Paracetamol Hepatotoxicity

Overdose Dose

• Single Dose: ≥10 g or 200 mg/kg in 24 hours (whichever is less)

• Chronic Use: ≥6 g or 150 mg/kg/day over 48 hours (especially in low-weight or malnourished patients)

Clinical Features

• Nausea, vomiting

• Right upper quadrant (RUQ) abdominal pain

• Elevated liver enzymes (AST/ALT often >1000 IU/L in severe cases)

• Jaundice if significant liver damage

• Coagulopathy (↑ INR, prolonged PT)

• Hypoglycaemia (due to impaired gluconeogenesis in severe cases)

Management

Initial Steps

1. Assess Ingestion History & Timing

   • Confirm dose, time of ingestion, and any co-ingestants

2. Activated Charcoal

   • If presentation <1 hour post-ingestion (reduces paracetamol absorption)

3. N-Acetylcysteine (NAC)

   • Begin as soon as possible according to an approved dosing protocol

   • Continue NAC even if patient presents late (beyond the typical 8-hour window)

   • NAC prevents hepatocellular damage by replenishing glutathione

Monitoring

• Liver Function Tests: AST, ALT, bilirubin

• Coagulation Profile: INR/PT (detects hepatic synthetic failure)

• Glucose Levels: Hypoglycaemia risk in severe liver injury

Supportive Care

• Manage potential hypoglycaemia with IV dextrose if needed

• Monitor fluid balance, renal function

• Avoid hepatotoxic drugs (e.g. further paracetamol, certain antibiotics)

• Consider ICU admission if severe toxicity or acute liver failure

Referral Criteria

• AST/ALT >1000 IU/L (suggests severe hepatic injury)

• Acute Liver Failure: Encephalopathy, coagulopathy (INR >1.5), significant jaundice

• Uncertain ingestion time or beyond typical treatment window (≥8 hours)

• Massive Overdose requiring closer monitoring or ICU

• Failure to respond to initial NAC therapy (persistent or rising transaminases, coagulopathy)