• Hong Liu, Xi Fu, Yi-Feng Ren, Shi-Yan Tan, Si-Rui Xiang, Chuan Zheng, Feng-Ming You, Wei Shi, and Lin-Jiong Li.
• Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, Sichuan Province, China.
• Pain Ther. 2021 Jun 1; 10 (1): 651-674.

IntroductionEvidence on the use of inhaled methoxyflurane in the management of trauma pain is conflicting and obfuscated. This study aimed to determine the efficacy and safety of inhaled methoxyflurane for trauma pain on the basis of published randomized controlled trials (RCTs).MethodsRCTs assessing the efficacy of methoxyflurane in adults or adolescents with acute trauma pain published in PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar were searched. The control groups were those that received placebo or standard analgesic treatment (SAT). The primary outcome was the change from baseline in pain scores during the first 30 min of treatment. Secondary outcomes included time to first pain relief, the proportion of patients experiencing pain relief, rescue analgesia rate, the treatment satisfaction of patients and investigators, and the methoxyflurane-related treatment-emergent adverse events (TEAEs).ResultsA total of nine RCTs (1806 patients) were identified. Results revealed that methoxyflurane provided a clinically unimportant benefit by improving the mean difference of change from baseline in pain intensity (from - 0.44 to - 1.23 cm, p < 0.001) at various time points within the first 20 min compared to control treatment. Besides, methoxyflurane decreased the time of onset of pain relief (mean difference - 5.29 min; 95% CI - 6.97 to - 3.62) and the proportion of patients who needed rescue analgesic medication (risk ratio 1.41; 95% CI 1.17-1.70) despite it increasing the risk of non-severe TEAEs (risk ratio 3.09; 95% CI 1.72-5.57). Notably, the benefit of almost all secondary pain-related outcomes was rendered clinically nonsignificant between methoxyflurane and SAT strata besides the time of onset of pain relief. The quality of evidence was low or very low in all outcomes.ConclusionsIn emergency situations without effective therapy, this systematic review and meta-analysis provides low-quality evidence that methoxyflurane can be used as a rapid-acting and effective treatment for acute trauma pain, although its utilization is associated a risk of non-severe TEAEs. However, the current evidence does not support the notion that inhaled methoxyflurane offered superior analgesic efficacy to SAT.Clinical Trial NumberPROSPERO registration number CRD42020223000.

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