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      Inhaled methoxyflurane (Penthrox) for analgesia in trauma: a systematic review protocol

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          Abstract

          Background

          More than 75% of patients presenting to the Emergency Department are suffering symptoms of pain. Despite this, 67% will not receive any analgesia. Methoxyflurane is a fluorinated hydrocarbon gas which has analgesic properties when inhaled. Penthrox is a methoxyflurane autoinhaler recently licenced in Europe. Its ease of administration, safety, and fast onset of action make it of particular relevance to emergency medicine. Additionally, outside the hospital, it has the advantage of increased temperature stability and portability over current standard care. New evidence of its efficacy is emerging; however, currently, its use in Europe is not widespread. The objective of this study will be to systematically evaluate the evidence on inhaled methoxyflurane to determine if it is a superior analgesia in the acute trauma setting.

          Methods

          We designed and registered a study protocol for a systematic review and meta-analysis on randomised controlled trials, comparing inhaled methoxyflurane and either placebo or standard care. A comprehensive search will be conducted from database inception onwards in MEDLINE, Embase, and the Cochrane CENTRAL database, concurrent with a search of the grey literature for other relevant studies, including clinical trial databases. Only randomised controlled trials will be included. No limitations will be imposed on publication status or language of publication. The primary outcome will be mean difference in patient-reported pain at time points within the first 30 min of administration. Secondary outcomes will be mean difference in time to clinically significant pain relief and relative risk of adverse effects. Two reviewers will independently screen all returned studies and collect data. Disagreements will be resolved through discussion or referral to a third reviewer. Individual study methodological quality will be appraised using an appropriate tool. If feasible, we will conduct a random effects meta-analysis; if this is not possible, we will construct a narrative synthesis.

          Discussion

          This systematic review will summarise the best available evidence and definitively establish if inhaled methoxyflurane is a superior analgesia to standard care in the acute trauma setting. This knowledge will directly impact emergency care in the UK and worldwide and may require amendments to European pain relief guidelines.

          Systematic review registration

          PROSPERO CRD42020189119.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13643-021-01600-0.

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          Most cited references31

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          Bias in meta-analysis detected by a simple, graphical test

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            Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement

            Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
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              RoB 2: a revised tool for assessing risk of bias in randomised trials

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                Author and article information

                Contributors
                michael.eager@outlook.com
                grant.nolan@nhs.net
                katie_tonks@outlook.com
                anoopama.ramjeeawon15@alumni.imperial.ac.uk
                nat.taylor5@doctors.org.uk
                Journal
                Syst Rev
                Syst Rev
                Systematic Reviews
                BioMed Central (London )
                2046-4053
                3 February 2021
                3 February 2021
                2021
                : 10
                : 47
                Affiliations
                [1 ]GRID grid.415490.d, ISNI 0000 0001 2177 007X, Academic Department of Military General Practice & Primary Care, Research and Clinical Innovation, Royal Centre for Defence Medicine, , HQ Joint Medical Group, ; ICT Centre, Vincent Drive, Edgbaston, Birmingham, B15 2SQ UK
                [2 ]GRID grid.412563.7, ISNI 0000 0004 0376 6589, Department of Anaesthetics and Critical Care, Queen Elizabeth Hospital, , University Hospitals Birmingham NHS Trust, ; Mindelsohn Way, Edgbaston, B15 2TH UK
                [3 ]GRID grid.83440.3b, ISNI 0000000121901201, Division of Surgery & Interventional Science, , University College London, Royal Free Hospital, ; Pond Street, London, NW3 2QG UK
                [4 ]GRID grid.439526.f, Department of Plastic and Reconstructive Surgery, Whiston Hospital, , St. Helens and Knowsley Teaching Hospitals NHS Trust, ; Warrington Road, Prescot, Merseyside, L35 5DR UK
                Author information
                https://orcid.org/0000-0002-9104-5954
                https://orcid.org/0000-0003-0220-3218
                http://orcid.org/0000-0002-3774-3276
                Article
                1600
                10.1186/s13643-021-01600-0
                7860209
                33536052
                427acf20-9173-4dc1-a677-e9904f0890f3
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 2 September 2020
                : 26 January 2021
                Categories
                Protocol
                Custom metadata
                © The Author(s) 2021

                Public health
                methoxyflurane,penthrox,systematic review,pain,injury,trauma,analgesia,pre-hospital,emergency
                Public health
                methoxyflurane, penthrox, systematic review, pain, injury, trauma, analgesia, pre-hospital, emergency

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