Table 2.
Overview of studies of methoxyflurane in patients with trauma pain
| Reference | Evidence level | Design | Number of patients (received analgesic methoxyflurane) | Age restriction (years)a | Efficacy results |
|---|---|---|---|---|---|
| Registration trial | |||||
| Coffey et al (2014)25,b | 1 | Randomized, double-blind, placebo- controlled, multicenter study | 300 (149) | ≥12 | • Significant reduction in 100 mm VAS pain scores compared with placebo at 5, 10, 15, and 20 minutes (P<0.0001) ○ Greatest estimated treatment effect of –18.5 mm seen at 15 minutes • Pain relief within 10 inhalations for 84.6% receiving methoxyflurane and 51% receiving placebo • 2 patients (1.3%) needed rescue medication vs 25 (16.8% in the placebo group; P=0.0002) • Global medication performance rated significantly better for methoxyflurane than placebo (P<0.0001) |
| Emergency department use | |||||
| Gillis et al (2008)28,b,c | 5 | Observational case series | (59) | >3 | • VNRS pain scores significantly reduced by 2.3 at 15 minutes and 3.3 at 30 minutes (P<0.025) |
| Konkayev (2013)29 | 2 | Prospective single center cohort study vs IM tramadol | 40 (20) | >18 | • After 5 minutes: ○ Pain scores had reduced from 4.1 to 0.6 with methoxyflurane and from 5.5 to 4.2 with tramadol ○ Anxiety scores had reduced from 3.9 to 0.4 with methoxyflurane and from 4.6 to 3.4 with tramadol • After 30 minutes, pain and anxiety scores were 0.2 in both groups |
| Prehospital use | |||||
| Buntine et al (2007)26 | 5 | Observational case series | (83) | >18 | • Mean (±SE) reduction in VNRS-II scores ○ 5 minutes: 2.47 (±0.24) ○ Arrival at hospital: 3.21 (±0.24) by arrival at hospital (both P<0.0001 vs baseline) • 72% of patients and 82% of paramedics were satisfied with the level of analgesia |
| Oxer and Wilkes (2007)30,b,c | 3 | Retrospective study vs IN fentanyl | 13,963 (10,706) | NR |
• For both agents, >90% of patients reported good or partial pain relief |
| Middleton et al (2010)27 | 3 | Retrospective study vs IV morphine and IN fentanyl | 42,844 (19,235) | 16–100 | • Mean (95% CI) reduction in VNRS-II: 3.2 (3.1, 3.2) for methoxyflurane; 4.5 (4.5, 4.6) for morphine; 4.5 (4.4, 4.6) for fentanyl • Effective analgesia (≥30% reduction in pain severity) achieved by 59.1% of patients receiving methoxyflurane, 81.8% receiving morphine, 80.0% receiving fentanyl |
| Lim et al (2016)31,c | 1 | Prospective, cluster- randomized, crossover study vs IM tramadol | 311 (135) | >16 | • Median (IQR) reduction in pain scores: ○ At 5 minutes: 3.0 (–1.3, 4.8) with methoxyflurane vs 1.0 (0.0, 2.0) with tramadol ○ At 10 minutes: 2.0 (–1.0, 3.0) with methoxyflurane vs 1.0 (0.0, 2.0) with tramadol • Median (IQR) time to effective analgesia: 3.0 (−1.0, 5.0) minutes with methoxyflurane vs 5.0 (–3.0, 5.0) minutes with tramadol • Median (IQR) time to administer first dose: 9.0 (–6.0, 14.0) minutes with methoxyflurane vs 11 (–8.0, 15.0) minutes with tramadol |
Notes: Evidence level: Level 1=evidence from meta-analysis or randomized clinical trials, Level 2=evidence from individual studies, Level 3=evidence from quasi-experimental studies, Level 4=evidence from descriptive studies, Level 5=evidence from case reports, Level 6=specialist opinion.
a
As stipulated in inclusion criteria.
b
Mixed population of adults and children.
c
Only available as an abstract.
Abbreviations: IQR, interquartile range; IV, intravenous; IN, intranasal; NR, not reported; VAS, visual analog scale; VNRS, verbal numeric rating scale; IM, intramuscula..