Nitrous oxide toxicity

Severe Myeloneuropathy from Acute High-Dose Nitrous Oxide (N2O) Abuse. Alt RS et al. J Emerg Med 2011;41:378-380.

This case report describes a 24-year-old man who presented to the emergency department because of difficulty walking, and problems with balance and hand coordination. Examination revealed impaired proprioception, cerebellar function, and light touch sensation in a stocking-glove distribution.

The patient reported that he typically used alcohol and cocaine daily. For several years he had occasionally inhaled nitrous oxide (laughing gas), but for the 2 weeks prior to presentation had increased his consumption from several whippets each month to 240 daily. Laboratory tests were consistent with nitrous oxide toxicity. He was treated with vitamin B12 but did not return for follow-up appointments.

The discussion makes the following important points about nitrous oxide toxicity:

• Nitrous oxide oxidizes cobalt in vitamin B12 from Co1+ to Co2+, inactivating the vitamin and inhibiting methionine synthesis.
• Nitrous oxide toxicity impairs nerve cell myelination.
• Although vitamin B12 levels can be normal in nitrous oxide toxicity (since the assay may not distinguish between the normal and oxidized forms) hallmarks of laboratory diagnosis are elevated levels of homocysteine and methylmalonic acid.
• Treatment of nitrous oxide-induced neurtoxicity involves administration of parenteral vitamin B12 and oral methionine.
• Although most texts state that neurotoxicity from nitrous oxide occurs only after chronic use, this case seems to have come on after 2 weeks of high-dose abuse.

Signs and symptoms of nitrous oxide-induced neurotoxicity include: numbness and tingling of the distal extremities and impairment of vibration sensation, light touch and pinprick, proprioception, and gait.

The case is not completely convincing as proof that nitrous oxide can cause neurotoxicity acutely — confounding factors include the long-term use of alcohol and cocaine, as well as the reported chronic intermittent abuse of nitrous oxide. But it does remind us of some key features of this fascinating neurotoxin.