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

A Prospective, Randomized, Controlled Trial Comparing Bispectral Index Monitoring to Electronic Alerts for Prevention of Awareness During Anesthesia in the General Population

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.

Study Overview

• Status: Completed
• Conditions: Awareness During General Anesthesia
• Intervention / Treatment: Device: Bispectral Index Monitor; Device: Electronic MAC alert

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.

• Study Type: Interventional
• Enrollment (Actual): 22185
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIS group; This group will have BIS values visible and will receive alerts when the value is >60.	Device: Bispectral Index Monitor; Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.
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; Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Incidences With Explicit Recall in the BIS Versus MAC Alert Groups.	By modified intention-to-treat analysis	Outcome of awareness is assessed 30-days after the operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dreams During Anesthesia Compared Between MAC or BIS Monitoring	Binary variables for whether participants recall dreaming or not.	During surgery (45 minutes - 18 hours), measured based on 30 day interviews
Percentage of Cases With Electronic Alerts		During surgery: (45 minutes - 18 hours)
Overall Use of Anesthetics Comparing the BIS to MAC Alerts.		During surgery (45 minutes - 18 hours)
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	During recovery room stay: 30 minutes to 6 hours
Number of Participants Without Nausea or Vomiting		During recovery room stay: 30 minutes to 6 hours
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).	30 days after surgery

Other Outcome Measures

Outcome Measure	Time Frame
Relationship Between BIS Values and Hemodynamic Parameters.	Outcome of hemodynamic stability is assessed
The Relationship Between Cumulative Deep Hypnotic Time, Anesthetic Doses, and Mortality.	Outcome of mortality is assessed
Predictors of Post-traumatic Stress Disorder Based on the Type of Awareness Event.	Outcome of post-traumatic stress disorder is assessed with the covariate of awareness
Anesthetic Induction Doses, Hypotension, and BIS Values.	Outcome of hypotension in relationship to induction doses and BIS values will be assessed
Meta-Analysis of Awareness Events in Conjunction With the BAG-RECALL Study Based at Washington University.	Outcome of awareness is assessed
Incidence of Post-traumatic Stress Disorder.	NEED VALUE HERE

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: University of Manitoba; Washington University School of Medicine; University of Chicago; American Society of Anesthesiologists; Foundation for Anesthesia Education and Research
• Investigators: Principal Investigator: George A. Mashour, M.D., Ph.D., University of Michigan

Publications and helpful links

General 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: May 29, 2008
• First Submitted That Met QC Criteria: May 29, 2008
• First Posted (Estimate): June 3, 2008

Study Record Updates

• Last Update Posted (Actual): December 7, 2017
• Last Update Submitted That Met QC Criteria: November 3, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: concentration; Awareness; BIS Monitor; electronic alerts; minimum; alveolar
• Other Study ID Numbers: HUM00013626

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No