What is the treatment for paracetamol (acetaminophen) poisoning?

Treatment of Paracetamol (Acetaminophen) Poisoning

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

Initial Assessment and Risk Stratification

Critical First Steps

• Obtain serum paracetamol concentration at least 4 hours post-ingestion (levels drawn earlier may be misleadingly low and not represent peak concentrations) 2
• Draw baseline liver function tests (AST, ALT), INR, creatinine, BUN, electrolytes, and glucose immediately 1, 2
• Assess exact time of ingestion—this is critical for nomogram use and treatment decisions 1, 3

When to Start NAC Immediately (Without Waiting for Labs)

Start NAC loading dose immediately in these scenarios:

• Unknown time of ingestion with any suspected overdose 1, 2
• Presentation >8 hours post-ingestion regardless of lab availability 1, 2
• Acetaminophen level unavailable within 8 hours of ingestion 2
• Any clinical evidence of hepatotoxicity (elevated transaminases, coagulopathy) 1, 2
• Suspected massive ingestion (>10g or >140 mg/kg) 1

Using the Rumack-Matthew Nomogram

The nomogram only applies to single acute ingestions with known timing, when levels are drawn 4-24 hours post-ingestion. 1, 2

Treatment Thresholds

• Treat if paracetamol concentration plots at or above the "possible toxicity" line (the lower, dotted line on the nomogram) 1, 2
• For extended-release formulations: obtain a second level 8-10 hours post-ingestion if the 4-hour level is below the treatment line 2

Critical Nomogram Limitations

• Does NOT apply to: repeated supratherapeutic ingestions, presentations >24 hours post-ingestion, unknown timing, or extended-release formulations 1
• May underestimate risk in: chronic alcoholics, malnourished patients, those on CYP2E1-inducing drugs (isoniazid), and cirrhotic patients 1, 3, 2
• Use lower treatment threshold for high-risk populations even with "non-toxic" nomogram levels 1, 3

NAC Dosing Regimens

Intravenous Protocol (21-Hour Standard Regimen)

• Loading dose: 150 mg/kg in 5% dextrose over 15 minutes 1, 2
• Second dose: 50 mg/kg over 4 hours 1, 2
• Third dose: 100 mg/kg over 16 hours 1, 2
• Total dose: 300 mg/kg over 21 hours 2

Oral Protocol (72-Hour Regimen)

• Loading dose: 140 mg/kg orally or via nasogastric tube 1
• Maintenance: 70 mg/kg every 4 hours for 17 additional doses 1
• Total duration: 72 hours 1

Both IV and oral regimens are equally effective when started early; IV may be preferred for vomiting patients or severe cases. 1

Adjunctive Treatment: Activated Charcoal

Give activated charcoal (1 g/kg orally) just prior to starting NAC if the patient presents within 4 hours of ingestion. 1

• Most effective within 1-2 hours but may provide benefit up to 4 hours post-ingestion 1
• Ensure airway protection, especially with co-ingestions (sedatives, alcohol) 1

Timing and Efficacy: The Critical Window

Treatment Efficacy by Time Interval

• 0-8 hours: 2.9% risk of severe hepatotoxicity—maximal protection 1, 4
• 8-10 hours: 6.1% risk of severe hepatotoxicity 1
• 10-24 hours: 26.4% risk of severe hepatotoxicity—efficacy diminishes but still beneficial 1, 4
• >24 hours: Limited efficacy for prevention, but still reduces mortality in established liver failure 1

NAC should never be withheld regardless of presentation time, as it reduces mortality from 80% to 52% even in fulminant hepatic failure. 1

Special Clinical Scenarios

Repeated Supratherapeutic Ingestions (RSI)

The nomogram does NOT apply—use these criteria instead: 1

• Treat with NAC if ≥10g or 200 mg/kg (whichever is less) in any 24-hour period 1
• Treat if ≥6g or 150 mg/kg (whichever is less) per 24-hour period for ≥48 hours 1
• Treat if serum paracetamol ≥10 mg/mL OR AST/ALT >50 IU/L 1

Established Hepatic Failure

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

• Reduces mortality from 80% to 52% 1
• Reduces cerebral edema from 68% to 40% 1
• Reduces need for inotropic support from 80% to 48% 1
• Early NAC (<10 hours) in fulminant failure: 100% survival 1, 3
• Late NAC (>10 hours) in fulminant failure: 37% mortality 1, 3

Cirrhotic Patients

Treat immediately with NAC—cirrhotics have increased susceptibility even at therapeutic doses. 3

• Chronic alcoholics develop severe hepatotoxicity with doses as low as 4-5g/day 1, 3
• Continue NAC beyond standard protocol if transaminases remain elevated 3
• Monitor for hepatic decompensation (ascites, encephalopathy, variceal bleeding) 3

Pregnancy

Treat with NAC according to standard protocols to prevent maternal and potentially fetal toxicity. 5

• Both oral and IV regimens are safe in pregnancy 5
• Paracetamol overdose does not increase adverse pregnancy outcomes unless severe maternal toxicity develops 5

When to Extend NAC Beyond Standard Protocol

Continue NAC beyond 21 hours (IV) or 72 hours (oral) if: 1, 3

• AST/ALT remains elevated or rising 1, 3
• INR remains elevated 1, 3
• Detectable paracetamol level persists 1, 3
• Delayed presentation (>24 hours post-ingestion) 1
• Extended-release formulation 1
• Repeated supratherapeutic ingestions 1
• Unknown time of ingestion with detectable levels 1

When NAC Can Be Safely Discontinued

Stop NAC only when ALL of the following criteria are met: 1

• Acetaminophen level is undetectable 1
• AST and ALT are normal or declining 1
• INR is normal 1
• No clinical signs of hepatotoxicity 1

For carefully selected low-risk patients with normal labs at presentation and 12 hours, a 12-hour NAC course may be safe, but this requires careful risk assessment. 1

Critical Red Flags Requiring ICU Care and Transplant Consultation

Immediately contact a liver transplant center if: 1

• AST/ALT >1000 IU/L (severe hepatotoxicity) 1
• Any coagulopathy (elevated INR) 1
• Encephalopathy 1
• Renal failure 1
• Metabolic derangements 1

Monitoring During Treatment

Laboratory Monitoring

• Repeat AST, ALT, INR, creatinine every 12-24 hours until declining 1
• Monitor for complications: encephalopathy, coagulopathy, renal failure, hypoglycemia 1

NAC Adverse Effects

• Anaphylactoid reactions (rash, urticaria, flushing, pruritus, bronchospasm, hypotension) occur most commonly during the loading dose 2, 6
• If serious reaction occurs: immediately stop infusion, treat the reaction, then carefully restart NAC at a slower rate 2
• Reactions are more common with IV administration during the initial high-concentration phase 6

Common Pitfalls to Avoid

• Never rely on reported ingestion quantity alone—history is often inaccurate 2
• Never use the nomogram for repeated supratherapeutic ingestions—it only applies to single acute overdoses 1
• Never withhold NAC in late presentations—it still reduces mortality even >24 hours post-ingestion 1, 4
• Never assume low/absent paracetamol levels rule out toxicity if ingestion was remote or occurred over several days 1
• Never stop NAC prematurely—ensure all discontinuation criteria are met 1
• Never forget that patients may have elevated transaminases despite "no risk" nomogram placement due to inaccurate history or increased susceptibility 1