What is the treatment for a patient with a paracetamol (acetaminophen) overdose to protect the liver?

Acetylcysteine for Liver Protection from Paracetamol Overdose

N-acetylcysteine (NAC) is the only proven antidote for paracetamol overdose and must be administered immediately to prevent hepatotoxicity, ideally within 8 hours of ingestion when it provides near-complete protection against liver damage. 1, 2

Immediate Treatment Protocol

Start NAC without delay in any patient with suspected or confirmed paracetamol overdose when:

• Serum paracetamol level plots above the "possible toxicity" line on the Rumack-Matthew nomogram (drawn 4-24 hours post-ingestion) 1, 2
• Time of ingestion is unknown but paracetamol is detectable 1
• Hepatotoxicity is already present (elevated transaminases) 1
• Acute liver failure with suspected paracetamol involvement, even without confirmatory history 1, 3

Do not wait for laboratory confirmation to start NAC if there is strong clinical suspicion. 3, 2

Timing Is Critical

The efficacy of NAC is directly tied to how quickly treatment begins:

• Within 8 hours: Only 2.9% develop severe hepatotoxicity—near-complete protection 1, 4
• Within 10 hours: 6.1% develop severe hepatotoxicity 1
• 10-24 hours: 26.4% develop severe hepatotoxicity 1
• After 24 hours: Still beneficial and must be given, though efficacy is significantly reduced 1, 3, 5

In the landmark study by Prescott et al., only 1 of 62 patients treated within 10 hours developed severe liver damage, compared to 33 of 57 (58%) who received supportive care alone. 4

NAC Dosing Regimens

Intravenous Protocol (21-hour regimen):

• Loading dose: 150 mg/kg in 5% dextrose over 15 minutes 1, 3
• Second dose: 50 mg/kg over 4 hours 1, 3
• Third dose: 100 mg/kg over 16 hours 1, 3

Oral Protocol (72-hour regimen):

• Loading dose: 140 mg/kg by mouth or nasogastric tube 1, 3
• Maintenance: 70 mg/kg every 4 hours for 17 additional doses 1, 3

Both routes are equally effective, though IV may be preferred for vomiting patients or those with established hepatotoxicity. 1

Activated Charcoal Consideration

Give activated charcoal (1 g/kg) just prior to starting NAC if the patient presents within 4 hours of ingestion. 1, 3 Do not delay NAC administration even if charcoal has been given. 3

Special Clinical Scenarios Requiring NAC

Established Hepatic Failure

Administer NAC immediately regardless of time since ingestion in any patient with acute liver failure from paracetamol. 1, 3 NAC reduces mortality from 80% to 52%, cerebral edema from 68% to 40%, and need for inotropic support from 80% to 48%. 1

High-Risk Populations

Treat with NAC even if paracetamol levels are in the "non-toxic" range for:

• Chronic alcohol users: Severe hepatotoxicity can occur with doses as low as 4-5 g/day 1
• Fasting patients 3
• Patients on enzyme-inducing drugs 1

Repeated Supratherapeutic Ingestions

Start NAC if:

• Serum paracetamol ≥10 mg/mL, OR 1
• AST or ALT >50 IU/L 1

Extended-Release Formulations

Serial paracetamol levels should be obtained as late increases may occur at 14 hours or beyond. 1, 3 Standard NAC dosing applies but monitoring may need extension. 3

When to Continue or Extend NAC Beyond Standard Protocol

Continue NAC beyond the standard 21-hour IV or 72-hour oral protocol in these situations:

• Delayed presentation (>24 hours post-ingestion) 1, 3
• Extended-release paracetamol 1, 3
• Repeated supratherapeutic ingestions 1, 3
• Unknown time of ingestion with detectable levels 1, 3
• Any elevation in AST or ALT above normal 1
• Rising transaminases 1
• Any coagulopathy 1

When NAC Can Be Stopped

NAC may be discontinued when all of the following criteria are met:

• Paracetamol level is undetectable 1
• Liver function tests remain completely normal 1
• No coagulopathy 1
• Patient is not in a high-risk category 1

Critical Pitfalls to Avoid

The Rumack-Matthew nomogram does NOT apply to:

• Presentations >24 hours after ingestion 1
• Repeated supratherapeutic ingestions 1
• Extended-release formulations 1

In these cases, base treatment decisions on paracetamol levels, liver function tests, and clinical presentation rather than nomogram placement. 1

Low or absent paracetamol levels do NOT rule out paracetamol poisoning if ingestion was remote or occurred over several days. 1 Very high aminotransferases (AST/ALT >3,500 IU/L) are highly correlated with paracetamol poisoning and should prompt NAC treatment even without confirmatory history. 1, 3

ICU-Level Care and Transplant Consultation

Contact a liver transplant center immediately for any patient with:

• Severe hepatotoxicity (AST >1,000 IU/L) 1
• Any coagulopathy 1
• Evidence of acute liver failure 1

These patients require ICU-level supportive care with monitoring for encephalopathy, renal failure, and metabolic derangements. 1

Adverse Effects

Monitor for NAC-related adverse effects including:

• Anaphylactic reactions (most common with IV route) 6, 7
• Cutaneous reactions (IV route) 6
• Nausea, vomiting, diarrhea (oral route) 6, 7
• Transient bronchospasm (1-2%) 6

These adverse effects should not prevent NAC administration, as the benefits far outweigh the risks. 6