Background
Despite a large volume of published literature supporting the efficacy and safety of methoxyflurane at analgesic concentrations[1], previous studies have been mostly observational and uncontrolled. This double-blind, randomised, placebo-controlled UK study[2,3] investigated the efficacy and safety of low-dose methoxyflurane analgesia administered via the Penthrox® inhaler for the treatment of moderate to severe trauma pain in the ED. We present results of a post hoc analysis of pain relief beyond 20 minutes after the start of treatment, and safety results, in a sub-group of adolescent patients aged 12-17 years (N=95).

Material and methods
At triage, 300 adult and adolescent patients were randomised 1:1 to receive methoxyflurane (up to 6 mL) or placebo (normal saline), self-administered via a Penthrox® inhaler. Rescue medication (paracetamol/opioids) was available immediately upon request. Visual analogue scale (VAS) pain intensity was assessed using the PainlogTM VAS at 5, 10, 15, 20 and 30 min, then every 30 minutes until discharge (data are presented for time points where n≥2). Adverse events (AEs) were recorded from enrolment until discharge, and at safety follow-up (Day 14±2).

Results 
The methoxyflurane subgroup (N=47) included 32 males and 15 females with a mean age of 14.4 years. The placebo subgroup (N=48) included 35 males and 13 females with a mean age of 13.5 years. Mean decreases in VAS pain intensity of -33.5, -38.7, -37.8 and -42.5 mm (from a baseline mean of 61.7 mm) were observed with methoxyflurane at 20 (n=38), 30 (n=32), 60 (n=5) and 90 minutes (n=2). Mean decreases of -25.3, -30.9, -26.9 and -31.0 mm (from a baseline mean of 61.0 mm) were observed with placebo at 20 (n=35), 30 (n=26), 60 (n=7) and 90 minutes (n=2). Fifty-five AEs were reported by 24 patients (51%) in the methoxyflurane group and 35 AEs were reported by 20 patients (42%) in the placebo group. The most common AEs were headache (methoxyflurane: 26%; placebo: 23%) and dizziness (methoxyflurane: 15%; placebo: 2%). No serious or severe AEs were reported. Two patients (4%) in each group discontinued treatment due to AEs.

Conclusion
These results show that the reduction in pain intensity with low-dose methoxyflurane analgesia is maintained for the duration of use in adolescent patients with acute trauma pain.

References
1.	Grindlay J, Babl FE. Emerg Med Australas;21:4-11, 2009.
2.	Coffey F et al. Emerg Med J;31:613-8, 2014.
3.	Coffey F et al. Adv Ther;33:2012-31, 2016.

Acknowledgements
The study was funded by Medical Developments International (MDI) Limited. Karen Mower (Scientific Editorial) provided medical writing services on behalf of Mundipharma Research Limited. Frank Coffey was paid travel and subsistence expenses by MDI for one investigator’s meeting. There were no other competing interests.

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05 / Subgroup analysis of the extended efficacy and safety of low-dose methoxyflurane analgesia in adolescent patients from the STOP! study with acute trauma pain