What is the treatment for paracetamol (acetaminophen) poisoning?

Treatment of Paracetamol (Acetaminophen) Poisoning

N-acetylcysteine (NAC) is the definitive treatment for paracetamol poisoning and should be administered immediately in suspected cases to prevent or minimize hepatic injury. 1

Initial Assessment and Management

1. Determine timing and amount of ingestion:

   • Obtain acetaminophen plasma level at least 4 hours post-ingestion
   • Plot level on Rumack-Matthew nomogram to determine toxicity risk
   • Remember that patient history of quantity ingested is often unreliable 2

2. Baseline laboratory tests:

   • Liver function tests (AST, ALT, bilirubin)
   • Coagulation studies (INR)
   • Renal function (creatinine, BUN)
   • Electrolytes and blood glucose 1, 2

3. Immediate treatment decisions:

   • If time of ingestion unknown: Administer NAC loading dose immediately
   • If acetaminophen level cannot be obtained within 8 hours or clinical evidence of toxicity exists: Administer full NAC treatment
   • If patient presents >8 hours after ingestion: Administer NAC immediately
   • If patient presents <8 hours after ingestion with known time and level: Use nomogram to determine treatment 2

N-Acetylcysteine Administration

Indications for NAC:

• Acetaminophen level at or above the "possible toxicity" line on nomogram (≥100 mg/L at 4 hours)
• Unknown time of ingestion with suspicion of overdose
• Presentation >8 hours after ingestion
• Clinical evidence of hepatotoxicity
• Extended-release formulation overdose 1, 2

Administration Protocol:

• Intravenous regimen (preferred):

  • Loading dose: 150 mg/kg over 15-60 minutes
  • First maintenance dose: 50 mg/kg over 4 hours
  • Second maintenance dose: 100 mg/kg over 16 hours
  • Total dose: 300 mg/kg over 21 hours 1, 2

• Oral regimen (alternative):

  • Loading dose: 140 mg/kg (diluted to 5% solution)
  • Maintenance dose: 70 mg/kg every 4 hours for 17 doses 1

• For massive overdose (>30g or >500 mg/kg):

  • Consider increased NAC dosing
  • Continue NAC beyond standard protocol if evidence of ongoing liver injury 1, 3

Special Considerations

1. Modified-release formulations:

   • All potentially toxic ingestions (≥10g or ≥200 mg/kg, whichever is less) should receive full NAC course
   • Consider second acetaminophen level 8-10 hours post-ingestion 2, 3

2. Risk factors for increased toxicity:

   • Chronic alcoholism
   • Malnutrition
   • CYP2E1 enzyme-inducing drugs (e.g., isoniazid)
   • Consider treating even if acetaminophen levels are in non-toxic range 2

3. Timing is critical:

   • NAC is most effective when given within 8-10 hours of ingestion
   • Treatment within this window virtually eliminates mortality risk
   • Efficacy diminishes progressively after 8 hours
   • Treatment should not be withheld even if >24 hours post-ingestion 1, 2, 4

Monitoring and Supportive Care

1. Laboratory monitoring:

   • Daily monitoring of serum bilirubin, INR, creatinine, and sodium
   • Monitor arterial ammonia levels (critical threshold: 150-200 μmol/L)
   • Follow liver function tests to assess response to treatment 1

2. Supportive measures:

   • IV fluids
   • Correction of coagulopathy (fresh frozen plasma and vitamin K)
   • Treatment of metabolic acidosis
   • Consider activated charcoal if presenting within 1-2 hours of ingestion 1, 3

3. Monitor for NAC adverse effects:

   • Hypersensitivity reactions (10-15% of patients)
   • Nausea, vomiting
   • Urticaria or bronchospasm (rare)
   • Manage with temporary discontinuation, antihistamines, and restart at slower rate 1

Severe Cases and Transplantation Considerations

1. Contact liver transplant center for:

   • Severe acute liver failure
   • Persistent severe coagulopathy
   • Encephalopathy
   • MELD score >30.5 1

2. Indications for transplantation evaluation:

   • No response after approximately 1 week of NAC therapy
   • Persistent severe coagulopathy and/or encephalopathy after 2-3 days 1

3. Management of hepatic encephalopathy:

   • Monitor for cerebral edema and intracranial hypertension
   • Consider intubation for airway protection in grade 3-4 encephalopathy 1

Prognosis

• Liver damage and death are associated with admission later than 15 hours after ingestion 4
• NAC treatment protects against liver damage if started early 4
• Without appropriate treatment, paracetamol poisoning is the commonest cause of severe acute liver injury in Western countries 5

The key to successful management of paracetamol poisoning is early recognition and prompt administration of NAC, with treatment decisions guided by the Rumack-Matthew nomogram and clinical presentation.