Our study was able to show that methoxyflurane can be used safely and effectively even under these highly specific circumstances. The ski patrol members were able to implement early and sufficient pain therapy for 59% of the injured patients in this study, without any need for additional pain medication and without any significant problems with handling and administration.

In patients with lower leg injuries, however, methoxyflurane seems to have insufficient pain-relieving effect. As a result, 10 out of 13 patients with this injury pattern required additional analgesic therapy by HEMS. From a practical point of view, this result could potentially be explained by the fact that this type of injury frequently requires movement of the injured part during splinting and packaging with an almost inevitable increase in pain, which may not be as significant in other body regions (e.g. shoulder, femur, forearm).

With the exception of the remote area of Zermatt, methoxyflurane alone was sufficient in two-thirds of patients at the ski resorts, meaning that no HEMS had to be called on to provide additional pain therapy. The patients could be transported to the valley by sledge and cable car and handed over to the EMS for transport to the hospital or general practitioner’s office without additional pain medication. If we only look at patients outside of the ski area of Zermatt, only 25 of 96 patients (26%) required any additional analgesic therapy from the HEMS teams.

In the entire study population (including Zermatt patients), 67 received additional analgesic therapy by HEMS. Due to the stated ban on administering methoxyflurane in the helicopter cabin, all patients’ inhalative therapy was terminated when they were handed over to the HEMS teams. The transport time from the ski areas to the nearest hospital was more than ten minutes in every case. Due to the rapid pharmacokinetics of methoxyflurane, it can be assumed that the analgesic effect was completely washed out during this time. This is certainly one possible reason for why additional intravenous pain medication was required. In addition, in half of these patients, the dosage required to achieve what the HEMS crew considered to be sufficient therapy was very low, amounting to only ≤ 100 µg fentanyl, with no need for ketamine. Only 32 (21%) of all patients in this study required higher doses of additional acute pain medication (fentanyl > 100 µg or ketamine at any dosage).

The side effects reported were all moderate and corresponded to those already described. No serious incidents occurred. This is consistent with the findings of several previous studies describing the safety of methoxyflurane [8,9,10,11,12].

Other studies that investigated therapeutic approaches to analgesic therapy without intravenous access (e.g. nalbuphine nasal or fentanyl buccal) [13, 14] showed better pain reduction (3 points on the NRS) as compared to methoxyflurane in this study. However, the clinical relevance of this difference is difficult to assess. The advantages of methoxyflurane compared to these drugs include the fact that the analgesic therapy is always patient controlled, and the analgesic effect can be easily controlled due to the rapid pharmacokinetics. Nasal administration can be more difficult for patients on the ski slopes due to cold-induced vasoconstriction of the nasal vessels leading to altered absorption or to a stuffy nose. Opiates carry a significant risk of respiratory depression. While this side effect was never described with methoxyflurane in the studies cited, it is listed in the drug descriptions of transmucosal fentanyl as ‘occasionally’ (i.e. in 1/1000 to 1/100 cases), which has also been confirmed in a study by Wedmore [15] on the battlefield. Here, one case of a severe respiratory depressant effect was reported in 286 applications. In addition, opioids are subject to very strict legal regulations in many places, which can make it more difficult to dispense them to ski patrol members. In contrast, disadvantages of methoxyflurane are higher costs and more complex preparation: The price of a methoxyflurane inhaler is about twice as high as that of a dose of buccal fentanyl or intranasal nalbuphine. While fentanyl for buccal use is available as a ready-to-use “lollipop”, the methoxyflurane inhaler must be filled manually before use. Egger et al. described the use of methoxyflurane in the Tyrolean mountains in their ‘PainDrop’ study. The use was protocolled in 20 patients, so the subgroups for the individual injury patterns were very small, resulting in limitations regarding the generalisability of the effectiveness per body region. The external influences also differed clearly compared to our study: the survey was carried out primarily in the summer months at temperatures of around 16 °C and at a moderate altitude of a median of 1,910 m above sea level. The study included mountain bikers who had suffered accidents, so it can be assumed that there were differences in the injury patterns of our patients, as well as the terrestrial conditions. Nevertheless, the authors arrived at comparable results: the initial pain score was 7.2 points, with a mean pain reduction of 2.9 points. In this study, too, no serious side effects occurred [16].

To our knowledge, this is the first study to analyse the effectiveness of methoxyflurane at high altitudes (in this study, it was used at up to 3,883 m above sea level) and cold temperatures. Windsor et al. postulated that the drop in outside temperature could have an influence on the saturated vapour pressure and thus the evaporation of volatile anesthetics [17]. However, we were able to show that the effectiveness of methoxyflurane is maintained even under these conditions.

Of course, our study does have limitations. First, it is based on a quality assurance study on the use of methoxyflurane. The patients were not followed up after they were transferred to the emergency room, and the datasets are partially incomplete. Thus, for example, the injury pattern was only correctly documented in about half of the applications, leading to small group sizes for the individual injury categories and limiting the concrete conclusions. Nevertheless, using the available dataset, we were able, for the first time, to assess the pain-relieving effect in relation to detailed body regions in patients on ski slopes. Second, the pain values were recorded directly by the SRS, who also gave the indication for use and the administration of methoxyflurane. There may have been a distortion in the assessment of the initial pain intensity due to suggestive influences from the SRS, if they were already convinced of or sceptical about the effectiveness of methoxyflurane. However, the chosen definition of effective therapy (reduction of NRS ≥ 2 and NRS after application ≤ 7) can still clearly discern clinical effectiveness. Third, the exact geographical and meteorological conditions were not recorded. This means that a statement about the effectiveness of methoxyflurane at high altitudes or at low outside temperatures is only possible to a limited extent. The ski areas studied are located at altitudes between approx. 1,300 and 3,883 m above sea level, and no relevant difference in effectiveness could be shown between the individual locations. By recording all applications within the defined period, a representative sample can still be assumed and the good applicability of methoxyflurane under these circumstances can be postulated.