Michael M Eager1,2, Grant S Nolan3,4, Kathryn Tonks2, Anoopama Ramjeeawon5, Natalie Taylor1. 1. 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. Department of Anaesthetics and Critical Care, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Trust, Mindelsohn Way, Edgbaston, B15 2TH, UK. 3. Division of Surgery & Interventional Science, University College London, Royal Free Hospital, Pond Street, London, NW3 2QG, UK. 4. Department of Plastic and Reconstructive Surgery, Whiston Hospital, St. Helens and Knowsley Teaching Hospitals NHS Trust, Warrington Road, Prescot, Merseyside, L35 5DR, UK. 5. Division of Surgery & Interventional Science, University College London, Royal Free Hospital, Pond Street, London, NW3 2QG, UK. anoopama.ramjeeawon15@alumni.imperial.ac.uk.
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 .
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 .
Authors: Jonathan A C Sterne; Jelena Savović; Matthew J Page; Roy G Elbers; Natalie S Blencowe; Isabelle Boutron; Christopher J Cates; Hung-Yuan Cheng; Mark S Corbett; Sandra M Eldridge; Jonathan R Emberson; Miguel A Hernán; Sally Hopewell; Asbjørn Hróbjartsson; Daniela R Junqueira; Peter Jüni; Jamie J Kirkham; Toby Lasserson; Tianjing Li; Alexandra McAleenan; Barnaby C Reeves; Sasha Shepperd; Ian Shrier; Lesley A Stewart; Kate Tilling; Ian R White; Penny F Whiting; Julian P T Higgins Journal: BMJ Date: 2019-08-28