Is N-acetylcysteine (NAC) indicated for a patient who has ingested 6g of paracetamol (acetaminophen)?

Should NAC Be Given for 6g of Paracetamol Poisoning?

Yes, N-acetylcysteine (NAC) should be administered for a 6g paracetamol ingestion, as this represents a potentially hepatotoxic dose that warrants treatment. 1

Risk Assessment for 6g Ingestion

• A 6g ingestion exceeds the toxic threshold of 4g/day and approaches the 7g threshold that the American College of Emergency Physicians identifies as "potentially hepatotoxic" regardless of nomogram placement. 1

• For patients weighing less than 60kg, a 6g ingestion represents >100 mg/kg, placing them at significantly higher risk for hepatotoxicity. 1

• Even in patients weighing more than 60kg, this dose exceeds safe therapeutic limits and requires treatment consideration based on serum levels and timing. 2, 1

Immediate Management Algorithm

Step 1: Administer activated charcoal (1 g/kg) if the patient presents within 4 hours of ingestion, just prior to starting NAC. 1, 3

Step 2: Draw serum paracetamol level at 4 hours post-ingestion (or immediately if >4 hours have elapsed) and obtain baseline liver function tests (AST, ALT) and prothrombin time. 1

Step 3: Plot the paracetamol level on the Rumack-Matthew nomogram (only valid for levels drawn 4-24 hours post-ingestion). 2, 1

Step 4: Initiate NAC immediately if:

• The level plots at or above the "possible toxicity" line on the nomogram 2, 1, 3
• Time of ingestion is unknown or unreliable 3
• Presentation is delayed beyond 24 hours (nomogram does not apply) 1, 3
• Any elevation in AST or ALT is present 1
• Patient has risk factors (chronic alcohol use, fasting, malnutrition) even with levels below typical treatment thresholds 2, 1

NAC Dosing Regimens

Intravenous protocol (preferred in most settings): 2, 3

• 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 (total 21-hour protocol)

Oral protocol (equally effective, particularly when treatment is delayed): 2, 3

• Loading dose: 140 mg/kg by mouth or nasogastric tube
• Maintenance: 70 mg/kg every 4 hours for 17 additional doses (total 72 hours)

Critical Timing Considerations

• NAC is most effective when started within 8 hours of ingestion, with only 2.9% developing severe hepatotoxicity when treated in this window. 2, 1

• Efficacy diminishes progressively after 8 hours: severe hepatotoxicity develops in 6.1% when started within 10 hours and 26.4% when started 10-24 hours post-ingestion. 2, 1

• NAC should never be withheld even in late presentations (>24 hours), as it still reduces mortality from 80% to 52% in established hepatic failure. 1, 3

High-Risk Populations Requiring Lower Treatment Threshold

• Chronic alcohol users should receive NAC even with paracetamol levels in the "non-toxic" range, as severe hepatotoxicity can occur with doses as low as 4-5g/day in this population. 2, 1

• Fasting or malnourished patients are at increased risk and may warrant NAC at lower paracetamol levels. 2

• Patients taking enzyme-inducing drugs should be treated if serum paracetamol ≥10 mg/mL or if AST or ALT >50 IU/L. 1

Common Pitfalls to Avoid

• Do not wait for confirmatory paracetamol levels if there is strong suspicion of significant overdose—start NAC immediately. 3

• Do not rely solely on the nomogram for patients presenting >24 hours post-ingestion; base treatment decisions on paracetamol levels, liver function tests, and clinical presentation. 1

• Low or absent paracetamol levels do NOT rule out paracetamol poisoning if ingestion was remote or occurred over several days. 1

• Patients may present with elevated transaminases despite being stratified as "no risk" on the nomogram due to inaccurate history or increased susceptibility. 1

Monitoring and Extended Treatment

• Continue NAC beyond the standard protocol if: delayed presentation (>24 hours), extended-release formulation, repeated supratherapeutic ingestions, unknown time of ingestion with detectable levels, chronic alcohol use, or any elevation in AST/ALT. 1, 3

• NAC can be discontinued when paracetamol level is undetectable AND liver function tests remain completely normal, but any elevation in transaminases mandates continuing or restarting treatment. 1

• Patients with severe hepatotoxicity (AST >1000 IU/L) or coagulopathy require ICU-level care and early consultation with transplant hepatology. 1