By DrBicuspid Staff

April 24, 2013 -- Giving nitrous oxide as part of general anesthesia for noncardiac surgery doesn't increase the rate of complications and death, and might even decrease the risk of such events, according to a pair of studies in Anesthesia & Analgesia (May 2013, Vol. 116:5, pp. 1034-1040).

But an accompanying series of editorials points out some important limitations of the two studies, which can't completely overcome previous concerns about the safety of using nitrous oxide as a surgical anesthetic (May 2013, Vol. 116:5, pp. 959-961).

The two new studies, based on large patient databases, question the harmful effects of nitrous oxide. Kate Leslie, MBBS, MD, of Royal Melbourne Hospital in Australia and colleagues analyzed data from a previous study of more than 8,300 patients undergoing surgery. That study was designed to assess the effects of giving one type of blood pressure drug (beta-blockers) during surgery, not the effects of nitrous oxide.

For their new study, Dr. Leslie and colleagues compared the risk of death or serious complications after surgery for patients who did and did not receive nitrous oxide as part of anesthesia; 29% of patients in the study received nitrous oxide. The results showed comparable rates of adverse outcomes between the groups. With or without nitrous oxide, the overall rate of death or serious complications was approximately 7%, including about a 6% rate of myocardial infarction. Risk of death after surgery was about 3% in both groups.

Meanwhile, Alparslan Turan, MD, of the Cleveland Clinic and colleagues reviewed more than 49,000 patients undergoing noncardiac surgery between 2005 and 2009. In this study, 45% of patients received nitrous oxide. The results suggested a significant reduction in the risk of death after surgery for patients receiving nitrous oxide: about one-third lower than in patients who did not receive nitrous oxide. There was also a 17% reduction in the combined rate of major complications and death.

Surprisingly, nitrous oxide was specifically associated with a 40% reduction in the risk of major lung- and breathing-related complications. However, the authors acknowledge the risk of "selection bias" -- anesthesiologists may have avoided using nitrous oxide in patients at risk of lung problems.

In one of three accompanying editorials, Thomas Vetter, MD, MPH, and Gerald McGwin Jr., MS, PhD, of University of Alabama at Birmingham highlight some important limitations of the study data. They note that, although both studies were large, they were not randomized trials.

Drs. Vetter and McGwin emphasize that even sophisticated techniques such as propensity score analysis can't account for all the differences between groups that may have affected responses to nitrous oxide. A randomized Evaluation of Nitrous Oxide Anaesthesia and Cardiac Morbidity After Major Surgery (ENIGMA-II) study is underway that may provide "additional, perhaps more definitive insight" on the risks and potential benefits of using nitrous oxide as part of general anesthesia, they noted.


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