Background Acute pain is often inadequately treated in adults with traumatic injury. Inhaled methoxyflurane, newly licensed in Europe for this indication, has limited evidence of clinical effectiveness in the prehospital setting. We aimed to investigate clinical effectiveness and costs of methoxyflurane administered by ambulance staff compared with usual analgesic practice (UAP) for patients with trauma.

Methods We used a non-randomised control group pragmatic design comparing methoxyflurane versus Entonox® and parenteral analgesics. Verbal numerical pain scores (VNPS) were gathered over time in adults with moderate to severe trauma pain attended by ambulance staff trained in administering and supplied with methoxyflurane. Comparator VNPS were obtained from database records of UAP in similar patients. Clinical efficacy was tested using an Ordered Probit panel regression model of pain linked by observational rules to VNPS. Scenario analyses were used to compare durations under analgesia spent in severe pain, and costs.

Results Over 12 months, 96 trained paramedics and technicians prepared 510 doses of methoxyflurane for administration to 483 patients. 32 patients reported side-effects, 19 of whom discontinued early. 13 patients, 10 aged over 75 years, were nonadherent to inhaler use instructions.

Modelling results showed statistically significant clinical effectiveness of methoxyflurane over each comparator (all p-values<0.001). Methoxyflurane’s time to achieve maximum pain relief was significantly faster (all p-values<0.001): 26.4 mins (95%CI 25.0-27.8) versus Entonox® 44.4 (39.5-49.3); 26.5 (25.0-27.9) versus IV morphine sulfate 41.8 (38.9-44.7); 26.5 (25.1-28.0) versus IV paracetamol 40.8 (34.7-46.9).

Scenario analyses of durations spent in severe pain were significantly less for methoxyflurane to comparators. Benefits of methoxyflurane were achieved at higher cost to comparators.

Conclusions Methoxyflurane reduced pain more rapidly and to a greater extent than Entonox® and more quickly than parenteral analgesics in adults with moderate or severe pain due to trauma attended by ambulance clinicians. Methoxyflurane provides a useful addition to prehospital analgesia.