• Alberto M Borobia, Sergio García Collado, Cardona César Carballo CC Hospital Universitario La Paz, Madrid, Spain; School of Medicine, Universidad Autónoma de Madrid, Hospital La Paz Institute for Health Research,, Rosa Capilla Pueyo, Alonso Cesáreo Fernández CF Hospital Clínico San Carlos, Madrid, Spain., Torres Ignacio Pérez IP Hospital Virgen del Rocío, Seville, Spain., María Corell González, José Ramón Casal Codesido, Betegón María Arranz MA Hospital de Viladecans, Barcelona, Spain., Luis Amador Barcela, Aitor Odiaga Andicoechea, Anselma Fernández Testa, Jorge Trigo Colina, Antonio Cid Dorribo, Carmen Del Arco Galán, Jose Carlos Martínez Ávila, Susana Traseira Lugilde, Antonio J Carcas Sansuán, and InMEDIATE Investigators Group.
• Hospital Universitario La Paz, Madrid, Spain; School of Medicine, Universidad Autónoma de Madrid, Hospital La Paz Institute for Health Research, and Spanish Clinical Research Network, Madrid, Spain. Electronic address: alberto.borobia@salud.madrid.org.
• Ann Emerg Med. 2020 Mar 1; 75 (3): 315-328.

Study ObjectiveThe 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.MethodsThis 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.ResultsThree 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.ConclusionThese results support consideration of methoxyflurane as a nonnarcotic, easy-to-administer, rapid-acting, first-line alternative to currently available analgesic treatments for trauma pain.Copyright © 2019 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

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