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The Association Between Nitrous Oxide and Postoperative Mortality and Morbidity After Noncardiac Surgery

Turan, Alparslan MD*; Mascha, Edward J. PhD*†; You, Jing MS*†; Kurz, Andrea MD*; Shiba, Ayako MD*; Saager, Leif MD*; Sessler, Daniel I. MD*‡

doi: 10.1213/ANE.0b013e31824590a5
Patient Safety: Research Report

BACKGROUND: Nitrous oxide (N2O) has been widely used in clinical anesthesia for >150 years. However, use of N2O has decreased in recent years because of concern about the drug’s metabolic side effects. But evidence that routine use of N2O causes clinically important toxicity remains elusive. We therefore evaluated the relationship between intraoperative N2O administration and 30-day mortality as well as a set of major inpatient postoperative complications (including mortality) in adults who had general anesthesia for noncardiac surgery.

METHODS: We evaluated 49,016 patients who had noncardiac surgery at the Cleveland Clinic between 2005 and 2009. Among 37,609 qualifying patients, 16,961 were given N2O (“nitrous,” 45%) and 20,648 were not (“nonnitrous,” 55%). Ten thousand seven hundred fifty-five nitrous patients (63% of the total) were propensity score-matched with 10,755 nonnitrous patients. Matched nitrous and nonnitrous patients were compared on 30-day mortality and a set of 8 in-hospital morbidity/mortality outcomes.

RESULTS: Inhalation of N2O intraoperatively was associated with decreased odds of 30-day mortality (odds ratio [OR]: 97.5% confidence interval, 0.67, 0.46–0.97; P = 0.02). Furthermore, nitrous patients had an estimated 17% (OR: 0.83, 0.74–0.92) decreased odds of experiencing major in-hospital morbidity/mortality than nonnitrous (P < 0.001). Among the individual morbidities, intraoperative N2O use was only associated with significantly lower odds of having pulmonary/respiratory morbidities (OR, 95% Bonferroni-adjusted CI: 0.59, 0.44–0.78).

CONCLUSIONS: Intraoperative N2O administration was associated with decreased odds of 30-day mortality and decreased odds of in-hospital mortality/morbidity. Aside from its specific and well-known contraindications, the results of this study do not support eliminating N2O from anesthetic practice.

Published ahead of print July 19, 2012

From the *Department of Outcomes Research and Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH; and Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada.

Ayako Shiba is currently affiliated with Anesthesiology Institute, Jikei University School of Medicine, Tokyo, Japan.

Accepted for publication December 1, 2011.

Published ahead of print July 19, 2012

Funding: Supported by internal funds. None of the authors has any personal financial interest in this research.

The authors declare no conflict of interest.

This report was previously presented, in part, at the American Society of Anesthesiologists 2010.

Address correspondence to Alparslan Turan, MD, Department of Outcomes Research, Cleveland Clinic, 9500 Euclid Avenue/P77, Cleveland, OH 44195. Address e-mail to

© 2013 International Anesthesia Research Society
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