S2467 Acute Liver Failure Associated With Therapeutic Doses of Intravenous Acetaminophen

Abstract

INTRODUCTION: Drug induced liver injury is an uncommon, but important phenomenon responsible for nearly half of all acute liver failure (ALF) cases in the US. The majority of these cases are due to Acetaminophen (APAP) which is hepatotoxic in a dose-dependent pattern. Current guidelines suggest that daily dosing of less than 4 grams a day is safe. However, this dose can be hepatotoxic in patients with underlying liver disease, longer duration of use or malnutrition. The following case demonstrates therapeutic acetaminophen dosing causing acute liver failure. CASE DESCRIPTION/METHODS: A 67-year-old Caucasian female with a BMI of 19.7 kg/m2.was admitted for bowel obstruction due to adenocarcinoma in the sigmoid colon. She had no history of liver disease, alcohol use, acetaminophen use and had normal aminotransferases on admission. The patient remained hemodynamically stable while a pre-surgical evaluation was conducted. She received an average of 3-4g/day of IV APAP for pain over 4 days and was on a liquid diet. On hospital day 5, laboratory evaluation showed an INR of 6.1, which was notably 1.0 before admission, and her liver chemistries were markedly elevated in a hepatocellular pattern. The patient had new psychomotor slowing meeting criteria for ALF. She was not a transplant candidate. Her acetaminophen level was 58.9 mcg/mL 2-hours after her last dose. APAP was discontinued and IV NAC was started. Evaluation of other causes of liver failure to include ultrasound of liver and serologic evaluation for EBV, CMV, HSV, HAV, HBV, HEV, AIH, and Wilson’s disease were unremarkable. Review of her medical record did not reveal any medications to explain her acute liver failure. The patient was closely monitored in the ICU and the coagulopathy, mental status and liver chemistries all improved. A presumptive diagnosis of APAP induced ALF was made. She subsequently underwent an open colectomy without complication. DISCUSSION: While generally safe in therapeutic dosing, we present a case of IV APAP causing ALF. Therapeutic dosing causing hepatoxicity has been associated with malnourishment, low BMI, advanced age, fasting, and longer duration of use. IV APAP has slightly different pharmacodynamics that may increase this risk but has been rarely described. This patient’s fasting state, age and malnutrition likely contributed to ALF. Similar to patient’s with cirrhosis, lower dosing (< 2 G/day) may be more appropriate in this patient population.Table 1.: Hospital Course with Laboratory Data.Figure 1.: Hospital Course with Laboratory Data.Figure 2.: Acetomenophen Dosing during admission.