What is the emergency management of a suspected paracetamol (acetaminophen) overdose, including assessment, N‑acetylcysteine administration, activated charcoal use, dosing regimens, and monitoring?

Emergency Management of Paracetamol Poisoning

Immediate Actions Upon Presentation

Start N-acetylcysteine (NAC) immediately if paracetamol overdose is suspected and the patient presents with elevated transaminases or within 8 hours of a potentially toxic ingestion (>10g or >200 mg/kg), without waiting for laboratory confirmation. 1

Initial Assessment and Stabilization

• Obtain critical history: exact time of ingestion, amount ingested, formulation (immediate vs extended-release), any co-ingestions, chronic alcohol use, and baseline liver disease 1
• Draw urgent labs immediately: paracetamol level (if 4-24 hours post-ingestion), AST, ALT, INR/PT, creatinine, and electrolytes 1
• Administer activated charcoal 1 g/kg orally if patient presents within 4 hours of ingestion and can protect their airway—give this just prior to starting NAC 1, 2
• Do not delay NAC while giving activated charcoal; they can be administered together despite theoretical concerns about adsorption 1, 3

NAC Administration Protocol

Standard Intravenous Regimen (Preferred)

Use the two-bag regimen which has similar efficacy but significantly fewer adverse reactions than the older three-bag protocol: 2

• Loading dose: 200 mg/kg in 5% dextrose over 4 hours 2
• Maintenance dose: 100 mg/kg over 16 hours 2
• Total duration: 20 hours for standard cases 2

Alternative Oral Regimen

If IV access is problematic or unavailable: 1, 4

• Loading dose: 140 mg/kg orally or via nasogastric tube, diluted to 5% solution 1
• Maintenance: 70 mg/kg every 4 hours for 17 additional doses (total 72 hours) 1, 4
• The 72-hour oral regimen may be superior when treatment is delayed beyond 10 hours 4

Risk Stratification Using the Rumack-Matthew Nomogram

The nomogram ONLY applies to single acute ingestions with known time of ingestion when paracetamol level is drawn 4-24 hours post-ingestion: 1

• Plot the paracetamol concentration against time since ingestion 1
• Treat with NAC if level plots at or above the "possible toxicity" line (150 µg/mL at 4 hours) 1, 5
• Critical timing windows for efficacy:
  • 0-8 hours: 2.9% develop severe hepatotoxicity with NAC 1, 4
  • 8-10 hours: 6.1% develop severe hepatotoxicity 1, 4
  • 10-24 hours: 26.4% develop severe hepatotoxicity 1, 4
  • 16-24 hours: 41% develop hepatotoxicity (still better than 58% in untreated controls) 1, 4

Special Scenarios Requiring Immediate NAC (Bypass Nomogram)

Start NAC immediately in these situations regardless of paracetamol level or nomogram placement: 1, 5

Established Hepatotoxicity

• Any elevation in AST or ALT above normal with suspected paracetamol exposure 1
• AST/ALT >1000 IU/L (severe hepatotoxicity)—requires ICU admission and transplant hepatology consultation 1
• Any coagulopathy (elevated INR) with suspected paracetamol exposure 1

Timing and History Issues

• Unknown time of ingestion with detectable paracetamol level 1, 5
• Presentation >24 hours post-ingestion (nomogram does not apply) 1, 5
• Acute liver failure where paracetamol overdose is suspected or possible, even without confirmatory history 1, 5

High-Risk Formulations and Patterns

• Extended-release paracetamol: treat all ingestions ≥10g or ≥200 mg/kg with full NAC course; if ≥30g or ≥500 mg/kg, use increased NAC dosing 2
• Repeated supratherapeutic ingestions: treat if ≥10g or 200 mg/kg in 24 hours, OR ≥6g or 150 mg/kg per day for ≥48 hours, OR paracetamol ≥10 mg/mL, OR AST/ALT >50 IU/L 1

High-Risk Populations

• Chronic alcohol users: treat even with levels in the "non-toxic" range, as severe hepatotoxicity occurs with doses as low as 4g/day 1
• Patients taking enzyme-inducing drugs (e.g., phenytoin, carbamazepine) 1
• Fasting or malnourished patients 5

Massive Overdose Protocol

For paracetamol concentrations plotting above the "300-line" on the nomogram (>300 µg/mL at 4 hours), increase NAC dosing: 1, 6

• 300-line: Consider increased dosing 6
• 450-line: Further dose escalation 6
• 600-line: Maximum dose escalation 6
• Specific increased regimens should follow institutional protocols or toxicology consultation 6

Monitoring and Duration of Treatment

Standard Monitoring

• Repeat paracetamol level at 4 hours if initial level drawn <4 hours post-ingestion 1
• For extended-release formulations: obtain serial paracetamol levels at 4,8, and 14 hours, as late peaks may occur 1
• Monitor AST, ALT, INR, creatinine every 12-24 hours during treatment 1

Criteria to Stop NAC After Standard Protocol

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

• Paracetamol level undetectable 1
• AST and ALT normal or declining 1
• INR normal 1
• Patient asymptomatic 1

Mandatory Extended NAC Treatment

Continue NAC beyond the standard 20-21 hour protocol in these situations: 1, 5

• Any elevation in AST or ALT above normal 1
• Rising transaminases 1
• Any coagulopathy 1
• Detectable paracetamol level at end of protocol 1
• Delayed presentation (>24 hours) 1
• Extended-release formulation 1, 2
• Repeated supratherapeutic ingestions 1
• Unknown time of ingestion 1
• Chronic alcohol use 1

Management of Acute Liver Failure

If AST/ALT >1000 IU/L or any signs of hepatic failure (encephalopathy, coagulopathy, elevated bilirubin): 1

• Continue or restart NAC immediately—reduces mortality from 80% to 52% regardless of time since ingestion 1, 7
• Admit to ICU for close monitoring 1
• Contact liver transplant center immediately for all cases of acute liver failure 1
• Monitor for complications: encephalopathy, cerebral edema, renal failure, hypoglycemia, metabolic acidosis 1
• NAC reduces cerebral edema from 68% to 40% and need for inotropic support from 80% to 48% in fulminant hepatic failure 1

Critical Pitfalls to Avoid

• Never delay NAC while awaiting paracetamol levels if there is strong clinical suspicion of significant overdose 1, 5
• Low or absent paracetamol levels do NOT rule out poisoning if ingestion was remote or occurred over several days 1
• The nomogram does NOT apply to: repeated supratherapeutic ingestions, extended-release formulations, unknown time of ingestion, or presentation >24 hours 1
• Do not stop NAC at 20 hours if any transaminase elevation persists—this is a common error that can lead to progression of liver injury 1
• Patients may develop hepatotoxicity despite "no risk" nomogram placement due to inaccurate history or increased susceptibility 1
• Even therapeutic doses of 4g/day for 14 days can cause ALT elevations >3× normal in 31-41% of healthy adults—consider this when interpreting mild transaminase elevations 1

Adverse Effects of NAC

• Anaphylactoid reactions occur more commonly with the older three-bag regimen; the two-bag regimen significantly reduces these reactions 2
• Common side effects: nausea, vomiting, skin rash (<5%), transient bronchospasm (1-2%) 7
• Management: slow or temporarily stop infusion for anaphylactoid reactions, treat symptomatically, then resume at slower rate 7