S5951 Beyond the Common: Methoxyflurane as a Cause of Acute Liver Failure

Introduction: Methoxyflurane, developed in 1959 from methyl alcohol and fluoroethylens, is a halogenated volatile analgesic used to manage acute pain. It reduces oligoanalgesia by overcoming barriers of other analgesics like nitrous oxide, ketamine, or opioids. Suitable for conscious adults, it effectively relieves moderate to severe traumatic pain. However, at higher doses, it poses significant risks, including toxicity from repeated exposure through multiple pathways. Over the past decades, hepatitis cases linked to methoxyflurane at analgesic doses have been reported. Case Description/Methods: A healthy 31-year-old man with a history of sleeve gastrectomy (2010) presented with jaundice and bilirubin >200 µmol/L. He had 9 episodes of vomiting and inability to tolerate oral intake, starting 4 days after inhaling a single ampule of methoxyflurane, after using 4 ampules the day before. He developed fever treated with augmentin. Over 2 days, mental status worsened, leading to transfer to the intensive care unit (ICU). On admission, he showed worsening jaundice, tachycardia, tachypnea, and altered mental state. Labs revealed PT 71.2 s, international normalized ratio 5.3, bilirubin (total 212 µmol/L), Creatinine 158 µmol/L, alanine aminotransferase 3182 U/L, aspartate aminotransferase 2807 U/L, and CRP 90.4 mg/L. Brain computed tomography was normal; abdominal computed tomography showed acute hepatitis. Diagnosed with methoxyflurane-induced liver failure and stage 3 kidney injury, he was listed for urgent transplant. On day 3, he underwent living donor liver transplantation. Histology showed extensive necrosis, hemorrhage, and capsule rupture. After 6 weeks in ICU, labs normalized. Post-discharge, he was counsel about the hepatotoxic potential of methoxyflurane. Discussion: Methoxyflurane once offered advantages like stability and prolonged analgesia, with around 10 million treated patients by 1970. It is a rapid, non-narcotic agent impacting neuronal transmission and GABA signaling. Compared to other halogenated anesthetics like halothane and enflurane, it can cause variable liver injury. Its metabolism produces reactive intermediates that modify proteins, creating neoantigens that provoke immune responses. Repeated or prolonged doses increase liver injury risk. Rare cases of severe hepatotoxicity include a 2010 report after sevoflurane use. While treatment is limited, liver transplantation is effective if performed early. This case underscores the importance of prompt recognition. Co-administration of Augmentin might have contributed, highlighting the need for clear medication guidance and strategies to reduce harm.