An interventional study of Depth of anesthesia titration using pEEG in Delirium, Postoperative, Anesthesia and Surgery-Complications, sponsored by Auckland City Hospital. Recruiting at 3 sites in New Zealand. Open to participants aged 55 Years and older. Per ClinicalTrials.gov, last updated 2025-09-25.
Sponsored by Auckland City Hospital · Not applicable, Interventional, and Prevention
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.
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.
763 studies on the registry are indexed under Emergence Delirium; 241 are open to participants now.
This study's planned enrollment of 2,766 is above the median of 120 across 475 interventional studies indexed under Emergence Delirium.
Browse Emergence Delirium studies →Auckland City Hospital is the lead sponsor of 6 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Bispectral Index (BIS) of 55
Behavioral: Depth of anesthesia titration using pEEG
Bispectral Index (BIS) of 40
Behavioral: Depth of anesthesia titration using pEEG
Titration of maintenance anesthetic agent (propofol infusion)
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.
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.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
Duration of delirium for the first 7 days after surgery
Time frame: 7 days after surgery
Incidence of awareness
Assessed using Brice questionnaire. The Brice questionnaire uses 6 questions to determine if there was risk of awareness under general anesthesia.
Time frame: Assessed once, between postoperative days 1 to 3
Adverse and serious adverse events
Time frame: Up to 1 year
Plan to share: No
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Auckland City Hospital