What is the treatment for a paracetamol (acetaminophen) overdose?

Treatment of Paracetamol (Acetaminophen) Overdose

N-acetylcysteine (NAC) is the definitive treatment for paracetamol overdose and should be administered promptly to patients with possible or probable risk for hepatotoxicity as determined by the Rumack-Matthew nomogram, ideally within 8 to 10 hours post-ingestion to reduce the incidence of severe hepatotoxicity and mortality. 1

Initial Assessment and Risk Stratification

• For single acute ingestions with known time of ingestion, use the Rumack-Matthew nomogram to determine risk of hepatotoxicity by plotting serum acetaminophen concentration drawn 4-24 hours post-ingestion 1
• The nomogram categorizes patients into three risk groups: probable risk, possible risk, and no risk 2
• Patients who cannot be risk-stratified using the nomogram include those with unknown time of ingestion, extended-release preparations, or repeated supratherapeutic ingestions 1

Initial Management

• For patients presenting within 4 hours of ingestion, administer activated charcoal (1g/kg orally) to reduce paracetamol absorption 2, 3
• Activated charcoal appears to have the best risk:benefit ratio among gastric decontamination methods if given within four hours of ingestion 4

N-acetylcysteine (NAC) Treatment Protocol

• Administer NAC to patients with either possible or probable risk for hepatotoxicity as determined by the Rumack-Matthew nomogram (Level B recommendation) 1
• Do not administer NAC to patients with no risk for hepatotoxicity as determined by the nomogram (Level B recommendation) 1
• The timing of NAC administration significantly impacts outcomes 1:
  • When initiated within 8 hours: 2.9% risk of severe hepatotoxicity
  • When initiated within 10 hours: 6.1% risk of severe hepatotoxicity
  • When initiated after 10 hours: 26.4% risk of severe hepatotoxicity

NAC Administration Regimen

• A two-bag intravenous NAC regimen (200 mg/kg over 4 hours, then 100 mg/kg over 16 hours) is recommended, which has similar efficacy but significantly fewer adverse reactions compared to the traditional three-bag regimen 3
• For massive paracetamol overdoses with concentrations more than double the nomogram line, increased doses of acetylcysteine should be administered 3

Special Clinical Scenarios

• Administer NAC to patients with hepatic failure thought to be due to acetaminophen (Level B recommendation) 1
• For repeated supratherapeutic ingestions, NAC should be administered if serum acetaminophen concentration is detectable or if aminotransferase concentrations are elevated (AST or ALT >50 IU/L) 2, 5
• All potentially toxic modified release paracetamol ingestions (≥10g or ≥200 mg/kg, whichever is less) should receive a full course of NAC 3
• For massive ingestions (≥30g or ≥500 mg/kg), increased doses of NAC should be administered 3

Monitoring During Treatment

• Monitor liver function tests and coagulation parameters during treatment 2, 6
• A normal admission ALT has a high negative predictive value (NPV of 98-100%) for subsequent development of hepatotoxicity, but an elevated admission ALT has a low positive predictive value (PPV of 14-23%) 6

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 2
• Hypersensitivity reactions may occur during and after acetylcysteine treatment, including hypotension, wheezing, shortness of breath, and bronchospasm 7
• For patients with multiple admissions for acetaminophen overdose, hepatotoxicity may occur in subsequent admissions even if not present initially 7

Treatment Efficacy

• No deaths occurred among patients treated with NAC within 24 hours in one large study 1
• Of 53 patients treated with intravenous NAC within 8 hours, only 2 (4%) developed hepatotoxicity, compared to 21 of 48 (44%) patients treated after 15 hours 7
• A modified 12-hour acetylcysteine regimen with a two-hour loading dose may be associated with fewer adverse reactions compared to traditional regimens 4