Anesthetic Depth and Postoperative Delirium Trial - 2 (ADAPT2)

A Randomised Controlled Trial to Reduce Postoperative Delirium Through Reduction in Intraoperative EEG Suppression in Older Surgical Patients Undergoing Major Noncardiac Surgery

Recent limited evidence suggests that anesthetic depth may influence postoperative cognitive outcomes, however, the mechanism between this association is unclear.

Study Overview

• Status: Completed
• Conditions: Delirium; Cognitive Disorders
• Intervention / Treatment: Other: Processed EEG-guided anesthetic depth

Detailed Description

Recently, it has been proposed that use of a processed electroencephalogram (EEG) monitor during surgery may be associated with a lower rate of postoperative delirium. In fact, some suggest that older patients undergoing surgery should routinely be monitored with an anesthetic depth monitor to allow the titration of anesthetics or sedation medications to lighter levels to promote better postoperative cognitive outcomes. Recent studies, including preliminary results from our group, have demonstrated electroencephalogram (EEG) suppression to be an independent risk factor for postoperative delirium.

Prior studies that have focused on risk prediction have shown age and prior cognitive impairment to be the most consistent risk factors for postoperative delirium. However, as of yet, no clinical trial has identified a relationship whether use of processed EEG monitor resulted in a reduction of incident postoperative delirium through a reduction in EEG suppression, with proper consideration of patients' baseline cognitive status as a potential moderator. Additionally, use of anesthetic depth monitor to keep patients' anesthetic depth above a specified value has never been validated or proven to be feasible or safe.

Accordingly, the investigators plan an exploratory study to: 1) determine whether the use of processed EEG to keep anesthetic depth above a specified level, results in a reduction in EEG suppression when compared to standard anesthetic care, 2) to determine whether preoperative level of cognitive function moderates the effect of group assignment on EEG suppression, and 3) to determine the feasibility and safety of using processed EEG-guided to keep patients' anesthetic depth above a specified value. A secondary aim was to determine the effect size for the intervention to reduce postoperative delirium for subjects with and without preoperative cognitive impairment for a future trial.

• Study Type: Interventional
• Enrollment (Actual): 205
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143-0648
      • University of California, San Francisco Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 65 years and older of age undergoing non-cardiac surgery, requiring hospital stay of 2 or more days.

Exclusion Criteria:

• patients who are not fluent in English or cannot provide informed consent
• patients who may not tolerate either light or deep anesthesia (history of heart failure, coronary artery disease, substance abuse)
• history of intraoperative recall or awareness during anesthesia
• pathologies of the brain which may affect EEG monitoring
• patients who are anticipated to have consecutive surgery within 3 days of first procedure
• patients who have had surgery with general anesthesia in the past 30 days

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
Placebo Comparator: Anesthetic Depth: standard care; A cohort of older patients undergoing major non-cardiac surgery will be randomized to receive routine anesthetic management not guided by the processed electroencephalogram	Other: Processed EEG-guided anesthetic depth; Investigators will undertake a randomized control trial in a cohort of older patients undergoing major non-cardiac surgery to receive either a control vs. an intervention of anesthesia as determined by a processed electroencephalogram
Experimental: Anesthetic Depth: interventional; A cohort of older patients undergoing major non-cardiac surgery will be randomized to receive anesthetic management guided by the processed electroencephalogram (processed EEG-guided anesthetic depth)	Other: Processed EEG-guided anesthetic depth; Investigators will undertake a randomized control trial in a cohort of older patients undergoing major non-cardiac surgery to receive either a control vs. an intervention of anesthesia as determined by a processed electroencephalogram

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative EEG Suppression	Intraoperative EEG suppression will be measured by processed EEG monitor	Patients will be monitored by processed EEG intraoperatively, for the duration of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preoperative level of cognitive function	Level of cognitive function will be measured by Telephone Interview for Cognitive Status	Up to one week before surgery
Patient intraoperative awareness and recall	Intraoperative recall and awareness measured using modified Brice questionnaire (2 question survey - each answered with a yes or no, with additional checkboxes for applicable descriptions of events recalled [e.g. "Hearing voices," "Feeling pain," etc]) Patients answering yes to either question are classified as accidental awareness after general anesthesia (AAGA), which is regarded as an intraoperative adverse event.	Intraoperative recall and awareness will be measured within 72 hours after end of surgery
Patient movement	Patient movement will be recorded from the anesthesia record	During surgery
Intraoperative systolic and diastolic blood pressure	Intraoperative systolic and diastolic blood pressure will be continuously downloaded onto a computer for subsequent analysis. Increases or decreases above the preoperative baseline measurements will be measured and recorded from the medical record	During surgery
Intraoperative heart rate	Intraoperative heart rate will be continuously downloaded onto a computer for subsequent analysis. Increases or decreases above the preoperative baseline measurements will be measured and recorded from the medical record	During surgery
Anesthesiologists' adherence to assigned processed EEG index in the interventional group	Anesthesiologists' assigned to patients randomized to the interventional group were given a short self-report survey at the end of each surgery (e.g. "Did the PSI go below the PSI threshold of 35 at any point during surgery?")	Anesthesiologists complete self-report within 72 hours after end of surgery. This outcome measure is collected once for each patient through study completion, an average of 2 years.
Postoperative delirium	Research staff, blinded to group assignment, will assess for delirium using the Confusion Assessment Method, a physician-validated screening tool for hospital delirium	Daily for three postoperative days.

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Virginia Polytechnic Institute and State University
• Investigators: Principal Investigator: Jacqueline Leung, MD, MPH, University of California, San Francisco

Publications and helpful links

General Publications

• Tang CJ, Jin Z, Sands LP, Pleasants D, Tabatabai S, Hong Y, Leung JM. ADAPT-2: A Randomized Clinical Trial to Reduce Intraoperative EEG Suppression in Older Surgical Patients Undergoing Major Noncardiac Surgery. Anesth Analg. 2020 Oct;131(4):1228-1236. doi: 10.1213/ANE.0000000000004713.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: October 29, 2013
• First Submitted That Met QC Criteria: November 13, 2013
• First Posted (Estimate): November 14, 2013

Study Record Updates

• Last Update Posted (Actual): December 18, 2019
• Last Update Submitted That Met QC Criteria: December 16, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Surgery; Aging; Cognition; Anesthesia; Electroencephalography; Delirium
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Cognition Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: ANESDEPTH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No