Real world safety of methoxyflurane analgesia in the emergency setting: a comparative hybrid prospective-retrospective post-authorisation safety study

BMC Emergency Medicine

Research

Ben Bloom¹  Stuart Pocock²  Sue Anne Yee³  Maggie Oh³  Michelle Bradney³  Ana Roncero⁴  Ignacio Mendez⁴  Nawab Qizilbash⁵  Heather Jarman⁶  Himanshu Kataria⁷ 

[1]Barts Health NHS Trust, London, UK

[2]London School of Hygiene & Tropical Medicine, London, UK

[3]Medical Developments International Limited, Victoria, Australia

[4]OXON Epidemiology, London, UK

[5]OXON Epidemiology, London, UK

[6]London School of Hygiene & Tropical Medicine, London, UK

[7]St Georges Hospital NHS Foundation Trust, London, UK

[8]St Helens and Knowsley NHS Foundation Trust (Whiston Hospital), Prescot, UK

关键词: Analgesia;    Emergency department;    Hepatotoxicity;    Nephrotoxicity;    Safety;   

DOI  :  10.1186/s12873-023-00862-2

 received in 2022-11-29, accepted in 2023-08-03,  发布年份 2023

来源: Springer

【 摘 要 】

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).

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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