Reprieve for intraoperative nitrous oxide

By Eleanor McDermid

A large analysis challenges the view that intraoperative nitrous oxide use should be avoided.

A team from the Cleveland Clinic in Ohio, USA, led by Alparslan Turan, found reduced mortality and morbidity in patients given the anesthetic.

The findings conflict with those of the randomized ENIGMA (Evaluation of N₂O [nitrous oxide] in Gas Mixture for Anesthesia) trial, which found that avoiding nitrous oxide reduced the rate of major complications. The current study is a retrospective, registry-based analysis; however, it includes more than 20,000 patients matched for propensity to receive nitrous oxide.

The 10,755 patients given nitrous oxide were 33% less likely to die within 30 days of surgery than 10,755 propensity-matched patients not given the anesthetic. They also had a 17% reduction in rates of in-hospital mortality and major morbidity.

Because the propensity-matched analysis excluded many patients from the original cohort (n=37,609), Turan et al also conducted a multivariate analysis that included all patients, obtaining essentially the same result.

"N₂O is the longest serving anesthetic," they write in Anesthesia and Analgesia. "Aside from its specific and well-known contraindications, the results of this study do not support eliminating N₂O from anesthetic practice."

In the propensity-matched analysis, patients given nitrous oxide had a 41% reduction in rates of pulmonary/respiratory complications. The researchers say that this "surprising" finding may be due to selection bias, in that nitrous oxide may have been avoided in patients with pre-existing pulmonary disease. But they say that nitrous oxide could also have a direct beneficial effect on the lung, through its interaction with N-methyl-D-aspartate receptors.

Rates of neurologic, infectious, urinary, hemorrhagic, wound, and peripheral vascular complications were unaffected by nitrous oxide use.

Cardiac complications were also no more or less frequent in patients given nitrous oxide than those not, and intraoperative blood pressure, heart rate, and need for vasoactive drugs were not influenced by nitrous oxide use. The ENIGMA trial found a trend toward more cardiac complications in patients given nitrous oxide, leading to the ongoing ENIGMA-2 trial, to address this specific question.

"In the meantime, our results do not suggest that N₂O should be avoided for fear of cardiovascular complications, especially since interventions to reduce plasma homocysteine concentrations do not reduce cardiovascular events in nonsurgical settings," say Turan et al.

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