Authors: Tom Bannister / Codes: HP1, NeuC10, NeuP1, NeuP6, NeuP8, PhC1, PhP3, SLO1, UP3 / Published: 17/06/2024

Scope / Reason for development

This scope of this guideline is limited to unregulated nitrous oxide (N2O) use. It does not relate to use of Entonox or delivery of anaesthesia, and is not applicable in settings other than Emergency Departments (EDs).

Summary of Recommendations

  1. Patients presenting with neurological abnormalities without obvious cause should have nitrous oxide considered as a potential cause for their symptoms.
  2. Systems should be in place to allow samples for homocysteine and methylmalonic acid analysis to be obtained in Emergency Departments. It is acknowledged that the result may take several days to return, and clear local protocols for ownership of these delayed results by whichever specialty is providing ongoing care are required.
  3. Emergency Medicine clinicians have a role to play in promoting consideration of nitrous oxide toxicity and can support diagnosis by ordering the correct investigations early in the patient’s journey.
  4. The majority of Emergency Medicine investigation is likely to focus on the exclusion of other causes of neuropathy.
  5. If a diagnosis of nitrous oxide toxicity is suspected, treatment should be initiated before the return of definitive diagnostic results.
  6. Patients presenting with potential consequences of drug use should have a full drug and alcohol history taken, and be offered referral to drug/alcohol liaison services. Nitrous oxide should be specifically asked about as patients may not consider it a ‘drug’.

Ensure that you read the full Suspected Nitrous Oxide Toxicity in the ED Guideline

Key Information

Patients may present with any of:

  • sensory deficits (either in a classic peripheral neuropathy pattern, or with isolated areas of numbness or paraesthesia)
  • motor deficits (classically described as predominantly lower limb, or with issues relating to fine motor control)
  • ataxia
  • urinary retention
  • erectile dysfunction
  • non-specific symptoms such as confusion, or personality change (including low mood or irritability)

Patients presenting with haematological abnormalities consistent with vitamin B12 deficiency should have N2O considered as a potential cause for their symptoms:

  • anaemia
  • macrocytosis
  • agranulocytosis or pancytopaenia

Because N2O oxidises cobalamin rather than destroying it, vitamin B12 levels may be normal, even if cobalamin is not functional. Look for other indications of poor cobalamin function:

  • Increased homocysteine levels.
  • Increased methylmalonic acid levels.

If a diagnosis of N2O toxicity is suspected, treatment should be initiated before the return of definitive diagnostic results. A suggested regime is:

  • Vitamin B12 1mg intramuscularly once daily
  • Folic acid 5mg orally once daily

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