Should nitrous oxide ever be used in oncology patients receiving methotrexate therapy?

Forster, V. J., Bell, G. and Halsey, C. (2020) Should nitrous oxide ever be used in oncology patients receiving methotrexate therapy? Pediatric Anesthesia, 30(1), pp. 9-16. (doi: 10.1111/pan.13760) (PMID:31667903)

201921.pdf - Accepted Version



Nitrous oxide (N2O) 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 N2O 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 N2O in children with ALL. In this article, we review the biochemical basis and scientific observations that suggest a significant interaction between N2O 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 N2O in children receiving concurrent methotrexate.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Bell, Mr Graham and Halsey, Professor Chris
Authors: Forster, V. J., Bell, G., and Halsey, C.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Pediatric Anesthesia
ISSN (Online):1460-9592
Published Online:31 October 2019
Copyright Holders:Copyright © 2019 John Wiley and Sons Ltd
First Published:First published in Pediatric Anesthesia 30(1):9-16
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173748Deciphering neurotoxicity during ALL therapy using a deep phenotyping-genotyping approachChristina HalseyGlasgow Children`s Hospital Charity (GCHC)GCHC/PSG/2016/11Institute of Cancer Sciences