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      Journal of Pain Research (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on reporting of high-quality laboratory and clinical findings in all fields of pain research and the prevention and management of pain. Sign up for email alerts here.

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      Low-Dose Methoxyflurane versus Standard of Care Analgesics for Emergency Trauma Pain: A Systematic Review and Meta-Analysis of Pooled Data

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          Abstract

          Purpose

          Undertreatment of trauma-related pain is common in the pre-hospital and hospital settings owing to barriers to the use of traditional standard of care analgesics. Low-dose methoxyflurane is an inhaled non-opioid analgesic with a rapid onset of pain relief that is approved for emergency relief of moderate-to-severe trauma-related pain in adults. This analysis was performed to compare the efficacy and safety of low-dose methoxyflurane with standard of care analgesics in adults with trauma-related pain.

          Methods

          A meta-analysis was performed on pooled data from randomized controlled trials identified via a systematic review. The primary endpoint was the pain intensity difference between baseline and various time intervals (5, 10, 15, 20, and 30 minutes) after initiation of treatment.

          Results

          The pain intensity difference was statistically superior with low-dose methoxyflurane compared with standard of care analgesics (overall estimated treatment effect=11.88, 95% CI=9.75–14.00; P<0.0001). The superiority of low-dose methoxyflurane was demonstrated at 5 minutes after treatment initiation and was maintained across all timepoints. Significantly more patients treated with methoxyflurane achieved response criteria of pain intensity ≤30 mm on a visual analog scale, and relative reductions in pain intensity of ≥30% and ≥50%, compared with patients who received standard of care analgesics. The median time to pain relief was shorter with methoxyflurane than with standard of care analgesics. The findings were consistent in a subgroup of elderly patients (aged ≥65 years).

          Conclusion

          Methoxyflurane can be considered as an alternative to standard of care analgesics in pre-hospital and hospital settings for treatment of adult patients with acute trauma-related pain.

          Most cited references22

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          Pain in the emergency department: results of the pain and emergency medicine initiative (PEMI) multicenter study.

          Pain is the most common reason for emergency department (ED) use, and oligoanalgesia in this setting is known to be common. The Joint Commission on Accreditation of Healthcare Organizations has revised standards for pain management; however, the impact of these regulatory changes on ED pain management practice is unknown. This prospective, multicenter study assessed the current state of ED pain management practice. After informed consent, patients aged 8 years and older with presenting pain intensity scores of 4 or greater on an 11-point numerical rating scale completed structured interviews, and their medical records were abstracted. Eight hundred forty-two patients at 20 US and Canadian hospitals participated. On arrival, pain intensity was severe (median, 8/10). Pain assessments were noted in 83% of cases; however, reassessments were uncommon. Only 60% of patients received analgesics that were administered after lengthy delays (median, 90 minutes; range, 0 to 962 minutes), and 74% of patients were discharged in moderate to severe pain. Of patients not receiving analgesics, 42% desired them; however, only 31% of these patients voiced such requests. We conclude that ED pain intensity is high, analgesics are underutilized, and delays to treatment are common. Despite efforts to improve pain management practice, oligoanalgesia remains a problem for emergency medicine. Despite the frequency of pain in the emergency department, few studies have examined this phenomenon. This study documents high pain intensity and suboptimal pain management practices in a large multicenter ED network in the United States and Canada. These findings suggest that there is much room for improvement in this area.
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            Undertreatment of acute pain (oligoanalgesia) and medical practice variation in prehospital analgesia of adult trauma patients: a 10 yr retrospective study.

            Prehospital oligoanalgesia is prevalent among trauma victims, even when the emergency medical services team includes a physician. We investigated if not only patients' characteristics but physicians' practice variations contributed to prehospital oligoanalgesia.
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              STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain

              Objective To evaluate the short-term efficacy and safety of methoxyflurane for the treatment of acute pain in patients presenting to an emergency department (ED) with minor trauma. Methods STOP! was a randomised, double-blind, multicentre, placebo-controlled study conducted at six sites in the UK. A total of 300 patients, 90 of whom were adolescent patients (age 12–17 years), were randomised 150:150 to receive either methoxyflurane via a Penthrox inhaler or placebo. The primary end point of the study was the change in pain intensity as measured using the visual analogue scale (VAS) from baseline to 5, 10, 15 and 20 min after the start of study drug inhalation. Patients were supplied with one inhaler containing 3 mL methoxyflurane or 5 mL placebo after enrolment and initial assessments. Age group (adolescent/adult) and baseline VAS score were controlled for in the statistical analyses. Results A total of 149 patients received methoxyflurane, and 149 patients received placebo. Demographic and baseline characteristics were comparable between the groups. Methoxyflurane reduced pain severity significantly more than placebo (p<0.0001) at all time points tested, with the greatest estimated treatment effect of −18.5 mm (adjusted change from baseline) seen at 15 min after the start of treatment. Methoxyflurane was well tolerated, with the majority of adverse reactions being mild, transient and in line with anticipated pharmacological action. Conclusion The results of this study suggest that methoxyflurane administered via the Penthrox inhaler is an efficacious, safe, and rapidly acting analgesic. Trial registration number: NCT01420159.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                jpr
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                20 January 2021
                2021
                : 14
                : 93-105
                Affiliations
                [1 ]Department of Emergency Medicine, Morgagni-Pierantoni Hospital , Forli, Italy
                [2 ]Clinical Pharmacology Department, La Paz University Hospital, School of Medicine, Universidad Autónoma de Madrid, IdiPAZ , Madrid, Spain
                [3 ]Emergency Department SAMU-SMUR 95, CHG Pontoise-Beaumont/Oise , Pontoise, France
                [4 ]DREEAM: Department of Research and Education in Emergency Medicine, Acute Medicine and Major Trauma, Nottingham University Hospitals NHS Trust , Nottingham, UK
                [5 ]eXYSTAT , Malakoff, France
                [6 ]Mundipharma Pharmaceuticals Srl , Milan, Italy
                [7 ]Mundipharma Pharmaceuticals S.L ., Madrid, Spain
                [8 ]Mundibiopharma Limited , Cambridge, UK
                Author notes
                Correspondence: Sara Dickerson Mundibiopharma Limited , Cambridge Science Park, Milton Road, CambridgeCB4 0AB, UKTel +44 1223 397684 Email Sara.Dickerson@mundipharma.com
                Author information
                http://orcid.org/0000-0002-9837-4638
                http://orcid.org/0000-0002-8584-3263
                http://orcid.org/0000-0002-4021-4463
                http://orcid.org/0000-0002-4628-7428
                http://orcid.org/0000-0002-9321-1602
                Article
                292521
                10.2147/JPR.S292521
                7829133
                33505170
                97ecf5d3-a102-4a75-8141-19b81060c01b
                © 2021 Fabbri et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 17 November 2020
                : 06 January 2021
                Page count
                Figures: 3, Tables: 12, References: 23, Pages: 13
                Funding
                Funded by: Mundibiopharma Limited;
                This systematic review and meta-analysis was funded by Mundibiopharma Limited, which was involved in all stages from study design to manuscript submission.
                Categories
                Original Research

                Anesthesiology & Pain management
                acute pain,inhaled analgesic,emergency service,wounds and injury,pain management,analgesia

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