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

Stuart Hartshorn, Patrick Dissmann, Frank Coffey, Mark Lomax, Stuart Hartshorn, Patrick Dissmann, Frank Coffey, Mark Lomax

Abstract

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: Clinicaltrials.gov identifier: NCT01420159, EudraCT number: 2011-000338-12.

Keywords: Penthrox; acute pain; analgesic; emergency department; injury; pediatric.

Conflict of interest statement

Disclosure Stuart Hartshorn reports a Chief Investigator grant and personal fees from MDI Limited outside of the submitted work. Patrick Dissmann reports personal fees from Mundipharma International, outside the submitted work. Frank Coffey reports grants from Nottingham University Hospital Trust, during the conduct of the study. Mark Lomax is an employee of Mundipharma Research Limited. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Participant flow. Abbreviation: ITT, intention-to-treat.
Figure 2
Figure 2
Number of inhalations to first pain relief (modified intention-to-treat population).
Figure 3
Figure 3
Satisfaction with treatment (global medication performance; modified intention-to-treat population). Notes:P-values are for the significance of the treatment effect based on proportional odds model adjusted for baseline visual analog scale pain score.

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