Methotrexate-induced stomatitis and other toxic effects may beincreased by use of nitrous oxide
Clinical evidence,mechanism, importance and management
A study in which intravenous methotrexate,cyclophosphamide and fluorouracil (CMF) were used within 36 hrs of mastectomy suggested that stomatitis may be caused by a toxic interaction between methotrexate and nitrous oxide used during anaesthesia. Stomatitis was much more common in those receiving CMF within 6 hrs of surgery (See reference number 1-3). A possible reason is that effects of methotrexate on tetrahydrofolate metabolism are increased by nitrous oxide, and this has been confirmed in animals (See reference number 4). It was found that incidence of stomatitis, severe leucopenia, thrombocytopenia, and of severe systemic and local infections could be reduced by giving calcium folinate (leucovorin) and intravenous hydration (See reference number 2,3). Alternatively, use of nitrous oxide shortly before methotrexate administration should be avoided (See reference number 4).
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