Folate for high-risk surgical patients
Sheffield, UK
E-mail: prashants75{at}gmail.com
Editor—It has long been known that an association exists between serum homocysteine concentration and cardiovascular disease, and several studies have shown that the association is causal. The results from a meta-analysis1 of single gene mutations in methylenetetrahydrofolate reductase have shown that a decrease in serum homocysteine of 3 µmol litre–1 (achievable by daily intake of about 0.8 mg folic acid) should reduce the risk of ischaemic heart disease by 16%, deep vein thrombosis by 25%, and stroke by 24%. Given such a substantial benefit in cardiovascular outcome, as also shown by your study,2 there is a case not only for excluding nitrous oxide from regular anaesthetic practice but also for administering regular folic acid before and after operation for our high-risk surgical patients.
Melbourne, Australia
* E-mail: p.myles{at}alfred.org.au
Editor—We thank Dr Sadhahalli for his letter, which raises some interesting points. We agree that nitrous oxide-induced hyper-homocysteinaemia could be a risk factor for postoperative cardiovascular morbidity. This problem may be exaggerated in patients with mutations in the methylenetetrahydrofolate reductase gene.3 However, this proposition is based on evidence from non-surgical populations and may not apply to the perioperative setting—witness the recent results from the POISE study.4 Nevertheless, the circumstantial evidence is troubling. We are in fact testing this hypothesis in 7000 patients at-risk of coronary artery disease (www.enigma2.org.au). Similarly, to recommend preoperative folate supplementation in high-risk surgical patients without evidence of its effectiveness or safety would be premature and could be misguided. For example, folate supplementation can precipitate severe neurological damage in patients with cobalamin deficiency.5 The points raised by Dr Sadhahalli are important and demand serious consideration from all anaesthetists. But, we must await definitive evidence from large-scale clinical trials before recommending changes in practice.6
References
1 Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. Br Med J (2002) 325:1202–6.
2 Myles PS, Chan MTV, Leslie K, Peyton P, Paech M, Forbes A. Effect of nitrous oxide on plasma homocysteine and folate in patients undergoing major surgery. Br J Anaesth (2008) 100:780–6.
3 Nagele P, Zeugswetter B, Wiener C, et al. Influence of methylenetetrahydrofolate reductase gene polymorphisms on homocysteine concentrations after nitrous oxide anesthesia. Anesthesiology (2008) 109:36–43.[Web of Science][Medline]
4 POISE Study Group. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomized controlled trial. Lancet (2008) 371:1839–47.[CrossRef][Web of Science][Medline]
5 Malouf M, Grimley EJ, Areosa SA. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst Rev (2003) CD004514.
6 Myles PS. Why we need large randomised studies in anaesthesia. Br J Anaesth (1999) 83:833–4.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||