Metoxifluran, an inhalation analgesic that opens up new possibilities in anesthesia

Endoskopist, Obstetrician-gynecologist, Orthopaedic Trauma, Surgeon, Urologist
Metoxifluran, an inhalation analgesic that opens up new possibilities in anesthesia

Abstract. Although numerous clinical guidelines for pain management have been published over the past decade, inadequate pain relief remains a major public health problem.

Currently, several methods of analgesia are available for the treatment of acute pain, including intravenous analgesia, epidural anesthesia, and oral administration of medications.

However, the existing methods of analgesia still do not cover all the needs of proper analgesia, the search for new forms of release, methods of administration and methods of analgesia continues.

Currently, non-invasive methods of analgesia are being actively implemented, which include a transdermal delivery system of analgesics (in particular, fentanyl hydrochloride), intranasal and inhalational analgesia, in which the delivery of analgesics is controlled by both the doctor and the patient.

The purpose of this article is to review the inhaled analgesic methoxyflurane, which is administered by means of an individual inhaler and is used for the treatment of acute pain.

Key words: methoxyflurane, analgesic, pain, analgesia.

Authors: Dmitriev D. V., Nazarchuk O. A., Babina Yu. M. (National Pirogov Memorial Medical University, Vinnytsia).

Literature:

  1. Miaskowski C. Patient-controlled Modalities for Acute Postoperative Pain Management. Journal of PeriAnesthesia Nursing [Internet]. 2005 Aug;20(4): 255–67. Available from: dx.doi.org/ 10.1016/j.jopan.2005.05.005
  2. US Department of Health and Human Services. Pain management best practices inter-agency task force report: updates, gaps, inconsistencies, and recommendations [Internet]. Washington: US Department of Health and Human Services; 2019. 112 p. Available from: hhs.gov/sites/default/files/pain-mgmt-best-practices-draft-final-report-05062019.pdf
  3. Hyland SJ, Wetshtein AM, Grable SJ, Jackson MP. Acute Pain Management Pearls: A Focused Review for the Hospital Clinician. Healthcare [Internet]. 2022 Dec 22;11(1):34. Available from: dx.doi.org/10.3390/healthcare11010034
  4. Lin RJ, Reid MC, Liu LL, Chused AE, Evans AT. The Barriers to High-Quality Inpatient Pain Management: A Qualitative Study. American Journal of Hospice and Palliative Medicine [Internet]. 2014 Apr 11;32(6):594–9. Available from: dx.doi.org/10.1177/1049909114530491
  5. Sinatra R. Causes and Consequences of Inadequate Management of Acute Pain. Pain Medicine [Internet]. 2010 Dec;11(12):1859–71. Available from: dx.doi.org/10.1111/j.1526-4637.2010.00983.x
  6. Gan TJ. Poorly controlled postoperative pain: prevalence, consequences, and prevention. Journal of Pain Research [Internet]. 2017 Sep; Volume 10:2287–98. Available from: dx.doi.org/10.2147/jpr.s144066
  7. McLennan J. Is Methoxyflurane a Suitable Battlefield Analgesic? Journal of the Royal Army Medical Corps [Internet]. 2007 Jun 1;153(2):111–3. Available from: dx.doi.org/10.1136/jramc-153-02-08
  8. Allan J, Cameron J, Bruno J. A Systematic Review of Recreational Nitrous Oxide Use: Implications for Policy, Service Delivery and Individuals. International Journal of Environmental Research and Public Health [Internet]. 2022 Sep 14;19(18):11567. Available from: dx.doi.org/10.3390/ijerph191811567
  9. Tomlin PJ. Methoxyflurane. Br J Anaesth. 1965;37(9):706–709.
  10. Mazze RI, Raja SN. Methoxyflurane Revisited. Anesthesiology: tale of an anesthetic from cradle to grave [Internet]. 2006 Oct 1;105(4):843–6. Available from: dx.doi.org/10.1097/00000542-200610000-00031
  11. Crandell WB, Pappas SG, Macdonald A. Nephrotoxicity Associated with Methoxyflurane Anesthesia. Anesthesiology [Internet]. 1966 Sep 1;27(5):591–607. Available from: dx.doi.org/10.1097/000005 42-196609000-00010
  12. Cousins MJ, Mazze RI. Methoxyflurane nephrotoxicity. A study of dose response in man. JAMA: The Journal of the American Medical Association [Internet]. 1973 Sep 24;225(13):1611–6. Available from: dx.doi.org/10.1001/jama.225.13.1611
  13. Kharasch ED, Schroeder JL, Liggitt HD, Park SB, Whittington D, Sheffels P. New Insights into the Mechanism of Methoxyflurane Nephrotoxicity and Implications for Anesthetic Development (Part 1). Anesthesiology [Internet]. 2006 Oct 1;105(4):726–36. Available from: dx.doi.org/10.1097/0000 0542-200610000-00019
  14. Kharasch ED, Schroeder JL, Liggitt HD, Ensign D, Whittington D. New Insights into the Mechanism of Methoxyflurane Nephrotoxicity and Implications for Anesthetic Development (Part 2). Anesthesiology [Internet]. 2006 Oct 1;105(4):737–45. Available from: dx.doi.org/10.1097/00000542-200610000-00020
  15. Mazze RI, Trudell JR, Cousins MJ. Methoxyflurane Metabolism and Renal Dysfunction. Anesthesiology [Internet]. 1971 Sep 1;35(3):247–52. Available from: dx.doi.org/10.1097/00000542-197109000-00004
  16. Food and Drug Administration, HHS. Determination that Penthrane (methoxyflurane) inhalation liquid, 99.9 percent, was withdrawn from sale for reasons of safety or effectiveness [Internet]. 2005 [cited 2023 Mar 21]. Available from: federalregister.gov/d/05-17559
  17. Australian product information – Penthrox® (Methoxyflurane) inhalation [Internet]. 1993 [Last update 2 Aug 2023]. Available from: ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=pi&q=methoxyflurane
  18. New Zealand Datasheet for Penthrox [Internet]. 2002. [Last update 17 Jan 2020]. Available from: medsafe.govt.nz/profs/datasheet/p/penthroxinh.pdf.
  19. Porter KM, Dayan AD, Dickerson S, Middleton PM. The role of inhaled methoxyflurane in acute pain management. Open Access Emergency Medicine [Internet]. 2018 Oct;Volume 10:149–64. Available from: dx.doi.org/10.2147/oaem.s181222
  20. Ikeda S. The Reincarnation of Methoxyflurane. Journal of Anesthesia History [Internet]. 2020 Jun;6(2):79–83. Available from: dx.doi.org/10.1016/j.janh.2019.07.001
  21. Penthrox® Summary of Product Characteristics [Internet]. [Last update 27 Mar 2023]. Available from: medicines.org.uk/emc/medicine/31391.
  22. Coffey F, Wright J, Hartshorn S, Hunt P, Locker T, Mirza K, et al. STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain. Emergency Medicine Journal [Internet]. 2014 Apr 17;31(8):613–8. Available from: dx.doi.org/10.1136/emermed-2013-202909
  23. Fabbri A, Carpinteri G, Ruggiano G, Bonafede E, Sblendido A, Farina A, et al. Methoxyflurane Versus Standard of Care for Acute Trauma-Related Pain in the Emergency Setting: Protocol for a Randomised, Controlled Study in Italy (MEDITA). Advances in Therapy [Internet]. 2018 Nov 22;36(1):244–56. Available from: dx.doi.org/10.1007/s12325-018-0830-x
  24. Raccomandazioni Intersocietarie Italiane (SIAARTI, SIMEU, SIS 118, AISD, SIARED, SICUT, IRC) sulla gestione del dolore in emergenza [Internet]. 2014. Available from: aisd.it/e107_files/downloads/raccintersocietarie_it_complete31052014.pdf
  25. Borobia AM, Collado SG, Cardona CC, Pueyo RC, Alonso CF, Torres IP, et al. Inhaled Methoxyflurane Provides Greater Analgesia and Faster Onset of Action Versus Standard Analgesia in Patients With Trauma Pain: InMEDIATE: A Randomized Controlled Trial in Emergency Departments. Annals of Emergency Medicine [Internet]. 2020 Mar;75(3):315–28. Available from: dx.doi.org/10.1016/j.annemergmed.2019.07.028
  26. Jephcott C, Grummet J, Nguyen N, Spruyt O. A review of the safety and efficacy of inhaled methoxyflurane as an analgesic for outpatient procedures. British Journal of Anaesthesia [Internet]. 2018 May;120(5):1040–8. Available from: dx.doi.org/10.1016/j.bja.2018.01.011
  27. Nguyen NQ, Toscano L, Lawrence M, Moore J, Holloway RH, Bartholomeusz D, et al. Patient-controlled analgesia with inhaled methoxyflurane versus conventional endoscopist-provided sedation for colonoscopy: a randomized multicenter trial. Gastrointestinal Endoscopy [Internet]. 2013 Dec;78(6):892–901. Available from: dx.doi.org/10.1016/j.gie.2013.05.023
  28. Grummet J, Huang S, Konstantatos A, Frydenberg M. The ‘green whistle’: A novel method of analgesia for transrectal prostate biopsy. BJU International [Internet]. 2012 Nov 29;110(S4):85–8. Available from: dx.doi.org/10.1111/j.1464-410x.2012.11613.x
  29. Lee C, Woo HH. Penthrox inhaler analgesia in transrectal ultrasound-guided prostate biopsy. ANZ Journal of Surgery [Internet]. 2014 May 30;85(6):433–7. Available from: dx.doi.org/10.1111/ans.12694
  30. Spruyt O, Westerman D, Milner A, Bressel M, Wein S. A randomised, double-blind, placebo-controlled study to assess the safety and efficacy of methoxyflurane for procedural pain of a bone marrow biopsy. BMJ Supportive & Palliative Care [Internet]. 2013 Jun 7;4(4):342–8. Available from: dx.doi.org/10.1136/bmjspcare-2013-000447
  31. Wasiak J, Mahar PD, Paul E, Menezes H, Spinks AB, Cleland H. Inhaled methoxyflurane for pain and anxiety relief during burn wound care procedures: an Australian case series. International Wound Journal [Internet]. 2012 Aug 27;11(1):74–8. Available from: dx.doi.org/10.1111/j.1742-481x.2012.01067.x
  32. Blair HA, Frampton JE. Methoxyflurane: A Review in Trauma Pain. Clinical Drug Investigation [Internet]. 2016 Oct 13;36(12):1067–73. Available from: dx.doi.org/10.1007/s40261-016-0473-0
  33. Ministry of Health of Ukraine. Guidelines regarding the anesthesia of victims during the evacuation stages [Metodychni rekomendatsiyi shchodo znebolennya postrazhdalykh na etapakh evakuatsiyi] [Internet]. 2022 Available from: moz.gov.ua/uploads/7/37722-dn_1122_28_06_2022_dod.pdf
  34. Frangos J, Belbachir A, Dautheville S, Jung C, Herklotz K, Amon F, et al. Non-interventional study evaluating exposure to inhaled, low-dose methoxyflurane experienced by hospital emergency department personnel in France. BMJ Open [Internet]. 2020 Feb;10(2): Available from: dx.doi.org/10.1136/bmjopen-2019-034647
  35. NATO stock number «Group 65: medical, dental, and veterinary equipment and supplies». NSN Lookup Available from: nsnlookup.com/search/nato-stock-number-nsn
9 November, 2023

Authors:

Babina Yu.M. Dmytriev D.V. Nazarchuk O.A.

Products:

Umerox® Device Umerox® Ingal

Learn more

The anesthesiologist and specialist on medical emergency conditions

The path to individualization of infusion therapy for emergency conditions according to the ROSE concept

Surgeon

Methoxyflurane: a historical review and safety analysis of its use as an analgesic in emergency and outpatient procedures

Surgeon

The piperacillin/tazobactam role in the treatment of complicated intra-abdominal infections (cIAI) in Ukrainian hospitals: 40 clinical cases series analysis

Surgeon

The first results of the international multicenter clinical study RheoSTAT-CP0669 on the effectiveness and safety of infusion solution Rheosorbilact® in the complex treatment of patients with burns

Surgeon

Application of “Refex” at patients with purulent infections of pararectal areas

Surgeon

Feedback on Revul hemostatic bandage based on chitosan from the Main Directorate of the National Guard of Ukraine