Nitrous oxide: neurological and haematological toxic effects. Update by the MHRA

Nitrous oxide: neurological and haematological toxic effects, especially with prolonged use

Keywords: Nitrous oxide, neurological, haematological toxicity

“Neurological and haematological toxic effects can occur with prolonged use of nitrous oxide. Neurological effects can occur without preceding overt haematological changes.Assessment of vitamin B12 levels should be considered before nitrous oxide anaesthesia in people with risk factors for deficiency.

Nitrous oxide is a medical gas used very widely in surgical anaesthesia. As a 50% mixture with oxygen (brands include Entonox), it is also widely used to relieve pain in childbirth and in acute trauma.

Risk with prolonged use

Nitrous oxide has a very good safety profile in normal use under the supervision of a healthcare professional. However, prolonged use may lead in rare cases to
megaloblastic anaemia and neurological toxic effects (myelopathy) due to inactivation of vitamin B12.
For this reason, nitrous oxide should not be given continuously for more than 24 hours or more frequently than every 4 days, without close clinical supervision and haematological monitoring.

Neurological toxic effects can occur without anaemia or macrocytosis, and even when B12 levels are in the normal range.

Vitamin B12 deficiency

In patients with subclinical deficiency of vitamin B12, neurological toxic effects have occurred after a single exposure to nitrous oxide during general anaesthesia.
Assessment of vitamin B12 levels should be considered before nitrous oxide anaesthesia in patients with risk factors for deficiency of this vitamin. Individuals at risk include elderly people, those who have a poor or vegetarian diet, and those with a history of anaemia.
Nitrous oxide is a licensed medicinal product. Updated Summaries of Product Characteristics will be available in due course.

Advice for healthcare professionals:

• Neurological and haematological toxic effects can occur with prolonged use of nitrous oxide. For this reason, nitrous oxide should not be given continuously for more than 24 hours, or more frequently than every 4 days, without close clinical supervision and haematological monitoring


• Neurological toxic effects can occur without preceding overt haematological changes


• Assessment of vitamin B12 levels should be considered before nitrous oxide anaesthesia in people with risk factors for deficiency of this vitamin.


Specialist haematological advice should be sought as appropriate”

Source:  Medicines and Healthcare products Regulatory Agency (MHRA). Drug Safety Update for December 2008 (PDF)

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