Low-Dose Methoxyflurane Versus Standard Of Care Analgesics For Emergency Trauma Pain: A Systematic Review And Meta-Analysis Of Pooled Data

Purpose: Undertreatment of trauma-related pain is common in the pre-hospital and hospital settings owing to barriers to the use of traditional standard of care analgesics. Low-dose methoxyflurane is an inhaled non-opioid analgesic with a rapid onset of pain relief that is approved for emergency relief of moderate-to-severe trauma-related pain in adults. This analysis was performed to compare the efficacy and safety of low-dose methoxyflurane with standard of care analgesics in adults with trauma-related pain.Methods: A meta-analysis was performed on pooled data from randomized controlled trials identified via a systematic review. The primary endpoint was the pain intensity difference between baseline and various time intervals (5, 10, 15, 20, and 30 minutes) after initiation of treatment.Results: The pain intensity difference was statistically superior with low-dose methoxyflurane compared with standard of care analgesics (overall estimated treatment effect=11.88, 95% CI=9.75-14.00; P<0.0001). The superiority of low-dose methoxyflurane was demonstrated at 5 minutes after treatment initiation and was maintained across all timepoints. Significantly more patients treated with methoxyflurane achieved response criteria of pain intensity <= 30 mm on a visual analog scale, and relative reductions in pain intensity of >= 30% and >= 50%, compared with patients who received standard of care analgesics. The median time to pain relief was shorter with methoxyflurane than with standard of care analgesics. The findings were consistent in a subgroup of elderly patients (aged >= 65 years).Conclusion: Methoxyflurane can be considered as an alternative to standard of care analgesics in pre-hospital and hospital settings for treatment of adult patients with acute trauma-related pain.