Acetaminophen or Paracetamol Poisoning

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Video lecture link:
​youtu.be/FcYBts1Wc70

Acute Paracetamol Poisoning

The 150 Rule:
Toxic dose is 150 mg/kg
Give NAC if level is above 150 mcg/mL four hours post-ingestion
Initial loading dose of NAC is 150 mg/kg IV (140 mg/kg PO)

Background:
Paracetamol (acetaminophen) is commonly used for pain relief and fever reduction in children.
It's found in many over-the-counter and prescription products.
Paracetamol overdose is the most common toxicological emergency.
Screening for paracetamol should occur in all overdose cases.

Pathophysiology:
Excess paracetamol is metabolized via the cytochrome P-450 pathway in the liver.
This produces a toxic metabolite called N-acetyl-p-benzoquinone imine (NAPQI).
Glutathione stores in the liver are overwhelmed by excess NAPQI in an overdose.
NAPQI leads to centrilobular hepatic necrosis.

Clinical Presentation - Stages of Toxicity:
Stage I (0-24 hours): Mild symptoms or asymptomatic
Stage II (24-72 hours): Right upper quadrant pain, liver enzymes begin to rise
Stage III (72-96 hours): Clinical hepatitis, hepatic failure, and coagulopathy manifest
Stage IV (beyond 5 days): Resolution of toxicity or progression to multiple organ failure

Diagnosis:
Obtain serum acetaminophen level as soon as possible in suspected overdose.
Use Rumack-Matthew nomogram to determine risk of hepatotoxicity.
Order additional tests if poisoning is confirmed: PT, AST, ALT.
Consider acetaminophen overdose in all patients, even if accidental ingestion seems unlikely.

Management:
N-Acetylcysteine (NAC) is the primary antidote for acetaminophen overdose.
NAC is most effective when administered within 8 hours of ingestion.
NAC can be given orally or intravenously.
Start NAC treatment even if degree of toxicity is uncertain.

Intravenous NAC Protocol:
Loading Dose: 150 mg/kg over 1 hour
Second Dose: 50 mg/kg over 4 hours
Final Dose: 100 mg/kg over 16 hours

Oral NAC Protocol:
Loading Dose: 140 mg/kg
Maintenance Doses: 70 mg/kg every 4 hours for 17 doses over 72 hours
Slide 8: Additional Management
Activated charcoal can be given in acute overdose if paracetamol is likely still in the GI tract.
Patients with fulminant liver failure may require a liver transplant.