Nitrous oxide toxicity

Nitrous oxide (N2O) toxicity has serious medical sequelae affecting both the CNS and the bone marrow. Neurological effects include encephalopathy, myelopathy, and neuropathy. This results from demyelination and gliosis due to selective inhibition of vitamin B12 1. Bone marrow toxicity may lead to myelosuppression, including neutropenia and megaloblastic anemia.

N2O is an established and widely used anesthetic gas though also misused quite commonly for recreational purposes as a legal 'high'. Canisters of nitrous oxide, colloquially known as “whippets”, "nangs", or "bulbs" 5, are used commercially as a propellant for whipped cream, and are commonly abused 6.

As an end user, nitrous oxide gas is a close-to-ideal recreational agent, it is legal, inexpensive, easily accessible, and not found on standard illicit substance screens. Physiologically, its effects manifest within seconds of inspiring the gas, and its offset is just as rapid, with no after effects, such that users may continue with their regular activities only minutes post-exposure.

In the 2013/14 Crime Survey for England and Wales, it was reported that almost 8% 16 to 24 year olds had used nitrous oxide recreationally in the previous 12 months 8.

Pre-existing vitamin B12 deficiency increases risk of nitrous oxide induced toxicity 8.

The classic neurological appearance of vitamin B12 deficiency is the so-called subacute combined degeneration of the cord manifested as damage to the dorsal columns of the spinal cord, responsible for the transmission of vibratory and proprioceptive input. Peripheral neuropathy, optic atrophy, and dementia can also occur.

Neurotoxicity is secondary to the selective inhibition of vitamin B12 (hydroxocobalamin), which serves as a cofactor for methionine synthase, which is an enzyme active in folate metabolism and the formation of myelin sheath phospholipids 2,4.

The end result of overexposure is demyelination and eventual gliosis, both within the central nervous system and to a lesser extent the peripheral nervous system. 

Radiographic features are identical to those of subacute combined degeneration of the cord.

  • T2: thoracic hyperintense signal involving the dorsal columns (inverted "V" sign), although less commonly lateral tracts of the spinal cord may also be affected; very rarely is there involvement of the anterior spinal cord

Treatment options include:

  • halting exposure to nitrous oxide
  • high dose of intramuscular vitamin B12, followed by oral supplementation
  • methionine supplementation has also been used 2

Despite optimal treatment some patients are left with a permanent deficit, including lifelong paraparesis.

Although there is no risk of physical addiction, the risk of a psychological N2O habit is a clear and present danger 8.

Nitrous oxide gas was first synthesized in 1772 by an English theologian and chemist, Joseph Priestly, chiefly remembered historically for his discovery of oxygen. Within only a few years it was already being abused as a recreational 'high', aware of this Humphrey Davy coined the term "laughing gas" 7,8. By 1844, Horace Wells, an American dentist, had reported its usefulness as an anesthetic gas.

On imaging, the differential diagnosis includes: 

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Article information

rID: 30559
Synonyms or Alternate Spellings:
  • Nitrous oxide gas induced toxicity
  • N2O gas toxicity
  • N2O toxicity
  • Nitrous oxide induced myeloneuropathy
  • Nitrous oxide toxicity myeloneuropathy

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