Inhaled Analgesic Matches Morphine for Prehospital Trauma Pain

Patients with fractures, falls, or traffic injuries often endure significant discomfort during extraction and transport, complicating assessment and movement. Early, needle‑free analgesia could improve the initial experience and workflow for ambulance teams. To help address this challenge, researchers have now evaluated an inhaled option against standard therapies in a randomized study.

Investigators from the University of Oslo, the Norwegian Air Ambulance Foundation, Oslo University Hospital, and Innlandet Hospital assessed inhaled methoxyflurane delivered via a handheld device for on‑scene pain relief. The work forms part of the PreMeFen study and was published in The Lancet in 2025. The approach aims to provide rapid, field‑ready analgesia without the delays associated with cannulation.

The randomized, non‑inferiority, three‑arm, phase 3 trial compared intravenous morphine, inhaled methoxyflurane, and intranasal fentanyl during ambulance care in Norway. It was conducted in the setting where care begins, with patients treated at the scene and during transport. Methoxyflurane inhalation has longstanding use in some regions but is relatively new in Norway and much of Europe.

The study found that inhaled methoxyflurane provided pain relief equivalent to intravenous morphine in the early treatment of acute, moderate to severe pain. The handheld device is easy to administer and does not require venous access, offering a practical alternative when environmental conditions or patient factors impede cannulation. Intranasal fentanyl, a synthetic opioid, was also evaluated as a needle‑free option for acute pain.

Authors describe this as the first randomized controlled study to directly compare these three analgesic strategies in prehospital practice. They note that broadening early analgesia options can help clinicians stabilize and move patients under challenging conditions, including hip fractures and other traumatic injuries. The results emphasize providing effective pain relief as early as possible in the care pathway.

“Inhaling methoxyflurane through a handheld inhaler provides pain relief as good as intravenous morphine in the early treatment of acute, moderate to severe pain. The drug is easy to administer, does not require access to a vein, and is therefore an effective and practical alternative to morphine,” said Randi Simensen, Ph.D. candidate at the Norwegian Air Ambulance Foundation and Innlandet Hospital, and a paramedic at Oslo University Hospital.

“When it comes to prehospital emergency care, we largely rely on research that is done inside hospitals and laboratories. This does not reflect the reality we work in. We need research that shows what's effective in our setting,” said Fridtjof Heyerdahl, researcher at the Institute of Clinical Medicine at the University of Oslo, senior researcher affiliated with the Norwegian Air Ambulance Foundation, and head of the Air Ambulance Department at Oslo University Hospital.

"This is the first study in the world that demonstrates that methoxyflurane has an important role in the earliest phase of prehospital emergency care. It is groundbreaking work to be able to establish this type of safe knowledge about new treatment," added Heyerdahl.

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Institute of Clinical Medicine at the University of Oslo
Oslo University Hospital