A randomized non-inferiority pilot study on the use of methoxyflurane (Penthrox®) for pain control in the emergency department

Background: Patients commonly visit the emergency department for pain after musculoskeletal injury, but the problem of oligoanalgesia is prevalent. Methoxyflurane (Penthrox®) is an inhalational analgesic for moderate to severe trauma-associated pain in stable and conscious patients. It is a fast-acting, effective analgesic that can be readily administered via a non-invasive route, making it an attractive agent for managing acute pain in the emergency departments. Objectives: The aim was to assess the analgesic efficacy of methoxyflurane in patients with acute traumatic pain by comparing it to ketorolac, a standard analgesic treatment for moderate pain in emergency departments in Hong Kong. Methods: This was a single-center, open-label, randomized controlled, parallel-group, non-inferiority pilot study that enrolled adult patients with moderate trauma-associated pain in an emergency department in Hong Kong. Patients were randomized 1:1 to the methoxyflurane group or the ketorolac group. The primary outcome was the change in pain intensity measured by visual analogue scale from baseline to 5, 15, 30, and 60 min after drug administration. Results: Twenty patients received methoxyflurane, and twenty patients received ketorolac. There were significant reductions in pain score over 60 min in both groups. The pain reduction at 5 min was significantly greater for the methoxyflurane group (−13.912 mm; 95% confidence interval = −20.008 to −7.817) than for the ketorolac group (−4.888 mm; 95% confidence interval = −10.983 to 1.208), with the treatment effect (−9.025 mm; 95% confidence interval = −17.656 to −0.393; p = 0.041) demonstrating superiority of methoxyflurane. The treatment effect at 15 and 30 min demonstrated non-inferiority of methoxyflurane versus ketorolac. Conclusion: Methoxyflurane provided non-inferior analgesia in the first 30 min with a faster onset of action when compared with ketorolac in moderate traumatic pain. It can be considered a non-invasive, rapid-acting, and effective first-line alternative to currently available analgesics for traumatic pain in emergency settings.