Background
Acute pain is a frequent complaint in the ED[1] but remains widely undertreated[2]. STOP! was a randomised, double-blind, placebo-controlled study that investigated the efficacy and safety of low-dose methoxyflurane analgesia administered via a handheld inhaler (Penthrox®, 3mL dose) for treatment of acute pain in patients aged ≥12 years presenting to the ED with non-life-threatening trauma. Reduction in pain intensity in the first 20 minutes of treatment has previously been reported[3]. The study included patients with moderate to severe pain (score of 4-7 on Numeric Rating Scale [NRS]). We describe patterns of inhaler use in a subgroup of adult and adolescent patients with severe pain (NRS=7) at baseline.

Material and methods
Patients were randomised at triage to methoxyflurane (3mL) or placebo (normal saline), both inhaled as needed from a Penthrox® inhaler. Patients could cover the diluter hole in the mouthpiece to inhale a higher concentration of study medication if required. A second inhaler and/or rescue medication (paracetamol/opioids) were provided if requested by the patient. Subgroup analyses of number of inhalations to first pain relief and inhaler use were performed. 

Results
The severe pain subgroup included 62 methoxyflurane-treated patients and 71 placebo-treated patients. The most common injury types were “other” (48.9%, mostly sprains, soft tissue injury and muscular pain), contusions (23.3%) and fractures (18.8%). Pain relief was achieved within 1-5 inhalations for 51.6% of methoxyflurane and 21.1% of placebo patients, and within 1-10 inhalations for 80.6% and 47.9% of patients, respectively. 11.3% of methoxyflurane-treated patients and 39.4% of placebo-treated patients experienced no pain relief without rescue medication.

Sixteen patients (25.8%) in the methoxyflurane group and 12 patients (16.9%) in the placebo group requested a second inhaler. Median time between dispensing of the first and second inhalers was 55.0 minutes for methoxyflurane and 37.5 minutes for placebo. A total of 21 patients (33.9%) in the methoxyflurane group and 28 patients (39.4%) in the placebo group covered the diluter hole when using the inhaler.  

Conclusion
Low-dose methoxyflurane was shown to provide rapid-acting analgesia within 1-10 inhalations in the majority (80.6%) of patients with severe trauma pain. 

References
1.	Cordell et al. Am J Emerg Med 2002;20:165–169.
2.	Pierik JGJ et al. Pain Med 2015;16:970-84.
3.	Coffey F et al. Emerg Med J 2014;31:613-8.

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.

® PENTHROX is a registered trademark of MDI Limited.




06 / Low dose methoxyflurane analgesia in the emergency department: a subgroup analysis of inhaler use in patients with severe acute trauma pain from the STOP! study