• Corpus ID: 11228634

When Nitrous Oxide is No Laughing Matter

@inproceedings{Baum2007WhenNO,
  title={When Nitrous Oxide is No Laughing Matter},
  author={Victor C Baum},
  year={2007}
}

• V. Baum
• Published 2007
• Medicine

First synthesized by Joseph Priestley in 1772, the psychotropic effects of nitrous oxide were first appreciated (in the first person) by Humphrey Davy. From the time that nitrous oxide was first used for analgesia by Horace Wells in December 1844 until 1956, nitrous oxide was considered to be completely benign. Although there were two isolated case reports, the first clear association of nitrous oxide and hematologic disease came in a report by Lassen, et al. in the Lancet in 1956.(1) They reported several patients with tetanus who were sedated with nitrous oxide for several days and developed evidence of aplastic anemia. They showed that the only drug that completely differentiated these patients from their patients who did not develop hematologic problems was nitrous oxide. They then studied it prospectively in a 10 year old boy. Granulocytopenia developed on the fourth day (of 50% N2O), the N2O was discontinued and thrombocytopenia followed within several days. A bone marrow biopsy was consistent with pernicious anemia with megaloblastic changes. The hematologic picture resolved after discontinuation of N2O. A similar picture was reported in cardiac surgery patients kept on 50% N2O for 24 hours during and after cardiac surgery.(2) A six hour exposure resulted in mild megaloblastic changes, and a 24 hour exposure in severe changes. In 1978, Sahenk reported a case of polyneuropathy from recreational N2O use(3) and Layzer reported on two dentists and a hospital technician who used N2O recreationally several times a week and developed a sensory polyneuropathy which resolved on discontinuation of N2O.(4) Layzer in a follow-up paper reported on 15 patients, 14 of whom were dentists.(5) The polyneuropathy was likened to that of vitamin BB12 deficiency. Several dentists were not recreational users but had heavy exposure in the course of their work. The concentration of inhaled N2O varied between 30-80%, and in some was never higher than 50%. The course of recovery was unaffected by treatment with steroids or vitamin B12. In a survey of 18,000 dentists and 18,000 dental assistants, Jay Brodsky was able to show that there was a gender independent association of neurologic findings similar to those of pernicious anemia with nitrous exposure.(6) Nitrous oxide irreversibly oxidizes the cobalt atom of vitamin B12, transferring it from the active Co(I) state to the inactive Co(II or III) state, inactivating it, somewhat analogous to the reduction of hemoglobin to methemoglobin. In this reaction nitrous oxide is reduced to nitrogen and oxygen. Although originally described by Banks in 1968,(7) this finding was not appreciated in the medical community. This eventually led to an investigation of the effects of N2O on a variety of B12-dependent enzyme systems, particularly by John Nunn and his group. Methionine is an essential amino acid that serves as a methyl donor (via its activated form S-adenosylmethionine) in hundreds of biologic reactions. The end product of methionine demethylation is homocysteine, whose remethylation is catalyzed by the vitamin B12 dependent enzyme methionine synthase (synthetase).