PHENOBARBITAL-INDUCED ACUTE LIVER INJURY

ABSTRACT

SESSION TITLE Drug-Induced and Associated Critical Care Cases Posters 2 SESSION TYPE Case Report Posters PRESENTED ON 10/19/2022 1245 pm - 0145 pm INTRODUCTION: Drug-induced hepatotoxicity is a well-known occurrence from a variety of different medications. However, phenobarbital (PHB) induced hepatotoxicity has not been well studied, and acute liver injury from PHB even less so. In this case, although our patient had many reasons to develop acute liver failure, including alcohol and toluene exposure, timing and investigations seem to point to PHB being responsible. CASE PRESENTATION Patient is a 39 y.o male with past medical history significant for hepatitis A and B, hyperlipidemia and alcohol abuse who was found unresponsive by EMS after friends reported witnessing patient drinking alcohol and sniffing paint thinner. Patient remained unresponsive on arrival and was intubated and transferred to the MICU. Patient was afebrile with BP 100/55 and otherwise normal vital signs. Significant labs on presentation included a WBC of 8.15, CO2 of 16, lactic acid of 3.6 and mildly elevated transaminases (ALT 59, AST 48). Urine toxicology was positive for marijuana. EKG, chest x-ray and CT Head without contrast unremarkable. COVID negative. Video EEG was negative except for generalized slowing. On hospital day 3, patient was increasingly agitated, at which point phenobarbital was started due to concerns for alcohol withdrawal. Hepatic function panel the following mornings showed significant increases in transaminases (ALT 972 and 5,746, AST 790 and 4,805) and total bilirubin (6.8 and 11.4), and mild increase in alkaline phosphatase (112 and 125), respectively. Hepatitis panel, acetaminophen level and salicylate level were unremarkable. RUQ ultrasound was also negative for pathology. Gastroenterology was consulted, who recommended starting NAC protocol. Phenobarbital was discontinued. Hepatic function panel the following morning showed significant improvement. Liver transplant was considered, however LFTs continued to downtrend and remainder of hospital course was unremarkable. DISCUSSION: PHB is an anticonvulsant developed primarily for seizure management. However its use has expanded to alcohol withdrawal and even sedative withdrawal. Studies have demonstrated in vitro liver toxicity as well as idiosyncratic reactions and acute liver failure in children (1) (2), with minimal documentation in adults. And while there has even been histological analysis with linkage of chronic phenobarbital use to hepatic necrosis and granulomatous formation (3), there has been minimal documentation regarding acute liver failure in an adults taking phenobarbital. CONCLUSIONS: In conclusion, it is clear that phenobarbital played a significant role in this patient's liver injury and may need to be considered in future episodes of acute liver injury with unclear etiology. Reference #1 Li AM, Nelson EA, Hon EK, Cheng FW, Chan DF, Sin NC, Ma KC, Cheung KL, Fok TF. Hepatic failure in a child with anti-epileptic hypersensitivity syndrome. J Paediatr Child Health. 2005 Apr;41(4)218-20. doi 10.1111/j.1440-1754.2005.00591.x. PMID 15813878;PMCID PMC7166358. Reference #2 Roberts EA, Spielberg SP, Goldbach M, Phillips MJ. Phenobarbital hepatotoxicity in an 8-month-old infant. J Hepatol. 1990 Mar;10(2)235-9. doi 10.1016/0168-8278(90)90058-y. PMID 2332596. Reference #3 Di Mizio Di Mizio, G., Gambardella, A., Labate, A., Perna, A., Ricci, P., & Quattrone, (2007). Hepatonecrosis and cholangitis related to long-term phenobarbital therapy An autopsy report of two patients. Seizure, 16(7), 653–656. https//doi.org/10.1016/j.seizure.2007.05.008 DISCLOSURES No relevant relationships by Zachary Banbury No relevant relationships by Michael Basir No relevant relationships by Inessa Bronshteyn No relevant relationships by Kyle Foster No relevant relationships by Anna-Belle Robertson