Monitoring Cobalamin Inactivation During Nitrous Oxide Anesthesia by Determination of Homocysteine and Folate in Plasma and Urine

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 < 0.001) up to 220% and 310%, respectively, in nitrous oxide-exposed patients, whereas plasma levels of methionine decreased (p < 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 < 0.025 and p < 0.0001, respectively). In eight patients receiving nitrous oxide anesthesia plasma homocysteine levels had not returned to preoperative levels within 1 week (p < 0.01). Urinary excretion of folate and homocysteine increased during and after nitrous oxide exposure (p < 0.01 and p < 0.002, respectively) and correlated with exposure time (p < 0.01 and p < 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. Clinical Pharmacology and Therapeutics (1991) 49, 385–393; doi:10.1038/clpt.1991.45