Bevan J C, Rosenblatt D S, Clow C L, Chapman V A
Can Anaesth Soc J. 1982 May;29(3):260-3. doi: 10.1007/BF03007127.
Research into the biotransformation of inhaled general anaesthetic agents, including nitrous oxide, has led to a better understanding of the underlying mechanisms. It is now known that nitrous oxide can react chemically with vitamin B12, oxidizing Cob(I)alamin to the inactive Cob(III) alamin form. Clinical and experimental evidence in mammals has confirmed that nitrous oxide toxicity, with symptoms suggestive of clinical vitamin B12 deficiency, occurs on exposure to nitrous oxide in a way which is dose and time related and reversible on withdrawal of the nitrous oxide. Nitrous oxide depresses the two known vitamin B12 dependent enzymes methylmalonyl CoA mutase and methionine synthetase by inactivation of their coenzymes adenosylcobalamin and methylcobalamin respectively. Methionine synthetase catalyses the conversion of homocystine to methionine, so interference with this reaction should cause methionine to be depleted and homocysteine to accumulate and to be excreted in the urine. We postulated that the detection of homocystinuria would therefore be an early indicator of nitrous oxide toxicity. Accordingly, we tested the first urine voided postoperatively of 41 patients undergoing nitrous oxide anaesthesia (17 neonates exposed to 50-66 per cent nitrous oxide for a mean of 3.0 hr, and 24 older patients exposed to 66 per cent nitrous oxide for a mean of 7.2 hr). None of these patients demonstrated homocystinuria.
