Anaesthetic depth and complications in major surgery

Professor Tim Short and Professor Kate Leslie AO FAHMS

Patients were enrolled between December 2012 and December 2017, at 73 centres in seven countries.

Australia, New Zealand, United Kingdom, United States of America, Ireland, China and the Netherlands.

The completion of the Balanced Anaesthesia Study brings to fruition 10 years of intense effort by the study team and the ANZCA Clinical Trials Network (CTN), with funding from the ANZCA Research Foundation and national funding bodies in New Zealand, Australia and internationally. Anaesthetists worldwide now have definitive evidence to guide their administration of volatile-based general anaesthesia in elderly patients. Observational studies conducted over a 15-year period suggested that deep anaesthesia was associated with worse outcomes than light general anaesthesia in elderly people having major surgery, however evidence from a large randomised controlled trial was lacking.

The Balanced Anaesthesia Study recruited patients aged 60 years and older, with significant comorbidity, having surgery with expected duration of more than 2 hours, and an anticipated hospital stay of at least 2 days. We randomly assigned patients who had increased risk of complications after major surgery to receive light (BIS = 50) or deep (BIS = 35) inhalational general anaesthesia (guided by processed electroencephalographic [EEG] monitoring). Anaesthetists also nominated an appropriate range for mean arterial pressure for each patient during surgery. The primary outcome was one-year all-cause mortality and secondary outcomes included major cardiovascular and infective complications.

6644 patients were enrolled, randomly assigned to treatment or control, and formed the intention-to-treat population (3316 in the light group and 3328 in the deep group ). We achieved clinically meaningful separation in anaesthetic depth between the two groups. BIS values were significantly different between the light and deep groups (47·2 [43·7 to 50·5] in the light group and 38·8 [36·3 to 42·4] in the deep group. Volatile anaesthetic use was 30% lower (minimum alveolar concentration 0·62 [0·52 to 0·73] and 0·88 [0·74 to 1·04], respectively) in the light than the deep group. Mean arterial pressure was 3·5 mm Hg (4%) higher (median 84·5 [IQR 78·0 to 91·3] and 81·0 [75·4 to 87·6], respectively). 1-year mortality was 6·5% (212 patients) in the light group and 7·2% (238 patients) in the deep group (hazard ratio 0·88, 95% CI 0·73 to 1·07, absolute risk reduction 0·8%, 95%  CI -0.5 to 2.0). Grade 3 adverse events occurred in 954 (29%) patients in the light group and 909 (27%) patients in the deep group; and grade 4 adverse events in 265 (8%) and 259 (8%) patients, respectively. The most commonly reported adverse events were infections, vascular disorders, cardiac disorders, and neoplasms.

We concluded that among older patients at increased risk of complications after major surgery, light general anaesthesia was not associated with lower one-year mortality than deep general anaesthesia. This was greatly reassuring to anaesthetists worldwide who had been concerned about the safety of their practice. Our trial defines a broad range of anaesthetic depth over which anaesthesia may be safely delivered when titrating volatile anaesthetic concentrations using a processed EEG monitor.

Health Research Council of New Zealand, the Australian National Health and Medical Research Council, the Research Grants Council of Hong Kong, the National Institute for Health and Research in the UK (portfolio status), and the National Institutes of Health in the USA.

Seed funding was received from ANZCA Research Foundation to complete the pilot study.

Short TG, Campbell D, Frampton C, Chan MTV, Myles PS, Corcoran TB, Sessler DI, Mills GH, Cata JP, Painter T, Byrne K, Han R, Chu MHM, McAllister DJ, Leslie K; Australian and New Zealand College of Anaesthetists Clinical Trials Network; Balanced Anaesthesia Study Group. Anaesthetic depth and complications after major surgery: an international, randomised controlled trial. Lancet. 2019 Nov 23;394(10212):1907-1914.

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 Aug 28:S0007-0912(21)00493-1. doi: 10.1016/j.bja.2021.07.021. Epub ahead of print. PMID: 34465469.

Short T, Leslie K, Campbell D, et al. A pilot study for a prospective, randomized, double-blind trial of the influence of anesthetic depth on long term outcome. Anesth Analg 2014; 118: 981–86.

Short TG, Leslie K, Chan MT, Campbell D, Frampton C, Myles P. Rationale and Design of the Balanced Anesthesia Study: A Prospective Randomized Clinical Trial of Two Levels of Anesthetic Depth on Patient Outcome After Major Surgery. Anesth Analg. 2015 Aug;121(2):357-65.

Leslie K, Myles PS, Forbes A, Chan MTV. The effect of BIS monitoring on long-term survival in the B-Aware trial. Anesth Analg 2010; 110: 816–22.

Presentations were made by the study principal investigator, Professor Tim Short, at the ANZCA Annual Scientific Meeting in Kuala Lumpur, Malaysia, and the American Society of Anesthesiologists’ Annual Meeting in Orlando, Florida, USA in 2019

ClinicalTrials.gov Identifier: NCT02073357

The abstract can be viewed on Pubmed