Chronic postsurgical pain in the evaluation of nitrous oxide in the gas mixture for anaesthesia (ENIGMA)-II trial

M. T. V. Chan, P. J. Peyton, P. S. Myles, K. Leslie, J. Kasza, M. J. Paech, W. S. Beattie, D. I. Sessler, Andrew Benjamin Forbes, A. Forbes, S. Wallace, Y. Chen, Y. Tian, W. K. K. Wu, Australian and New Zealand College of Anaesthetists Clinical Trials Network for the ENIGMA-II investigators

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background. Previous animal and clinical studies showed that nitrous oxide may produce long-termanalgesia. 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. Methods. We 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. Results. At 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 polymorphismand who received nitrous oxide during surgery were less likely to report chronic postsurgical pain. Conclusions. Nitrous 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.

Original languageEnglish
Pages (from-to)801-811
Number of pages11
JournalBritish Journal of Anaesthesia
Volume117
Issue number6
DOIs
Publication statusPublished - 12 Dec 2016

Keywords

  • cHROnic pain
  • Nitrous oxide
  • Polymorphism
  • Single nucleotide
  • Surgery

Cite this

Chan, M. T. V., Peyton, P. J., Myles, P. S., Leslie, K., Kasza, J., Paech, M. J., ... Australian and New Zealand College of Anaesthetists Clinical Trials Network for the ENIGMA-II investigators (2016). Chronic postsurgical pain in the evaluation of nitrous oxide in the gas mixture for anaesthesia (ENIGMA)-II trial. British Journal of Anaesthesia, 117(6), 801-811. https://doi.org/10.1093/bja/aew338
Chan, M. T. V. ; Peyton, P. J. ; Myles, P. S. ; Leslie, K. ; Kasza, J. ; Paech, M. J. ; Beattie, W. S. ; Sessler, D. I. ; Forbes, Andrew Benjamin ; Forbes, A. ; Wallace, S. ; Chen, Y. ; Tian, Y. ; Wu, W. K. K. ; Australian and New Zealand College of Anaesthetists Clinical Trials Network for the ENIGMA-II investigators. / Chronic postsurgical pain in the evaluation of nitrous oxide in the gas mixture for anaesthesia (ENIGMA)-II trial. In: British Journal of Anaesthesia. 2016 ; Vol. 117, No. 6. pp. 801-811.
@article{45316661afe24a2aa7d66ac7ef33437a,
title = "Chronic postsurgical pain in the evaluation of nitrous oxide in the gas mixture for anaesthesia (ENIGMA)-II trial",
abstract = "Background. Previous animal and clinical studies showed that nitrous oxide may produce long-termanalgesia. 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. Methods. We 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. Results. At 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 polymorphismand who received nitrous oxide during surgery were less likely to report chronic postsurgical pain. Conclusions. Nitrous 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.",
keywords = "cHROnic pain, Nitrous oxide, Polymorphism, Single nucleotide, Surgery",
author = "Chan, {M. T. V.} and Peyton, {P. J.} and Myles, {P. S.} and K. Leslie and N. Buckley and J. Kasza and Paech, {M. J.} and Beattie, {W. S.} and Sessler, {D. I.} and Forbes, {Andrew Benjamin} and A. Forbes and S. Wallace and Y. Chen and Y. Tian and Wu, {W. K. K.} and {Australian and New Zealand College of Anaesthetists Clinical Trials Network for the ENIGMA-II investigators}",
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Chan, MTV, Peyton, PJ, Myles, PS, Leslie, K, Kasza, J, Paech, MJ, Beattie, WS, Sessler, DI, Forbes, AB, Forbes, A, Wallace, S, Chen, Y, Tian, Y, Wu, WKK & Australian and New Zealand College of Anaesthetists Clinical Trials Network for the ENIGMA-II investigators 2016, 'Chronic postsurgical pain in the evaluation of nitrous oxide in the gas mixture for anaesthesia (ENIGMA)-II trial', British Journal of Anaesthesia, vol. 117, no. 6, pp. 801-811. https://doi.org/10.1093/bja/aew338

Chronic postsurgical pain in the evaluation of nitrous oxide in the gas mixture for anaesthesia (ENIGMA)-II trial. / Chan, M. T. V.; Peyton, P. J.; Myles, P. S.; Leslie, K.; Kasza, J.; Paech, M. J.; Beattie, W. S.; Sessler, D. I.; Forbes, Andrew Benjamin; Forbes, A.; Wallace, S.; Chen, Y.; Tian, Y.; Wu, W. K. K.; Australian and New Zealand College of Anaesthetists Clinical Trials Network for the ENIGMA-II investigators.

In: British Journal of Anaesthesia, Vol. 117, No. 6, 12.12.2016, p. 801-811.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Chronic postsurgical pain in the evaluation of nitrous oxide in the gas mixture for anaesthesia (ENIGMA)-II trial

AU - Chan, M. T. V.

AU - Peyton, P. J.

AU - Myles, P. S.

AU - Leslie, K.

AU - Buckley, N.

AU - Kasza, J.

AU - Paech, M. J.

AU - Beattie, W. S.

AU - Sessler, D. I.

AU - Forbes, Andrew Benjamin

AU - Forbes, A.

AU - Wallace, S.

AU - Chen, Y.

AU - Tian, Y.

AU - Wu, W. K. K.

AU - Australian and New Zealand College of Anaesthetists Clinical Trials Network for the ENIGMA-II investigators

PY - 2016/12/12

Y1 - 2016/12/12

N2 - Background. Previous animal and clinical studies showed that nitrous oxide may produce long-termanalgesia. 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. Methods. We 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. Results. At 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 polymorphismand who received nitrous oxide during surgery were less likely to report chronic postsurgical pain. Conclusions. Nitrous 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.

AB - Background. Previous animal and clinical studies showed that nitrous oxide may produce long-termanalgesia. 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. Methods. We 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. Results. At 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 polymorphismand who received nitrous oxide during surgery were less likely to report chronic postsurgical pain. Conclusions. Nitrous 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.

KW - cHROnic pain

KW - Nitrous oxide

KW - Polymorphism

KW - Single nucleotide

KW - Surgery

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DO - 10.1093/bja/aew338

M3 - Article

VL - 117

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JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

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