Cognitive Outcomes and Neuroimages Associated With Anesthesia-Related EEG Signatures

July 28, 2023 updated by: Patrick L. Purdon, Massachusetts General Hospital
In this study, we propose to evaluate the relationship between the alpha oscillation dynamics and the signals derived from the brain images related to brain aging.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

In 1955 Bedford reported the "adverse cerebral effects of anesthesia on old people" and suggested precautions in relation to operations on the elderly. Since then, many studies have investigated the incidence of and the risk factors for postoperative cognitive dysfunction (POCD). The incidence ranges from 8.9% to 46.1% and advanced age, preoperative mild cognitive impairment, extensive surgical procedures and other factors have been identified as important risk factors. The incidence has been reported to be as high as 41.4% at hospital discharge and 12.7% at 3 months after surgery in the elderly (60 years or older). Postoperative delirium (POD) is a more acute complication of major surgery, affecting 10-70% of surgical patients 60 years and older. Some studies have shown the association between POD and early POCD, and even POD and POCD are commonly reported as being part of the same continuum. Whether this is true or not, both represent postoperative cognitive deterioration, and age is the predominant risk factor for both.

Every day in the United States, nearly 100,000 patients undergo general anesthesia and sedation for surgical and diagnostic procedures. Approximately 35% of all surgical procedures are performed on adults older than 65 years. Considering the aging surgical population, the burden of postoperative cognitive disorders will almost certainly increase over time.

Although many factors, such as surgical stress, inflammation, and other comorbidities may contribute to POCD, there is evidence that anesthetic exposure plays a major role. Pre-clinical studies have demonstrated that exposure to anesthetic drugs is neurotoxic, and that older animals are particularly vulnerable. It is also generally understood that the elderly are more sensitive to anesthetics, meaning that lower doses of anesthetic drugs are required to induce and maintain unconsciousness. This has led to age-adjusted guidelines for anesthetic dosing, which in theory could be used to mitigate potentially harmful anesthetic exposures. However, these guidelines describe the age-dependent dose-response relationships for a population of patients; individual drug requirements can vary significantly, by a factor of ~2 above or below the levels recommended by population-based models. In the absence of a means to measure and monitor individual drug responses, anesthesiologists would tend to err on the side of administering more anesthetic than required, to minimize the probability of patient awareness across the population as a whole.

Fortunately, in recent years, significant progress has been made to understand the neural mechanisms of anesthesia-induced unconsciousness, making it possible to monitor individual patients' drug responses using the electroencephalogram (EEG). Increasing concentrations of the commonly-used GABAergic anesthetic drugs, such as propofol and sevoflurane, induce a stereotyped sequence of brain oscillations with increasing drug concentration. These brain oscillations are directly related to the states of sedation and unconsciousness induced by anesthetic drugs, and readily observed using the EEG. At lower concentrations, propofol and sevoflurane, two of the most commonly used anesthetic drugs, induce beta oscillations (12-25 Hz). At concentrations producing unconsciousness for general anesthesia, these drugs produce frontal alpha (8-12 Hz) and slow (0.1 to 1 Hz) oscillations. At still higher concentrations, propofol and sevoflurane produce a pattern referred to as burst suppression, a deep state of brain inactivation in which brain activity is punctuated by long periods of neuronal and EEG silence. However, it is now known that elderly patients do not always exhibit this canonical EEG signature under general anesthesia. First, it was described that ageing was associated with a decrease in the frontal alpha power. Then, other studies suggested that older patients with poor preoperative cognitive performance also lack the alpha band under anesthesia. And finally, our group demonstrated that a low alpha power is also associated with a higher risk to develop burst suppression under anesthesia. Nonetheless, the potential mechanism related to the lower alpha power with ageing and cognitive function remains unknown. In this study, we propose to evaluate the relationship between the alpha oscillation dynamics and the signals derived from brain images related to brain aging.

We hypothesize that: 1) Brain imaging signals will correlate with the alpha power induced by anesthetics, and 2) Aging brain imaging features will be associated with postoperative cognitive recovery.

Study Type

Observational

Enrollment (Actual)

24

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

45 subjects (male and female) aged 65 and above scheduled for open or laparoscopic general surgical procedures under general anesthesia

Description

Inclusion Criteria:

  • 65 years old or above (male and female)
  • American Society of Anesthesiologists (ASA) physical status classification of I, II or III.
  • Candidates scheduled for open or laparoscopic general surgical procedures under general anesthesia
  • No cognitive impairment base on Telephone Interview for Cognitive Status (TICS)
  • Fluency in English Language

Exclusion Criteria:

  • Prior diagnosis of dementia
  • Prior diagnosis of Alzheimer's Disease
  • Prior history of psychiatric or neurological diseases including:
  • Schizophrenia
  • Parkinsonism
  • Epilepsy or seizure
  • Brain injury
  • Brain tumors/metastases
  • Encephalitis
  • Stroke, CVA, TIA
  • Drug or alcohol abuse:
  • Any history of IV drug abuse
  • Alcohol/drug (non-IV) abuse <10 years
  • Language impairment
  • Hearing or visual impairment
  • Severe obesity (BMI ≥40 kg/m2)
  • MRI contraindications, such as presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments, or foreign objects in the eyes, skin, or body
  • Body weight of > 300 lbs. (weight limit of the MRI table)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Active Comparator: Treatment Group
Anesthesiologists in the treatment group use the unprocessed EEG waveforms and EEG spectrogram to maintain appropriate levels of unconsciousness for general anesthesia while avoiding burst suppression.
Device: EEG
the anesthesiologists (attending faculty, residents, and CRNAs) in the treatment group use the unprocessed EEG waveforms and EEG spectrogram to maintain appropriate levels of unconsciousness for general anesthesia while avoiding burst suppression. The presence of slow (0.1-1 Hz) and frontal alpha (8-12 Hz) oscillations on EEG time trace and spectrogram will be used as indicators of anesthesia-induced unconsciousness in these patients who are receiving propofol and sevoflurane for induction and maintenance of general anesthesia, respectively.
No Intervention: Control Group
Anesthesiologists managing patients assigned to the control group will manage each anesthetic based on their clinical judgment, using standard monitoring required by American Society of Anesthesiologists (ASA), which include cardiac and respiratory monitoring, but not EEG monitoring.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Postoperative Delirium Incidence
Time Frame: on postoperative day 1
postoperative delirium will be assessed using 3-Minute Diagnostic Interview for Confusion Assessment Method (CAM)
on postoperative day 1
Postoperative Cognitive Decline
Time Frame: one week before the surgery and postoperative day 7
postoperative cognitive dysfunction will be assessed using the Montreal Cognitive Assessment (MoCA)
one week before the surgery and postoperative day 7
Intraoperative Burst Suppression Time
Time Frame: during the surgical procedure under general anesthesia
we will use the EEG data recorded during the surgical procedure to calculate time spent in burst suppression
during the surgical procedure under general anesthesia

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Investigators

  • Principal Investigator: Patrick L. Purdon, PhD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 13, 2019

Primary Completion (Actual)

May 11, 2023

Study Completion (Estimated)

May 11, 2024

Study Registration Dates

First Submitted

February 14, 2018

First Submitted That Met QC Criteria

February 20, 2018

First Posted (Actual)

February 22, 2018

Study Record Updates

Last Update Posted (Actual)

August 1, 2023

Last Update Submitted That Met QC Criteria

July 28, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 2017P000413

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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