Nitrous oxide-related postoperative nausea and vomiting depends on duration of exposure

Anesthesiology. 2014 May;120(5):1137-45. doi: 10.1097/ALN.0000000000000122.


Background: Inclusion of nitrous oxide in the gas mixture has been implicated in postoperative nausea and vomiting (PONV) in numerous studies. However, these studies have not examined whether duration of exposure was a significant covariate. This distinction might affect the future place of nitrous oxide in clinical practice.

Methods: PubMed listed journals reporting trials in which patients randomized to a nitrous oxide or nitrous oxide-free anesthetic for surgery were included, where the incidence of PONV within the first 24 postoperative hours and mean duration of anesthesia was reported. Meta-regression of the log risk ratio for PONV with nitrous oxide (lnRR PONVN2O) versus duration was performed.

Results: Twenty-nine studies in 27 articles met the inclusion criteria, randomizing 10,317 patients. There was a significant relationship between lnRR PONVN2O and duration (r = 0.51, P = 0.002). Risk ratio PONV increased 20% per hour of nitrous oxide after 45 min. The number needed to treat to prevent PONV by avoiding nitrous oxide was 128, 23, and 9 where duration was less than 1, 1 to 2, and over 2 h, respectively. The risk ratio for the overall effect of nitrous oxide on PONV was 1.21 (CIs, 1.04-1.40); P = 0.014.

Conclusions: This duration-related effect may be via disturbance of methionine and folate metabolism. No clinically significant effect of nitrous oxide on the risk of PONV exists under an hour of exposure. Nitrous oxide-related PONV should not be seen as an impediment to its use in minor or ambulatory surgery.

Publication types

  • Meta-Analysis

MeSH terms

  • Anesthetics, Inhalation / administration & dosage*
  • Anesthetics, Inhalation / adverse effects*
  • Humans
  • Nitrous Oxide / administration & dosage*
  • Nitrous Oxide / adverse effects*
  • Postoperative Nausea and Vomiting / chemically induced*
  • Postoperative Nausea and Vomiting / diagnosis*
  • Randomized Controlled Trials as Topic / methods
  • Regression Analysis
  • Time Factors


  • Anesthetics, Inhalation
  • Nitrous Oxide