Dataset Information

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

ABSTRACT:

Introduction

Acute 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.

Methods

Patients 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.

Results

300 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.

Conclusion

The 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.

Funding

Medical Developments International (MDI) Limited and Mundipharma Research GmbH & Co.KG.

Trial registration

Clinicaltrials.gov identifier: NCT01420159, EudraCT number: 2011-000338-12.

SUBMITTER: Coffey F

PROVIDER: S-EPMC5083764 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThe undertreatment of acute pain presents a significant challenge in the Emergency Department. This post hoc subgroup analysis of a previously reported randomized controlled UK study reports the efficacy and safety of low-dose methoxyflurane analgesia in treating adolescent patients with moderate-to-severe trauma pain.Patients and methodsThree hundred patients (96 in the adolescent subgroup) aged ≥12 years requiring analgesia for acute trauma pain (pain score of 4-7 on the Numerical Rating Scale) at triage were randomized 1:1 to methoxyflurane (up to 6 mL) or placebo (normal saline), both administered using a Penthrox® inhaler. The patient could request rescue medication (paracetamol/opioids) at any time. The primary endpoint was the change from baseline in visual analog scale (VAS) pain intensity.ResultsMean VAS pain score for the adolescent subgroup at baseline was ~ 61 mm. Adjusted mean change in VAS pain intensity from baseline to 5, 10, 15, and 20 minutes was -24.5, -28.1, -31.6, and -31.7 mm for methoxyflurane and -14.6, -18.8, -19.2, and -23.7 mm for placebo, with a statistically significant treatment effect in favor of methoxyflurane overall across all four time points (-9.9 mm; 95% CI: -17.4, -2.4 mm; P=0.0104). Median time to first pain relief was significantly shorter with methoxyflurane (1 minute) than placebo (3 minutes, P<0.0001). Pain relief was reported within 1-10 inhalations in 95.7% of methoxyflurane-treated patients and 64.6% of placebo-treated patients. Rescue medication was requested by two (4.3%) methoxyflurane-treated patients and three (6.3%) placebo-treated patients. Over 95% of patients, physicians, and nurses rated methoxyflurane treatment as "Excellent", "Very Good" or "Good" compared with between 64% and 68% for placebo. The incidence of adverse events was higher with methoxyflurane (51%) than placebo (42%), mostly comprising mild/transient dizziness and headache.ConclusionThis subgroup analysis shows that low-dose inhaled methoxyflurane is a rapid-acting and effective analgesic in adolescent patients presenting with moderate-to-severe trauma pain.Trial registrationClinicaltrials.gov identifier: NCT01420159, EudraCT number: 2011-000338-12.

Project description:IntroductionRacial disparities in pain management have been reported among emergency department (ED) patients. In this study we evaluated the association between patients' self-identified race/ethnicity and the administration of opioid analgesia among ED patients with abdominal pain, the most common chief complaint for ED presentations in the United States.MethodsThis was a retrospective cohort study of adult (age ≥18 years) patients who presented to the ED of a single center with abdominal pain from January 1, 2019-December 31, 2020. We collected demographic and clinical information, including patients' race and ethnicity, from the electronic health record. The primary outcome was the ED administration of any opioid analgesic (binary). Secondary outcomes included the administration of non-opioid analgesia (binary) and administration of any analgesia (binary). We used logistic regression models to estimate odds ratios (OR) of the association between a patient's race/ethnicity and analgesia administration. Covariates included age, sex, initial pain score, Emergency Severity Index, and ED visits in the prior 30 days. Subgroup analyses were performed in non-pregnant patients, those who underwent any imaging study, were admitted to the hospital, and who underwent surgery within 24 hours of ED arrival.ResultsWe studied 7,367 patients: 45% (3,314) were non-Hispanic (NH) White; 28% (2,092) were Hispanic/Latinx; 19% (1,384) were NH Black, and 8% (577) were Asian. Overall, 44% (3,207) of patients received opioid analgesia. In multivariable regression models, non-White patients were less likely to receive opioid analgesia compared with White patients (OR 0.73, 95% CI 0.65-0.83 for Hispanic/Latinx patients; OR 0.62, 95% CI 0.54-0.72 for Black patients; and OR 0.64, 95% CI 0.52-0.78 for Asian patients). Black patients were also less likely to receive non-opioid analgesia, and Black and Hispanic/Latinx patients were less likely than White patients to receive any analgesia. The associations were similar across subgroups; however, the association was attenuated among patients who underwent surgery within 24 hours of ED arrival.ConclusionHispanic/Latinx, Black, and Asian patients were significantly less likely to receive opioid analgesia than White patients when presenting to the ED with abdominal pain. Black patients were also less likely than White patients to receive non-opioid analgesia.

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Project description:BackgroundLow-dose analgesic methoxyflurane (Penthrox®) was approved in Europe for emergency relief of moderate to severe pain in conscious adults with trauma in 2015. A comparative post-authorisation safety study (PASS) was conducted to assess the risk of hepatotoxicity and nephrotoxicity with methoxyflurane during routine clinical practice.MethodsThis was a comparative hybrid prospective-retrospective cohort study. The comparative cohorts consisted of adults who were given methoxyflurane (methoxyflurane cohort) or another analgesic (concurrent cohort) routinely used for moderate to severe trauma and associated pain in the emergency setting (ambulance and Emergency Department) in the UK between December 2016 and November 2018. Hepatic and renal events were captured in the ensuing 12 weeks. A blinded clinical adjudication committee assessed events. A historical comparator cohort (non-concurrent cohort) was identified from patients with fractures in the English Hospital Episode Statistics (HES) accident and emergency database from November 2013 and November 2015 (before commercial launch of methoxyflurane). Hepatic and renal events were captured in the ensuing 12 weeks via linkage with the Clinical Practice Research Datalink (CPRD) and HES hospital admissions databases.ResultsOverall, 1,236, 1,101 and 45,112 patients were analysed in the methoxyflurane, concurrent and non-concurrent comparator cohorts respectively. There was no significant difference in hepatic events between the methoxyflurane and concurrent cohorts (1.9% vs. 3.0%, P = 0.079) or between the methoxyflurane and non-concurrent cohorts (1.9% vs. 2.5%, P = 0.192). Renal events were significantly less common in the methoxyflurane cohort than in the concurrent cohort (2.3% vs. 5.6%, P < 0.001). For methoxyflurane versus non-concurrent cohort the lower occurrence of renal events (2.3% vs. 3.2%, P = 0.070) was not statistically significant. Multivariable adjustment did not change these associations.ConclusionsMethoxyflurane administration was not associated with an increased risk of hepatotoxicity or nephrotoxicity compared with other routinely administered analgesics and was associated with a reduced risk of nephrotoxicity compared with other routinely administered analgesics.Trial registrationStudy registered in the EU PAS Register (ENCEPP/SDPP/13040).

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