Nitrous oxide exposure does not seem to be associated with increased mortality, stroke, and myocardial infarction: a non-randomized subgroup analysis of the General Anaesthesia compared with Local Anaesthesia for carotid surgery (GALA) trial

Br J Anaesth. 2012 Sep;109(3):361-7. doi: 10.1093/bja/aes164. Epub 2012 Jun 17.


Background: Nitrous oxide has been associated with increased vascular risk in the perioperative period. Here, we conducted a secondary analysis of the GALA trial to ascertain the impact of nitrous oxide on outcomes after carotid surgery under general anaesthesia (GA).

Methods: One thousand seven hundred and seventy-three patients underwent GA, but 158 patients were excluded from this analysis as nitrous oxide use was unknown. The decision to use nitrous oxide was at the discretion of the anaesthetist and was not randomized. Six hundred and seventy-one patients received nitrous oxide and 944 patients did not. Logistic regression was used to analyse the same primary outcome as the original trial (risk of death, stroke, or myocardial infarction within 30 days of the operation).

Results: Patients who received nitrous oxide were more likely to have had coronary artery disease, peripheral vascular disease, and atrial fibrillation (all P<0.05). Overall, there were 35 (5.2%) primary outcome events in patients receiving nitrous oxide compared with 44 (4.7%) in those who did not [relative risk 1.12, 95% confidence interval (CI: 0.73, 1.73); P=0.63]. The adjustment for the imbalanced baseline variables using logistic regression reduced the point estimate of harm for nitrous oxide [adjusted odds ratio 1.09, 95% CI (0.68, 1.74); P=0.73].

Conclusions: Given the greater prevalence of vascular risk factors in the nitrous oxide group and the lack of any definite effect on the primary outcome measure, these data do not support a clinically meaningful adverse effect of nitrous oxide on our composite outcome in patients undergoing carotid surgery.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia, General*
  • Anesthesia, Local*
  • Anesthetics, Inhalation / adverse effects*
  • Endarterectomy, Carotid*
  • Female
  • Humans
  • Male
  • Myocardial Infarction / chemically induced*
  • Myocardial Infarction / mortality
  • Nitrous Oxide / adverse effects*
  • Stroke / chemically induced*
  • Stroke / mortality


  • Anesthetics, Inhalation
  • Nitrous Oxide