STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain

Frank Coffey, John Wright, Stuart Hartshorn, Paul Hunt, Thomas Locker, Kazim Mirza, Patrick Dissmann, Frank Coffey, John Wright, Stuart Hartshorn, Paul Hunt, Thomas Locker, Kazim Mirza, Patrick Dissmann

Abstract

Objective: To evaluate the short-term efficacy and safety of methoxyflurane for the treatment of acute pain in patients presenting to an emergency department (ED) with minor trauma.

Methods: STOP! was a randomised, double-blind, multicentre, placebo-controlled study conducted at six sites in the UK. A total of 300 patients, 90 of whom were adolescent patients (age 12-17 years), were randomised 150:150 to receive either methoxyflurane via a Penthrox inhaler or placebo. The primary end point of the study was the change in pain intensity as measured using the visual analogue scale (VAS) from baseline to 5, 10, 15 and 20 min after the start of study drug inhalation. Patients were supplied with one inhaler containing 3 mL methoxyflurane or 5 mL placebo after enrolment and initial assessments. Age group (adolescent/adult) and baseline VAS score were controlled for in the statistical analyses.

Results: A total of 149 patients received methoxyflurane, and 149 patients received placebo. Demographic and baseline characteristics were comparable between the groups. Methoxyflurane reduced pain severity significantly more than placebo (p<0.0001) at all time points tested, with the greatest estimated treatment effect of -18.5 mm (adjusted change from baseline) seen at 15 min after the start of treatment. Methoxyflurane was well tolerated, with the majority of adverse reactions being mild, transient and in line with anticipated pharmacological action.

Conclusion: The results of this study suggest that methoxyflurane administered via the Penthrox inhaler is an efficacious, safe, and rapidly acting analgesic.

Trial registration number: NCT01420159.

Keywords: Analgesia/Pain Control; Emergency Department; Research, Clinical.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

Figure 1
Figure 1
Patient disposition (all patients).

References

    1. Stephen CR. Clinical applications of methoxyflurane. Acta Anaesthesiol Scand Suppl 1966;24:215–22
    1. Tomi KT, Mashimo T, Tashiro C, et al. Alterations in pain threshold and psychomotor response associated with subanaesthetic concentrations of inhalation anaesthetics in humans. Br J Anaesth 1993;70:684–6
    1. Crandell WB, Pappas SG, Macdonald A. Nephrotoxicity associated with methoxyflurane anaesthesia. Anesthesiology 1966;27:591–607
    1. Mazze R, Cousins M. Biotransformation of methoxyflurane. Int Anesthesiol Clin 1974;12:93–105
    1. Bergsjo P, Lindbaek E. Comparison between nitrous oxide and methoxyflurane for obstetrical analgesia. Acta Obstet Gynecol Scand 1971;50:285–90
    1. Fielding ME, Hurry DJ. Analgesia in instrumental vaginal delivery by the intermittent self-administration of methoxyflurane using a disposable vaporizer. Br J Anaesth 1972;44:386–90
    1. Marx GF, Chen LK, Tabora JA. Experiences with a disposable inhaler for methoxyflurane analgesia during labour: clinical and biochemical results. Can Anaesth Soc J 1969;16:66–71
    1. Yakaitis RW, Cooke JE, Redding JS. Self-administered methoxyflurane for postoperative pain: effectiveness and patient acceptance. Anesth Analg 1972;51:208–12
    1. Yakaitis RW, Redding JS. Self-administered methoxyflurane for improved postoperative ventilation. Anesth Analg 1970;49:345–50
    1. Packer KJ. Methoxyflurane analgesia for burns dressings. Postgrad Med J 1972;48:128–32
    1. Packer KJ, Titel JH. Methoxyflurane analgesia for burns dressings: experience with the analgizer. Br J Anaesth 1969;41:1080–5
    1. Romagnoli AL, Busque L, Power DJ. The “analgizer” in a general hospital: a preliminary report. Can Anaesth Soc J 1970;17:275–8
    1. Lewis LA. Methoxyflurane analgesia for office surgery. Surgical gem. J Dermatol Surg Oncol 1984;10:85–6
    1. Grummet J, Huang S, Konstantatos A, et al. The ‘green whistle’: a novel method of analgesia for transrectal prostate biopsy. Br J Urol 2012;110(Suppl):85–8
    1. Nguyen NQ, Toscano L, Lawrence M, et al. Patient-controlled analgesia with inhaled methoxyflurane versus conventional endoscopist-provided sedation for colonoscopy: a randomized, multi-centre trial. Gastrointest Endosc 2013;78:892–901
    1. Grindlay J, Babl FE. Review article: efficacy and safety of methoxyflurane analgesia in the emergency department and prehospital setting. Emerg Med Australas 2009;21:4–11
    1. Gallagher EJ, Liebman M, Bijur PE. Prospective validation of clinically important changes in pain severity measured on a visual analog scale. Ann Emerg Med 2001;38:633–8
    1. Farrar JT, Young JP, Jr, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94:149–58
    1. Chaplain S, Zeppetella G. Instanyl: intranasal fentanyl for treating breakthrough pain. Prescriber 2010;19:40–1
    1. Tveita T, Thoner J, Klepstad P, et al. A controlled comparison between single doses of intravenous and intramuscular morphine with respect to analgesic effects and patient safety. Acta Anaesthesiol Scand 2008;52:920–5
    1. Johnston S, Wilkes GJ, Thompson JA, et al. Inhaled methoxyflurane and intranasal fentanyl for prehospital management of visceral pain in an Australian ambulance service. Emerg Med J 2011;28:57–63
    1. Tomlin PJ, Jones BC, Edwards R, et al. Subjective and objective sensory responses to inhalation of nitrous oxide and methoxyflurane. Br J Anaesth 1973;45:719–25
    1. Abdullah WA, Sheta SA, Nooh NS. Inhaled methoxyflurane (Penthrox) sedation for third molar extraction: a comparison to nitrous oxide sedation. Aust Dent J 2011;56:296–301
    1. Chin R, McCaskill M, Browne G, et al. A randomised control trial on inhaled methoxyflurane pain relief, in children with upper limb fracture. J Paediatr Child Health 2002;38:A13–14
    1. Spruyt O, Westerman D, Milner A, et al. A randomised, double-blind, placebo-controlled study to assess the safety and efficacy of methoxyflurane for procedural pain of a bone marrow biopsy. BMJ Support Palliat Care 2013; Published Online First: 7 June 2013 doi:

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