title: Effect of nitrous oxide on plasma homocysteine and folate in patients undergoing major surgery.
abstract: BACKGROUND
  Nitrous oxide (N(2)O) inhibits methionine synthetase resulting in elevated plasma homocysteine (Hcy) concentration after surgery. In epidemiological studies, hyperhomocysteinaemia is associated with increased risk of cardiovascular disease and dementia.
  
  
  METHODS
  Blood samples were obtained to measure plasma folate and Hcy concentrations from two centres participating in a multicentre randomized trial investigating the effects of N(2)O on the outcome after major surgery. The effect of N(2)O and duration of anaesthesia on plasma Hcy, and the relationship between hyperhomocysteinaemia and outcomes were assessed.
  
  
  RESULTS
  We enrolled 394 patients. The N(2)O Group had an increase in plasma Hcy concentration after surgery when compared with the N(2)O-free Group: 11.1 (3.8) vs 8.5 (4.0) micromol litre(-1), P<0.0005. Postoperative hyperhomocysteinaemia was associated with an increased risk of major complications: risk ratio (RR) 2.8 (95% CI: 1.4-5.4), P=0.002 and cardiovascular events, RR 5.1 (95% CI: 3.1-8.5), P<0.0005. There was a significant association between duration of anaesthesia and the relative change in plasma Hcy concentration, particularly in the N(2)O Group: r=0.42, P<0.001.
  
  
  CONCLUSIONS
  N(2)O increases plasma Hcy concentration; this effect is greater with a longer duration of anaesthesia. Hyperhomocysteinaemia is a risk factor for major postoperative complications. N(2)O-induced increases in plasma Hcy concentration may be a cause of postoperative cardiovascular morbidity.
authors.affiliation: Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Monash University, Commercial Road, Melbourne, Victoria 3004, Australia. p.myles@alfred.org.au
authors.forename: P S
authors.initials: PS
authors.lastname: Myles
authors.forename: M T V
authors.initials: MT
authors.lastname: Chan
authors.forename: K
authors.initials: K
authors.lastname: Leslie
authors.forename: P
authors.initials: P
authors.lastname: Peyton
authors.forename: M
authors.initials: M
authors.lastname: Paech
authors.forename: A
authors.initials: A
authors.lastname: Forbes
mesh_terms: D000328:Adult; D000368:Aged; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000139:chemically induced*; D007432:Intraoperative Period; D008297:Male; D008875:Middle Aged; D009609:Nitrous Oxide / Q000009:adverse effects*; D011183:Postoperative Complications / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D018685:Anesthetics, Inhalation; D006710:Homocysteine; D005492:Folic Acid; D009609:Nitrous Oxide