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Low-dose methoxyflurane analgesia in adolescent patients with moderate-to-severe trauma pain: a subgroup analysis of the STOP! study

Authors Hartshorn S, Dissmann P, Coffey F, Lomax M

Received 25 September 2018

Accepted for publication 21 January 2019

Published 15 February 2019 Volume 2019:12 Pages 689—700


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Erica Wegrzyn

Stuart Hartshorn,1 Patrick Dissmann,2 Frank Coffey,3 Mark Lomax4

1Emergency Department, Birmingham Children’s Hospital, Birmingham, UK; 2Academic Department of Emergency Medicine, James Cook University Hospital, Middlesbrough, UK; 3DREEAM: Department of Research and Education in Emergency Medicine, Acute Medicine and Major Trauma, Nottingham University Hospitals NHS Trust, Nottingham, UK; 4Data Management & Statistics, Mundipharma Research Limited, Cambridge, UK

Introduction: The undertreatment of acute pain presents a significant challenge in the Emergency Department. This post hoc subgroup analysis of a previously reported randomized controlled UK study reports the efficacy and safety of low-dose methoxyflurane analgesia in treating adolescent patients with moderate-to-severe trauma pain.
Patients and methods: Three hundred patients (96 in the adolescent subgroup) aged ≥12 years requiring analgesia for acute trauma pain (pain score of 4–7 on the Numerical Rating Scale) at triage were randomized 1:1 to methoxyflurane (up to 6 mL) or placebo (normal saline), both administered using a Penthrox® inhaler. The patient could request rescue medication (paracetamol/opioids) at any time. The primary endpoint was the change from baseline in visual analog scale (VAS) pain intensity.
Results: Mean VAS pain score for the adolescent subgroup at baseline was ~61 mm. Adjusted mean change in VAS pain intensity from baseline to 5, 10, 15, and 20 minutes was −24.5, –28.1, –31.6, and –31.7 mm for methoxyflurane and −14.6, –18.8, –19.2, and –23.7 mm for placebo, with a statistically significant treatment effect in favor of methoxyflurane overall across all four time points (–9.9 mm; 95% CI: −17.4, –2.4 mm; P=0.0104). Median time to first pain relief was significantly shorter with methoxyflurane (1 minute) than placebo (3 minutes, P<0.0001). Pain relief was reported within 1–10 inhalations in 95.7% of methoxyflurane-treated patients and 64.6% of placebo-treated patients. Rescue medication was requested by two (4.3%) methoxyflurane-treated patients and three (6.3%) placebo-treated patients. Over 95% of patients, physicians, and nurses rated methoxyflurane treatment as “Excellent”, “Very Good” or “Good” compared with between 64% and 68% for placebo. The incidence of adverse events was higher with methoxyflurane (51%) than placebo (42%), mostly comprising mild/transient dizziness and headache.
Conclusion: This subgroup analysis shows that low-dose inhaled methoxyflurane is a rapid-acting and effective analgesic in adolescent patients presenting with moderate-to-severe trauma pain.

Trial registration: identifier: NCT01420159, EudraCT number: 2011-000338-12.

Keywords: acute pain, analgesic, emergency department, injury, pediatric, Penthrox

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