Aims and Objectives 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.

The primary aim of this systematic review and meta-analysis was to determine the success rate of M&R with IMF compared to standard PSA. Secondary aims were to compare length of stay, adverse events, patient satisfaction, and cost-effectiveness.

Method and Design This systematic review was planned, conducted, and reported in accordance with PRISMA. All studies of IMF for M&R of acute traumatic limb injuries were included. 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. Two studies were suitable for meta-analysis and the Sidik-Jonkman random-effects model was utilised. Freeman-Tukey variance-stabilising transformation of the effect size was used to minimise risk of inappropriate down-weighting of studies with proportions close to 0 or 1.

Thematic analysis was undertaken for the themes of length of stay, adverse events, patient satisfaction, and cost-effectiveness.

Results and Conclusion Six studies were included, one was a small prospective case series, one a prospective case-control, one a mixed-methods questionnaire and interview, and three were retrospective observational studies, two of which directly compare IMF and standard PSA for M&R. The meta-analysis for procedural success failed to identify a statistically significant difference between the pooled effect estimate and the null value for Risk Ratio (of 1), with p=0.16 suggesting no difference in performance between IMF and PSA. The review also observed a shorter length of stay, a low rate of adverse events, and overall positive patient satisfaction with IMF. There may be cost-savings associated with IMF.