What is the management for acute acetaminophen (N-acetylcysteine) toxicity?

Management of Acute Acetaminophen Toxicity

N-acetylcysteine (NAC) should be initiated immediately in suspected acetaminophen overdose without waiting for acetaminophen level results, with dosing determined by the Rumack-Matthew nomogram once levels are available. 1

Initial Assessment and Diagnosis

• Obtain acetaminophen plasma level at least 4 hours post-ingestion
• Plot level on Rumack-Matthew nomogram to determine toxicity risk:

  • 200 mg/L at 4 hours: Probable hepatotoxicity

  • 100-200 mg/L at 4 hours: Possible hepatotoxicity
  • <100 mg/L at 4 hours: No risk 1
• Obtain baseline labs including:
  • Liver function tests
  • Coagulation studies (INR)
  • Renal function
  • Electrolytes
  • Blood glucose 1

Treatment Protocol

When to Initiate NAC

• Start NAC immediately if:
  • Time of ingestion unknown with suspicion of overdose
  • Acetaminophen level at or above "possible toxicity" line (≥100 mg/L)
  • Acetaminophen concentration unavailable within 8 hours of ingestion
  • Clinical evidence of acetaminophen toxicity exists
  • Patient presents >8 hours after known ingestion 1, 2

NAC Administration Options

1. Intravenous NAC (preferred route):

   • Total dose: 300 mg/kg given as 3 separate doses over 21 hours
   • Loading dose: 150 mg/kg over 15-60 minutes
   • Second dose: 50 mg/kg over 4 hours
   • Third dose: 100 mg/kg over 16 hours 1, 2

2. Oral NAC (alternative):

   • Loading dose: 140 mg/kg (diluted to 5% solution)
   • Maintenance: 70 mg/kg every 4 hours for 17 doses 1

Important: NAC is hyperosmolar (2600 mOsmol/L) and must be diluted in sterile water, 0.45% sodium chloride, or 5% dextrose prior to IV administration 2

Monitoring and Supportive Care

• Daily monitoring of:

  • Serum bilirubin
  • INR
  • Serum creatinine
  • Serum sodium
  • Arterial ammonia levels (critical threshold: 150-200 μmol/L) 1

• Provide supportive care:

  • IV fluids
  • Correction of coagulopathy (fresh frozen plasma and vitamin K as needed)
  • Treatment of metabolic acidosis
  • Supplemental oxygen if SpO₂ < 94% (target 94-98%) 1

Managing NAC-Related Adverse Effects

• Monitor for hypersensitivity reactions (10-15% of patients):
  • Common: nausea, vomiting, skin rash (<5%)
  • Rare but serious: bronchospasm (1-2%), hypotension, wheezing
• If serious reaction occurs:
  1. Immediately discontinue infusion
  2. Treat with antihistamines and epinephrine if necessary
  3. Restart at a slower rate after treatment of hypersensitivity 1

Special Considerations

Severe Cases/Hepatic Encephalopathy

• Consider intubation for airway protection in grade 3-4 encephalopathy
• Contact liver transplant center for:
  • Severe acute liver failure
  • Persistent severe coagulopathy
  • Encephalopathy
  • MELD score >30.5 1

Treatment Duration Considerations

• Standard treatment duration is 21 hours (IV) or 72 hours (oral)
• Consider continuing NAC beyond standard duration if:
  • Persistent elevation of acetaminophen levels
  • Worsening liver function tests
  • Development of hepatic encephalopathy 1, 2

Adjunctive Therapies

• Consider fomepizole for severe acidosis not responding to standard NAC therapy
• Consider renal replacement therapy (hemodialysis or continuous renal replacement therapy) for severe acidosis with altered mental status 1

Common Pitfalls to Avoid

1. Delaying NAC administration while waiting for acetaminophen levels - start immediately in suspected cases
2. Miscalculating NAC doses - weight-based dosing requires careful calculation
3. Failing to recognize late presenters - patients presenting >8 hours post-ingestion require immediate NAC regardless of levels
4. Stopping NAC too early - continue treatment until acetaminophen is undetectable and liver function normalizes in severe cases
5. Overlooking pregnancy considerations - NAC crosses the placenta and delaying treatment increases risk of maternal and fetal morbidity/mortality 1, 2