This quality assurance study shows that it is feasible to delegate administration of methoxyflurane inhalation to non-medical professionals such as ski patrols. Delegating medical treatment to non-medical professionals has both legal and ethical implications. The prerequisite is a legal framework where the ski patrollers are acting as aiding personnel for the responsible physician after sound training programs and development of standard operating procedures (SOPs). Such arrangements must follow national legislation, and will hence vary between countries. Independent of the legal status, the ethical aspects require that the system with the non-medical professional at the patient’s side, and the remote responsible physician together can handle any event caused by the treatment.

This study showed a clinically and statistically significant reduction in NRS 5–10 min after initiation of methoxyflurane administration. Although the median NRS remained elevated and with patient still in need for additional analgesics, the reduction from high (median NRS 8) to moderate (median NRS 5) pain score is of great value in a situation with few other safe alternatives for managing acute traumatic pain. Most patients experienced good or moderate effects of the treatment. The side effects were expected and mild, and there were no events requiring a physician on site.

A statistically significant pain reduction is not necessarily clinically relevant if pain relief is not perceived. In postoperative acute pain, Cepeda et al. showed that for moderate pain, “minimal” improvement of pain needed a decrease in NRS of 1.3 units, and “much” improvement was achieved with a decrease in NRS of 2.4 (35% reduction), while with severe pain, a corresponding “much” improvement needed a decrease in NRS of 3.5 units (45% reduction) [16]. Similarly, for cancer-related breakthrough pain, an adequate relief in pain was achieved by optimal sensitivity/specificity-cut-off when the change in pain intensity score was > 33% [17]. Pain and pain relief are perceived differently in different settings and with different pain mechanisms. Our patients had all acute trauma-related pain. Although the median NRS after treatment was high, the median reduced NRS of three units corresponded to the clinically meaningful reduction in pain referred to above, which was also reflected by the perceived effect where 80% stated good and 18% moderate effects.

The pain reduction from median NRS 8 to median NRS 5 also corresponds to other European studies where methoxyflurane is used for prehospital pain management, and with similar median initial NRS [18, 19]. These studies were performed by trained ambulance workers in Austria and Sweden, respectively. Interestingly, our study shows a similar clinical effect when administered by non-medical ski patrollers in an alpine setting. Pain reduction to enable the transport of ski trauma patients is important, and in this context, the initial transport off the slope can be considered as a necessary but painful procedure. A British review concluded that inhaled methoxyflurane is an attractive alternative to standard sedation techniques for outpatient procedures, especially in patients at risk for sedative complications [13]. Although our clinical experience is that the most severe injuries with high NRS require administration of more potent analgesics, methoxyflurane has a role in the initial phase where no alternative analgesics are available.

According to the SPC [12], methoxyflurane can be stored in low temperature, which is of value in the alpine setting. The median temperature in this study was – 3 C°. The simple and swift administration is an advantage, and the patient can start inhalation within a few minutes after arrival of the ski patrol in all weather conditions. A short time on the scene (in our study, the median was 10 minutes) is crucial for reducing the risk of hypothermia. The time-efficacy of methoxyflurane is also described in a report by Young et al. [20] with 71 min shorter time in emergency department (ED) for patients who received treatment with methoxyflurane. The self-titration by the patient was especially useful for missions in difficult terrain and during transport in a rescue bag. This quick approach is also of value to other prehospital providers [18, 21].

Our study did not uncover any severe adverse events, which is in accordance with the studies from Sweden and Austria [18, 19]. However, our study is not designed to detect severe complications. Nevertheless, the overall experience with methoxyflurane is that the drug is safe to use in low doses and with short-term use [6, 9, 19, 21]. The safety profile and effectiveness used by a non-medical ski patrol opens the possibility to improve trauma treatment and pain management early in the chain of acute trauma handling. These first responders work with limited time and competence of analgetic treatment.

We consider methoxyflurane to have a good safety profile, but it is important to recognize situations where special caution should be taken, for example where the risk of aspiration is elevated, when other reasons for reduced consciousness are evident, and where the strong odor might be an issue. Thus, we experienced that close contact between prescriber, ski patrol, and local prehospital care providers is essential, and must be organized carefully and within the healthcare regulations.

This is not an efficacy or a safety study, and we do not compare the effect to other analgesic agents. Although we found a statistically significant pain reduction in our sample, the rather small number of patients means that one should be cautious in generalizing to a larger population, for which a proper controlled trial is needed. This is solely a quality assessment and feasibility study, and the findings are based on observations made by non-medical personnel, with inherent limitations. Nevertheless, the personnel were thoroughly trained and instructed to follow the procedures and fill out the forms. We therefore believe that both the pain scores and the observations are of good quality.

Future studies on the prehospital administration of methoxyflurane could also focus on other non-medical mountain patrols, other non-medical first responders, or participants in remote high-altitude expeditions (4, 22, 23). Randomized controlled trials in the pre-hospital setting to compare methoxyflurane to other well-known substances such as IV morphine or IN fentanyl will also help to inform decision-making for pain therapy strategies in austere environments.