The effects of nitrous oxide on vitamin B12 and homocysteine levels in methyltetrahydrofolate reductase gene mutation.

BACKGROUND We aimed to investigate the effects of nitrous oxide on plasma total homocysteine and vitamin B12 levels in patients with or without methyltetrahydrofolate reductase (MTHRF) gene mutation. METHODS After obtaining the ethics committee approval and written informed consents of patients, 93 patients between 18-70 years of age scheduled for surgery anticipated to last 1-4 hours were enrolled in the study. Patients with contraindications for nitrous oxide use were excluded. Preoperatively, blood samples were obtained from all patients for the determination of MTHFR gene mutation. Anesthesia induction was achieved with 3 mg.kg-1 of propofol and 1 µg.kg-1 of fentanyl. Anesthesia maintenance was performed with sevoflurane and with a carrier gas composed of 40 % O2 and 60 % N2O. Venous blood samples were obtained after venous canulation, and 24 hours after extubation for the analysis of plasma total homocysteine, vitamin B12 levels. RESULTS Eighty-one patients were included in the study. Postoperative vitamin B12 levels were found to be significantly lower when compared with their preoperative levels (p<0.05). It was found that MTHRF gene polymorphism had no significant effect on postoperative plasma total homocysteine and serum vitamin B12 levels (p>0.05). Postoperative plasma total homocysteine levels were found to be significantly different between patients with operation times under and over 3 hours (p=0.028). CONCLUSIONS We conclude that MTHRF gene polymorphism had no significant effects on postoperative plasma total homocysteine levels. However, we found that homocysteine levels might rise in patients who received general anesthesia with nitrous oxide for longer than 3 hours (Tab. 7, Ref. 26).

[1]  P. Myles,et al.  Effect of Nitrous Oxide Anesthesia on Plasma Homocysteine and Endothelial Function , 2008, Anesthesiology.

[2]  M. Mittlböck,et al.  Influence of Methylenetetrahydrofolate Reductase Gene Polymorphisms on Homocysteine Concentrations after Nitrous Oxide Anesthesia , 2008, Anesthesiology.

[3]  J. Nofer,et al.  Impaired vitamin B12 metabolic status in healthcare workers occupationally exposed to nitrous oxide. , 2007, British journal of anaesthesia.

[4]  R. Frumento,et al.  General anesthesia and methylenetetrahydrofolate reductase deficiency , 2007, Journal of Anesthesia.

[5]  T. Ulutin,et al.  Molecular Analysis of Factor V Leiden, Factor V Hong Kong, Factor II G20210A, Methylenetetrahydrofolate Reductase C677T, and A1298C Mutations Related to Turkish Thrombosis Patients , 2007, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[6]  S. Vollset,et al.  The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease. , 2006, The Journal of nutrition.

[7]  H. Muir,et al.  Reversible nitrous oxide myelopathy and a polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase. , 2006, British journal of anaesthesia.

[8]  K. Hogan,et al.  Adverse effect of nitrous oxide in a child with 5,10-methylenetetrahydrofolate reductase deficiency. , 2003, The New England journal of medicine.

[9]  J. Weimann.  Toxicity of nitrous oxide. , 2003, Best practice & research. Clinical anaesthesiology.

[10]  J. Spence,et al.  Preoperative Oral B Vitamins Prevent Nitrous Oxide-Induced Postoperative Plasma Homocysteine Increases , 2001, Anesthesia and Analgesia.

[11]  N. Badner,et al.  Nitrous Oxide-Induced Increased Homocysteine Concentrations Are Associated with Increased Postoperative Myocardial Ischemia in Patients Undergoing Carotid Endarterectomy , 2000, Anesthesia and analgesia.

[12]  G. Wells,et al.  Neonatal and fetal methylenetetrahydrofolate reductase genetic polymorphisms: an examination of C677T and A1298C mutations. , 2000, American journal of human genetics.

[13]  H. Willenbring,et al.  Genomic structure and transcript variants of the human methylenetetrahydrofolate reductase gene , 2000, European Journal of Human Genetics.

[14]  R. Rozen,et al.  The thermolabile variant 677C→T can further reduce activity when expressed in CIS with severe mutations for human methylenetetrahydrofolate reductase , 2000, Human mutation.

[15]  N. Akar,et al.  Effect of methylenetetrahydrofolate reductase 677 C-T, 1298 A-C, and 1317 T-C on factor V 1691 mutation in Turkish deep vein thrombosis patients. , 2000, Thrombosis research.

[16]  B. Brenner,et al.  Thrombophilia-associated pregnancy wastage. , 1999, Fertility and sterility.

[17]  R. Rozen,et al.  A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. , 1998, Molecular genetics and metabolism.

[18]  R K Gordon,et al.  S‐Adenosylmetliionine and methylation , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[19]  H. Keating,et al.  Patient-controlled analgesia with nitrous oxide in cancer pain. , 1996, Journal of pain and symptom management.

[20]  J. Nunn,et al.  Rate of Inactivation of Human and Rodent Hepatic Methionine Synthase by Nitrous Oxide , 1988 .

[21]  R. Matthews,et al.  In vitro inactivation of methionine synthase by nitrous oxide. , 1986, The Journal of biological chemistry.

[22]  D. Mollin,et al.  INCIDENCE AND PATHOGENESIS OF ACUTE MEGALOBLASTIC BONE-MARROW CHANGE IN PATIENTS RECEIVING INTENSIVE CARE , 1982, The Lancet.

[23]  T. Isbir,et al.  C677T mutation of methylenetetrahydrofolate reductase gene and serum homocysteine levels in Turkish patients with coronary artery disease , 2006, Cell biochemistry and function.

[24]  D. Jaffe,et al.  A randomized clinical trial of continuous-flow nitrous oxide and midazolam for sedation of young children during laceration repair. , 2001, Annals of emergency medicine.

[25]  B. Krauss,et al.  Continuous-flow nitrous oxide: searching for the ideal procedural anxiolytic for toddlers. , 2001, Annals of emergency medicine.