• Lancet · Nov 2019

    Randomized Controlled Trial Multicenter Study

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

    Among older patients undergoing major surgery, there is no difference in 1-year mortality between light and deep general anaesthesia.

    • Timothy G Short, Douglas Campbell, Christopher Frampton, Chan Matthew T V MTV Chinese University of Hong Kong, Hong Kong Special Administrative Area, China., Paul S Myles, Tomás B Corcoran, Daniel I Sessler, Gary H Mills, Juan P Cata, Thomas Painter, Kelly Byrne, Ruquan Han, Chu Mandy H M MHM Pamela Youde Nethersole Eastern Hospital, Hong Kong Special Administrative Area, China., Davina J McAllister, Kate Leslie, Australian and New Zealand College of Anaesthetists Clinical Trials Network, and Balanced Anaesthesia Study Group.
    • Auckland City Hospital, Auckland, New Zealand; University of Auckland, Auckland, New Zealand. Electronic address: tims@adhb.govt.nz.
    • Lancet. 2019 Nov 23; 394 (10212): 1907-1914.

    BackgroundAn association between increasing anaesthetic depth and decreased postoperative survival has been shown in observational studies; however, evidence from randomised controlled trials is lacking. Our aim was to compare all-cause 1-year mortality in older patients having major surgery and randomly assigned to light or deep general anaesthesia.MethodsIn an international trial, we recruited patients from 73 centres in seven countries who were aged 60 years and older, with significant comorbidity, having surgery with expected duration of more than 2 h, 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 general anaesthesia (bispectral index [BIS] target 50) or deep general anaesthesia (BIS target 35). Anaesthetists also nominated an appropriate range for mean arterial pressure for each patient during surgery. Patients were randomly assigned in permuted blocks by region immediately before surgery, with the patient and assessors masked to group allocation. The primary outcome was 1-year all-cause mortality. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000632897, and is closed to accrual.FindingsPatients were enrolled between Dec 19, 2012, and Dec 12, 2017. Of the 18 026 patients screened as eligible, 6644 were enrolled, randomly assigned to treatment or control, and formed the intention-to-treat population (3316 in the BIS 50 group and 3328 in the BIS 35 group). The median BIS was 47·2 (IQR 43·7 to 50·5) in the BIS 50 group and 38·8 (36·3 to 42·4) in the BIS 35 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) and volatile anaesthetic use was 0·26 minimum alveolar concentration (30%) lower (0·62 [0·52 to 0·73] and 0·88 [0·74 to 1·04], respectively) in the BIS 50 than the BIS 35 group. 1-year mortality was 6·5% (212 patients) in the BIS 50 group and 7·2% (238 patients) in the BIS 35 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 BIS 50 group and 909 (27%) patients in the BIS 35 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.InterpretationAmong patients at increased risk of complications after major surgery, light general anaesthesia was not associated with lower 1-year mortality than deep general anaesthesia. Our trial defines a broad range of anaesthetic depth over which anaesthesia may be safely delivered when titrating volatile anaesthetic concentrations using a processed electroencephalographic monitor.FundingHealth Research Council of New Zealand; National Health and Medical Research Council, Australia; Research Grant Council of Hong Kong; National Institute for Health and Research, UK; and National Institutes of Health, USA.Copyright © 2019 Elsevier Ltd. All rights reserved.

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    This article appears in the collections: Postoperative mortality and intraoperative anesthetic depth and Landmark articles in Anesthesia.



    Among older patients undergoing major surgery, there is no difference in 1-year mortality between light and deep general anaesthesia.

    Daniel Jolley  Daniel Jolley

    What’s all the fuss?

    Significant observational evidence suggested an association between mortality and deep anaesthesia, in particular a 2017 meta-analysis. However it has been suspected that anaesthetic depth may merely be a surrogate marker for intraoperative hypotension, a well-established risk factor for post-operative mortality and morbidity.

    With this large RCT, the Balanced Anaesthesia Study Group has shown that deep general anaesthesia is not associated with an increase 1-year mortality.

    What did they do?

    The researchers conducted an ambitious, large (6,644 patients), multi-center, randomised controlled trial. Patients aged ≥60 years undergoing major surgery (expected ≥2h surgery and ≥2d hospital stay) were randomised to receive volatile general anaesthesia targeting BIS 50 or BIS 35.

    To minimise intra-operative blood pressure as a confounder, anaesthetists were required to specify a target MAP before BIS-group allocation.

    They found...

    Not only was there no mortality difference between the BIS 50 and BIS 35 groups, there were also no major or moderate morbidity differences, or difference in recovery or length of stay. BIS targets were adequately achieved, though not perfect, and MAP was clinically similar for both groups.

    Context is everything

    This is about as high-quality as a large, modern study looking at longer-term outcomes can get. It is widely applicable to most populations and common general anaesthetic scenarios, except for a few important caveats:

    • Very few ASA 4 (5%) patients were enrolled.
    • Only volatile-maintenance anaesthesia was studied not propofol/TIVA.
    • We can draw no conclusion regarding the consequences of extreme-depth (ie. BIS << 35).
    • The actual depth difference between the BIS-35 and BIS-50 groups was not as much as perhaps ideal: mean BIS 39 vs 47 respectively...

    Final thought

    ...there was (only) one case of awareness in the light-depth BIS 50 group, despite 39% of patients receiving volatile < 0.7 MAC.

    Daniel Jolley  Daniel Jolley
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