Inhaled methoxyflurane for the management of trauma related pain in patients admitted to hospital emergency departments: a randomised, double-blind placebo-controlled trial (PenASAP study)

Eur J Emerg Med. 2020 Dec;27(6):414-421. doi: 10.1097/MEJ.0000000000000686.


Background: Oligo-analgesia is common in the emergency department (ED). This study aimed at reporting, when initiated by triage nurse, the superior efficacy of inhaled methoxyflurane plus standard of care (m-SoC) analgesia versus placebo plus SoC (p-SoC) for moderate-to-severe trauma-related pain in the hospital ED.

Methods: A randomised, double-blind, placebo-controlled trial was conducted at eight EDs. Adults with pain score ≥4 (11-point numerical rate scale, NRS) at admission were randomised to receive one or two inhalers containing m-SoC or p-SoC. Primary outcome measure was time until pain relief ≤30 mm, assessed on the 100-mm Visual Analogic Scale (VAS).

Results: A total of 351 patients were analysed (178 m-SoC; 173 p-SoC). Median pain prior to first inhalation was 66 mm, 75% had severe pain (NRS 6-10). Median time to pain relief was 35 min [95% confidence interval (CI), 28-62] for m-SoC versus not reached in p-SoC (92 - not reached) [hazard ratio), 1.93 (1.43-2.60), P < 0.001]. Pain relief was most pronounced in the severe pain subgroup: hazard ratio, 2.5 (1.7-3.7). As SoC, 24 (7%) patients received weak opioids (6 versus 8%), 4 (1%) strong opioid and 44 (13%) escalated to weak or strong opioids (8 versus 17%, respectively, P = 0.02). Most adverse events were of mild (111/147) intensity.

Conclusions: In this study, we report that methoxyflurane, initiated at triage nurse as part of a multimodal analgesic approach, is effective in achieving pain relief for trauma patients. This effect was particularly pronounced in the severe pain subgroup.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Pain* / drug therapy
  • Adult
  • Analgesia*
  • Analgesics, Opioid
  • Anesthetics, Inhalation* / therapeutic use
  • Double-Blind Method
  • Emergency Service, Hospital
  • Hospitals
  • Humans
  • Methoxyflurane* / therapeutic use


  • Analgesics, Opioid
  • Anesthetics, Inhalation
  • Methoxyflurane