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BJA Advance Access originally published online on April 9, 2008
British Journal of Anaesthesia 2008 100(6):780-786; doi:10.1093/bja/aen085
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2008. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Effect of nitrous oxide on plasma homocysteine and folate in patients undergoing major surgery

P. S. Myles1,*, M. T. V. Chan2, K. Leslie3, P. Peyton4, M. Paech5,6 and A. Forbes7

1 Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Monash University, Commercial Road, Melbourne, Vic. 3004, Australia
2 Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong
3 Department of Anaesthesia and Pain Management and Department of Pharmacology, Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia
4 Department of Anaesthesia, Austin Hospital, Melbourne, Australia
5 School of Medicine and Pharmacology, University of Western Australia, Perth, Australia
6 Department of Anaesthesia and Pain Medicine, King Edward Memorial Hospital for Women, Perth, Australia
7 Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia

* Corresponding author. E-mail: p.myles{at}alfred.org.au

Background: Nitrous oxide (N2O) 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 N2O on the outcome after major surgery. The effect of N2O and duration of anaesthesia on plasma Hcy, and the relationship between hyperhomocysteinaemia and outcomes were assessed.

Results: We enrolled 394 patients. The N2O Group had an increase in plasma Hcy concentration after surgery when compared with the N2O-free Group: 11.1 (3.8) vs 8.5 (4.0) µmol 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 N2O Group: r=0.42, P<0.001.

Conclusions: N2O increases plasma Hcy concentration; this effect is greater with a longer duration of anaesthesia. Hyperhomocysteinaemia is a risk factor for major postoperative complications. N2O-induced increases in plasma Hcy concentration may be a cause of postoperative cardiovascular morbidity.

Keywords: anaesthetic gases, nitrous oxide; complications, postoperative; metabolism, folic acid; metabolism, homocysteine; surgery, postoperative period


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