What is the treatment regimen for acetaminophen overdose using N-acetylcysteine (NAC)?

N-acetylcysteine (NAC) Treatment Regimen for Acetaminophen Overdose

The standard N-acetylcysteine (NAC) treatment for acetaminophen overdose consists of an oral regimen with a loading dose of 140 mg/kg followed by maintenance doses of 70 mg/kg every 4 hours for 17 additional doses (total of 18 doses over 72 hours), or an intravenous regimen of 300 mg/kg total dose administered as 150 mg/kg over 15-60 minutes, followed by 50 mg/kg over 4 hours and 100 mg/kg over 16 hours. 1, 2

Initial Management

1. Immediate Actions:

   • Initiate NAC immediately if ≤24 hours have elapsed since ingestion, without waiting for acetaminophen levels 1, 2
   • Consider gastric decontamination:
     • Gastric lavage or induced emesis with syrup of ipecac (15 mL for children, 30 mL for adults)
     • Activated charcoal may be indicated for mixed overdoses, but administer before NAC as it can adsorb NAC 2

2. Baseline Assessment:

   • Draw blood for:
     • Acetaminophen plasma level
     • Liver function tests (AST, ALT, bilirubin, prothrombin time)
     • Renal function (creatinine, BUN)
     • Blood glucose and electrolytes 1, 2

NAC Administration Protocols

Oral Protocol (FDA-approved)

• Loading dose: 140 mg/kg
• Maintenance dose: 70 mg/kg every 4 hours for 17 additional doses (72 hours total)
• Preparation: Dilute 20% solution with diet cola or other soft drinks to a 5% concentration
• If vomiting occurs: Repeat dose if vomiting occurs within 1 hour of administration
• Alternative administration: May be given via duodenal intubation if patient cannot tolerate oral administration 2

Intravenous Protocol

• Total dose: 300 mg/kg administered as:
  • 150 mg/kg over 15-60 minutes (loading dose)
  • 50 mg/kg over 4 hours
  • 100 mg/kg over 16 hours (21 hours total) 1

Treatment Decision Based on Acetaminophen Levels

1. If acetaminophen level is clearly in toxic range:

   • Continue with maintenance doses as scheduled 2

2. If acetaminophen level cannot be obtained:

   • Proceed with full treatment course 2

3. If acetaminophen level is in non-toxic range AND overdose occurred ≥4 hours before testing:

   • Discontinue NAC administration 2

4. If acetaminophen level is in non-toxic range BUT time of ingestion is unknown or <4 hours:

   • Obtain a second plasma level to determine if full treatment is necessary 2

Duration of Treatment and Monitoring

• Early presenters (within 8 hours): NAC is highly protective regardless of initial acetaminophen concentration 3
• Continue NAC beyond the initial protocol if:
  • Patient has elevated liver enzymes
  • INR >2.0
  • Patient is clinically unstable 1
• Monitor for hypersensitivity reactions to NAC (10-15%) and manage with antihistamines and epinephrine if necessary 1
• Daily monitoring: Repeat liver function tests, renal function, blood glucose, and electrolytes daily if acetaminophen levels are in potentially toxic range 2

Special Considerations

• High-risk patients (chronic alcoholism, malnutrition, use of CYP2E1 inducers) should be considered for treatment even with non-toxic levels 1
• Massive overdoses (>500 mg/kg) may benefit from adjunctive treatments such as fomepizole and hemodialysis in addition to NAC 4
• Oral vs. IV administration: Research suggests that the oral NAC protocol may preserve more hepatocytes than the 21-hour IV protocol for patients presenting within 24 hours of ingestion 5

Treatment Efficacy

• NAC significantly reduces hepatotoxicity (18% vs 58%), mortality (0.7% vs 6%), progression to grade III-IV encephalopathy (51% vs 75%), and need for vasopressors (48% vs 80%) 1
• Early administration (within 8 hours of ingestion) is the most critical factor in preventing morbidity and mortality 1
• No significant difference in outcomes when NAC is started 0-4 hours versus 4-8 hours after ingestion, but efficacy decreases with further delay 3

Common Pitfalls and Caveats

• Do not wait for acetaminophen levels before initiating NAC if acetaminophen overdose is suspected and ≤24 hours have elapsed since ingestion 1, 2
• Do not administer activated charcoal after NAC as it can reduce NAC effectiveness 2
• The 21-hour IV NAC infusion may be too short in some cases, while the full 72-hour oral course may be unnecessary in others 5
• Standard treatment nomograms may underestimate risk for patients presenting within 8 hours of overdose 5
• Monitor for and manage hypersensitivity reactions to NAC, which occur in 10-15% of patients 1