What is the treatment for an acetaminophen (N-acetylcysteine) overdose?

Treatment for Acetaminophen Overdose

N-acetylcysteine (NAC) is the definitive treatment for acetaminophen overdose and should be administered as soon as possible, ideally within 8-10 hours of ingestion, to reduce the risk of hepatotoxicity and mortality. 1, 2

Initial Assessment and Risk Stratification

• For single acute ingestions with known time of ingestion within 24 hours, use the Rumack-Matthew nomogram to determine risk for hepatotoxicity by plotting acetaminophen serum concentration (drawn 4-24 hours post-ingestion) 1
• Risk categories on the nomogram include:
  • Probable risk - above the treatment line
  • Possible risk - in the intermediate zone
  • No risk - below the treatment line 1

Treatment Protocol

Acute Single Ingestion with Known Time (≤24 hours)

• Administer NAC to patients with either possible or probable risk for hepatotoxicity as determined by the Rumack-Matthew nomogram 1
• Do not administer NAC to patients with no risk for hepatotoxicity as determined by the nomogram 1
• Treatment timing is critical:
  • NAC initiated within 8 hours: 2.9% risk of severe hepatotoxicity
  • NAC initiated within 10 hours: 6.1% risk of severe hepatotoxicity
  • NAC initiated after 10 hours: 26.4% risk of severe hepatotoxicity 1, 3

Special Scenarios Requiring NAC

• Patients with hepatic failure due to acetaminophen (Level B recommendation) 1
• Patients with hepatotoxicity due to acetaminophen with suspected or known overdose, including repeated supratherapeutic ingestions (Level C recommendation) 1
• Patients with detectable acetaminophen levels and unknown time of ingestion 1
• Extended-release acetaminophen overdose (treatment must be individualized due to prolonged absorption) 1

NAC Administration Routes and Dosing

• Oral NAC regimen: 140 mg/kg loading dose followed by 70 mg/kg every 4 hours for a total of 72 hours 3
• IV NAC regimen: 150 mg/kg loading dose, followed by maintenance doses for a total of 300 mg/kg over 21 hours 3, 4
• Dilution of oral NAC minimizes the propensity to aggravate vomiting 2
• For high-risk ingestions (levels >300 mg/L at 4 hours), standard dosing is effective if started within 8 hours 4

Special Considerations

• For repeated supratherapeutic ingestions, consider NAC if:
  • Serum acetaminophen concentration ≥10 mg/mL, or
  • Elevated aminotransferase concentrations (AST or ALT >50 IU/L) 1
• Patients with acetaminophen-induced liver injury should receive prompt NAC therapy 5
• For patients with acute liver failure of any etiology, consultation with a liver transplant center is recommended 5

Supportive Care

• Maintain fluid and electrolyte balance based on clinical evaluation 2
• Treat hypoglycemia as necessary 2
• Administer vitamin K1 if prothrombin time ratio exceeds 1.5 or fresh frozen plasma if the prothrombin time ratio exceeds 3.0 2
• Avoid diuretics and forced diuresis 2

Common Pitfalls and Caveats

• Patients may present with elevated hepatic transaminases despite being stratified as "no risk" on the nomogram due to inaccurate history or increased susceptibility 1
• Delayed presentation (>24 hours) requires treatment decisions based on acetaminophen levels and liver function tests rather than the nomogram 1
• NAC treatment may need to be extended in patients with persistently elevated acetaminophen levels or signs of hepatic injury 6
• Anaphylactic reactions are the most common adverse effect of IV NAC, while gastrointestinal effects predominate with oral administration 3