Delirium, PostoperativeBalanced-2NCT06268080
Depth of Anesthesia on Postoperative Delirium and Cognitive After Surgery
A study testing Depth of anesthesia titration using pEEG in people with Delirium, Postoperative and Anesthesia, run by Auckland City Hospital at 3 sites in New Zealand.
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. Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Delirium, Postoperative, Anesthesia, Surgery-Complications
- What is being tested?
- Depth of anesthesia titration using pEEG
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,766 participants
- Where
- 3 sitesNew Zealand
- Study dates
- 20 May 2024to 31 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
New Zealand3 sites, 3 recruiting
- Not yet recruiting
North Shore Hospital
Auckland, North Island, 0622
- Recruiting
Christchurch Hospital
Christchurch, South Island, 4710
- Recruiting
Auckland City Hospital, Health New Zealand
Grafton, Auckland, 1024
Davina J McAllister, DipNursing, +64 274891940, davinams@adhb.govt.nz
Jessica Wiles, JWiles@adhb.govt.nz
About this study
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?
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.
Read more
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.
Read the detailed 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.
- Conditions
- Delirium, Postoperative, Anesthesia, Surgery-Complications, Cognition Disorder, Delirium, Cognitive Decline
- Being tested
- Depth of anesthesia titration using pEEG
- Keywords
- randomized controlled trial, multicentre, clinical trial, depth of anaesthesia, postoperative delirium
- Medical subject headings
- Emergence Delirium, Cognition Disorders, Delirium, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Depth of anesthesia titration using pEEGBehavioural
Titration of maintenance anesthetic agent (propofol infusion)
| Study group | Role | What they receive |
|---|---|---|
| Light general anesthesia | Experimental | Bispectral Index (BIS) of 55 Receives: Behavioral: Depth of anesthesia titration using pEEG |
| Deep general anesthesia | Active comparator | Bispectral Index (BIS) of 40 Receives: Behavioral: Depth of anesthesia titration using pEEG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Assessed using Confusion Assessment Method - Severity Short Form (CAM-S)
The CAM-S uses the 4 features of delirium and rates them as absent, mild or marked. Possible scores are o to 7, with higher scores indicating more severe delirium.
Measured: 7 days after surgery
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-Addenbrooke'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.
The Mini-ACE questionnaire is scored out of 30, with lower scores indicating more severe cognitive impairment. The Lawton-Brody's instrumental ADL scale is scored out of 8 for women, and 5 for men, with higher scores indicating more independence.
Measured: Assessed at 90 days and 1 year after surgery
Postoperative cognitive decline
Defined by a 2 or more-point drop in Mini-Addenbrooke's Cognitive Examination scores.
The Mini-ACE questionnaire is scored out of 30, with lower scores indicating more severe cognitive impairment.
Measured: Assessed at 90 days and 1 year after surgery
Functional decline
As measured by the change in Lawton-Brody's instrumental ADL scores
The Lawton-Brody's instrumental ADL scale is scored out of 8 for women, and 5 for men, with higher scores indicating more independence.
Measured: Assessed at 90 days and 1 year after surgery
All-cause mortality
Measured: Assessed at 1 year after surgery
Duration of delirium
Duration of delirium for the first 7 days after surgery
Measured: 7 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2024
- Study start20 May 2024
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Delirium, PostoperativeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicentre, prospective, randomized, active control, parallel group, intention to treat, safety and efficacy study.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 2,766 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Auckland City Hospital
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Carolyn Deng, Principal investigator, Auckland City Hospital, Health New Zealand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06268080
- Sponsor's protocol ID
- A+9317
- Acronym
- Balanced-2
- Status last verified
- Sep 2025
- First submitted
- 13 Feb 2024
- Last updated
- 25 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34465469Sumner 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.
PubMed 35183345Deng 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.
PubMed 37144615Evered 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.
PubMed 30336844
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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?
- ClinicalTrials.gov ID
- NCT06268080
- Acronym / sponsor ID
- Balanced-2 / A+9317
- Conditions
- Delirium, Postoperative, Anesthesia, Surgery-Complications, Cognition Disorder, Delirium, Cognitive Decline
- Keywords
- randomized controlled trial, multicentre, clinical trial, depth of anaesthesia, postoperative delirium
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,766 participants (estimated)
- Lead sponsor
- Auckland City HospitalOther government
- Study start
- 20 May 2024 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 20 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Multicentre, prospective, randomized, active control, parallel group, intention to treat, safety and efficacy study.
| Arm | Type | Receives |
|---|---|---|
| Light general anesthesia | Experimental | Behavioral: Depth of anesthesia titration using pEEGBispectral Index (BIS) of 55 |
| Deep general anesthesia | Active comparator | Behavioral: Depth of anesthesia titration using pEEGBispectral Index (BIS) of 40 |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Depth of anesthesia titration using pEEGTitration of maintenance anesthetic agent (propofol infusion) | Behavioural | Deep general anesthesia, Light general anesthesia |
Primary outcome
Incidence of postoperative delirium (POD)
Time frame: 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.
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.
6 secondary outcomes
Incidence of severe delirium
Time frame: 7 days after surgery
Incidence of new mild and major postoperative neurocognitive disorders
Time frame: Assessed at 90 days and 1 year after surgery
Postoperative cognitive decline
Time frame: Assessed at 90 days and 1 year after surgery
Functional decline
Time frame: Assessed at 90 days and 1 year after surgery
All-cause mortality
Time frame: Assessed at 1 year after surgery
Duration of delirium
Time frame: 7 days after surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2025.
- Background: PubMed 34465469Evered 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.
- Background: PubMed 35183345Sumner 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.
- Background: PubMed 37144615Deng 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.
- Background: PubMed 30336844Evered 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Carolyn Deng principal investigator
Auckland City Hospital, Health New Zealand
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Depth of anesthesia titration using pEEG in people with Delirium, Postoperative and Anesthesia, run by Auckland City Hospital at 3 sites in New Zealand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Davina J McAllister, DipNursing (+64 274891940, davinams@adhb.govt.nz), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of postoperative delirium (POD) (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06268080, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2025.