Trauma/original research
Inhaled Methoxyflurane Provides Greater Analgesia and Faster Onset of Action Versus Standard Analgesia in Patients With Trauma Pain: InMEDIATE: A Randomized Controlled Trial in Emergency Departments

https://doi.org/10.1016/j.annemergmed.2019.07.028Get rights and content
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Study objective

The objective of the InMEDIATE study was to evaluate the change in intensity of traumatic pain over the first 20 min in adult patients treated with methoxyflurane versus standard analgesic treatment in Spain. This the first randomized, active-controlled, multicenter trial of methoxyflurane in the emergency setting in Europe.

Methods

This was a randomized, controlled study that enrolled adult patients with acute moderate to severe (score ≥4 on the 11-point Numeric Rating Scale) trauma-associated pain in 14 Spanish emergency departments. Patients were randomized 1:1 to methoxyflurane (up to 2×3 mL) or standard analgesic treatment. Coprimary endpoints were the change from baseline in Numeric Rating Scale pain intensity score during the first 20 minutes of treatment and time to first pain relief.

Results

Three hundred five patients were randomized (methoxyflurane 156; standard analgesic treatment 149). Most patients in the standard analgesic treatment group (70%) received intravenous first-step analgesics and 9.4% of patients were treated with opioids. Mean decrease from baseline in Numeric Rating Scale pain intensity score was greater for methoxyflurane than standard analgesic treatment at all points, with a significant treatment difference overall up to 20 minutes (repeated-measures model 2.47 versus 1.39; treatment difference 1.00; 95% confidence interval 0.84 to 1.32). Median time to first pain relief was significantly shorter for methoxyflurane than standard analgesic treatment (3 versus 10 minutes). Methoxyflurane achieved better patient and clinician ratings for pain control and comfort of treatment than standard analgesic treatment and exceeded patient and clinician expectations of treatment in, respectively, 77% and 72% of cases compared with 38% and 19% for standard analgesic treatment.

Conclusion

These results support consideration of methoxyflurane as a nonnarcotic, easy-to-administer, rapid-acting, first-line alternative to currently available analgesic treatments for trauma pain.

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Please see page 316 for the Editor’s Capsule Summary of this article.

Supervising editor: Robert D. Welch, MD, MS. Specific detailed information about possible conflict of interest for individual editors is available at https://www.annemergmed.com/editors.

Author contributions: All authors conceptualized and contributed to the study design and data collection, and reviewed and revised the article. JCMÁ provided statistical expertise on study design and analyzed the data. AMB supervised study design, patient recruitment, and data collection. All authors approved the final article as submitted and agree to be accountable for all aspects of the work. AMB takes responsibility for the paper as a whole.

All authors attest to meeting the four ICMJE.org authorship criteria: (1) Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND (2) Drafting the work or revising it critically for important intellectual content; AND (3) Final approval of the version to be published; AND (4) Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The study was funded by Mundipharma Pharmaceuticals S.L. but was designed, conducted, and analyzed by the coordinators of the Pain Group of the Spanish Society of Emergency Medicine (SEMES) and representatives of the SCReN. Costs for article processing and Open Access were funded by Mundibiopharma Limited The Scientific Committee of the study comprises members of SEMES and SCReN. The SCReN, PT13/0002, is funded by the Plan Estatal of Investigación, Desarrollo e Innovación 2013-2016 and by the Subdirección General de Evaluación y Fomento de la Investigación–Instituto de Salud Carlos III. It is also cofinanced with funding from FEDER. Drs. Borobia, Capilla Pueyo, Carcas Sansuán, Casal Codesido, Fernández Testa, and Martínez Ávila received fees as members of the trial scientific committee. Drs. Borobia, Capilla Pueyo, Corell González, Fernández Alonso, Fernández Testa, García Collado, and Pérez Torres received fees as speakers. Susana Traseira Lugilde is an employee of Mundipharma Pharmaceuticals S.L. Support for Ms. Mower was funded by Mundipharma Research Limited.

Trial registration numbers: EudraCT: 2017-000338-70; ClinicalTrials.gov: NCT03256903

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