Clinical trial NCT00682825: Study Evaluating Whether the Bispectral Index Prevents Patients at Higher Risk From Being Awake During Surgery and Anesthesia
Official title: BAG-RECALL Study: BIS or Anesthesia Gas to Reduce Explicit Recall
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Explicit Recall of Intra-Operative Events
Keywords: Anesthesia
Awareness
Bispectral
BIS
Recall
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Foundation for Anesthesia Education and Research
name: American Society of Anesthesiologists
name: University of Chicago
name: University of Manitoba
name: University of Michigan
First posted: 2008-05-22
Enrollment: 6000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

MUST HAVE:

General Anesthesia with volatile anesthetic

PATIENT CHARACTERISTICS

Major Criteria (Must have any 1 of the following:)

1. Planned open heart surgery
2. Medications - anticonvulsants, abuse of opiates, benzodiazepines, cocaine
3. EF\<40%
4. Prior history of awareness (recall)
5. History of difficult intubation or anticipated difficult intubation
6. ASA IV or V status
7. Aortic stenosis
8. End stage lung disease
9. Marginal exercise tolerance not secondary to musculoskeletal dysfunction
10. Pulmonary hypertension
11. Daily alcohol consumption

Exclusion Criteria:

1. Surgical procedure that prevents the use of the BIS (e.g. surgery of forehead)
2. Patient positioning prevents use of the BIS
3. Surgery with wake-up test.
4. Less than 18 years of age
5. Vulnerable populations, such as those with dementia and those unable to provide informed consent.
6. Stroke with residual neurological deficits

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Primary outcomes:
measure: The incidence of explicit recall of events during the surgical and anesthetic periods.
timeFrame: Three years
Secondary outcomes:
measure: 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).
timeFrame: Three years
measure: Incidence of post-traumatic stress disorder (PTSD).
timeFrame: Five years
measure: Association between type of awareness event and PTSD, and whether the PTSD is associated with late reporting (30 days) of awareness.
timeFrame: 5 years
measure: Types of dreams and their relationship to BIS and ETAG.
timeFrame: Three years
measure: 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.
timeFrame: Four years
measure: Relationship between BIS, heart rate and blood pressure.
timeFrame: Three years
measure: Relationship between BIS and anesthesia dose and concentration.
timeFrame: Three years
measure: Association between baseline BIS values, patient health and early (one-month) and late (one-year) mortality.
timeFrame: Four years
measure: Interaction between hemispheric dominance and BIS.
timeFrame: Three years
measure: Effect of red hair phenotypes on the relationship between ETAG and BIS.
timeFrame: Three years
measure: Refinement of risk factors for anesthesia awareness.
timeFrame: Three years
measure: Relationship between rising BIS in the PACU and first memory after surgery.
timeFrame: Three years
measure: Postoperative delirium.
timeFrame: Three years
measure: BIS and mixed venous saturation.
timeFrame: Three years
measure: Induction of anesthesia and hypotension.
timeFrame: Three years
measure: Incidence of postoperative nausea and vomiting.
timeFrame: Three years
measure: Incidence of and severity of postoperative pain.
timeFrame: Three years
measure: Effect of BIS and ETAG protocols on time to open eyes, time to extubation, and time spent in the postoperative recovery unit.
timeFrame: Three years
measure: Effect of a defasciculating dose of a non-depolarizing muscle relaxant on BIS.
timeFrame: Three years
measure: The effect of patient temperature on BIS.
timeFrame: Three years
measure: 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.
timeFrame: Three years
measure: Relationship between BIS, ETAG and EEG parameters.
timeFrame: Three years
measure: Annual assessment of practitioners' abilities to interpret BIS tracings and to identify artefacts.
timeFrame: Three years
measure: Differences in anesthesia practice among four institutions in the USA and Canada as judged by anesthetic doses and BIS readings.
timeFrame: Three years
measure: Effect of BIS and ETAG protocols on anesthetic dose administration and on BIS readings.
timeFrame: Three years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: St Louis
country: United States
facility: Washington University
state: Missouri
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
Study officials:
affiliation: Washington University School of Medicine
name: Michael S Avidan, MBBCh FCA
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Chicago
name: David Glick, MD
role: STUDY_DIRECTOR
affiliation: University of Manitoba
name: Eric Jacobsohn, MBChB
role: STUDY_CHAIR
affiliation: University of Chicago
name: Michael O'Connor, MD
role: STUDY_DIRECTOR
affiliation: Washington University School of Medicine
name: Alex S Evers, MD
role: STUDY_CHAIR
References:
citation: Myles PS, Leslie K, McNeil J, Forbes A, Chan MT. Bispectral index monitoring to prevent awareness during anaesthesia: the B-Aware randomised controlled trial. Lancet. 2004 May 29;363(9423):1757-63. doi: 10.1016/S0140-6736(04)16300-9.
citation: Avidan MS, Zhang L, Burnside BA, Finkel KJ, Searleman AC, Selvidge JA, Saager L, Turner MS, Rao S, Bottros M, Hantler C, Jacobsohn E, Evers AS. Anesthesia awareness and the bispectral index. N Engl J Med. 2008 Mar 13;358(11):1097-108. doi: 10.1056/NEJMoa0707361.
citation: Avidan MS, Palanca BJ, Glick D, Jacobsohn E, Villafranca A, O'Connor M, Mashour GA; BAG-RECALL Study Group. Protocol for the BAG-RECALL clinical trial: a prospective, multi-center, randomized, controlled trial to determine whether a bispectral index-guided protocol is superior to an anesthesia gas-guided protocol in reducing intraoperative awareness with explicit recall in high risk surgical patients. BMC Anesthesiol. 2009 Nov 30;9:8. doi: 10.1186/1471-2253-9-8.
citation: Mashour GA, Tremper KK, Avidan MS. Protocol for the "Michigan Awareness Control Study": A prospective, randomized, controlled trial comparing electronic alerts based on bispectral index monitoring or minimum alveolar concentration for the prevention of intraoperative awareness. BMC Anesthesiol. 2009 Nov 5;9:7. doi: 10.1186/1471-2253-9-7.
citation: Mashour GA, Esaki RK, Tremper KK, Glick DB, O'Connor M, Avidan MS. A novel classification instrument for intraoperative awareness events. Anesth Analg. 2010 Mar 1;110(3):813-5. doi: 10.1213/ANE.0b013e3181b6267d. Epub 2009 Aug 27.
citation: Willingham M, Ben Abdallah A, Gradwohl S, Helsten D, Lin N, Villafranca A, Jacobsohn E, Avidan M, Kaiser H. Association between intraoperative electroencephalographic suppression and postoperative mortality. Br J Anaesth. 2014 Dec;113(6):1001-8. doi: 10.1093/bja/aeu105. Epub 2014 May 22.
citation: Whitlock EL, Torres BA, Lin N, Helsten DL, Nadelson MR, Mashour GA, Avidan MS. Postoperative delirium in a substudy of cardiothoracic surgical patients in the BAG-RECALL clinical trial. Anesth Analg. 2014 Apr;118(4):809-17. doi: 10.1213/ANE.0000000000000028.
citation: Avidan MS, Jacobsohn E, Glick D, Burnside BA, Zhang L, Villafranca A, Karl L, Kamal S, Torres B, O'Connor M, Evers AS, Gradwohl S, Lin N, Palanca BJ, Mashour GA; BAG-RECALL Research Group. Prevention of intraoperative awareness in a high-risk surgical population. N Engl J Med. 2011 Aug 18;365(7):591-600. doi: 10.1056/NEJMoa1100403.