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Should nitrous oxide ever be used in oncology patients receiving methotrexate therapy?
Author(s) -
Forster Victoria J.,
Bell Graham,
Halsey Christina
Publication year - 2020
Publication title -
pediatric anesthesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.704
H-Index - 82
eISSN - 1460-9592
pISSN - 1155-5645
DOI - 10.1111/pan.13760
Subject(s) - medicine , methotrexate , nitrous oxide , neurotoxicity , chemotherapy , anesthesia , acute lymphocytic leukemia , pharmacology , lymphoblastic leukemia , intensive care medicine , leukemia , oncology , toxicity
Nitrous oxide (N 2 O) is frequently used for short anesthesia/analgesia in children undergoing painful or repetitive procedures. Children with acute lymphoblastic leukemia (ALL) require repeated lumbar punctures with direct instillation of intrathecal chemotherapy, usually the anti‐folate agent methotrexate, during their treatment. These procedures are frequently performed under anesthesia. Concerns have been intermittently raised about a drug interaction between methotrexate and N 2 O that may potentiate the undesirable side effects of methotrexate, including neurotoxicity. However, the clinical evidence consists mainly of isolated case reports leading to a lack of consensus among pediatric anesthetists about the relative risk benefits of using N 2 O in children with ALL. In this article, we review the biochemical basis and scientific observations that suggest a significant interaction between N 2 O and methotrexate due to their dual inhibition of the key enzyme methionine synthase. The possible role of this interaction in potentiating neurotoxicity in children with cancer is discussed, and arguments and counterarguments about the clinical significance of this largely theoretical relationship are explored. Following comprehensive review of all the available data, we make the case for the circumstantial evidence being sufficiently compelling to prompt a review of practice by pediatric anesthetists and call for a precautionary approach by avoiding the use of N 2 O in children receiving concurrent methotrexate.