M T V Chan1, P J Peyton2,3, P S Myles4,5,6, K Leslie6,7,8,9, N Buckley10, J Kasza6, M J Paech11,12, W S Beattie13,14, D I Sessler15, A Forbes6, S Wallace4,5, Y Chen16, Y Tian16, W K K Wu16,17,18. 1. Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China mtvchan@cuhk.edu.hk. 2. Department of Anaesthesia, Austin Hospital, Melbourne, Victoria, Australia. 3. Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia. 4. Department of Anaesthesia and Perioperative Medicine, The Alfred Hospital, Melbourne, Victoria, Australia. 5. Department of Anaesthesia and Perioperative Medicine, Monash University, Melbourne, Victoria, Australia. 6. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. 7. Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Melbourne, Victoria, Australia. 8. Anaesthesia, Perioperative and Pain Medicine Unit, and. 9. Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, Victoria, Australia. 10. Department of Anesthesia, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada. 11. Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, Perth, Western Australia, Australia. 12. School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia. 13. Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada. 14. Department of Anaesthesia, Toronto General Hospital, Toronto, Ontario, Canada. 15. Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, USA. 16. Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China. 17. Li Ka Shing Institute of Health Sciences, Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China. 18. State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
Abstract
BACKGROUND: Previous 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. METHODS: We conducted a telephone interviewat 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 polymorphism and who receivednitrous 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. CLINICAL TRIAL REGISTRATION: NCT00430989.
RCT Entities:
BACKGROUND: Previous 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. 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 polymorphism and 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. CLINICAL TRIAL REGISTRATION: NCT00430989.
Authors: Juan P Cata; Pascal Owusu-Agyemang; Dhanalakshmi Koyyalagunta; German Corrales; Lei Feng; Keith Fournier Journal: J Pain Res Date: 2021-08-13 Impact factor: 3.133