Comparison of inhalational methoxyflurane, intranasal fentanyl, and intravenous morphine for treatment of prehospital acute pain in Norway (PreMeFen): a randomised, non-inferiority, three-arm, phase 3 trial
Editorial: Methoxyflurane: a promising non-intravenous, non-opioid analgesic.
April MD, et al. Lancet. 2026 Dec 20;406(10522):2870-2872. doi: 10.1016/S0140-6736(25)01532-6.
Methodology: 4/5
Usefulness: 4/5
Question and Methods: PreMeFen is a randomised, open-label, non-inferiority, three-arm trial to determine if methoxyflurane or intranasal fentanyl is as effective as intravenous morphine for prehospital acute pain.
Findings: Methoxyflurane was non-inferior to fentanyl (–1·33 [95% CI –2·01 to –0·64]) and morphine (–0·36 [–1·03 to 0·31]). Intranasal fentanyl was not non-inferior to morphine at 10 min (0·91 [0·27 to 1·55]).
Limitations: The study used an open-label design, excluded 2/3 of screened participants and had a 17% loss to follow-up. 40% of methoxyflurane patients required rescue medications.
Interpretation: Methoxyflurane is a fast-acting, non-invasive, safe bridge for early analgesia, though its shorter duration often necessitates transitioning to longer-acting analgesic agents.
