In emergency medical services (or ambulance services) it is common to treat severe pain by administering morphine and similar substances intravenously. This is achieved by inserting an intravenous cannula into a vein.
"This is a good treatment, but in some situations, it can be challenging to insert a cannula, particularly when it's dark, cold or windy at the scene. Some patients are also afraid of needles. In that case, it can take some time before patients receive satisfactory pain relief," Fridtjof Heyerdahl, researcher at the Institute of Clinical Medicine at the University of Oslo (UiO), says.
He is also a senior researcher affiliated with the Norwegian Air Ambulance Foundation (SNLA) and Oslo University Hospital (OUS), and is the head of the Air Ambulance Department at OUS.
Injured in a car wreck
Typical patients include those who have sustained injuries while skiing, fallen from a ladder or construction site, or been injured in a traffic collision. It could be a patient with a broken leg, acute back pain, or chest pain.
The patient often needs to be moved down stairs, across difficult terrain, and into an ambulance or helicopter before being transported to a hospital.
"Many of the patients who need an ambulance have injuries or conditions causing a lot of pain. In many instances, we are unable to relieve their pain well enough immediately. Acute pain is extremely distressing, and patients are often frightened and vulnerable," Heyerdahl explains.
"The fact that we now, to a greater extent, can do something about this is of huge importance to the patients," he says.
Pain relief without needles
In the PreMeFen study, he and his colleagues compared three treatment options for pain management in an ambulance situation. The study is published in the journal The Lancet.
"There are other ways to provide pain relief than through a needle. We wanted to investigate whether these function as well as intravenous morphine does," he explains.
They had three groups of patients. The first group received morphine via a cannula, the standard treatment that has been used for decades.
The second group received the medication methoxyflurane, which was administered using a handheld inhaler. Although this treatment has been used for a long time in some parts of the world, it is quite new in Norway and the rest of Europe.
The last group received a nasal spray with the medication fentanyl, a synthetic opioid that has been used for many years. However, administrating fentanyl as a nasal spray for acute pain is relatively new.
More tools in the toolbox
Now the results are clear:
"Inhaling methoxyflurane through a handheld inhaler provides pain relief as good as intravenous morphine in the early treatment of acute, moderate to severe pain," Randi Simensen says. She is a PhD candidate at the Norwegian Air Ambulance Foundation and Innlandet Hospital, and a paramedic at OUS.
"The drug is easy to administer, does not require access to a vein and is therefore an effective and practical alternative to morphine," she points out.
Simensen has over twenty years of experience in working in the ambulance service.
"It's difficult to provide pain relief in the field, often under demanding conditions. The initial phase of patient care, when the patient is in pain, is the most challenging. Often, we must move them before we can provide optimal pain relief. That's horrible for both the patients and the ambulance personnel," she says.
Now, more tools are available in their toolbox.
"We can now provide effective pain relief for patients in whom intravenous access is difficult or not immediately available. This does not mean that every patient with acute pain should receive inhaled pain reliever, but it does mean that we now have an additional treatment option," Simensen says.
Receiving pain patients in the ambulance every day
"Providing effective pain relief as early as possible is important for the patient's overall experience during a medical emergency. For example, it can provide rapid relief for a patient with a hip fracture who has been lying on the ground for a prolonged period," Simensen explains.
She is supported by paramedic Joakim Kolstad at Innlandet Hospital, one of the ambulance workers who has participated in the PreMeFen study.
"Every day we transport patients who need pain relief in the ambulance, and this is one of our main focuses. When pain is relieved, patients regain a sense of control over their situation," Kolstad says.
The first study of its kind in the world
The PreMeFen study is the first randomized controlled study in the world that directly compares these three analgetic-pain relieving-strategies. And it is done in the ambulance service, where the patients are.
"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," Heyerdahl says, and adds:
"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."
"Our job is to have the right medications available and to provide the best possible pain relief for our patients. Decisions about which medications should be used in different parts of the healthcare system are made elsewhere," Simensen says.
"Our focus is simple: there is no reason for patients to experience more pain than necessary."
Reference
Simensen R, Fjose LO, Thorsen K, Olsen IC, Rehn M, Hagemo J, Smalberget L, Heyerdahl F (2025). 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. The Lancet. DOI 10.1016/S0140-6736(25)01575-2
