Depth of Anaesthesia and Long-term Survival: The Balanced Anaesthesia Follow-up Study (BALANCEDLT)

Depth of Anaesthesia and Long-term Survival in Elderly Surgical Patients: The Balanced Anaesthesia Study Long-term Follow-up Study

Anaesthetic depth and complications after major surgery: an international, randomised controlled trial - The BALANCED trial.

In this large, international, randomised controlled trial that enrolled patients aged 60 years and over with significant comorbidity and at increased risk of complications after major surgery, we found no evidence that light general anaesthesia (bispectral index 50) was superior to deep general anaesthesia (bispectral index 35) in reducing 1-year mortality. The BALANCED long term follow up study will look at whether depth of anesthesia affects long term (beyond 1 year) survival.

The primary hypothesis is that targetting BIS 50 will result in superior long term survival compared to targetting BIS 35.

The two secondary hypotheses are that BIS titration to BIS 50 will

1. reduce local cancer recurrence or metastatic spread and consequently improve long-term survival
2. reduce postoperative delirium and associated cognitive impairment and consequently improve long-term survival

Both these mechanisms would be expected to take longer to manifest as reduced survival than 1-year all-cause mortality primary outcome in the Balanced trial. Trials of cancer outcomes often use 5-year survival or similar timeframes to determine evidence of clinical benefit. A steeper cognitive trajectory due to intermediate outcomes such as delirium and cognitive impairment may take longer than 1 year to produce a clinically important difference in survival 30. The 10.6% relative risk reduction seen in the Balanced trial could translate to a statistically and clinically meaningful survival difference in this high-risk population. This population may have 5-year survival of ~80% translating to an absolute survival difference of ~2% potentially (if the ~10% RRR is maintained beyond 1 year). The alternative is that there is no long-term mortality difference which would provide continuing clinical guidance of the safety of current practice in patients who are not at high risk of delirium. This study could provide a rationale for trials in larger populations (such as the total Balanced trial population) or targeted subgroups such as cancer and delirium to provide further mechanistic insights.

Long-term survival is an important patient-centred outcome. The mechanisms described above may manifest in longer-term outcomes providing a clear rationale for the current trial.

Study Overview

• Status: Active, not recruiting
• Conditions: Surgery--Complications; Long Term Adverse Effects; Post-Operative Confusion; Cognitive Dysfunction, Postoperative
• Intervention / Treatment: Other: Anaesthesia Depth

• Study Type: Observational
• Enrollment (Actual): 6644

Contacts and Locations

Study Locations

• New Zealand
  • Auckland
    • Auckland, Auckland, New Zealand, 1023
      • Auckland City Hopsital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

All participants who were recruited to the BALANCED Trial and who met the inclusion and no exclusion criteria for analysis of the long term outcome.

Description

Inclusion and exclusion criteria will be the same as the Balanced trial with participants limited to those sites described above. Survival data will be censored at date of accessing mortality database.

Inclusion

1. Age over 60 years and over
2. ASA physical status 3 or 4
3. Surgery expected to last over 2 hours
4. Hospital length of stay expected to be 2 nights or more
5. General anaesthesia with or without major regional block
6. Able to monitor BIS throughout anaesthesia

Exclusion

1. Unable to monitor BIS
2. Unable to consent
3. Surgery with 'wake up' test
4. Propofol infusion for part or all of maintenance of anaesthesia
5. Previous enrolment in Balanced study

Exclusion The intention-to-treat (ITT) population is defined as all randomised participants who met the inclusion and exclusion criteria who had surgery.

The per-protocol (PP) population is defined as all randomised participants in the study who meet all the inclusion/exclusion criteria for BALANCED with BIS group classified according to the actual median BIS value achieved irrespective of randomisation.

Participants were allocated to the BIS=50 group if the achieved median BIS is between 45 and 55 inclusive, and to the BIS=35 group if the achieved median BIS is between 30 and 40 inclusive. Participants who are not within these ranges will be excluded from these analyses.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Anaesthesia Depth BIS 35; BIS 35	Other: Anaesthesia Depth
Anaesthesia Depth BIS 50; BIS 50	Other: Anaesthesia Depth

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Survival	Between one year and eight years after randomization to the BALANCED Trial

Collaborators and Investigators

• Sponsor: Auckland City Hospital
• Collaborators: Health Research Council, New Zealand; Australian and New Zealand College of Anaesthetists
• Investigators: Principal Investigator: Timothy Dr Short, Auckland City Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2012
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: July 7, 2021
• First Submitted That Met QC Criteria: July 7, 2021
• First Posted (Actual): July 16, 2021

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Incidence; Anesthesia; Delirium; Long Term Survival
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Postoperative Cognitive Complications; Long Term Adverse Effects; Delirium; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: A+9283; ACTRN12612000632897 (Registry Identifier: Australia New Zealand Clinical Trials Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data sharing requests will be assessed by the Balanced Study Steering.Committee.

Individual, deidentified participant data used in these analyses will be shared 2 years after publication by request from any qualified investigator after approval of a protocol, statistical analysis plan, and receipt of a signed data access agreement via the Research Office of Auckland District Health Board, New Zealand; and after obtaining the approval of the New Zealand Health and Disability Ethics Committees for the project and data release

• IPD Sharing Time Frame: within 2 years
• IPD Sharing Access Criteria: Will be available on the clintrials.govt website
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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