Depth of Anesthesia on Postoperative Delirium and Cognitive After Surgery

NCT06268080 | Recruiting DMC

• 1 other identifier: A+9317
• Study Type: interventional
• Target: 2,766
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this clinical trial (Balanced-2 study) is to compare light to deep general anesthesia using widely available brain monitors, to see if 'light' anesthesia could reduce rates of delirium, cognitive decline, and disability in older adults undergoing major surgery. Delirium is the most common serious surgical complication, occurring in an estimated one in four older adults undergoing major surgery. Delirium causes significant distress to patients and family, and is associated with prolonged hospital stay, physical disability, progression to dementia-like illnesses, and discharge to long-term care. Between 10 - 30% of adults aged 70 years and above have surgery every year, and preserving brain health and wellbeing is an important priority during this time. Older adults (aged ≥65 years, or Indigenous, Pacific patients aged ≥55 years) undergoing major surgery with general anesthesia (excluding heart and brain surgery) and able to provide consent will be able to participate. Participants will be randomized to two groups - a lighter general anesthesia group and a deeper general anesthesia group using processed electroencephalography (a brain monitor that provides information on depth of anesthesia using brain waves). The anesthesiologist will titrate anesthetic drugs according to the brain monitor. Participants will be followed up to determine if they experience delirium after surgery, and longer term impact of delirium such as cognitive and physical decline will also be measured. If found to be effect, this simple, cheap, and widely available treatment could reduce disability, preserve brain health and wellbeing of many older adults undergoing surgery worldwide, and save millions in healthcare dollars.

Conditions

Delirium, Postoperative; Anesthesia; Surgery-Complications; Cognition Disorder; Delirium; Cognitive Decline

Keywords

randomized controlled trial; multicentre; clinical trial; depth of anaesthesia; postoperative delirium

Outcome Measures

Primary Outcomes (1)

• Incidence of postoperative delirium (POD)

  Assessed using the Three-minute Diagnostic Interview for the Confusion Assessment Method (3D-CAM) or if patients are in the intensive care unit (ICU), the Confusion Assessment Method for the ICU (CAM-ICU). Delirium testing will occur between 0600 and 1000 and 1800 to 2200 daily including weekends. Delirium is present if both features (1) altered mental status/fluctuating course and (2) inattention are present, and features (3) altered level of consciousness, OR (4) disorganized thinking are present.

  Administered twice a daily for up to 3 postoperative days or until discharge if discharge occurs before day 3, including weekends. Further once daily testing from days 4 to 7 if screens positive.

Secondary Outcomes (6)

• Incidence of severe delirium

  7 days after surgery

• Incidence of new mild and major postoperative neurocognitive disorders

  Assessed at 90 days and 1 year after surgery

• Postoperative cognitive decline

  Assessed at 90 days and 1 year after surgery

• Functional decline

  Assessed at 90 days and 1 year after surgery

• All-cause mortality

  Assessed at 1 year after surgery

Other Outcomes (2)

• Incidence of awareness

  Assessed once, between postoperative days 1 to 3

• Adverse and serious adverse events

  Up to 1 year

Study Arms (2)

Light general anesthesia

EXPERIMENTAL

Bispectral Index (BIS) of 55

Behavioral: Depth of anesthesia titration using pEEG

Deep general anesthesia

ACTIVE COMPARATOR

Bispectral Index (BIS) of 40

Behavioral: Depth of anesthesia titration using pEEG

Interventions

Depth of anesthesia titration using pEEG BEHAVIORAL

Titration of maintenance anesthetic agent (propofol infusion)

Deep general anesthesia; Light general anesthesia

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged ≥ 65 years, and Māori, Pacific or Indigenous participants aged ≥ 55 years who are undergoing major elective or non-elective surgery with expected surgical duration ≥ 2 hours and postoperative hospital stay ≥ 2 nights.
• Having general anesthesia using total intravenous anesthesia (TIVA) with pEEG monitoring
• Able to provide informed consent (including patients with mild preoperative neurocognitive disorders)

You may not qualify if:

• Intracranial or cardiac surgery
• Undergoing surgery with 'wake up' test
• Previous enrollment in Balanced-2 study
• Terminal illness with expected survival \<3 months
• Emergency surgery within 6 hours of presentation to hospital
• Cognitive impairment with no capacity to consent or activated enduring power of attorney
• Clinically impaired and unable to consent due to acute pathology or preoperative delirium

Sponsors & Collaborators

• Auckland City Hospital: lead

Study Sites (3)

Auckland City Hospital, Health New Zealand

Grafton, Auckland, 1024, New Zealand

RECRUITING

North Shore Hospital

Auckland, North Island, 0622, New Zealand

NOT YET RECRUITING

Christchurch Hospital

Christchurch, South Island, 4710, New Zealand

RECRUITING

Related Publications (4)

• Evered LA, Chan MTV, Han R, Chu MHM, Cheng BP, Scott DA, Pryor KO, Sessler DI, Veselis R, Frampton C, Sumner M, Ayeni A, Myles PS, Campbell D, Leslie K, Short TG. Anaesthetic depth and delirium after major surgery: a randomised clinical trial. Br J Anaesth. 2021 Nov;127(5):704-712. doi: 10.1016/j.bja.2021.07.021. Epub 2021 Aug 28.

  PMID: 34465469 BACKGROUND

• Sumner M, Deng C, Evered L, Frampton C, Leslie K, Short T, Campbell D. Processed electroencephalography-guided general anaesthesia to reduce postoperative delirium: a systematic review and meta-analysis. Br J Anaesth. 2023 Feb;130(2):e243-e253. doi: 10.1016/j.bja.2022.01.006. Epub 2022 Feb 17.

  PMID: 35183345 BACKGROUND

• Deng C, Sidebotham D. Using the Delphi process to determine the minimum clinically important effect size for the Balanced-2 randomised controlled trial. Clin Trials. 2023 Oct;20(5):473-478. doi: 10.1177/17407745231173058. Epub 2023 May 5.

  PMID: 37144615 BACKGROUND

• Evered L, Silbert B, Knopman DS, Scott DA, DeKosky ST, Rasmussen LS, Oh ES, Crosby G, Berger M, Eckenhoff RG; Nomenclature Consensus Working Group. Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018. Br J Anaesth. 2018 Nov;121(5):1005-1012. doi: 10.1016/j.bja.2017.11.087. Epub 2018 Jun 15.

  PMID: 30336844 BACKGROUND

MeSH Terms

Conditions

Emergence Delirium; Cognition Disorders; Delirium; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Study Officials

• Carolyn Deng

  Auckland City Hospital, Health New Zealand

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Davina J McAllister, DipNursing

CONTACT

+64 274891940; davinams@adhb.govt.nz

Carolyn Deng

CONTACT

+64 21666294; carolynd@adhb.govt.nz

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinding of procedural anesthesiologist is not possible. Patients, surgeons, and all outcome assessors will be blinded. One unblinded research coordinator at each site will collect pEEG related data points. Other research coordinators will be blinded as to treatment allocation and will collect data relating to primary and secondary outcomes. Clinicians carrying out participant usual care will be able to unblind study allocation if necessary by viewing the patients anesthesia record via password protected, accessing clinician identity logged, Electronic Health Record (EHR). This record will be unavailable for access by other means.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Multicentre, prospective, randomized, active control, parallel group, intention to treat, safety and efficacy study.

Study Record Dates

• First Submitted: February 13, 2024
• First Posted: February 20, 2024
• Study Start: May 20, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (3)