What is the treatment for paracetamol (Acetaminophen) poisoning?

Paracetamol (Acetaminophen) Poisoning: Features and Treatment

N-acetylcysteine (NAC) is the definitive treatment for paracetamol poisoning and should be administered immediately when toxicity is suspected or confirmed to prevent hepatotoxicity and reduce mortality.

Clinical Features of Paracetamol Poisoning

• Initial phase (0-24 hours): Often asymptomatic or mild symptoms including nausea, vomiting, malaise, and abdominal pain
• Hepatotoxicity phase (24-72 hours): Right upper quadrant pain, elevated liver enzymes
• Fulminant hepatic failure phase (72-96 hours): Jaundice, coagulopathy, encephalopathy, acidosis
• Recovery phase (4-14 days): Resolution of symptoms if treatment successful

Assessment and Risk Stratification

1. Determine type of ingestion:

   • Acute single ingestion
   • Extended-release formulation ingestion
   • Repeated supratherapeutic ingestion (RSI)

2. Laboratory evaluation:

   • Serum paracetamol concentration (at least 4 hours post-ingestion)
   • Liver function tests (AST, ALT, bilirubin, INR)
   • Renal function (creatinine, BUN)
   • Electrolytes and blood glucose
   • Acid-base status

3. Risk assessment using Rumack-Matthew nomogram for acute single ingestions with known time 1:

   • "Possible toxicity" line: Treat if level ≥100 mg/L at 4 hours post-ingestion
   • "Probable toxicity" line: Treat if level ≥200 mg/L at 4 hours post-ingestion

Treatment Protocol

Immediate Management

1. Gastrointestinal decontamination:

   • Activated charcoal if within 1-2 hours of ingestion 2

2. NAC administration 3, 1:

   • Initiate NAC immediately if:
     • Acetaminophen level above "possible toxicity" line on nomogram
     • Unknown time of ingestion with detectable acetaminophen level
     • Presentation >8 hours after ingestion
     • Clinical evidence of hepatotoxicity
     • Unable to obtain acetaminophen level within 8 hours

NAC Dosing Regimen

Intravenous NAC administration (preferred) 3, 1:

• 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

Oral NAC administration (alternative) 3:

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

Special Scenarios

1. Massive overdose (>30g or >500 mg/kg) 2:

   • Consider increased NAC dosing (200 mg/kg over 4 hours, then 100 mg/kg over 16 hours)
   • Continue NAC beyond 21 hours if evidence of ongoing liver injury

2. Extended-release formulations 4, 2:

   • Obtain second acetaminophen level 8-10 hours post-ingestion
   • Treat all potentially toxic ingestions (≥10g or ≥200 mg/kg)
   • Consider extended NAC treatment

3. Repeated supratherapeutic ingestion (RSI) 4, 1:

   • Initiate NAC if:
     • Detectable acetaminophen level
     • Elevated transaminases (AST/ALT >50 IU/L)
   • Continue treatment until clinical improvement and normalization of liver function

Monitoring and Supportive Care

1. Laboratory monitoring:

   • Serial acetaminophen levels until undetectable
   • Liver function tests every 12-24 hours
   • Coagulation parameters (INR)
   • Renal function and electrolytes

2. Supportive care 3:

   • IV fluids (10% dextrose/normal saline) at 1.5-2 times maintenance rate
   • Correction of coagulopathy with vitamin K and fresh frozen plasma if needed
   • Treatment of metabolic acidosis
   • Supplemental oxygen if SpO2 <94%

3. NAC-related adverse effects management 3, 1:

   • Monitor for hypersensitivity reactions (10-15% of patients)
   • Common side effects: nausea, vomiting
   • Rare: urticaria, bronchospasm
   • Treatment: temporarily discontinue infusion, administer antihistamines, restart at slower rate

Prognosis and Transplant Considerations

• Early NAC treatment (within 8-10 hours) prevents hepatotoxicity in most cases 4, 5
• Late NAC treatment (10-24 hours) still beneficial but less effective 6
• Consider liver transplantation if 3:
  • No response after 1 week of NAC therapy
  • Persistent severe coagulopathy and/or encephalopathy after 2-3 days
  • Consult with liver transplant center early

Key Pitfalls to Avoid

1. Delaying NAC treatment while waiting for acetaminophen levels
2. Relying solely on patient history for timing and amount of ingestion
3. Failing to recognize high-risk patients (chronic alcoholism, malnutrition, CYP2E1 enzyme inducers)
4. Discontinuing NAC too early in patients with evidence of liver injury
5. Missing repeated supratherapeutic ingestions which may present with established hepatotoxicity

The time-critical nature of NAC administration cannot be overstated - treatment within 8 hours of ingestion provides the best outcomes, but NAC should still be administered regardless of time since ingestion if toxicity is suspected 4, 6.