Nitrous oxide toxicity

Background

• Nitrous oxide toxicity is often associated with inhalation of whipped cream or small nitrous oxide cannisters (whippets)
• Commonly abused drug notable for its short-lived euphoric and calming effects through noncompetitive NMDA antagonism and GABA-A agonism.
• Nitrous is much more soluble in blood and will quickly diffuse from the blood to a closed space.
• Beyond the gaseous effects nitrous oxide mainly disrupts B12 by oxidizing the cobalt ion which irreversibly inhibits methionine synthase
• Epidemiology
  • Rates of nitrous oxide misuse vary significantly by country and are generally higher in Europe and the United States.
  • The World Drug Report found nitrous oxide use (i.e. at least once in last 12 months) in 16-24 year olds doubled globally between 2015 to 2021, from 10% to 20%.
• Most nitrous oxide misuse is sporadic and without significant health consequences. This and its ease of availability may lead users to erroneously view it as safe.

Differential Diagnosis

Acute complications

• Pneumothorax (induced by forceful inhalation or high-pressure tank siphoning)
• Tympanic membrane rupture
• Tracheal trauma
• Air emboli
• Thrombotic events (rare, typically in subacute toxicity from homocysteine elevation)
  • Venous thromboembolism
  • Acute arterial ischemia

Chronic complications

• Bone marrow suppression (from long term exposure)
  • Leukopenia
  • Megaloblastic anemia
  • Thrombocytopenia
• Peripheral neuropathy
• Subacute combined degeneration of the spinal cord

Evaluation

• Nitrous oxide use is undetectable by standard drug screens, which makes obtaining a thorough history crucial.
• Neuro deficits:
  • Consult poison control for recommendations.
  • May be exacerbated in cases of underlying B12 deficiency.

See Also

• Nitrous oxide
• Vitamin B12 deficiency