Methoxyflurane Analgesia in Adult Patients in the Emergency Department: A Subgroup Analysis of a Randomized, Double-blind, Placebo-controlled Study (STOP!)

Abstract

IntroductionAcute pain remains highly prevalent in the Emergency Department (ED) setting. This double-blind, randomized, placebo-controlled UK study investigated the efficacy and safety of low-dose methoxyflurane analgesia for the treatment of acute pain in the ED in the adult population of the STOP! trial.MethodsPatients presenting to the ED requiring analgesia for acute pain (pain score of 4–7 on the Numerical Rating Scale) due to minor trauma were randomized in a 1:1 ratio to receive methoxyflurane (up to 6 mL) or placebo (normal saline), both via a Penthrox® (Medical Developments International Limited, Scoresby, Australia) inhaler. Rescue medication (paracetamol/opioids) was available immediately upon request. Change from baseline in visual analog scale (VAS) pain intensity was the primary endpoint.Results300 adult and adolescent patients were randomized; data are presented for the adult subgroup (N = 204). Mean baseline VAS pain score was ~66 mm in both groups. The mean change from baseline to 5, 10, 15 and 20 min was greater for methoxyflurane (−20.7, −27.4, −33.3 and −34.8 mm, respectively) than placebo (−8.0, −11.1, −12.3 and −15.2 mm, respectively). The primary analysis showed a highly significant treatment effect overall across all four time points (−17.4 mm; 95% confidence interval: −22.3 to −12.5 mm; p < 0.0001). Median time to first pain relief was 5 min with methoxyflurane [versus 20 min with placebo; (hazard ratio: 2.32; 95% CI: 1.63, 3.30; p < 0.0001)]; 79.4% of methoxyflurane-treated patients experienced pain relief within 1–10 inhalations. 22.8% of placebo-treated patients requested rescue medication within 20 min compared with 2.0% of methoxyflurane-treated patients (p = 0.0003). Methoxyflurane treatment was rated ‘Excellent’, ‘Very Good’ or ‘Good’ by 77.6% of patients, 74.5% of physicians and 72.5% of nurses. Treatment-related adverse events (mostly dizziness/headache) were reported by 42.2% of patients receiving methoxyflurane and 14.9% of patients receiving placebo; none caused withdrawal and the majority were mild and transient.ConclusionThe results of this study support the evidence from previous trials that low-dose methoxyflurane administered via the Penthrox inhaler is a well-tolerated, efficacious and rapid-acting analgesic.FundingMedical Developments International (MDI) Limited and Mundipharma Research GmbH & Co.KG.Trial registrationClinicaltrials.gov identifier: NCT01420159, EudraCT number: 2011-000338-12.

<p>Inhaled Methoxyflurane versus Intravenous Morphine for Severe Trauma Pain in the Emergency Setting: Subgroup Analysis of MEDITA, a Multicenter, Randomized, Controlled, Open-Label Trial</p>

“…In STOP!, Global Medication Performance was rated as "Excellent", "Very Good" or "Good" by 77.6% of adult patients. 29 In InMEDIATE, patients scored methoxyflurane a median of 9 out of 10 for pain control, comfort of treatment and safety (AEs), and methoxyflurane treatment exceeded patient's expectations in 77% of cases. 20 Although a larger proportion of patients experienced AEs with methoxyflurane (20%) than IV morphine (5%) in our study, methoxyflurane AEs were mild and transient, and only 6% of patients in the methoxyflurane group discontinued treatment due to AEs.…”

A review of the safety and efficacy of inhaled methoxyflurane as an analgesic for outpatient procedures

“…Clinical trials have confirmed that this agent provides effective pain relief in acute trauma with no evidence of either renal or hepatic toxicity. 17,18 The portability, safety profile, and rapid onset of analgesia means that this formulation of methoxyflurane is a very common type of pain relief given by Australian paramedics, 19,20 and more than 5 million doses of inhaled methoxyflurane have been used in trauma patients with no significant adverse events reported. 21 Recent studies have confirmed the cardiovascular and respiratory stability of this agent in the pre-hospital setting, not only for trauma pain, but also for acute visceral pain.…”

Penthrox: a breath of PHEC air for the military?

“…The inhaler (figure 1) has an activated charcoal (AC) chamber which absorbs exhaled methoxyflurane and reduces the risk of exposure of active drug to the supervising healthcare practitioner 8 10 11…”