Awareness During General AnesthesiaMACSNCT00689091
Bispectral Index (BIS) Versus Electronic Alerts in the Prevention of Anesthesia Awareness: the Michigan Awareness Control Study
A study testing Bispectral Index Monitor and Electronic MAC alert in people with Awareness During General Anesthesia, run by University of Michigan at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Awareness During General Anesthesia
- What is being tested?
- Bispectral Index Monitor and Electronic MAC alert
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22,185 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to Jun 2010
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least 18 years of age, English-speaking, available for follow-up interview at one month.
Who cannot join
- Pre-existing neurologic or neuropsychiatric condition, surgical manipulation around forehead, not available for follow-up interview.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Medical School, University Hospital
Ann Arbor, Michigan, 48109
About this study
Official title: 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.
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:
- data capture is possible (i.e., not a paper record)
- data capture is active (i.e., "patient in room" has been electronically entered and end-tidal [Et] CO2 is detected)
- case has been identified as a general anesthetic
- "anesthesia induction end" has already been documented
- request for recovery room bed or transport to an intensive care unit has not been documented
- surgical dressing completion has not been documented
- The alerting system checks the most recent value (within a specified time period) of:
- Et Sevoflurane (MAC=2.0)
- Et Isoflurane (MAC=1.2)
- Et Desflurane (MAC=6)
- 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.
- Conditions
- Awareness During General Anesthesia
- Being tested
- Bispectral Index Monitor, Electronic MAC alert
- Keywords
- Awareness, BIS Monitor, electronic alerts, minimum, alveolar, concentration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bispectral Index MonitorDevice
Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.
Electronic MAC alertDevice
Comparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols.
| Study group | Role | What they receive |
|---|---|---|
| BIS group | Experimental | This group will have BIS values visible and will receive alerts when the value is >60. Receives: Device: Bispectral Index Monitor |
| MAC Alert | Active comparator | This group will receive an alert if total MAC (including intravenous infusions) is <0.5 age-adjusted. Receives: Device: Electronic MAC alert |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Percentage of Incidences With Explicit Recall in the BIS Versus MAC Alert Groups.
By modified intention-to-treat analysis
Measured: Outcome of awareness is assessed 30-days after the operation
Secondary outcomes (6)
Number of Participants With Dreams During Anesthesia Compared Between MAC or BIS Monitoring
Binary variables for whether participants recall dreaming or not.
Measured: During surgery (45 minutes - 18 hours), measured based on 30 day interviews
Percentage of Cases With Electronic Alerts
Measured: During surgery: (45 minutes - 18 hours)
Overall Use of Anesthetics Comparing the BIS to MAC Alerts.
Measured: 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
Measured: During recovery room stay: 30 minutes to 6 hours
Number of Participants Without Nausea or Vomiting
Measured: 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).
Measured: 30 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2008 (estimated)
- Study startMay 2008
- Primary completionApr 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Awareness During General AnesthesiaStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 22,185 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation for Anesthesia Education and Research, American Society of Anesthesiologists, Washington University School of Medicine, University of Chicago, University of Manitoba
- Responsible party
- Principal investigator, George Mashour, University of Michigan
- Investigators
- George A. Mashour, M.D., Ph.D., Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00689091
- Sponsor's protocol ID
- HUM00013626
- Acronym
- MACS
- Status last verified
- Nov 2017
- First submitted
- 29 May 2008
- Last updated
- 7 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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 25249789Shanks 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 25010744Avidan 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 19948045Mashour 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
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Controlled Trial Comparing Bispectral Index Monitoring to Electronic Alerts for Prevention of Awareness During Anesthesia in the General Population
- ClinicalTrials.gov ID
- NCT00689091
- Acronym / sponsor ID
- MACS / HUM00013626
- Conditions
- Awareness During General Anesthesia
- Keywords
- Awareness, BIS Monitor, electronic alerts, minimum, alveolar, concentration
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22,185 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- Foundation for Anesthesia Education and Research, American Society of Anesthesiologists, Washington University School of Medicine, University of Chicago, University of Manitoba
- Study start
- May 2008
- Primary completion
- Apr 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 3 Jun 2008 (estimated)
- Results
- Posted 17 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- data capture is possible (i.e., not a paper record)
- data capture is active (i.e., "patient in room" has been electronically entered and end-tidal [Et] CO2 is detected)
- case has been identified as a general anesthetic
- "anesthesia induction end" has already been documented
- request for recovery room bed or transport to an intensive care unit has not been documented
- surgical dressing completion has not been documented
- The alerting system checks the most recent value (within a specified time period) of:
- Et Sevoflurane (MAC=2.0)
- Et Isoflurane (MAC=1.2)
- Et Desflurane (MAC=6)
- 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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BIS group | Experimental | Device: Bispectral Index MonitorThis group will have BIS values visible and will receive alerts when the value is >60. |
| MAC Alert | Active comparator | Device: Electronic MAC alertThis group will receive an alert if total MAC (including intravenous infusions) is <0.5 age-adjusted. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- At least 18 years of age, English-speaking, available for follow-up interview at one month.
Key exclusion criteria (1 listed)
- Pre-existing neurologic or neuropsychiatric condition, surgical manipulation around forehead, not available for follow-up interview.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bispectral Index MonitorComparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols. | Device | BIS group |
| Electronic MAC alertComparison of two different alerting protocols. One using the bispectral index monitor and one using the MAC alerting protocols. | Device | MAC Alert |
Primary outcome
The Percentage of Incidences With Explicit Recall in the BIS Versus MAC Alert Groups.
Time frame: Outcome of awareness is assessed 30-days after the operation
By modified intention-to-treat analysis
6 secondary outcomes
Number of Participants With Dreams During Anesthesia Compared Between MAC or BIS Monitoring
Time frame: During surgery (45 minutes - 18 hours), measured based on 30 day interviews
Percentage of Cases With Electronic Alerts
Time frame: During surgery: (45 minutes - 18 hours)
Overall Use of Anesthetics Comparing the BIS to MAC Alerts.
Time frame: During surgery (45 minutes - 18 hours)
Time Till Discharge Readiness
Time frame: During recovery room stay: 30 minutes to 6 hours
Number of Participants Without Nausea or Vomiting
Time frame: During recovery room stay: 30 minutes to 6 hours
Comparison of the Prospective and Retrospective Approaches to the Study Awareness Incidence.
Time frame: 30 days after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25249789Vance 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.
- Derived from this study: PubMed 25010744Shanks 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.
- Derived from this study: PubMed 19948045Avidan 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.
- Derived from this study: PubMed 19891771Mashour 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.
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Awareness During General Anesthesia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
George A. Mashour, M.D., Ph.D. principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bispectral Index Monitor and Electronic MAC alert in people with Awareness During General Anesthesia, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Percentage of Incidences With Explicit Recall in the BIS Versus MAC Alert Groups. (time frame: Outcome of awareness is assessed 30-days after the operation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00689091, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2017.