The effectiveness of inhaled methoxyflurane compared to procedural sedation for the reduction of acute traumatic limb injuries – a systematic review and meta-analysis

Background: Manipulation and reduction (M&R) of an injured limb is often required to reduce pain, bleeding and restore anatomical alignment, typically using procedural sedation and analgesia (PSA). Inhaled methoxyflurane (IMF) may be a suitable alternative that is simple to administer, does not require intravenous access, and has a favourable side effect profile. The objective of this systematic review and meta-analysis was to determine the effectiveness of IMF compared to PSA for M&R in acute traumatic limb injury. The primary outcome measure was procedural success rate. The secondary outcomes were to compare the length of stay, adverse events, patient satisfaction and cost-effectiveness. Methods: This systematic review was planned, conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and is registered on PROSPERO CRD42024561087. A literature search was conducted and included studies from database inception to the search date (22 February 2024), using MEDLINE, EMBASE, Cochrane, CINAHL and PubMed platforms. All studies involving the use of IMF for M&R of acute traumatic limb injuries were included. Animal studies, case-reports, non-English language publications and opinion articles were excluded. The risk of bias was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Meta-analysis was undertaken for the primary outcome of procedural success. Narrative synthesis was undertaken for the themes of length of stay, adverse events, patient satisfaction and cost-effectiveness. Results: Fifty one abstracts were screened through a database search, reference review, and search of the grey literature. Following full-text review and exclusions, a total of six studies were included, with two suitable for meta-analysis. No significant differences in performance were observed between IMF and PSA (RR 0.90, 95% confidence interval 0.77–1.04, p = 0.16). Patients receiving IMF had a shorter emergency department length of stay, a low incidence of adverse events, and overall positive patient satisfaction. There may be cost-savings associated with the use of IMF. Conclusion: Inhaled methoxyflurane was observed to perform no differently to procedural sedation for the successful manipulation and reduction of acute traumatic limb injuries in the emergency department. The overall quality of the evidence is poor, and further higher-level evidence is required. © The Author(s) 2025.