Overview
Definition
Overdose of acetaminophen, leading to severe acute liver failure.
Epidemiology
The most common cause of acute liver failure in the US.
Etiology & Risk Factors
- Normally, acetaminophen is metabolized by glucuronidation/sulfation. In overdose, these pathways saturate, and metabolism shifts to CYP450, creating a toxic metabolite (NAPQI).
- NAPQI depletes glutathione stores, leading to direct hepatocellular necrosis.
Clinical Symptoms
- Stage 1 (0-24h): Often asymptomatic, or mild nausea/vomiting
- Stage 2 (24-72h): RUQ abdominal pain, elevated AST/ALT (can be >10,000)
- Stage 3 (72-96h): Fulminant hepatic failure, jaundice, coagulopathy, hepatic encephalopathy, death
- Stage 4 (4 days to 2 weeks): Resolution and recovery for those who survive
Clinical Approach
Diagnosis
- Serum Acetaminophen level: Draw at 4 hours post-ingestion (or ASAP if later)
- Rumack-Matthew Nomogram: Used to plot the acetaminophen level against time since ingestion to determine if treatment is needed
- Hepatic Panel: AST, ALT, Bilirubin, PT/INR
Management
- Activated Charcoal: If patient presents within 1-2 hours of ingestion
- N-Acetylcysteine (NAC): The definitive antidote. Acts as a glutathione substitute to detoxify NAPQI. Nearly 100% effective if given within 8 hours of ingestion.
- Liver Transplant: For severe, irreversible acute liver failure (King's College Criteria)
Complications
- Acute Liver Failure (requiring transplant)
- Cerebral edema
- Death