Acetaminophen Overdose

Acetaminophen (Paracetamol) Overdose

Overview

Acetaminophen overdose is a leading cause of acute liver failure worldwide. Toxicity occurs from excessive ingestion (intentional or accidental) that overwhelms normal metabolic pathways, leading to accumulation of NAPQI (N-acetyl-p-benzoquinone imine), a hepatotoxic metabolite.

• Toxic dose (single ingestion): > 150 mg/kg in children or > 7.5–10 g in adults.

• Clinical stages:

  1. 0–24 h: Nausea, vomiting, malaise, diaphoresis.

  2. 24–72 h: Right upper quadrant pain, elevated liver enzymes, hepatomegaly.

  3. 72–96 h: Peak hepatotoxicity → jaundice, coagulopathy, hypoglycemia, encephalopathy.

  4. 4 days–2 weeks: Recovery (if survived) or progression to liver failure/death.

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Treatment Options

1. Emergency Measures

• Activated charcoal:

  • 1 g/kg PO (max 50 g) within 1–2 hours of ingestion if patient presents early and airway protected.

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2. Antidote – N-Acetylcysteine (NAC)

• Replenishes glutathione, detoxifies NAPQI.

• Most effective within 8–10 hours, but benefit even if started later.

Oral regimen:

• Loading: 140 mg/kg PO once.

• Maintenance: 70 mg/kg PO q4h × 17 doses (total 72 h).

IV regimen (21-hour protocol):

• Loading: 150 mg/kg IV over 1 h (in 200 mL 5% dextrose).

• 2nd: 50 mg/kg IV over 4 h (in 500 mL).

• 3rd: 100 mg/kg IV over 16 h (in 1000 mL).

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3. Supportive Therapy

• IV fluids for dehydration.

• Antiemetics: ondansetron 4 mg IV/PO q8h PRN.

• Vitamin K (10 mg IV) for coagulopathy.

• Glucose infusion for hypoglycemia.

• Hemodialysis: in massive overdose (> 1,000 mg/kg) or severe acidosis/lactic acidosis.

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4. Advanced/Rescue Management

• Liver transplantation in fulminant hepatic failure (criteria: pH < 7.3, INR > 6.5, creatinine > 300 µmol/L, grade III–IV encephalopathy).

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Supportive & Monitoring Measures

• Serum acetaminophen level (4 hours post-ingestion) and plot on Rumack–Matthew nomogram to assess risk.

• Serial liver function tests (AST, ALT, INR, bilirubin).

• Monitor renal function and electrolytes.

• ICU admission if encephalopathy or coagulopathy.

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Key Notes

• N-acetylcysteine (NAC) is life-saving and should be given empirically if overdose suspected, do not wait for lab results if presentation is late.

• Mortality is highest in patients presenting >24 h after ingestion without treatment.

• Combination products (acetaminophen + opioids/antihistamines) increase risk of accidental overdose.

• Public education on maximum daily dose (≤ 4 g in adults) is crucial for prevention.