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Letters to the Editor
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Adverse drug reactions
Prolonged use of nitrous oxide and oxygen mixture
From Dr M. E. Brown, MRPharmS and Dr J. Hoodless
The purpose of this letter is to remind and alert clinical pharmacists
about the potential adverse effects of the extended use of nitrous oxide
and oxygen mixtures. Those pharmacists who work in hospitals and perhaps
some community settings may consider it appropriate to draw this to the
attention of prescribing medical practitioners.
Generally 50 per cent nitrous oxide and 50 per cent oxygen mixtures have
a good safety record in short-term pain management. However, three reports
of suspected adverse drug reactions received via the yellow card scheme
alerted us to instances in hospitals where patients have experienced suspected
ADRs. Those patients had received 50 per cent nitrous oxide and 50 per
cent oxygen mixtures on a regular daily basis for extended periods of
weeks or months (personal communication, Committee on Safety of Medicines).
Unusually lengthy administration may be connected with ADRs which are reported
in medical literature such as Doran et al.1
We realise that there may be exceptional reasons for extended use. However,
the summary of product characteristics for Linde’s Equanox, for example,
states that it should not be used for more than 24 hours without monitoring
of peripheral blood for features of megaloblastic anaemia and leukopenia.
Administration more frequently than every four days should be accompanied
by routine blood tests for evidence of megaloblastic change in red cells
and hypersegmentation of neutrophils. The patient information leaflet alerts
patients that blood may be taken to check red and white blood cells.
The mechanism of the adverse drug reaction is that nitrous oxide inactivates
vitamin B12. That is a co-factor in methionine synthesis. The result is
interference with folate metabolism. Prolonged administration of nitrous
oxide impairs methionine and DNA synthesis. Results include megaloblastic
bone marrow changes and possibly myeloneuropathy and subacute combined
degeneration. Patients starting with a pre-existing depletion of vitamin
B12 stores such as strict vegetarians may be most at risk. Injection of
vitamin B12 may be required.
Malcolm E. Brown
Judith Hoodless
Qualified persons
Linde Gas UK Ltd, Manchester
Reference
1. Doran M, Rassam SS, Jones LM, Underhill S. Toxicity after intermittent
inhalation of nitrous oxide for analgesia. BMJ 2004;328:1364–5.
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