What is the treatment for paracetamol (acetaminophen) poisoning?

Treatment of Paracetamol (Acetaminophen) Poisoning

Administer N-acetylcysteine (NAC) immediately to all patients with suspected or confirmed paracetamol overdose when serum levels plot above the "possible toxicity" line on the Rumack-Matthew nomogram, or when timing is unknown, or when hepatotoxicity is already present—ideally within 8 hours of ingestion to maximize efficacy. 1

Initial Assessment and Immediate Actions

Time-Critical Evaluation

• Obtain serum paracetamol concentration at least 4 hours post-ingestion for acute overdose, as levels drawn earlier may be misleadingly low and not represent peak concentrations 2
• If time of ingestion is unknown: Start NAC loading dose immediately without waiting for laboratory results, then obtain paracetamol level to guide continuation of treatment 1, 2
• If patient presents >8 hours post-ingestion: Start NAC loading dose immediately regardless of whether levels are available yet 1, 2
• If paracetamol level cannot be obtained within 8 hours OR there is clinical evidence of toxicity: Start NAC immediately and continue full 21-hour protocol 2

Essential Laboratory Testing

• Draw baseline liver function tests (AST, ALT), INR, bilirubin, creatinine, BUN, glucose, and electrolytes at presentation 2
• Assess for hepatotoxicity markers: any elevation in AST/ALT above normal warrants NAC treatment 1

Risk Stratification Using the Rumack-Matthew Nomogram

When to Use the Nomogram

The nomogram ONLY applies when: 1

• Single acute ingestion with known time of ingestion
• Paracetamol level drawn between 4-24 hours post-ingestion
• Patient presents <24 hours after ingestion

Nomogram Interpretation

• Plot the paracetamol concentration against time post-ingestion 1, 2
• Treat with NAC if level plots at or above the "possible toxicity" line (the lower dotted line on the nomogram) 1, 2
• The nomogram may underestimate risk in high-risk patients including those with chronic alcohol use, malnutrition, or taking CYP2E1-inducing drugs (e.g., isoniazid)—consider treating even if levels are in the "non-toxic" range 1, 2

Critical Pitfall

The nomogram does NOT apply to: 1

• Presentations >24 hours post-ingestion
• Repeated supratherapeutic ingestions
• Extended-release paracetamol formulations
• Unknown time of ingestion

NAC Dosing Protocols

Intravenous Regimen (21-Hour Protocol)

Total dose: 300 mg/kg over 21 hours in three divided doses: 1, 2

• Loading dose: 150 mg/kg in 5% dextrose over 15 minutes
• Second dose: 50 mg/kg over 4 hours
• Third dose: 100 mg/kg over 16 hours

NAC must be diluted prior to IV administration as it is hyperosmolar (2600 mOsmol/L); use sterile water, 0.45% sodium chloride, or 5% dextrose 2

Oral Regimen (72-Hour Protocol)

Alternative to IV when appropriate: 1

• Loading dose: 140 mg/kg orally or via nasogastric tube, diluted to 5% solution
• Maintenance: 70 mg/kg every 4 hours for 17 additional doses (total 72 hours)

The 72-hour oral regimen is as effective as the 20-hour IV regimen and may be superior when treatment is delayed 1

Adjunctive Treatment: Activated Charcoal

• Give activated charcoal 1 g/kg orally just prior to starting NAC if patient presents within 4 hours of ingestion 1, 2
• Most effective within 1-2 hours but may provide benefit up to 4 hours post-ingestion 1
• Ensure airway protection is adequate, especially with co-ingestions 1

Timing and Efficacy: The Critical Window

Optimal Treatment Window (0-8 Hours)

• NAC started within 8 hours: 2.9% risk of severe hepatotoxicity 1
• This represents maximal hepatoprotection and near-complete prevention of liver damage 1, 3

Diminishing Efficacy (8-24 Hours)

• NAC started within 10 hours: 6.1% risk of severe hepatotoxicity 1
• NAC started 10-24 hours post-ingestion: 26.4% risk of severe hepatotoxicity 1
• Among high-risk patients treated 16-24 hours after ingestion, hepatotoxicity develops in 41%—still better than untreated controls (58%) 1

Late Presentation (>24 Hours)

NAC should still be administered even in late presentations as it reduces mortality and improves outcomes in established hepatotoxicity 1, 3

• Treatment decisions must be based on paracetamol levels, liver function tests, and clinical presentation rather than nomogram placement 1
• In fulminant hepatic failure, NAC reduces mortality from 80% to 52%, cerebral edema from 68% to 40%, and need for inotropic support from 80% to 48% 1

Special Clinical Scenarios

Repeated Supratherapeutic Ingestions

The Rumack-Matthew nomogram does NOT apply 1, 2

Treat with NAC if: 1

• ≥10 g or 200 mg/kg (whichever is less) during a single 24-hour period, OR
• ≥6 g or 150 mg/kg (whichever is less) per 24-hour period for ≥48 hours, OR
• Serum paracetamol ≥10 mg/mL, OR
• AST or ALT >50 IU/L

Extended-Release Paracetamol

• Obtain a second paracetamol level 8-10 hours after ingestion if the 4-hour level is below the treatment line, due to prolonged absorption 1, 2
• Treat if the second level plots above the "possible toxicity" line 1, 2

Established Hepatotoxicity or Fulminant Hepatic Failure

Administer NAC immediately regardless of time since ingestion (Level B recommendation) 1

• Very high aminotransferases (AST/ALT >3,500 IU/L) are highly correlated with paracetamol poisoning and warrant NAC even with inadequate history 1
• Early NAC (<10 hours) in fulminant hepatic failure: 100% survival 1
• Late NAC (>10 hours) in fulminant hepatic failure: 37% mortality, 51% requiring dialysis 1

High-Risk Populations

Use a lower threshold for treatment in: 1, 4

• Chronic alcohol users: Severe hepatotoxicity documented with doses as low as 4-5 g/day; treat even with levels in "non-toxic" range
• Cirrhotic patients: Increased susceptibility to hepatotoxicity even at therapeutic doses; start NAC immediately 4
• Malnourished patients or those taking CYP2E1-inducing drugs: Consider treating even if nomogram suggests low risk 1, 2

Duration of NAC Treatment

When to Stop NAC After Standard 21-Hour Protocol

NAC can be discontinued when ALL of the following criteria are met: 1

• Paracetamol level is undetectable
• AST and ALT remain normal (no elevation above normal)
• INR is normal
• Patient is clinically well

When to Extend NAC Beyond 21 Hours

Continue NAC if ANY of the following are present: 1

• AST or ALT remains elevated or rising
• INR remains elevated
• Detectable paracetamol level persists
• Delayed presentation (>24 hours post-ingestion)
• Extended-release paracetamol
• Repeated supratherapeutic ingestions
• Unknown time of ingestion with detectable levels
• Chronic alcohol use or other risk factors

For established hepatotoxicity (AST/ALT >1000 IU/L), continue NAC until transaminases are declining and INR normalizes 1

Critical Disposition and Monitoring

ICU-Level Care Required For:

• Severe hepatotoxicity (AST >1000 IU/L) or coagulopathy 1
• Any evidence of liver failure: encephalopathy, coagulopathy, renal failure, metabolic derangements 1
• Contact liver transplant center immediately when there is any evidence of liver failure 1

Monitoring During Treatment

• Serial liver function tests and INR to assess for developing or worsening hepatotoxicity 1, 2
• Watch for complications of acute liver failure: encephalopathy (asterixis, altered mental status), coagulopathy, renal failure, hypoglycemia 1
• Monitor for NAC hypersensitivity reactions (rash, urticaria, facial flushing, pruritus, bronchospasm, hypotension) particularly during the loading dose 2

Common Pitfalls to Avoid

• Do not wait for paracetamol levels if patient presents >8 hours post-ingestion or time is unknown—start NAC immediately 1, 2
• Do not rely solely on reported ingestion quantity—history is often inaccurate and unreliable 2
• Do not use the nomogram for repeated supratherapeutic ingestions, extended-release formulations, or presentations >24 hours 1
• Low or absent paracetamol levels do NOT rule out paracetamol poisoning if ingestion was remote or occurred over several days 1
• Patients may develop hepatotoxicity despite being stratified as "no risk" on the nomogram due to inaccurate history or increased susceptibility 1
• Treatment after 15 hours is less effective but should never be withheld as it still provides benefit and reduces mortality 1, 3
• Bilateral lower limb motor and sensory deficits are NOT caused by paracetamol toxicity—investigate alternative causes such as spinal cord compression, compartment syndrome, or unrelated neurological conditions 5