Monitoring cobalamin inactivation during nitrous oxide anesthesia by determination of homocysteine and folate in plasma and urine

Abstract

The effects of nitrous oxide-induced cobalamin inactivation on homocysteine and folate metabolism have been investigated. Plasma levels of cobalamin, folate, homocysteine, and methionine were determined in 40 patients before and after operation under nitrous oxide anesthesia (range of exposure time, 70 to 720 minutes). Twelve patients anesthetized with total intravenous anesthesia served as control subjects (range of exposure time, 115 to 600 minutes). Postoperative plasma levels of folate and homocysteine increased (p less than 0.001) up to 220% and 310%, respectively, in nitrous oxide-exposed patients, whereas plasma levels of methionine decreased (p less than 0.025). Response occurred after 75 minutes of nitrous oxide exposure. The percentage increase of plasma folate and homocysteine correlated significantly with exposure time (p less than 0.025 and p less than 0.0001, respectively). In eight patients receiving nitrous oxide anesthesia plasma homocysteine levels had not returned to preoperative levels within 1 week (p less than 0.01). Urinary excretion of folate and homocysteine increased during and after nitrous oxide exposure (p less than 0.01 and p less than 0.002, respectively) and correlated with exposure time (p less than 0.01 and p less than 0.005, respectively). It can be concluded that disturbance of homocysteine and folate metabolism by nitrous oxide develops with little delay and return to normal levels requires several days. Elevation of plasma homocysteine levels may therefore be used for monitoring nitrous oxide-induced cobalamin inactivation.

Screening for Serum Total Homocysteine in Newborn Children

“…B 12 deficiency could be one explanation (64 ), but in samples with extremely low methionine (which consistently had increased folate), B 12 was in the high range and tHcy was within the reference interval. Nitrous oxide exposure, which inactivates methionine synthase and thereby leads to increased serum folate, low methionine, and increased tHcy (65 ), is yet another possibility. However, at least in adults, the nitrous oxide effect on folate and methionine concentrations is short, whereas the effect on tHcy persists for many days (65,66 ).…”

“…Nitrous oxide exposure, which inactivates methionine synthase and thereby leads to increased serum folate, low methionine, and increased tHcy (65 ), is yet another possibility. However, at least in adults, the nitrous oxide effect on folate and methionine concentrations is short, whereas the effect on tHcy persists for many days (65,66 ). Thus, the findings in these babies are not consistent with nitrous oxide exposure.…”

Impaired Homocysteine Metabolism and Atherothrombotic Disease

“…In addition to the increase in folate requirement, the oral contraceptivedependent hyperhomocysteinemia can result from an altered vitamin B 6 metabolism. Nitrous oxide (N 2 O), an anesthetic gas that inhibits methionine synthase activity, also induces hyperhomocysteinemia (Ermens et al, 1991;Frontiera et al, 1994). Finally, cardiac and renal transplantation generate hyperhomocysteinemia that might depend on the onset of folate or vitamin B 6 deficiency combined with the use of immunosuppressive agents such as cyclosporine, which may interfere with the renal clearance of plasma homocysteine (Bostom et al, 1997).…”

The association of homocysteine and coronary artery disease

“…20 Nitrous oxide alters cobalamine metabolism within 1 h of administration, resulting in increased Hcy concentrations that can remain elevated for longer than 1 week. 21 Fenofibrate, bezafibrate, and colestipol in combination with niacin result in hyperhomocysteinemia by yet to be defined mechanisms. 22,23 Tobacco and caffeinated coffee are also associated with increased Hcy concentrations.…”