“Too Much of a Good Thing”: Inadvertent Acetaminophen Overdose in a
Low-Weight Elderly Patient
Theodore Joseph Miller1,2, B.S., Linda
Qiu1,2, B.S., Andrew Nevin1,2, M.
Ed, M.D., Ronald Williams1,2, M.D., and Wilbert
Beachy1,2, 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