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CompletedNCT00689091MACSUpdated Dec 7, 2017Results posted

Bispectral Index (BIS) Versus Electronic Alerts in the Prevention of Anesthesia Awareness: the Michigan Awareness Control Study

An interventional study of Bispectral Index Monitor and Electronic MAC alert in Awareness During General Anesthesia, sponsored by University of Michigan. Completed at 1 site in United States. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2017-12-07.

Sponsored by University of Michigan · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
22,185
Allocation
Randomized
Ages
18 Years to 100 Years
Sex
All
01

Study summary

Awareness during anesthesia is a problem receiving increased attention by patients, clinicians, and the general public. The incidence of intraoperative awareness has been reported to be between 1-2/1000 cases, but recent data suggest that this may be an overestimate. The Bispectral Index (BIS) Monitor is an electroencephalographic method of assessing depth of anesthesia that has been shown in one study to reduce the incidence of awareness during anesthesia in the high-risk population (Myles et al, 2004). In the study of Myles et al, the number needed to treat (NNT) in order to prevent one case of awareness in the high-risk population was 138, with an associated cost of approximately US$2200. Since the NNT and the associated cost of treatment would be much higher in the general population, the efficacy of the BIS monitor in preventing awareness in all anesthetized patients needs to be clearly established. Furthermore, recent data suggest that the BIS may not be useful in the high-risk population. The investigators propose a prospective, randomized, controlled trial comparing the BIS monitor to electronic alerts based on non-electroencephalographic gauges of anesthetic depth.

Read the detailed description

Electronic alerts have been developed and employed at our institution and have been shown to increase compliance with both clinical and administrative tasks (O'Reilly et al, 2006; Kheterpal et al, 2007). The investigators have developed electronic alerts for the purpose of informing the clinician of potentially insufficient anesthesia based on minimum alveolar concentration (MAC). The algorithm is as follows:

  • Every 5 minutes the alerting system checks every active case in our operating rooms. It takes approximately 1 second for this scan of all active cases to occur.

  • Conditions for an "active case" are:

    1. data capture is possible (i.e., not a paper record)
    2. data capture is active (i.e., "patient in room" has been electronically entered and end-tidal [Et] CO2 is detected)
    3. case has been identified as a general anesthetic
    4. "anesthesia induction end" has already been documented
    5. request for recovery room bed or transport to an intensive care unit has not been documented
    6. surgical dressing completion has not been documented

  • The alerting system checks the most recent value (within a specified time period) of:

    1. Et Sevoflurane (MAC=2.0)
    2. Et Isoflurane (MAC=1.2)
    3. Et Desflurane (MAC=6)
    4. Et Nitrous Oxide (MAC=105) and compares it to the MAC of each agent. It adds the resulting MAC values together for "current total MAC."
  • The system then checks for a charted propofol infusion in mcg/kg/min and divides by 150, assuming that 150 mcg/kg/min is "1.0 MAC" for propofol. The analogous concept of MAC for propofol is "Cp50"- the plasma or blood concentrations at which 50% of patients do not move in response to a noxious stimulus. Since the investigators do not have the technology at our institution to calculate Cp50 or Cp50-awake, the investigators have chosen the above propofol dose as an initial value based on clinical experience. The resultant MAC equivalent is added to current total MAC.
  • The system next checks for a dexmedetomidine infusion with a rate of 0.2 mcg/kg/hour or greater. If present, it multiplies the current total inhalational MAC by 2, as dexmedetomidine can reduce MAC by 50%.
  • At this point, the "current total MAC" is defined as: Et Sevo /2 + Et Iso /1.2 + Et Des/6 + Et Nitrous /105 + propofol rate (in mcg/kg/min)/150. If dexmedetomidine is >0.2 mcg/kg/hour, inhalational MAC is multiplied by 2.
  • If this total mac \< 0.50, it checks to see if a bolus of propofol, midazolam, etomidate, or thiopental has been given in the preceding 10 minutes.
  • It alerts the clinician signed into the case within 30-60 seconds if total age-adjusted MAC \< 0.50 AND no bolus has been documented in the last 10 minutes.

This will be the protocol in the MAC-guided group. In the BIS-guided group an electronic alert will be sent if the BIS value is >60. If an alert is triggered, the clinician electronically signed into the case receives an alphanumeric page stating "Potentially insufficient anesthesia, please check vaporizers and intravenous lines."

The investigators are collaborating with Washington University, the University of Chicago, and the University of Mannitoba, who will also be testing a MAC-based protocol in comparison to the BIS.

02

Conditions studied

  • Awareness During General Anesthesia

Keywords

  • Awareness
  • BIS Monitor
  • electronic alerts
  • minimum
  • alveolar
  • concentration
03

In context

Lead sponsor

University of Michigan is the lead sponsor of 1,475 studies on the registry; 196 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 128 (79%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 100 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • At least 18 years of age, English-speaking, available for follow-up interview at one month.

Exclusion criteria

Exclusion Criteria:

  • Pre-existing neurologic or neuropsychiatric condition, surgical manipulation around forehead, not available for follow-up interview.
05

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
22,185 participants (actual)

Study arms

  • Experimental
    BIS group

    This group will have BIS values visible and will receive alerts when the value is \>60.

    Device: Bispectral Index Monitor

  • Active comparator
    MAC Alert

    This group will receive an alert if total MAC (including intravenous infusions) is \<0.5 age-adjusted.

    Device: Electronic MAC alert

Interventions

  • DeviceBispectral Index Monitor

    Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.

  • DeviceElectronic MAC alert

    Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.

06

What researchers measure

Primary outcomes

  1. The Percentage of Incidences With Explicit Recall in the BIS Versus MAC Alert Groups.

    By modified intention-to-treat analysis

    Time frame: Outcome of awareness is assessed 30-days after the operation

Secondary outcomes

  1. Number of Participants With Dreams During Anesthesia Compared Between MAC or BIS Monitoring

    Binary variables for whether participants recall dreaming or not.

    Time frame: During surgery (45 minutes - 18 hours), measured based on 30 day interviews

  2. Percentage of Cases With Electronic Alerts

    Time frame: During surgery: (45 minutes - 18 hours)

  3. Overall Use of Anesthetics Comparing the BIS to MAC Alerts.

    Time frame: During surgery (45 minutes - 18 hours)

  4. Time Till Discharge Readiness

    measured in time within Post Anesthesia Care Unit ( PACU) until the participant is ready for discharge from PACU based on a composite of factors, including pain and neurologic status

    Time frame: During recovery room stay: 30 minutes to 6 hours

  5. Number of Participants Without Nausea or Vomiting

    Time frame: During recovery room stay: 30 minutes to 6 hours

  6. Comparison of the Prospective and Retrospective Approaches to the Study Awareness Incidence.

    There is controversy regarding the appropriate technique for assessing awareness during anesthesia with explicit recall. A total cohort was utilized to compare the incidence of awareness with recall as determined by formal interview vs. the incidence of awareness with recall based on spontaneous reports (in the same cohort).

    Time frame: 30 days after surgery

Other outcomes

  1. Relationship Between BIS Values and Hemodynamic Parameters.

    Time frame: Outcome of hemodynamic stability is assessed

  2. The Relationship Between Cumulative Deep Hypnotic Time, Anesthetic Doses, and Mortality.

    Time frame: Outcome of mortality is assessed

  3. Predictors of Post-traumatic Stress Disorder Based on the Type of Awareness Event.

    Time frame: Outcome of post-traumatic stress disorder is assessed with the covariate of awareness

  4. Anesthetic Induction Doses, Hypotension, and BIS Values.

    Time frame: Outcome of hypotension in relationship to induction doses and BIS values will be assessed

  5. Meta-Analysis of Awareness Events in Conjunction With the BAG-RECALL Study Based at Washington University.

    Time frame: Outcome of awareness is assessed

  6. Incidence of Post-traumatic Stress Disorder.

    Time frame: NEED VALUE HERE

07

Results

Posted Nov 17, 2014

Participant flow

Participant flow — Overall Study
MilestoneBispectral Index GroupMinimum Anesthesia Contration Alert
Started1083110770
Completed94609376
Not completed13711394

Outcome measures

PrimaryThe Percentage of Incidences With Explicit Recall in the BIS Versus MAC Alert Groups.

By modified intention-to-treat analysis

Time frame:
Outcome of awareness is assessed 30-days after the operation
Reported as:
Number · Percentage of participants/30days
The Percentage of Incidences With Explicit Recall in the BIS Versus MAC Alert Groups.
Percentage of participants/30daysBIS GroupMAC Alert
The Percentage of Incidences With Explicit Recall in the BIS Versus MAC Alert Groups.0.08 (0.04 to 0.16)0.12 (0.07 to 0.21)
SecondaryNumber of Participants With Dreams During Anesthesia Compared Between MAC or BIS Monitoring

Binary variables for whether participants recall dreaming or not.

Time frame:
During surgery (45 minutes - 18 hours), measured based on 30 day interviews
Reported as:
Count of participants · Participants
Number of Participants With Dreams During Anesthesia Compared Between MAC or BIS Monitoring
ParticipantsMAC AlertBIS Group
No dreaming91749352
Dreaming202108
SecondaryPercentage of Cases With Electronic Alerts
Time frame:
During surgery: (45 minutes - 18 hours)
Reported as:
Mean · Percentage of cases
Percentage of Cases With Electronic Alerts
Percentage of casesMAC AlertBIS Group
Percentage of Cases With Electronic Alerts2.4 ± 7.52.3 ± 6.6
SecondaryOverall Use of Anesthetics Comparing the BIS to MAC Alerts.
Time frame:
During surgery (45 minutes - 18 hours)
Reported as:
Median · mg
Overall Use of Anesthetics Comparing the BIS to MAC Alerts.
mgMAC AlertBIS Group
Overall Use of Anesthetics Comparing the BIS to MAC Alerts.0.9 (0.8 to 1.1)0.9 (0.8 to 1.1)
SecondaryTime Till Discharge Readiness

measured in time within Post Anesthesia Care Unit ( PACU) until the participant is ready for discharge from PACU based on a composite of factors, including pain and neurologic status

Time frame:
During recovery room stay: 30 minutes to 6 hours
Reported as:
Median · minutes
Time Till Discharge Readiness
minutesMAC AlertBIS Group
Time Till Discharge Readiness98 (66 to 140)95 (64 to 138)
SecondaryNumber of Participants Without Nausea or Vomiting
Time frame:
During recovery room stay: 30 minutes to 6 hours
Reported as:
Count of participants · Participants
Number of Participants Without Nausea or Vomiting
ParticipantsMAC AlertBIS Group
No nausea61844042
No vomiting71494617
SecondaryComparison of the Prospective and Retrospective Approaches to the Study Awareness Incidence.

There is controversy regarding the appropriate technique for assessing awareness during anesthesia with explicit recall. A total cohort was utilized to compare the incidence of awareness with recall as determined by formal interview vs. the incidence of awareness with recall based on spontaneous reports (in the same cohort).

Time frame:
30 days after surgery
Reported as:
Number · participants
Comparison of the Prospective and Retrospective Approaches to the Study Awareness Incidence.
participantsSpontaneous ReportingFormal Interview Report
Yes (awareness with recall)319
No (no awareness with recall)1883318817
Other pre-specifiedRelationship Between BIS Values and Hemodynamic Parameters.
Time frame:
Outcome of hemodynamic stability is assessed

Results for this outcome have not been posted.

Other pre-specifiedThe Relationship Between Cumulative Deep Hypnotic Time, Anesthetic Doses, and Mortality.
Time frame:
Outcome of mortality is assessed

Results for this outcome have not been posted.

Other pre-specifiedPredictors of Post-traumatic Stress Disorder Based on the Type of Awareness Event.
Time frame:
Outcome of post-traumatic stress disorder is assessed with the covariate of awareness

Results for this outcome have not been posted.

Other pre-specifiedAnesthetic Induction Doses, Hypotension, and BIS Values.
Time frame:
Outcome of hypotension in relationship to induction doses and BIS values will be assessed

Results for this outcome have not been posted.

Other pre-specifiedMeta-Analysis of Awareness Events in Conjunction With the BAG-RECALL Study Based at Washington University.
Time frame:
Outcome of awareness is assessed

Results for this outcome have not been posted.

Other pre-specifiedIncidence of Post-traumatic Stress Disorder.
Time frame:
NEED VALUE HERE

Results for this outcome have not been posted.

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Bispectral Index Group—0/9,460 (0%)0/9,460 (0%)
Miniumum Anesthesia Concentration Alert—0/9,376 (0%)0/9,376 (0%)
Most frequent other events
Most frequent other events
EventBispectral Index GroupMiniumum Anesthesia Concentration Alert
Non life threatening adverse eventsCardiac disorders0/94600/9376

Baseline characteristics

Age, Continuous
Age, Continuous(years)Bispectral Index GroupMinimum Anesthesia Concentration AlertTotal
Median53 (41 to 64)53 (41 to 64)53 (41 to 64)
Sex: Female, Male
Sex: Female, Male(Participants)Bispectral Index GroupMinimum Anesthesia Concentration AlertTotal
Female5,2235,17510398
Male4,2374,2018438
08

Study locations

1 site
  • University of Michigan Medical School, University Hospital
    Ann Arbor, Michigan 48109, United States
09

References and documents

Publications

  • Vance JL, Shanks AM, Woodrum DT. Intraoperative bispectral index monitoring and time to extubation after cardiac surgery: secondary analysis of a randomized controlled trial. BMC Anesthesiol. 2014 Sep 18;14:79. doi: 10.1186/1471-2253-14-79. eCollection 2014. PubMed 25249789 ↗
  • Shanks AM, Avidan MS, Kheterpal S, Tremper KK, Vandervest JC, Cavanaugh JM, Mashour GA. Alerting thresholds for the prevention of intraoperative awareness with explicit recall: a secondary analysis of the Michigan Awareness Control Study. Eur J Anaesthesiol. 2015 May;32(5):346-53. doi: 10.1097/EJA.0000000000000123. PubMed 25010744 ↗
  • 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. PubMed 19948045 ↗
  • 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. PubMed 19891771 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 7, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00689091
Lead sponsor
University of Michigan
Collaborators
Foundation for Anesthesia Education and Research, American Society of Anesthesiologists, Washington University School of Medicine, University of Chicago, University of Manitoba
Responsible party
George Mashour (Assistant Professor of Anesthesiology and Neurosurgery, University of Michigan) — Principal investigator
First posted
Jun 3, 2008
Start date
May 2008
Primary completion
Apr 2010
Completion
Jun 2010
Results posted
Nov 17, 2014
Last update
Dec 7, 2017

Study contacts

George A. Mashour, M.D., Ph.D.
principal investigator · University of Michigan

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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