What is the treatment for paracetamol (acetaminophen) poisoning?

Treatment of Paracetamol (Acetaminophen) Poisoning

Immediately administer N-acetylcysteine (NAC) to all patients with paracetamol levels above the treatment line on the Rumack-Matthew nomogram, or when hepatotoxicity is suspected, as this is the only proven antidote that reduces mortality and prevents liver failure. 1

Initial Management and Decontamination

• Administer activated charcoal (1 g/kg orally) within 4 hours of ingestion, ideally within 1-2 hours, just prior to starting NAC 1, 2
• Do not delay NAC administration while waiting for activated charcoal 1
• Ensure adequate airway protection before giving activated charcoal, especially with co-ingestions 1

Risk Assessment Using the Rumack-Matthew Nomogram

• Obtain serum paracetamol concentration at least 4 hours post-ingestion (earlier levels are unreliable and may underestimate peak concentrations) 1, 2
• Plot the concentration on the Rumack-Matthew nomogram to determine treatment need 1, 2
• The nomogram only applies to single acute ingestions with known timing within 24 hours 1
• Patients with levels at or above the "possible toxicity" line (150 mg/L at 4 hours in the US; 100 mg/L at 4 hours in the UK) require NAC treatment 1, 3

Critical Caveat About the Nomogram

• The nomogram underestimates risk in chronic alcoholics, malnourished patients, and those on CYP2E1-inducing drugs (e.g., isoniazid) - treat these patients even with "non-toxic" levels 1, 2
• Severe hepatotoxicity has been documented with doses as low as 4-5 g/day in chronic alcohol users 4

NAC Dosing Regimen

• Total dose: 300 mg/kg intravenous over 21 hours, given as three separate infusions 2
• NAC must be diluted before administration (hyperosmolar at 2600 mOsmol/L) 2
• Loading dose: 150 mg/kg over 15 minutes to 2 hours (slower infusion reduces adverse reactions) 2, 3
• Second dose: 50 mg/kg over 4 hours 2
• Third dose: 100 mg/kg over 16 hours 2

Alternative Two-Bag Regimen

• Newer protocol: 200 mg/kg over 4 hours, then 100 mg/kg over 16 hours - this has similar efficacy but significantly reduced adverse reactions compared to the three-bag regimen 5

Time-Critical Treatment Windows

• NAC initiated within 8 hours: 2.9% risk of severe hepatotoxicity 1
• NAC initiated within 10 hours: 6.1% risk of severe hepatotoxicity 1
• NAC initiated after 10 hours: 26.4% risk of severe hepatotoxicity 1
• Treatment remains beneficial even beyond 24 hours, though efficacy is significantly diminished 1, 6

Special Clinical Scenarios Requiring Immediate NAC

Unknown Time of Ingestion

• Administer NAC loading dose immediately without waiting for laboratory results 1, 2
• Obtain paracetamol concentration to guide continuation of treatment 2

Presentation >8 Hours Post-Ingestion

• Start NAC immediately before obtaining paracetamol levels 1, 2
• Do not wait for nomogram interpretation 1

Acetaminophen Level Unavailable Within 8 Hours

• Administer full 21-hour NAC course immediately 2

Fulminant Hepatic Failure

• Administer NAC regardless of time since ingestion (Level B recommendation) 1
• NAC reduces mortality from 80% to 52%, cerebral edema from 68% to 40%, and need for inotropic support from 80% to 48% 1
• Early NAC treatment (<10 hours) in fulminant hepatic failure results in 100% survival 1
• Late NAC treatment (>10 hours) results in 37% mortality and 51% requiring dialysis 1

Repeated Supratherapeutic Ingestions (RSTI)

• The Rumack-Matthew nomogram does NOT apply 2
• Administer NAC if serum paracetamol concentration ≥10 mg/mL OR if AST or ALT >50 IU/L 1
• Obtain paracetamol concentration and liver function tests to guide treatment 2

Extended-Release Formulations

• Obtain second paracetamol level 8-10 hours post-ingestion if first level (at 4 hours) is below treatment line 2
• All potentially toxic ingestions (≥10 g or ≥200 mg/kg) should receive full NAC course 5

Massive Overdoses

• Ingestions ≥30 g or ≥500 mg/kg require increased doses of NAC 5
• Paracetamol concentrations more than double the nomogram line warrant increased NAC dosing 5

Monitoring During Treatment

• Obtain baseline labs: AST, ALT, bilirubin, INR, creatinine, BUN, glucose, and electrolytes 2
• Monitor for hypersensitivity reactions during NAC infusion 2
• If severe hypersensitivity occurs, immediately discontinue infusion, treat the reaction, then carefully restart NAC 2

Disposition Based on Severity

• Patients with AST >1000 IU/L or coagulopathy require ICU-level care and early transplant hepatology consultation 1
• Liver damage (defined as ALT >1000 U/L) is associated with presentation >15 hours after ingestion 6

Common Pitfalls to Avoid

• Do not rely on patient-reported ingestion quantity - history is often inaccurate 2
• Do not use the nomogram for presentations >24 hours post-ingestion - base treatment decisions on paracetamol levels and liver function tests 1
• Do not withhold NAC in late presenters - it does not worsen outcomes and may still provide benefit 2
• Do not assume therapeutic doses are safe in high-risk patients - therapeutic doses of 4 g/day for 14 days cause ALT elevation >3× normal in 31-41% of healthy adults 4
• Reduce total fluid volume in patients <40 kg or those requiring fluid restriction to avoid fluid overload 2