Nitrous oxide-induced increased homocysteine concentrations are associated with increased postoperative myocardial ischemia in patients undergoing carotid endarterectomy

Anesth Analg. 2000 Nov;91(5):1073-9. doi: 10.1097/00000539-200011000-00006.


Nitrous oxide anesthesia causes increased postoperative plasma homocysteine levels. Acute increases in plasma homocysteine are associated with impaired endothelial function and procoagulant effects. This nitrous oxide-induced plasma homocysteine increase may therefore affect the risk of perioperative cardiovascular events. This prospective, randomized study was therefore designed to evaluate the effect of nitrous oxide anesthesia and postoperative plasma homocysteine levels on myocardial ischemia in patients undergoing carotid endarterectomy. After institutional review board approval and written informed consent, 90 ASA Class I-III patients presenting for elective carotid endarterectomy were randomized to receive general anesthesia with or without nitrous oxide. Prior to induction, on arrival in the postanesthesia care unit, and after 48 h, blood samples were obtained for homocysteine analysis. Three hours prior to induction and for 48 h postoperatively patients were monitored by a three-channel, seven-lead Holter monitor. Postoperatively in the postanesthesia care unit and at 48 h the nitrous oxide group had increased mean plasma homocysteine concentrations of 15.5 +/- 5.9 and 18.8 +/- 14.7 when compared with the nonnitrous group of 11.4 +/- 5.2 and 11.3 +/- 4.0 micromol/L, P: < 0.001. The nitrous oxide group had an increased incidence of ischemia (46% vs. 25%, P: < 0.05), significantly more ischemia (63 +/- 71 vs. 40 +/- 68 min, P: < 0.05), had more ischemic events (82 vs. 53, P: < 0.02), and had more ischemic events lasting 30 min (23 vs. 14, P: < 0.05) than the nonnitrous group. This study reconfirmed that intraoperative nitrous oxide is associated with postoperative increases in plasma homocysteine concentration. This was associated with an increase in postoperative myocardial ischemia.

Implications: Use of nitrous oxide during carotid artery surgery induces increases in postoperative plasma homocysteine concentration and is associated with increases in postoperative myocardial ischemia.

Publication types

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

MeSH terms

  • Aged
  • Anesthesia, General
  • Anesthetics, Inhalation / adverse effects*
  • Double-Blind Method
  • Endarterectomy, Carotid*
  • Female
  • Homocysteine / blood*
  • Humans
  • Male
  • Myocardial Ischemia / blood*
  • Myocardial Ischemia / diagnosis
  • Myocardial Ischemia / etiology*
  • Nitrous Oxide / adverse effects*
  • Prospective Studies
  • Risk Factors


  • Anesthetics, Inhalation
  • Homocysteine
  • Nitrous Oxide