Low-Dose Methoxyflurane versus Standard of Care Analgesics for Emergency Trauma Pain: A Systematic Review and Meta-Analysis of Pooled Data

Andrea Fabbri,¹ Alberto M Borobia,² Agnes Ricard-Hibon,³ Frank Coffey,⁴ Aurore Caumont-Prim,⁵ François Montestruc,⁵ Amedeo Soldi,⁶ Susana Traseira Lugilde,⁷ Sara Dickerson<sup>8

1</sup>Department of Emergency Medicine, Morgagni-Pierantoni Hospital, Forli, Italy; ²Clinical Pharmacology Department, La Paz University Hospital, School of Medicine, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain; ³Emergency Department SAMU-SMUR 95, CHG Pontoise-Beaumont/Oise, Pontoise, France; ⁴DREEAM: Department of Research and Education in Emergency Medicine, Acute Medicine and Major Trauma, Nottingham University Hospitals NHS Trust, Nottingham, UK; ⁵eXYSTAT, Malakoff, France; ⁶Mundipharma Pharmaceuticals Srl, Milan, Italy; ⁷Mundipharma Pharmaceuticals S.L., Madrid, Spain; ⁸Mundibiopharma Limited, Cambridge, UK

Correspondence: Sara Dickerson
Mundibiopharma Limited, Cambridge Science Park, Milton Road, Cambridge CB4 0AB, UK
Tel +44 1223 397684
Email Sara.Dickerson@mundipharma.com

Purpose: Undertreatment of trauma-related pain is common in the pre-hospital and hospital settings owing to barriers to the use of traditional standard of care analgesics. Low-dose methoxyflurane is an inhaled non-opioid analgesic with a rapid onset of pain relief that is approved for emergency relief of moderate-to-severe trauma-related pain in adults. This analysis was performed to compare the efficacy and safety of low-dose methoxyflurane with standard of care analgesics in adults with trauma-related pain.
Methods: A meta-analysis was performed on pooled data from randomized controlled trials identified via a systematic review. The primary endpoint was the pain intensity difference between baseline and various time intervals (5, 10, 15, 20, and 30 minutes) after initiation of treatment.
Results: The pain intensity difference was statistically superior with low-dose methoxyflurane compared with standard of care analgesics (overall estimated treatment effect=11.88, 95% CI=9.75– 14.00; P< 0.0001). The superiority of low-dose methoxyflurane was demonstrated at 5 minutes after treatment initiation and was maintained across all timepoints. Significantly more patients treated with methoxyflurane achieved response criteria of pain intensity ≤ 30 mm on a visual analog scale, and relative reductions in pain intensity of ≥ 30% and ≥ 50%, compared with patients who received standard of care analgesics. The median time to pain relief was shorter with methoxyflurane than with standard of care analgesics. The findings were consistent in a subgroup of elderly patients (aged ≥ 65 years).
Conclusion: Methoxyflurane can be considered as an alternative to standard of care analgesics in pre-hospital and hospital settings for treatment of adult patients with acute trauma-related pain.

Keywords: acute pain, inhaled analgesic, emergency service, wounds and injury, pain management, analgesia