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

Australian and New Zealand College of Anaesthetists Clinical Trials Network, Balanced Anaesthesia Study Group

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    Background: An 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. Methods: In 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. Findings: Patients 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. Interpretation: Among 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. Funding: Health 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.

    Original languageEnglish (US)
    Pages (from-to)1907-1914
    Number of pages8
    JournalThe Lancet
    Volume394
    Issue number10212
    DOIs
    StatePublished - Nov 23 2019

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    Anesthetics
    Randomized Controlled Trials
    General Anesthesia
    Mortality
    National Institutes of Health (U.S.)
    New Zealand
    Arterial Pressure
    Research
    Numbers Needed To Treat
    Heart Neoplasms
    Health
    Hong Kong
    Observational Studies
    Blood Vessels
    Registries
    Biomedical Research
    Comorbidity
    Length of Stay
    Anesthesia
    Clinical Trials

    ASJC Scopus subject areas

    • Medicine(all)

    Cite this

    Australian and New Zealand College of Anaesthetists Clinical Trials Network, & Balanced Anaesthesia Study Group (2019). Anaesthetic depth and complications after major surgery: an international, randomised controlled trial. The Lancet, 394(10212), 1907-1914. https://doi.org/10.1016/S0140-6736(19)32315-3

    Anaesthetic depth and complications after major surgery : an international, randomised controlled trial. / Australian and New Zealand College of Anaesthetists Clinical Trials Network; Balanced Anaesthesia Study Group.

    In: The Lancet, Vol. 394, No. 10212, 23.11.2019, p. 1907-1914.

    Research output: Contribution to journalArticle

    Australian and New Zealand College of Anaesthetists Clinical Trials Network & Balanced Anaesthesia Study Group 2019, 'Anaesthetic depth and complications after major surgery: an international, randomised controlled trial', The Lancet, vol. 394, no. 10212, pp. 1907-1914. https://doi.org/10.1016/S0140-6736(19)32315-3
    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. The Lancet. 2019 Nov 23;394(10212):1907-1914. https://doi.org/10.1016/S0140-6736(19)32315-3
    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. In: The Lancet. 2019 ; Vol. 394, No. 10212. pp. 1907-1914.
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    title = "Anaesthetic depth and complications after major surgery: an international, randomised controlled trial",
    abstract = "Background: An 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. Methods: In 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. Findings: Patients 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. Interpretation: Among 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. Funding: Health 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.",
    author = "{Australian and New Zealand College of Anaesthetists Clinical Trials Network} and {Balanced Anaesthesia Study Group} and Short, {Timothy G.} and Douglas Campbell and Christopher Frampton and Chan, {Matthew T.V.} and Myles, {Paul S.} and Corcoran, {Tom{\'a}s B.} and Sessler, {Daniel I.} and Mills, {Gary H.} and Cata, {Juan P.} and Thomas Painter and Kelly Byrne and Ruquan Han and Chu, {Mandy H.M.} and McAllister, {Davina J.} and Kate Leslie and M. Shulman and S. Wallace and C. Farrington and W. Gallagher and A. Ditoro and P. Peyton and S. Baulch and A. Dalyell and S. Sidiropoulos and J. Reynolds and J. Rowley and N. Tan and D. McCallum and E. O'Loughlin and S. Wong and K. Owen and Sim, {I. K.} and L. Glazov and P. Coutts and M. Pushpanathan and V. Findlay and M. Paech and D. Cavill and A. Chuan and L. Pope and J. Lucas and B. Robinson and A. Millard and S. Allen and M. Allen and S. McKeown and P. Sivalingam and T. Wilkes and C. Jowett and S. Williams",
    year = "2019",
    month = "11",
    day = "23",
    doi = "10.1016/S0140-6736(19)32315-3",
    language = "English (US)",
    volume = "394",
    pages = "1907--1914",
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    TY - JOUR

    T1 - Anaesthetic depth and complications after major surgery

    T2 - an international, randomised controlled trial

    AU - Australian and New Zealand College of Anaesthetists Clinical Trials Network

    AU - Balanced Anaesthesia Study Group

    AU - Short, Timothy G.

    AU - Campbell, Douglas

    AU - Frampton, Christopher

    AU - Chan, Matthew T.V.

    AU - Myles, Paul S.

    AU - Corcoran, Tomás B.

    AU - Sessler, Daniel I.

    AU - Mills, Gary H.

    AU - Cata, Juan P.

    AU - Painter, Thomas

    AU - Byrne, Kelly

    AU - Han, Ruquan

    AU - Chu, Mandy H.M.

    AU - McAllister, Davina J.

    AU - Leslie, Kate

    AU - Shulman, M.

    AU - Wallace, S.

    AU - Farrington, C.

    AU - Gallagher, W.

    AU - Ditoro, A.

    AU - Peyton, P.

    AU - Baulch, S.

    AU - Dalyell, A.

    AU - Sidiropoulos, S.

    AU - Reynolds, J.

    AU - Rowley, J.

    AU - Tan, N.

    AU - McCallum, D.

    AU - O'Loughlin, E.

    AU - Wong, S.

    AU - Owen, K.

    AU - Sim, I. K.

    AU - Glazov, L.

    AU - Coutts, P.

    AU - Pushpanathan, M.

    AU - Findlay, V.

    AU - Paech, M.

    AU - Cavill, D.

    AU - Chuan, A.

    AU - Pope, L.

    AU - Lucas, J.

    AU - Robinson, B.

    AU - Millard, A.

    AU - Allen, S.

    AU - Allen, M.

    AU - McKeown, S.

    AU - Sivalingam, P.

    AU - Wilkes, T.

    AU - Jowett, C.

    AU - Williams, S.

    PY - 2019/11/23

    Y1 - 2019/11/23

    N2 - Background: An 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. Methods: In 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. Findings: Patients 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. Interpretation: Among 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. Funding: Health 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.

    AB - Background: An 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. Methods: In 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. Findings: Patients 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. Interpretation: Among 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. Funding: Health 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.

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    U2 - 10.1016/S0140-6736(19)32315-3

    DO - 10.1016/S0140-6736(19)32315-3

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    VL - 394

    SP - 1907

    EP - 1914

    JO - The Lancet

    JF - The Lancet

    SN - 0140-6736

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