Depth of Anesthesia on Postoperative Delirium and Cognitive After Surgery

Anesthesia Clinical Trial

— Balanced-2  

Official title:

Preserving Brain Health After Surgery: Does Light General Anesthesia Reduce Postoperative Delirium and Cognitive Decline Compared With Deep General Anesthesia in Older Adults?

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06268080
• Other study ID #: A+9317
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 31, 2024
• Est. completion date: December 31, 2028

Study information

• Verified date: February 2024
• Source: Auckland City Hospital
• Contact: Davina McAllister
• Phone: +64 274891940
• Email: davinams[@]adhb.govt.nz
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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, Pasific 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.

Description:

The Balanced-2 study is a randomized clinical trial studying the effects of depth of anesthesia on the incidence of postoperative delirium, and its associated longer-term impact including cognitive, physical decline and mortality. The study follows accumulating evidence that titrating general anesthesia (GA) using processed electroencephalography (pEEG) can reduce the incidence of postoperative delirium, and has the most immediate promise as a preventative strategy.

The evidence to date is limited by 1) significant statistical heterogeneity between studies, 2) poor adherence to the intervention, resulting in poor or no separation between the intervention and standard care groups in some studies, 3) exclusion of high risk patients such as those with cognitive impairment, 4) evidence limited to inhalation anesthetic agents only.

The Balanced-2 study will recruit participants who are at higher risk of postoperative delirium (based on eligibility criteria), undergoing major surgery with total intravenous anesthesia (TIVA), with robust processes to ensure adherence and group separation. Participants will be randomized in a 1:1 ratio using a web-based service in permuted blocks of 8 patients according to region and stratified by surgical urgency and pre-existing neurocognitive disorders, to either light GA or deep GA from 10 mins after induction of anesthesia to emergence. Depth of anesthesia will be titrated using pEEG monitors such as the commonly used Bispectral index (BIS) and Patient State Index (PSI). The procedural anesthesiologist will pre-specify an individual mean arterial pressure (MAP) target before randomisation to avoid confounding. There will be limitations on the use of ketamine, nitrous oxide, clonidine and dexmedetomidine due to interference with pEEG, but all other aspects of care are determined by the procedural anesthesiologist or according to standard institutional protocol.

The sample size was based on calculations using the minimum clinically important effect size, as determined by a Delphi process with 2 stakeholder groups. A statistical analysis plan will be published prior to trial commencement.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 2766
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

Inclusion Criteria:

• Patients aged = 65 years, and Maori, 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)

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Anesthesia
• Cognition Disorder
• Cognition Disorders
• Cognitive Decline
• Cognitive Dysfunction
• Delirium
• Delirium, Postoperative
• Emergence Delirium

Intervention

Behavioral:
• Depth of anesthesia titration using pEEG
Processed EEG targeting will be achieved using titration of intravenous propofol (maintenance anesthetic agent).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Auckland City Hospital

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of awareness	Assessed using Brice questionnaire	Assessed once, between postoperative days 1 to 3
Other	Adverse and serious adverse events		Up to 1 year
Primary	Incidence of postoperative delirium (POD)	Assessed using the three-minute diagnostic interview for the confusion assessment method (CAM)-defined POD (3D-CAM) or if patients are in the intensive care unit (ICU), the CAM-ICU. Delirium testing will occur between 0600 and 1000 and 1800 to 2200 daily including weekends.	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	Incidence of severe delirium	Assessed using 3D-CAM-S tool	7 days after surgery
Secondary	Incidence of new mild and major postoperative neurocognitive disorders	Diagnosis of new postoperative neurocognitive disorder requires 1) subjective complaint using standardized questionnaire, 2) objective testing using Mini-Addenbrook's Cognitive Examination (ACE), and for a diagnosis of major postoperative neurocognitive disorder, 3) evidence of functional decline using Lawton-Brody's instrumental activities of daily living (ADL) scale	Assessed at 90 days and 1 year after surgery
Secondary	Postoperative cognitive decline	Defined by a 2 or more-point drop in Mini-ACE scores	Assessed at 90 days and 1 year after surgery
Secondary	Functional decline	As measured by the change in Lawton-Brody's instrumental ADL scores	Assessed at 90 days and 1 year after surgery
Secondary	All-cause mortality		Assessed at 1 year after surgery
Secondary	Duration of delirium	Duration of delirium for the first 7 days after surgery	7 days after surgery