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

NCT ID: NCT04965324

Last Updated: 2021-07-23

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 6644 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-12-19
• Study Completion Date: 2021-05-31

Brief Summary

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.

Conditions

Post-Operative Confusion; Long Term Adverse Effects; Surgery--Complications; Cognitive Dysfunction, Postoperative

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Anaesthesia Depth BIS 35

BIS 35

Anaesthesia Depth

Intervention Type: OTHER

Anaesthesia Depth BIS 50

BIS 50

Anaesthesia Depth

Intervention Type: OTHER

Interventions

Anaesthesia Depth

Intervention Type: OTHER

Eligibility Criteria

Exclusion Criteria

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

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.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Health Research Council, New Zealand

OTHER

Sponsor Role: collaborator

Australian and New Zealand College of Anaesthetists

OTHER

Sponsor Role: collaborator

Auckland City Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Timothy Dr Short

Role: PRINCIPAL_INVESTIGATOR

Auckland City Hospital

Locations

Auckland City Hopsital

Auckland, , New Zealand

Countries

New Zealand

Other Identifiers

ACTRN12612000632897

Identifier Type: REGISTRY

Identifier Source: secondary_id

A+9283

Identifier Type: -

Identifier Source: org_study_id