“Too Much of a Good Thing”: Inadvertent Acetaminophen Overdose in a Low-Weight Elderly Patient

Theodore Joseph Miller^1,2, B.S., Linda Qiu^1,2, B.S., Andrew Nevin^1,2, M. Ed, M.D., Ronald Williams^1,2, M.D., and Wilbert Beachy^1,2, M.D.

Affiliations:

Pennsylvania State College of Medicine, Hershey, PA¹, Milton S. Hershey Medical Center, Hershey, PA²

Corresponding Author: Theodore Joseph Miller, tmiller51@pennstatehealth.psu.edu

Introduction:

Acetaminophen toxicity is a significant cause of acute liver failure (ALF), particularly in vulnerable populations with impaired metabolism. We present a case of an 89-year-old woman with frail habitus and no prior liver disease, who developed ALF after receiving standard adult acetaminophen dosing for acute pain. Despite adhering to recommended dosing guidelines, the patient’s advanced age, low body weight, and diminished metabolic capacity predisposed her to toxicity. Prompt treatment with N-acetylcysteine facilitated recovery. This case underscores the need for individualized acetaminophen dosing in at-risk populations, emphasizing a weight-based approach to mitigate preventable complications from standard dosing presumed to be safe.

Therapeutic misadventure with acetaminophen (“Tylenol”) is not an uncommon phenomenon. In fact, inadvertent poisoning with Tylenol is a common cause of iatrogenic liver failure and the second most common cause of liver transplantation worldwide (1). Considerations of acetaminophen for acute pain, therefore, must appropriately weigh therapeutic outcomes along with the patient-specific risk factors. This is doubly true in individuals who have impaired ability to metabolize acetaminophen or physiologically diminished clearance capacity, glucuronidation ability, and glutathione production (2). These predisposing factors, including elderly status, frail habitus, cognitive decline, decreased metabolic capacity due to genetic factors, certain medications, herbs, or supplements that engage CYP2E1, or alcohol depletion of glutathione stores, create unfavorable conditions for acetaminophen metabolization. This heightens the subsequent risk for supratherapeutic overdosing on standardized adult regimens. We present a case of acute synthetic liver failure (ALF) after standard adult acetaminophen dosing for acute pain in an elderly female patient without any pre-existing liver disease.

Case History/Examination:

An 89-year-old woman was presented to the emergency department with a chief concern of lethargy and abdominal pain. Vital signs were notable for a temperature of 36.3°C and a low normal blood pressure at 108/53 with a weight of 34.3 kg. Laboratory evaluation revealed a WBC of 12.95 K/uL, a Cr of 1.75 mg/dL which represented an acute kidney injury, and with acute hepatocellular liver injury (bilirubin: 1.4 mg/dL; ALP: 112 units/L) with (AST: 931 units/L, ALT: 640 units/L). Acetaminophen level was 45 ug/mL with a lactate of 2.8 mmol/L.

The patient’s medical history was notable for osteoporosis, dementia, and complete heart block s/p pacemaker. Of note, she had been recently evaluated in the emergency department and diagnosed with uncomplicated cystitis and started on scheduled Tylenol 1,000 mg every eight hours and cephalexin.

The patient was admitted to the internal medicine service. N-acetylcysteine (NAC) was started upon admission. The patient developed acute liver failure after admission, becoming encephalopathic and demonstrating worsening transaminitis (AST: 4,321 units/L, ALT: 2,541 units/L) as well as signs of synthetic liver failure with an INR/PT of 3.1 and 32.0, respectively.

The patient continued to receive NAC for 12 days. Transient melanotic-appearing stools were noted with stable Hgb and no blood transfusion requirements, which was treated with pantoprazole IV BID. Albumin infusions were initiated to support her volume status as she developed worsening AKI, ultimately plateauing at 3.03 and likely representative of ATN which eventually improved and fully resolved with supportive care and diuresis. Her transaminases reached a nadir of ALT: 126 and AST 38. She was eventually discharged safely to an inpatient subacute rehabilitation facility with an arrangement for strength rehabilitation.

Differential Diagnosis:

Differential diagnosis included drug-induced liver injury versus undifferentiated shock leading to perfusion-related liver injury. Acetaminophen toxicity was strongly suspected given a history of doses of acetaminophen reaching nearly 30 mg/kg/dose and a presenting toxic acetaminophen level.

Conclusion and Results:

Acetaminophen is a commonly available, over-the-counter analgesic-antipyretic that is generally safe at recommended doses and with therapeutic dosing dependent on a patient’s weight, age, and clinical status (3). Metabolic processing of acetaminophen typically leads to almost complete renal excretion, with approximately 5% becoming metabolized via cytochrome P450 complexes into N-acetyl-p-benzoquinoneimine (NAPQI) (4). As demonstrated in Figure 1, small amounts can be rapidly conjugated with hepatic glutathione to form nontoxic, urine-soluble compounds, yet the accumulation of NAPQI can be hepatotoxic and occurs with large acetaminophen doses due to the rate-limited reduction by glutathione. When left unnoticed and untreated, overwhelming NAPQI production from acetaminophen toxicity can subsequently progress to acute liver failure, which is marked by hepatic encephalopathy (4). Temporal criteria of less than 26 weeks, along with no prior history of cirrhosis or liver disease, must also exist for an ALF diagnosis - a diagnosis that carries a substantial morbidity and mortality risk (5, 6).

Figure 1: Metabolic Processing Flowchart of Acetaminophen