Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

BACKGROUND: Globally there are >200 million major surgical procedures undertaken annually, and about 20% of these involve patients who have coronary artery disease. Many receive nitrous oxide, which impairs methionine synthase, thus inhibiting folate synthesis and increasing postoperative homocysteine levels. Nitrous oxide anesthesia leads to postoperative endothelial dysfunction, and there is some evidence that it increases myocardial ischemia and, possibly, myocardial infarction. We have initiated the Nitrous oxide and perioperative cardiac morbidity (ENIGMA-II) Trial to test the hypothesis that in inpatients undergoing anesthesia for major noncardiac surgery, avoidance of nitrous oxide will reduce the incidence of death and major cardiovascular events. METHODS: ENIGMA-II is a 7,000-patient, international randomized trial involving patients at risk of coronary artery disease undergoing noncardiac surgery. The patients, health care providers (except for the anesthesiologists), data collectors, and outcome adjudicators are blinded to whether patients receive nitrous oxide-containing or nitrous oxide-free anesthetic. The primary outcome is a composite of death and major nonfatal events (ie, myocardial infarction, cardiac arrest, pulmonary embolism, and stroke) at 30 days after surgery. RESULTS: At present, ENIGMA-II has randomized >1,000 patients in 22 hospitals in 5 countries. To date, patients' mean age is 70 years, 66% are men, 38% have a history of coronary artery disease, 19% have a history of cerebrovascular disease, and 84% have a history of hypertension. Most patients have undergone intra-abdominal 28%, vascular 32%, and orthopedic 16% surgery. CONCLUSIONS: The ENIGMA-II Trial will be the largest study yet conducted to ascertain the benefits and risks of removing nitrous oxide from the gas mixture in anesthesia. The results of this large international trial will guide the clinical care of the hundreds of millions of adults undergoing noncardiac surgery annually.

Original publication

DOI

10.1016/j.ahj.2008.11.015

Type

Journal article

Journal

Am Heart J

Publication Date

03/2009

Volume

157

Pages

488 - 494.e1

Keywords

Aged, Anesthetics, Inhalation, Cardiovascular Diseases, Female, Homocysteine, Humans, Length of Stay, Male, Nitrous Oxide, Pneumonia, Postoperative Complications, Research Design, Risk Assessment, Surgical Procedures, Operative, Surgical Wound Infection, Vomiting