Is N-acetylcysteine (NAC) indicated for a patient with suspected paracetamol (acetaminophen) overdose after ingesting 6gm?

Should NAC be Given for 6g Paracetamol Ingestion?

Yes, NAC should be administered immediately for a 6g paracetamol ingestion, as this represents a potentially hepatotoxic dose that warrants treatment regardless of nomogram placement in most clinical scenarios. 1, 2

Why This Dose Requires Treatment

• A 6g ingestion exceeds the toxic threshold and represents a potentially hepatotoxic dose requiring NAC administration 3
• For patients weighing less than 60kg, this represents >100 mg/kg, placing them at significantly higher risk 2
• Paracetamol is a dose-related toxin where ingestions as low as 3-4g/day can cause severe liver injury in susceptible individuals 2

Immediate Management Algorithm

Within 4 Hours of Ingestion

• Administer activated charcoal (1g/kg) just prior to starting NAC if the patient presents within 4 hours 1, 2
• Start NAC immediately without waiting for serum levels 1, 2

Timing-Based Treatment Strategy

• The critical window is 0-8 hours post-ingestion, where NAC provides maximal hepatoprotection with only 2.9% developing severe hepatotoxicity 2
• Between 8-10 hours: severe hepatotoxicity develops in 6.1% of at-risk patients 2
• After 10 hours: severe hepatotoxicity develops in 26.4% of at-risk patients 2
• NAC should be initiated as soon as possible, ideally within 8-10 hours of ingestion 1

Laboratory Assessment

• Obtain serum paracetamol level at least 4 hours post-ingestion 3
• Obtain baseline liver function tests (AST, ALT) and prothrombin time to assess for developing hepatotoxicity 2
• Do not delay NAC administration while awaiting confirmatory acetaminophen levels if there is strong suspicion of significant overdose 1

NAC Dosing Regimens

Intravenous Protocol (21-hour)

• 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

Oral Protocol (72-hour)

• Loading dose: 140 mg/kg by mouth or nasogastric tube 1
• Maintenance: 70 mg/kg every 4 hours for 17 additional doses 1

Special Considerations for High-Risk Patients

Chronic Alcohol Users

• Should be treated with NAC even with levels in the "non-toxic" range, as severe hepatotoxicity can occur with doses as low as 4-5g/day 2
• These patients have a significantly lower threshold for hepatotoxicity 2

Other High-Risk Groups

• Fasting patients may develop toxicity at lower doses and should receive NAC even if levels are below typical treatment threshold 1
• Patients taking enzyme-inducing drugs require treatment at lower thresholds 2

Critical Pitfalls to Avoid

• Never delay NAC while awaiting laboratory confirmation when paracetamol overdose is suspected 1, 4
• Low or absent acetaminophen levels do NOT rule out poisoning if ingestion was remote or occurred over several days 2
• The Rumack-Matthew nomogram underestimates risk for patients presenting within 8 hours of overdose ingestion 2
• Activated charcoal should not delay NAC administration 1

When to Continue Beyond Standard Protocol

Certain scenarios mandate longer NAC courses:

• Delayed presentation (>24 hours post-ingestion) 2
• Extended-release paracetamol formulations 1, 2
• Repeated supratherapeutic ingestions 2
• Unknown time of ingestion with detectable levels 2
• Any elevation in AST or ALT above normal 2
• Rising transaminases or any coagulopathy 2

Monitoring During Treatment

• Serial liver function tests including AST, ALT, and INR 4
• Watch for hypersensitivity reactions including nausea, vomiting, skin rash (<5%), or bronchospasm (1-2%) 4, 3
• If hepatotoxicity develops (AST/ALT >1000 IU/L), continue NAC until transaminases are declining and INR normalizes 2