N20 is minimally metabolized. Nitrous oxide metabolism shows us that N20 oxidizes the cobalt in vitamin B12, converting the monovalent form to bivalent form which fails to function as a methyl carrier.
Nitrous oxide metabolism is an irreversible oxidation. Vitamin B12 is a cofactor for methionine synthetase and is involved in the production of 5,10 methylene tetrahydrofolate which is essential for DNA synthesis.
Chronic exposure to high concentrations of N20 may result in a condition resembling subacute combined degeneration of the spinal cord. ‘Short-term exposures may result in megaloblastic anaemia and agranulocytosis.
The administration of folic acid 30 mg twice a day may prevent development of megaloblastic changes due to N,O. Megaloblastic anaemia has been reported among dentists and dental assistants where high concentrations of N20 are used.
In Nitrous oxide metabolism we see the permitted level of N20 in the operation theaters is 25 ppm. N20 is not a trigger for malignant hyperthermia.
Miller’s Anesthesia 7th Edition says the following about Nitrous oxide metabolism –
Nitrous oxide (N2O) is the only nonhalogenated anesthetic that currently remains in routine clinical use. This agent is not metabolized in human tissue. However, by means of a physicochemical reaction of N2O with vitamin B12, N2O is reductively metabolized by rat and human intestinal bacteria to molecular nitrogen (N2). Reduction of N2O in bacteria may occur via a single electron transfer process that results in the formation of nitrogen gas (N2) and free radicals. N2O can oxidize vitamin B12 and inhibit its coenzyme function. For example, this could affect the activity of methionine synthase, which catalyzes the transmethylation from methyltetrahydrofolate and homocysteine to produce tetrahydrofolate and methionine. Inhibition of methionine synthase has the potential to lead to decreased levels of tetrahydrofolate and methionine and subsequent impairment of DNA synthesis and “carbon 1” metabolic reactions, including methylation. However, such an effect on the activity of vitamin B12 would probably be inconsequential with the short courses of exposure to N2O during anesthesia.