<p>Low-dose methoxyflurane analgesia in adolescent patients with moderate-to-severe trauma pain: a subgroup analysis of the STOP! study</p>

Abstract

Introduction The undertreatment of acute pain presents a significant challenge in the Emergency Department. This post hoc subgroup analysis of a previously reported randomized controlled UK study reports the efficacy and safety of low-dose methoxyflurane analgesia in treating adolescent patients with moderate-to-severe trauma pain. Patients and methods Three hundred patients (96 in the adolescent subgroup) aged ≥12 years requiring analgesia for acute trauma pain (pain score of 4–7 on the Numerical Rating Scale) at triage were randomized 1:1 to methoxyflurane (up to 6 mL) or placebo (normal saline), both administered using a Penthrox ® inhaler. The patient could request rescue medication (paracetamol/opioids) at any time. The primary endpoint was the change from baseline in visual analog scale (VAS) pain intensity. Results Mean VAS pain score for the adolescent subgroup at baseline was ~ 61 mm. Adjusted mean change in VAS pain intensity from baseline to 5, 10, 15, and 20 minutes was −24.5, −28.1, −31.6, and −31.7 mm for methoxyflurane and −14.6, −18.8, −19.2, and −23.7 mm for placebo, with a statistically significant treatment effect in favor of methoxyflurane overall across all four time points (−9.9 mm; 95% CI: −17.4, −2.4 mm; P =0.0104). Median time to first pain relief was significantly shorter with methoxyflurane (1 minute) than placebo (3 minutes, P <0.0001). Pain relief was reported within 1–10 inhalations in 95.7% of methoxyflurane-treated patients and 64.6% of placebo-treated patients. Rescue medication was requested by two (4.3%) methoxyflurane-treated patients and three (6.3%) placebo-treated patients. Over 95% of patients, physicians, and nurses rated methoxyflurane treatment as “Excellent”, “Very Good” or “Good” compared with between 64% and 68% for placebo. The incidence of adverse events was higher with methoxyflurane (51%) than placebo (42%), mostly comprising mild/transient dizziness and headache. Conclusion This subgroup analysis shows that low-dose inhaled methoxyflurane is a rapid-acting and effective analgesic in adolescent patients presenting with moderate-to-severe trauma pain. Trial registration Clinicaltrials.gov identifier: NCT01420159, EudraCT number: 2011-000338-12.

Analgesic Efficacy, Practicality and Safety of Inhaled Methoxyflurane Versus Standard Analgesic Treatment for Acute Trauma Pain in the Emergency Setting: A Randomised, Open-Label, Active-Controlled, Multicentre Trial in Italy (MEDITA)

“…rated methoxyflurane treatment as excellent, very good or good [25], and patients in InMEDIATE rated methoxyflurane a median of 9 out of 10 for pain control, comfort of treatment and safety (AEs) [32]. No effects of methoxyflurane on vital sign parameters were observed, consistent with reports from other clinical trials in Europe [18, 25, 26, 32] and findings of two observational studies including 1217 patients treated with methoxyflurane in the prehospital setting in Australia [20, 37]. No cases of methoxyflurane abuse were identified in our study.…”

“…Given the intravenous administration of the comparator treatment, the change in the first 10 min post baseline reflected the most challenging comparison for methoxyflurane, and was directly relevant to the indication for methoxyflurane of emergency relief of moderate-to-severe trauma pain [19]. Previous studies have shown that methoxyflurane is effective at the 20-min time point [18, 25, 26, 32], thus the 10-min endpoint utilized in this study provides additional information about the efficacy profile of inhaled methoxyflurane. The secondary analysis of the change in VAS pain intensity to later time points also showed significantly larger reductions in pain intensity for methoxyflurane versus SAT up to 25 min.…”

“…Its use as emergency analgesia is supported by robust data in the literature [21–23]. To date, key data in Europe are from STOP!, a randomised, double-blind, placebo-controlled UK study in 300 patients with acute trauma pain (baseline score of 4–7 on the 11-point numeric rating scale, NRS) [18, 25, 26]. STOP!…”

Does Inhaled Methoxyflurane Implement Fast and Efficient Pain Management in Trauma Patients? A Systematic Review and Meta-Analysis

“…Methoxyflurane is a highly volatile halogenated ether that is administered through a portable inhaler [12]. Recently, the value of methoxyflurane at subanesthetic concentrations has continued to attract a lot of attention owing to its rapid analgesia and without significant nephrotoxicity [13][14][15][16][17][18][19][20][21]. On the basis of the results of the STOP!…”

Exposure to Methoxyflurane: Low-Dose Analgesia and Occupational Exposure

“…A total of 35% of patients in this study rated their pain as severe, and 30% of eligible people declined to participate (46). In a subsequent study (28) for which two further subgroup analyses have also been published (35,47), 150 patients presented to an emergency department with a mean pain level of 64 mm on a 100 mm VAS but received placebo for 20 minutes (28). While this study also gained ethical approval, given the previously described availability of literature demonstrating methoxyflurane analgesic efficacy it does not seem to conform to the Declaration of Helsinki on the use of placebo control (48).…”