, abuse of opiates, benzodiazepines, cocaine EF<40% Prior history of awareness (recall) History of difficult intubation or anticipated difficult intubation ASA IV or V status Aortic stenosis End stage lung disease Marginal exercise tolerance not secondary to musculoskeletal dysfunction Pulmonary hypertension Daily alcohol consumption Exclusion Criteria: Surgical procedure that prevents the use of the BIS (e.g. surgery of forehead) Patient positioning prevents use of the BIS Surgery with wake-up test. Less than 18 years of age Vulnerable populations, such as those with dementia and those unable to provide informed consent. Stroke with residual neurological deficits -

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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Bispectral index-guided protocol | Behavioral: Bispectral index protocol<br>* Aim to titrate anesthesia to maintain BIS between 40 and 60.<br>|
| Active Comparator: 2<br>End-tidal anesthetic gas-guided protocol | Behavioral: End tidal anesthetic gas-guided<br>* Aim to maintain anesthetic gas between 0.7 and 1.3 MAC equivalents<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of explicit recall of events during the surgical and anesthetic periods. |  | Three years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Meta-analysis for anesthesia awareness incorporating higher risk patients from the completed B-Unaware Trial (NCT00281489), the BAG-RECALL Trial, and the Michigan Awareness Control Study (MACS)(NCT00689091). |  | Three years | 
| Incidence of post-traumatic stress disorder (PTSD). |  | Five years | 
| Association between type of awareness event and PTSD, and whether the PTSD is associated with late reporting (30 days) of awareness. |  | 5 years | 
| Types of dreams and their relationship to BIS and ETAG. |  | Three years | 
| The relationship between deep hypnotic time, anesthetic dose (MAC), mean arterial pressure, and end tidal carbon dioxide, and early (one-month) and late (one-year) mortality. |  | Four years | 
| Relationship between BIS, heart rate and blood pressure. |  | Three years | 
| Relationship between BIS and anesthesia dose and concentration. |  | Three years | 
| Association between baseline BIS values, patient health and early (one-month) and late (one-year) mortality. |  | Four years | 
| Interaction between hemispheric dominance and BIS. |  | Three years | 
| Effect of red hair phenotypes on the relationship between ETAG and BIS. |  | Three years | 
| Refinement of risk factors for anesthesia awareness. |  | Three years | 
| Relationship between rising BIS in the PACU and first memory after surgery. |  | Three years | 
| Postoperative delirium. |  | Three years | 
| BIS and mixed venous saturation. |  | Three years | 
| Induction of anesthesia and hypotension. |  | Three years | 
| Incidence of postoperative nausea and vomiting. |  | Three years | 
| Incidence of and severity of postoperative pain. |  | Three years | 
| Effect of BIS and ETAG protocols on time to open eyes, time to extubation, and time spent in the postoperative recovery unit. |  | Three years | 
| Effect of a defasciculating dose of a non-depolarizing muscle relaxant on BIS. |  | Three years | 
| The effect of patient temperature on BIS. |  | Three years | 
| Incidence of recall of traveling to the OR among patients who receive midazolam in the holding area and whose initial BIS reading in the OR is > 60. |  | Three years | 
| Relationship between BIS, ETAG and EEG parameters. |  | Three years | 
| Annual assessment of practitioners' abilities to interpret BIS tracings and to identify artefacts. |  | Three years | 
| Differences in anesthesia practice among four institutions in the USA and Canada as judged by anesthetic doses and BIS readings. |  | Three years | 
| Effect of BIS and ETAG protocols on anesthetic dose administration and on BIS readings. |  | Three years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BIS, Anesthesia, Awareness, Bispectral, Recall