• M T V Chan, P J Peyton, P S Myles, K Leslie, N Buckley, J Kasza, M J Paech, W S Beattie, D I Sessler, A Forbes, S Wallace, Y Chen, Y Tian, W K K Wu, and and the Australian and New Zealand College of Anaesthetists Clinical Trials Network for the ENIGMA-II investigators.
• Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China mtvchan@cuhk.edu.hk.
• Br J Anaesth. 2016 Dec 1; 117 (6): 801-811.

BackgroundPrevious animal and clinical studies showed that nitrous oxide may produce long-term analgesia. The aim of this study was to evaluate the effect of nitrous oxide in preventing chronic postsurgical pain. We also explored whether methylenetetrahydrofolate reductase gene polymorphisms (1298A>C, 667C>T) would enhance nitrous oxide analgesia.MethodsWe conducted a telephone interview at 12 months after surgery on 2924 (41.1%) patients enrolled in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia-II trial. Pain at the wound site was recorded using the modified brief pain inventory and the neuropathic pain questionnaire. General health status was measured using the EQ-5D questionnaire. Genotyping was performed in a subset of 674 Asian patients in Hong Kong.ResultsAt 12 months after surgery, 356 (12.2%) patients reported chronic postsurgical pain at the wound site and 112 (3.8%) patients had severe pain and required regular analgesic interventions. Nitrous oxide did not affect the rate of chronic postsurgical pain (11.8% nitrous oxide group; 12.5% no nitrous oxide group), relative risk (95% confidence intervals): 0.94 (0.75-1.17), P=0.57. However, in a planned subgroup analysis, nitrous oxide reduced the risk of chronic postsurgical pain in Asian patients, relative risk (95% confidence intervals): 0.70 (0.50-0.98), P=0.031. Patients who were homozygous for either gene polymorphism and who received nitrous oxide during surgery were less likely to report chronic postsurgical pain.ConclusionsNitrous oxide administration had no impact on chronic postsurgical pain, but benefits may still be possible in Asian patients and patients with variants in methylenetetrahydrofolate reductase gene.Clinical Trial RegistrationNCT00430989.© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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