Posted: July 4th, 2024

Case Study: Acetaminophen Overdose in a Young Adult

Case Study: Acetaminophen Overdose in a Young Adult
History: A 22-year-old female presents to the emergency department with complaints of nausea, vomiting, and abdominal pain. The patient reports ingesting approximately 50 tablets of extra-strength acetaminophen (500 mg each) 36 hours ago in a suicide attempt. She initially felt fine but developed symptoms over the past 12 hours.
PMH: Depression, treated with sertraline.
Medications: Sertraline 50 mg daily.
Physical Examination:
T: 99.1°F, HR: 110 bpm, RR: 20 breaths per minute, BP: 110/70 mm Hg
General: Appears ill, diaphoretic.
HEENT: Scleral icterus noted.
Pulmonary: Clear to auscultation bilaterally.
CV: Tachycardic, no murmurs.
Abdomen: Right upper quadrant tenderness, no rebound or guarding.
Neurologic: Alert and oriented, no focal deficits.
Laboratory Results:
AST: 3500 U/L
ALT: 4200 U/L
Total bilirubin: 3.5 mg/dL
INR: 2.1
Serum acetaminophen level: 150 μg/mL
Questions:

What are the stages of acetaminophen toxicity, and which stage is this patient likely in?
What is the mechanism of acetaminophen-induced hepatotoxicity?
How is the risk of hepatotoxicity assessed in acetaminophen overdose?
What is the primary antidote for acetaminophen toxicity, and how does it work?
What are the indications for liver transplantation in severe acetaminophen-induced hepatotoxicity?

Acetaminophen Overdose: Pathophysiology, Assessment, and Management
Acetaminophen (paracetamol) overdose represents a significant cause of drug-induced liver injury worldwide. This paper examines the stages of toxicity, mechanisms of hepatotoxicity, risk assessment, antidotal therapy, and indications for liver transplantation in severe cases.
Stages of Acetaminophen Toxicity
Acetaminophen toxicity progresses through four distinct stages. The first stage, occurring within 24 hours of ingestion, is characterized by nonspecific symptoms such as nausea, vomiting, and malaise. The second stage, from 24 to 72 hours post-ingestion, may show an apparent improvement in symptoms despite the onset of hepatotoxicity. The third stage, typically 72 to 96 hours after ingestion, manifests with overt hepatic failure, including jaundice, coagulopathy, and encephalopathy. The fourth stage involves either recovery or progression to multi-organ failure and death (Chiew et al., 2020).
Based on the patient’s presentation 36 hours post-ingestion with elevated liver enzymes, coagulopathy, and hyperbilirubinemia, she is likely in the late second or early third stage of toxicity.
Mechanism of Acetaminophen-Induced Hepatotoxicity
Acetaminophen hepatotoxicity results from the production of a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), by the cytochrome P450 system. Under normal circumstances, NAPQI is rapidly conjugated with glutathione and excreted. However, in overdose, glutathione stores become depleted, allowing NAPQI to accumulate and bind to cellular proteins, leading to hepatocyte death. This process triggers an inflammatory response, further exacerbating liver injury (McGill and Jaeschke, 2019).
Risk Assessment in Acetaminophen Overdose
The risk of hepatotoxicity in acetaminophen overdose is assessed using the Rumack-Matthew nomogram, which plots serum acetaminophen levels against time since ingestion. Treatment is indicated for levels above the “possible hepatotoxicity” line. However, the nomogram is only valid for single acute ingestions with a known time of ingestion and when measured between 4 and 24 hours post-ingestion (Heard, 2021).
For patients presenting later or with unclear ingestion histories, risk assessment relies on clinical and laboratory parameters, including elevated liver enzymes, coagulopathy, and acidosis. The patient in this case study demonstrates clear evidence of hepatotoxicity based on her markedly elevated transaminases and coagulopathy.
Antidotal Therapy: N-acetylcysteine
N-acetylcysteine (NAC) serves as the primary antidote for acetaminophen toxicity. Its mechanism of action is multifaceted. Primarily, NAC replenishes glutathione stores, enhancing the detoxification of NAPQI. Additionally, NAC acts as a free radical scavenger and improves mitochondrial energy metabolism. NAC administration is most effective when given within 8 hours of ingestion but may provide benefit even in late-presenting patients with established hepatotoxicity (Chiew et al., 2020).
NAC can be administered orally or intravenously. The standard oral protocol involves a loading dose of 140 mg/kg followed by 70 mg/kg every 4 hours for 17 doses. The intravenous regimen typically consists of a loading dose of 150 mg/kg over 1 hour, followed by 50 mg/kg over 4 hours, and then 100 mg/kg over 16 hours (Heard, 2021).
Indications for Liver Transplantation
In severe cases of acetaminophen-induced hepatotoxicity, liver transplantation may be necessary. The decision to proceed with transplantation is based on prognostic criteria, most commonly the King’s College Criteria. These criteria include arterial pH <7.3 after fluid resuscitation, or the presence of all three of the following: prothrombin time >100 seconds (INR >6.5), serum creatinine >3.4 mg/dL, and grade III or IV encephalopathy (Wendon et al., 2020).
Additional factors considered in transplantation decisions include the rate of decline in liver function, presence of concurrent renal failure, and overall clinical trajectory. Early consultation with a liver transplant center is recommended for patients with severe acetaminophen-induced hepatotoxicity.
In conclusion, acetaminophen overdose requires prompt recognition, risk assessment, and initiation of appropriate therapy. While N-acetylcysteine remains the mainstay of treatment, severe cases may necessitate liver transplantation. Understanding the pathophysiology and management principles of acetaminophen toxicity is crucial for optimal patient outcomes.
References
Chiew, A.L., Gluud, C., Brok, J., Buckley, N.A., 2020. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database of Systematic Reviews, 7(7), CD003328.
Heard, K., 2021. Acetaminophen (paracetamol) poisoning in adults: treatment. UpToDate. Waltham, MA: UpToDate Inc.
McGill, M.R., Jaeschke, H., 2019. Mechanistic biomarkers in acetaminophen-induced hepatotoxicity and acute liver failure: from preclinical models to patients. Expert Opinion on Drug Metabolism & Toxicology, 15(12), pp.1033-1048.
Wendon, J., Cordoba, J., Dhawan, A., Larsen, F.S., Manns, M., Samuel, D., Simpson, K.J., Yaron, I., Bernardi, M., 2020. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. Journal of Hepatology, 73(1), pp.187-208.

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