Nitrous oxide (N2O) Other names: N2O

There is a risk of additive effects when nitrous oxide (contained in nitrous oxide) is used in combination with drugs having a central depressant action (e.g. opiates, benzodiazepines and other psychotropics). If concomitant central acting agents are used the risk for pronounced sedation and depression of protecting reflexes should be acknowledged.

The use of higher levels of oxygen can increase the risk of pulmonary toxicity in patients who have been administered bleomycin, amiodarone and nitrofurantoin or similar antibiotics. In these cases nitrous oxide should be administered with caution and at levels kept as low as possible.

The nitrous oxide inactivates vitamin B₁₂ and potentiates the effects of methotrexate on folate metabolism.

The nitrous oxide causes inactivation of vitamin B₁₂, which is a co-factor of methionine synthase. Folate metabolism is consequently interfered with and DNA synthesis is impaired following prolonged administration of nitrous oxide. Prolonged or frequent use of nitrous oxide may result in megaloblastic marrow changes, myeloneuropathy and sub acute combined degeneration of the spinal cord.

Nitrous oxide should not be used for more than a total of 24 hours, or more frequently than every 4 days, without close clinical supervision and haematological monitoring. Specialist advice should be sought from a haematologist in such cases. Haematological assessment should include an assessment for megaloblastic change in red cells and hypersegmentation of neutrophils. Neurological toxicity can occur without anaemia or macrocytosis and with B₁₂ levels in the normal range.

Mild skeletal teratogenic changes have been observed in pregnant rat embryos when the dam has been exposed to high concentrations of nitrous oxide during the period of organogenesis.

However, no increased incidence of foetal malformation has been discovered in 8 epidemiological studies and case reports in human beings.

There is no published material that shows that nitrous oxide is toxic to the human foetus. Therefore, there is no absolute contra-indication to its use in the first 16 weeks of pregnancy.

There are no known adverse effects to using nitrous oxide during the breast-feeding period.

Adverse psychometric effects will normally cease shortly after the administration of nitrous oxide has stopped due to the rapid elimination of the nitrous oxide component of the medical gas mixture from the body.

When nitrous oxide is used as a sole analgesic/sedative agent, driving and use of complex machinery is not recommended until:

• the healthcare professional has judged that the patient has returned to their normal mental status
• the patient feels that they are competent to drive after the relevant procedure is completed
• at least 30 minutes has elapsed after the administration of nitrous oxide has ceased.

Additional care is needed when nitrous oxide is administered to a patient who has been given concomitant medication.