• Lancet · Oct 2014

    Randomized Controlled Trial Multicenter Study

    The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): a randomised, single-blind trial.

    Nitrous oxide use in non-cardiac surgery does not increase the risk of death, cardiovascular complications or wound infection.

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    • Paul S Myles, Kate Leslie, Matthew T V Chan, Andrew Forbes, Philip J Peyton, Michael J Paech, W Scott Beattie, Daniel I Sessler, P J Devereaux, Brendan Silbert, Thomas Schricker, Sophie Wallace, and ANZCA Trials Group for the ENIGMA-II investigators.
    • Lancet. 2014 Oct 18;384(9952):1446-54.

    BackgroundNitrous oxide is commonly used in general anaesthesia but concerns exist that it might increase perioperative cardiovascular risk. We aimed to gather evidence to establish whether nitrous oxide affects perioperative cardiovascular risk.MethodsWe did an international, randomised, assessor-blinded trial in patients aged at least 45 years with known or suspected coronary artery disease having major non-cardiac surgery. Patients were randomly assigned via automated telephone service, stratified by site, to receive a general anaesthetic with or without nitrous oxide. Attending anaesthetists were aware of patients' group assignments, but patients and assessors were not. The primary outcome measure was a composite of death and cardiovascular complications (non-fatal myocardial infarction, stroke, pulmonary embolism, or cardiac arrest) within 30 days of surgery. Our modified intention-to-treat population included all patients randomly assigned to groups and undergoing induction of general anaesthesia for surgery. This trial is registered at ClinicalTrials.gov, number NCT00430989.FindingsOf 10,102 eligible patients, we enrolled 7112 patients between May 30, 2008, and Sept 28, 2013. 3543 were assigned to receive nitrous oxide and 3569 were assigned not to receive nitrous oxide. 3483 patients receiving nitrous oxide and 3509 not receiving nitrous oxide were assessed for the primary outcome. The primary outcome occurred in 283 (8%) patients receiving nitrous oxide and in 296 (8%) patients not receiving nitrous oxide (relative risk 0·96, 95% CI 0·83–1·12; p=0·64). Surgical site infection occurred in 321 (9%) patients assigned to nitrous oxide, and in 311 (9%) patients in the no-nitrous oxide group (p=0·61), and severe nausea and vomiting occurred in 506 patients (15%) assigned to nitrous oxide and 378 patients (11%) not assigned to nitrous oxide (p<0·0001).InterpretationOur findings support the safety profile of nitrous oxide use in major non-cardiac surgery. Nitrous oxide did not increase the risk of death and cardiovascular complications or surgical-site infection, the emetogenic effect of nitrous oxide can be controlled with antiemetic prophylaxis, and a desired effect of reduced volatile agent use was shown.FundingAustralian National Health and Medical Research Council; Australian and New Zealand College of Anaesthetists; Heart and Stroke Foundation of Quebec, Heart and Stroke Foundation of Ontario, Canada; General Research Fund of the Research Grant Council, Hong Kong Special Administrative Region, China.

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    This article appears in the collections: Landmark articles in Anesthesia and Is nitrous oxide use safe in anesthesia?.

    Notes

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    1

    Nitrous oxide use in non-cardiac surgery does not increase the risk of death, cardiovascular complications or wound infection.

    Daniel Jolley  Daniel Jolley
     
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