BIS Monitor Anesthesia for Neurocognitive Disorder

(POEGEA Trial)

Overseen By Nadia Godin

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: Ciusss de L'Est de l'Île de Montréal

Disqualifiers: Dementia, Severe cognitive impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 17

Duration: Intraoperative

314 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of the study is to investigate, in patients aged 70 years and over undergoing major non-cardiac surgery, the effect of electroencephalic (EEG)-guided anesthesia on postoperative neurocognitive disorders when controlling for intraoperative nociception, personalized blood pressure targets and using full information provided by the processed EEG monitor (including burst suppression ratio, density spectral array and raw EEG waveform). This prospective, randomized, controlled trial will be conducted in a single Canadian university hospital. Patients aged 70 years and over, undergoing elective major non-cardiac surgery will be included. The administration of sevoflurane will be adjusted to maintain a BIS value between 40 and 60, a suppression Ratio at 0%, a direct EEG display without any suppression time and a spectrogram with most of the EEG wave frequency within the alpha, theta and delta frequencies in the EEG-guided group. In the control group sevoflurane will be administered to achieve an age-adjusted minimum alveolar concentration of \[0.8-1.2\]. A nociception monitor will guide intraoperative opioids' infusion and individual blood pressure targets will be personalized in both groups. The primary endpoint is the incidence of neurocognitive disorder (NCD) at postoperative day 1 evaluated by the Montréal Cognitive Assessment. Secondary endpoints include the incidence of postoperative neurocognitive disorder at different timepoints and the evaluation of cognitive trajectories among EEG-guided and control groups.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of EEG-guided anesthesia for neurocognitive disorder?

Research suggests that EEG-guided anesthesia, which uses brain activity monitoring, can reduce the risk of patients becoming aware during surgery. However, there is not enough evidence to show it prevents neurocognitive disorders or improves long-term outcomes after surgery. ^{1 2 3 4 5}

Is BIS Monitor Anesthesia safe for humans?

Research shows that using the BIS monitor during anesthesia can help reduce the amount of anesthesia needed and speed up recovery, which suggests it is generally safe. It also helps prevent anesthesia awareness, a serious complication, indicating its safety in monitoring anesthesia levels. ^{4 6 7 8 9}

How is EEG-guided anesthesia different from other treatments for neurocognitive disorder?

EEG-guided anesthesia, using the Bispectral Index (BIS), is unique because it monitors brain activity to ensure the right depth of anesthesia, reducing the risk of awareness during surgery. This approach is different from standard methods that rely solely on anesthetic gas levels, offering a more precise way to manage anesthesia. ^{1 4 9 10 11}

Research Team

Philippe Richebé, MD, PhD

Principal Investigator

Hôpital Maisonneuve-Rosemont - CIUSSS de l'Est de l'Ile de Montréal - Canada

Eligibility Criteria

This trial is for patients aged 70 or older who are undergoing major non-cardiac surgery and have an expected anesthesia time over 60 minutes. They must be able to communicate in English or French, without severe cognitive impairments from conditions like dementia, and not require emergency surgery.

Inclusion Criteria

My surgery is expected to last over an hour under anesthesia.

I am 70 years old or older.

Seen for assessment by internal medicine and/or anesthesiology at the preoperative clinic (CIEPC)

Exclusion Criteria

I have a condition like dementia that severely affects my thinking.

I cannot communicate in French or English.

I need surgery urgently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants undergo EEG-guided or standard care anesthesia during major non-cardiac surgery

Intraoperative

1 visit (in-person)

Postoperative Monitoring

Participants are assessed for neurocognitive disorders and other outcomes at multiple postoperative timepoints

90 days

Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for long-term cognitive outcomes and quality of life

90 days

Follow-up assessments at days 15, 30, and 90

Treatment Details

Interventions

• Electroencephalic (EEG)-guided anesthesia

Trial Overview The study tests if EEG-guided anesthesia can reduce postoperative neurocognitive disorders compared to standard care in elderly patients after major surgery. One group's anesthesia is adjusted using BIS monitor readings; the control group receives a standard dose of sevoflurane.

Participant Groups

Group I: Electroencephalographic (EEG)-guided group Active Control 1 Intervention

Information provided by the BIS (Medtronic, Canada) monitor will guide the volatile anesthetic administration in the EEG-guided group to maintain a BIS value between 40 and 60, a Suppression Ratio (SR; % of time with suppressed brain electrical activity) at 0% or the closest, a direct EEG display without any suppression time and a spectrogram (DSA or density spectral array) with most of the EEG wave frequency within the Alpha (8-12Hz), Theta (4-8Hz) and Delta (0.5-4Hz) frequencies.

Group II: Standard Care (SC) group Active Control 1 Intervention

In the standard care group, the age-adjusted Minimum Alveolar Concentration (MAC-age) of sevoflurane will be kept at \[0.8-1.2\] MAC.

Who Is Running the Clinical Trial?

Ciusss de L'Est de l'Île de Montréal

Lead Sponsor

Trials

81

Recruited

6,400+

Medtronic

Industry Sponsor

Trials

627

Recruited

767,000+

Geoff Martha

Medtronic

Chief Executive Officer since 2020

Finance degree from Penn State University

Dr. Richard Kuntz

Medtronic

Chief Medical Officer since 2023

MD, MSc

Findings from Research

In a study of 22 patients undergoing general anesthesia, the use of earplugs significantly lowered the Bispectral Index (BIS) scores, indicating a potential reduction in the risk of intraoperative awareness, which can occur in about 1% of high-risk patients.

The findings suggest that auditory stimuli can influence EEG readings during anesthesia, and using earplugs may be a simple and safe method to enhance patient safety by potentially reducing the incidence of awareness during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auditory stimuli as a contributor to consciousness while under general anesthesia. Thiele, RH., Knipper, E., Dunn, LK., et al.[2013]

The study involved 40 unpremedicated surgical patients, with 20 receiving thiopental and 20 receiving propofol, and it demonstrated that the bispectral index (BIS) can effectively predict the likelihood of recovery of consciousness after anesthesia.

A BIS score below 65 indicates less than a 5% chance of regaining consciousness within 50 seconds, providing a useful tool for anesthesiologists to assess patient awareness during general anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recovery of consciousness after thiopental or propofol. Bispectral index and isolated forearm technique. Flaishon, R., Windsor, A., Sigl, J., et al.[2022]

EEG monitoring during anesthesia can significantly reduce the rate of unintentional awareness in patients undergoing total intravenous anesthesia, making it a valuable tool for anesthetic management.

While EEG-guided anesthesia shows similar efficacy in preventing awareness compared to traditional monitoring methods, there is currently insufficient evidence to support its use for preventing postoperative delirium, neurocognitive disorders, or long-term mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on the Role of Neuromonitoring in Perioperative Outcomes: Electroencephalography. Chan, MTV., Hedrick, TL., Egan, TD., et al.[2020]

In a study involving 2000 patients, both BIS-guided and ETAG-guided anesthesia protocols resulted in the same low incidence of anesthesia awareness, with only two cases in each group, indicating that neither method significantly reduced the risk of this complication.

The BIS monitoring did not lead to lower administration of anesthetic gases compared to the ETAG method, suggesting that routine use of BIS monitoring may not be necessary in standard anesthesia practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anesthesia awareness and the bispectral index. Avidan, MS., Zhang, L., Burnside, BA., et al.[2022]

In a systematic review of 10 trials involving 3,891 elderly patients, BIS-guided anesthesia did not significantly reduce the incidence of postoperative delirium (POD) compared to standard care, indicating that it may not be effective for this specific outcome.

However, BIS-guided anesthesia was associated with a lower incidence of postoperative cognitive dysfunction (POCD) and improved recovery metrics, such as faster extubation and discharge times from the post-anesthesia care unit (PACU).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispectral Index (BIS) Monitoring and Postoperative Delirium in Elderly Patients Undergoing Surgery: A Systematic Review and Meta-Analysis With Trial Sequential Analysis. Chew, WZ., Teoh, WY., Sivanesan, N., et al.[2023]

Processed EEG monitoring, particularly using bispectral index (BIS), has been shown to reduce the amount of anesthesia needed during procedures, leading to faster recovery times for patients.

Research indicates that processed EEG monitoring can enhance perioperative safety by helping to prevent intraoperative awareness, which is a critical concern during anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Processed EEG and patient outcome. Monk, TG.[2022]

Using bispectral index (BIS) monitoring during anesthesia led to a significant reduction in propofol infusion rates (from 134 to 116 microg x kg[-1] x min[-1]) and improved recovery times, with patients extubated sooner and more oriented upon arrival in the postanesthesia care unit (PACU).

The study involved 302 patients and showed that while BIS monitoring improved recovery metrics, it did not change the intraoperative course, suggesting that BIS can effectively guide propofol administration without affecting overall anesthesia management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispectral index monitoring allows faster emergence and improved recovery from propofol, alfentanil, and nitrous oxide anesthesia. BIS Utility Study Group. Gan, TJ., Glass, PS., Windsor, A., et al.[2022]

Cerebral monitoring using EEG-based devices, such as BIS and PSA, can improve the titration of anaesthetic and analgesic drugs during surgery, potentially leading to better patient outcomes.

The review also highlights that these monitoring devices may positively influence recovery profiles and reduce postoperative side effects, although the impact on anaesthetic costs requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of cerebral monitoring during anaesthesia: effect on recovery profile. White, PF.[2019]

In a study of 60 outpatients undergoing gynecologic laparoscopic surgery, using auditory evoked potential (AAI) and Bispectral Index (BIS) monitoring allowed for better titration of desflurane, resulting in shorter awakening and discharge times compared to standard monitoring practices.

Patients in the BIS and AAI guided groups reported significantly higher quality of recovery scores upon discharge, indicating that these monitoring techniques enhance recovery outcomes after general anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does the use of electroencephalographic bispectral index or auditory evoked potential index monitoring facilitate recovery after desflurane anesthesia in the ambulatory setting? White, PF., Ma, H., Tang, J., et al.[2022]

Electroencephalogram-based monitoring, specifically using the bispectral index (BIS), can significantly improve the assessment of sedation levels in critically ill patients, especially those receiving neuromuscular blockade (NMB).

In a study involving 15 ICU patients, BIS monitoring was crucial in guiding sedation management for 9 of them, highlighting its potential to prevent both inadequate and excessive sedation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of bispectral index monitoring on sedation and outcomes in critically ill adults: a case series. Arbour, R.[2019]

The bispectral index (BIS) is a novel EEG processing method that effectively monitors the depth of total anesthesia during surgeries, providing reliable evaluations across various anesthetics used over a 3-year period.

While BIS is convenient and reliable for assessing anesthesia depth, the authors also acknowledge some disadvantages of the method, suggesting that further improvements in expert evaluation monitors could enhance its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bispectral index (BIS)--a new ideology in solving an old problem]. Vinogradov, VL., Likhvantsev, VV., Subbotin, VV., et al.[2006]

References

1. United States pubmed.ncbi.nlm.nih.gov

Auditory stimuli as a contributor to consciousness while under general anesthesia. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Recovery of consciousness after thiopental or propofol. Bispectral index and isolated forearm technique. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on the Role of Neuromonitoring in Perioperative Outcomes: Electroencephalography. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Anesthesia awareness and the bispectral index. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Bispectral Index (BIS) Monitoring and Postoperative Delirium in Elderly Patients Undergoing Surgery: A Systematic Review and Meta-Analysis With Trial Sequential Analysis. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Processed EEG and patient outcome. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Bispectral index monitoring allows faster emergence and improved recovery from propofol, alfentanil, and nitrous oxide anesthesia. BIS Utility Study Group. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Use of cerebral monitoring during anaesthesia: effect on recovery profile. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Does the use of electroencephalographic bispectral index or auditory evoked potential index monitoring facilitate recovery after desflurane anesthesia in the ambulatory setting? [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Impact of bispectral index monitoring on sedation and outcomes in critically ill adults: a case series. [2019]

11. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Bispectral index (BIS)--a new ideology in solving an old problem]. [2006]