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

• Sponsor: University of Michigan (Other)
• Overall Status: Completed
• CT.gov ID: NCT00689091
• Collaborator: Foundation for Anesthesia Education and Research (Other), American Society of Anesthesiologists (Other), Washington University School of Medicine (Other), University of Chicago (Other), University of Manitoba (Other)
• Enrollment: 22,185
• Location: 1
• Arms: 2
• Duration (Months): 25
• Patients Per Site Per Month: 887.3

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Awareness During General Anesthesia	Device: Bispectral Index Monitor; Device: Electronic MAC alert	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 22185 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Prospective, Randomized, Controlled Trial Comparing Bispectral Index Monitoring to Electronic Alerts for Prevention of Awareness During Anesthesia in the General Population
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. The Percentage of Incidences With Explicit Recall in the BIS Versus MAC Alert Groups. [Outcome of awareness is assessed 30-days after the operation]

   By modified intention-to-treat analysis

Secondary Outcome Measures

1. Number of Participants With Dreams During Anesthesia Compared Between MAC or BIS Monitoring [During surgery (45 minutes - 18 hours), measured based on 30 day interviews]

   Binary variables for whether participants recall dreaming or not.

2. Percentage of Cases With Electronic Alerts [During surgery: (45 minutes - 18 hours)]

3. Overall Use of Anesthetics Comparing the BIS to MAC Alerts. [During surgery (45 minutes - 18 hours)]

4. Time Till Discharge Readiness [During recovery room stay: 30 minutes to 6 hours]

   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

5. Number of Participants Without Nausea or Vomiting [During recovery room stay: 30 minutes to 6 hours]

6. Comparison of the Prospective and Retrospective Approaches to the Study Awareness Incidence. [30 days after surgery]

   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).

Other Outcome Measures

1. Relationship Between BIS Values and Hemodynamic Parameters. [Outcome of hemodynamic stability is assessed]

2. The Relationship Between Cumulative Deep Hypnotic Time, Anesthetic Doses, and Mortality. [Outcome of mortality is assessed]

3. 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]

4. Anesthetic Induction Doses, Hypotension, and BIS Values. [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. [Outcome of awareness is assessed]

6. Incidence of Post-traumatic Stress Disorder. [NEED VALUE HERE]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: 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:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Medical School, University Hospital	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan
• Foundation for Anesthesia Education and Research
• American Society of Anesthesiologists
• Washington University School of Medicine
• University of Chicago
• University of Manitoba

Investigators

• Principal Investigator: George A. Mashour, M.D., Ph.D., University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: George Mashour, Assistant Professor of Anesthesiology and Neurosurgery, University of Michigan
• ClinicalTrials.gov Identifier: NCT00689091
• Other Study ID Numbers: HUM00013626
• First Posted: Jun 3, 2008
• Last Update Posted: Dec 7, 2017
• Last Verified: Nov 1, 2017

• Keywords provided by George Mashour, Assistant Professor of Anesthesiology and Neurosurgery, University of Michigan: Awareness; BIS Monitor; electronic alerts; minimum; alveolar; concentration

Study Results

Participant Flow

Pre-assignment Detail	22,185 patients were recruited but 584 were excluded after recruitment due to change in anesthetic technique, case cancellation, withdrawal, or death. Therefore, 21,601 patients were randomized.

Arm/Group Title	Bispectral Index Group	Minimum Anesthesia Contration Alert
Arm/Group Description	This group will have BIS values visible and will receive alerts when the value is >60. Bispectral Index Monitor: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.	This group will receive an alert if total MAC (Minimum Anesthesia Concenration) (including intravenous infusions) is <0.5 age-adjusted. Electronic MAC alert: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.
Period Title: Overall Study
STARTED	10831	10770
COMPLETED	9460	9376
NOT COMPLETED	1371	1394

Baseline Characteristics

Arm/Group Title	Bispectral Index Group	Minimum Anesthesia Concentration Alert	Total
Arm/Group Description	This group will have BIS values visible and will receive alerts when the value is >60. Bispectral Index Monitor: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.	This group will receive an alert if total MAC (including intravenous infusions) is <0.5 age-adjusted. Electronic MAC alert: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.	Total of all reporting groups
Overall Participants	9,460	9,376	18836
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	53	53	53
Sex: Female, Male (Count of Participants)
Female	5,223 NaN	5,175 NaN	10398 55.2%
Male	4,237 NaN	4,201 NaN	8438 44.8%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BIS Group	MAC Alert
Arm/Group Description	This group will have BIS values visible and will receive alerts when the value is >60. Bispectral Index Monitor: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.	This group will receive an alert if total MAC (including intravenous infusions) is <0.5 age-adjusted. Electronic MAC alert: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.
Measure Participants	9,460	9,376
Number (95% Confidence Interval) [Percentage of participants/30days]	0.08 NaN	0.12 NaN

2. Secondary Outcome

Title	Number of Participants With Dreams During Anesthesia Compared Between MAC or BIS Monitoring
Description	Binary variables for whether participants recall dreaming or not.
Time Frame	During surgery (45 minutes - 18 hours), measured based on 30 day interviews

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MAC Alert	BIS Group
Arm/Group Description	This group will receive an alert if total MAC (including intravenous infusions) is <0.5 age-adjusted. Electronic MAC alert: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.	This group will have BIS values visible and will receive alerts when the value is >60. Bispectral Index Monitor: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.
Measure Participants	9376	9460
No dreaming	9174 NaN	9352 NaN
Dreaming	202 NaN	108 NaN

3. Secondary Outcome

Title	Percentage of Cases With Electronic Alerts
Time Frame	During surgery: (45 minutes - 18 hours)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MAC Alert	BIS Group
Arm/Group Description	This group will receive an alert if total MAC (including intravenous infusions) is <0.5 age-adjusted. Electronic MAC alert: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.	This group will have BIS values visible and will receive alerts when the value is >60. Bispectral Index Monitor: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.
Measure Participants	9376	9460
Mean (Standard Deviation) [Percentage of cases]	2.4 (7.5)	2.3 (6.6)

4. Secondary Outcome

Title	Overall Use of Anesthetics Comparing the BIS to MAC Alerts.
Time Frame	During surgery (45 minutes - 18 hours)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MAC Alert	BIS Group
Arm/Group Description	This group will receive an alert if total MAC (including intravenous infusions) is <0.5 age-adjusted. Electronic MAC alert: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.	This group will have BIS values visible and will receive alerts when the value is >60. Bispectral Index Monitor: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.
Measure Participants	9376	9460
Median (Inter-Quartile Range) [mg]	0.9	0.9

5. Secondary Outcome

Title	Time Till Discharge Readiness
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MAC Alert	BIS Group
Arm/Group Description	This group will receive an alert if total MAC (including intravenous infusions) is <0.5 age-adjusted. Electronic MAC alert: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.	This group will have BIS values visible and will receive alerts when the value is >60. Bispectral Index Monitor: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.
Measure Participants	9376	9460
Median (Inter-Quartile Range) [minutes]	98	95

6. Secondary Outcome

Title	Number of Participants Without Nausea or Vomiting
Time Frame	During recovery room stay: 30 minutes to 6 hours

Outcome Measure Data

Analysis Population Description

Nausea and vomiting numbers were dependent on nurse reporting; as not all nurses did, the participants analyzed are fewer than the total number in the study.

Arm/Group Title	MAC Alert	BIS Group
Arm/Group Description	This group will receive an alert if total MAC (including intravenous infusions) is <0.5 age-adjusted. Electronic MAC alert: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.	This group will have BIS values visible and will receive alerts when the value is >60. Bispectral Index Monitor: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.
Measure Participants	7329	4707
No nausea	6184 NaN	4042 NaN
No vomiting	7149 NaN	4617 NaN

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Spontaneous Reporting	Formal Interview Report
Arm/Group Description	any time up to 30 days	at 30 days
Measure Participants	18836	18836
Yes (awareness with recall)	3 NaN	19 NaN
No (no awareness with recall)	18833 NaN	18817 NaN

8. Other Pre-specified Outcome

Title	Relationship Between BIS Values and Hemodynamic Parameters.
Time Frame	Outcome of hemodynamic stability is assessed

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	The Relationship Between Cumulative Deep Hypnotic Time, Anesthetic Doses, and Mortality.
Time Frame	Outcome of mortality is assessed

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Other Pre-specified Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Other Pre-specified Outcome

Title	Anesthetic Induction Doses, Hypotension, and BIS Values.
Time Frame	Outcome of hypotension in relationship to induction doses and BIS values will be assessed

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Other Pre-specified Outcome

Title	Meta-Analysis of Awareness Events in Conjunction With the BAG-RECALL Study Based at Washington University.
Time Frame	Outcome of awareness is assessed

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Other Pre-specified Outcome

Title	Incidence of Post-traumatic Stress Disorder.
Time Frame	NEED VALUE HERE

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Bispectral Index Group		Miniumum Anesthesia Concentration Alert
Arm/Group Description	This group will have BIS values visible and will receive alerts when the value is >60. Bispectral Index Monitor: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.		This group will receive an alert if total MAC (including intravenous infusions) is <0.5 age-adjusted. Electronic MAC alert: Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.
All Cause Mortality
	Bispectral Index Group		Miniumum Anesthesia Concentration Alert
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bispectral Index Group		Miniumum Anesthesia Concentration Alert
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9460 (0%)		0/9376 (0%)
Other (Not Including Serious) Adverse Events
	Bispectral Index Group		Miniumum Anesthesia Concentration Alert
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9460 (0%)		0/9376 (0%)
Cardiac disorders
Non life threatening adverse events	0/9460 (0%)		0/9376 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.