Background
Although methoxyflurane has been used for pain relief in anaesthetic doses (administered via the Penthrox® inhaler, 3mL dose) for over 40 years, there are limited data from the ED setting, or outside Australia and New Zealand.  This double-blind, randomised, placebo-controlled UK study[1,2] evaluated the short-term efficacy and safety of methoxyflurane at low analgesic doses in treating adult and adolescent patients presenting to the ED with moderate to severe trauma pain.  We present results of a sub-analysis of 2 pain endpoints and rescue medication use in adolescent patients aged 12-17 years (N=95).

Material and methods
300 adult and adolescent patients were randomised 1:1 to receive methoxyflurane (up to 6mL) or placebo (normal saline), both inhaled as required from a Penthrox® inhaler. Rescue medication (paracetamol/opioids) was available immediately upon request. Pain relief was assessed using a 0-100 visual analogue scale (VAS; PainlogTM) at 5, 10, 15 and 20 minutes after the start of treatment. The primary efficacy endpoint was change from baseline in VAS pain intensity, analysed using repeated measures ANCOVA. Median time to first pain relief and rescue medication use were also analysed. 

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±SD VAS pain scores at baseline were 61.7±16.56 mm in the methoxyflurane group and 61.0±13.33 mm in the placebo group. Mean change in VAS pain intensity from baseline to 5, 10, 15 and 20 min was greater for methoxyflurane (-24.5, -28.1, -31.6 and -31.7 mm, respectively) than placebo (-14.6, -18.8, -19.2 and -23.7 mm, respectively). Overall, over the first 20 minutes of treatment, there was a highly significant treatment difference (estimated treatment effect, -9.9 mm; 95% CI: -17.4, -2.4; p=0.0104). Time to first pain relief was significantly shorter with methoxyflurane than placebo (median 1 min versus 3 min, hazard ratio: 2.35; 95% CI: 1.48, 3.76; p=0.0003). Only 2 methoxyflurane-treated patients and 3 placebo-treated patients requested rescue medication. 

Conclusion
The results of this study show that low-dose methoxyflurane administered via the Penthrox® inhaler is a rapid-acting and effective analgesic in adolescent patients presenting with acute trauma pain.

References
1.	Coffey F et al. Emerg Med J;31:613-8, 2014.
2.	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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04 / Short-term efficacy of low-dose methoxyflurane analgesia in adolescent patients presenting to the emergency department with acute trauma pain: a sub-analysis of a randomised, double-blind, placebo controlled UK study