Bupivacaine Induced Hepatotoxicity after Continuous Infusion for Pain Control

Abstract

Purpose: Background: Bupivacaine is increasingly used as a local anesthetic. Hepatotoxicity from this medication is not well recognized. We present a case report of drug-induced liver injury from bupivacaine use. Case: 51 year old white male without a significant PMH except dyslipidemia was admitted to the hospital for an elective hernia repair with mesh placement. Prior to hospital admission he was taking simvastatin 20 mg for about 10 years without clinical or laboratory side effects. He denied alcohol use. On admission, complete blood cell count, basic metabolic panel and liver function tests were within normal range. A Q-pump with continuous bupivacaine infusion was placed at the site of surgery and continued for 3 days to control pain. A total dose of 770 mg was received. After discharge, the patient experienced dizziness, diaphoresis and hypotension. Symptoms resolved after the Q-pump was stopped. Ten days after, he presents with increasing fatigue, pruritus, dark urine and acholic stools. CBC and LFTs were abnormal (Table). Simvastatin was discontinued. Liver ultrasound and CT scan plus serologic markers for acute viral hepatitis were negative. Symptoms and LFTs continued to worsen (Table). Additional work up for chronic liver disease was negative. A liver biopsy showed mild mixed portal inflammation, low grade ductular reaction, hepatocanalicular cholestasis and mild portal and periportal fibrosis. Repeat LFTs returned to normal at 7 weeks and symptoms resolved. Discussion: Bupivacaine hydrochloride is a local anesthetic, increasingly used in ambulatory operative anesthesia and in the treatment of chronic pain due to low incidence of transient neurological syndrome and improved analgesic effect. It is metabolized in the liver via conjugation with glucuronic acid. We present a case of bupivacaine induced hepatotoxicity based on the temporal association of symptoms with the introduction of bupivacaine, the exclusion of other risk factors for hepatotoxicity, and the improvement with withdrawal of the medication. Lack of laboratory or clinical side effects to simvastatin prior to surgery and the laboratory pattern of cholestatic hepatitis makes simvastatin an unlikely cause of this liver injury. Development of dizziness, hypotension and esoinophilia suggest an allergic mechanism. Local infiltration of the medication in the wound area may explain its prolonged toxicity. Competitive inhibition of CYP3A4 may account for bupivacaine-simvastatin interaction and enhanced toxicity. A previous case report of cholestatic hepatitis from continuous epidural block with bupivacaine suggest that bupivacaine causes cholestatic hepatitis pattern of liver injury when used locally and epidurally.Table 1: Liver function test at 3 weeks and 4 weeks post bupivacaine infusion