What is the treatment for acetaminophen toxicity?

Treatment for Acetaminophen Toxicity

N-acetylcysteine (NAC) is the definitive treatment for acetaminophen poisoning and should be administered immediately when toxicity is suspected or confirmed to prevent hepatotoxicity and reduce mortality. 1

Initial Assessment and Management

1. Gastrointestinal decontamination:

   • Empty the stomach promptly by lavage or by inducing emesis with syrup of ipecac 2
   • Consider activated charcoal if within 4 hours of ingestion 3
   • Note: Activated charcoal adsorbs NAC, so administer lavage before NAC if activated charcoal has been given 2

2. Laboratory evaluation:

   • Obtain acetaminophen plasma level
   • Baseline liver function tests (AST, ALT, bilirubin)
   • Coagulation parameters (prothrombin time)
   • Renal function (creatinine, BUN)
   • Blood glucose and electrolytes 2

NAC Administration

Oral NAC Protocol:

• Loading dose: 140 mg/kg (diluted to 5% solution)
• Maintenance dose: 70 mg/kg every 4 hours for 17 doses 1, 2
• If patient vomits within 1 hour of administration, repeat the dose 2
• For persistent vomiting, consider duodenal intubation or IV administration 2

Intravenous NAC Protocol:

• Loading dose: 150 mg/kg over 15-60 minutes
• First maintenance dose: 50 mg/kg over 4 hours
• Second maintenance dose: 100 mg/kg over 16 hours 1

Risk Stratification

1. Known time of single acute ingestion within 24 hours:

   • Use Rumack-Matthew nomogram to determine risk of hepatotoxicity
   • Initiate NAC if acetaminophen level is at or above the "possible toxicity" line (≥100 mg/L) 1

2. Unknown time of ingestion or presentation >24 hours:

   • Administer NAC if acetaminophen is detectable or if there are elevated transaminases 4, 1

3. Extended-release formulations:

   • Obtain a second acetaminophen level 8-10 hours post-ingestion
   • Treat all potentially toxic ingestions (≥10g or ≥200 mg/kg) 1

4. Repeated supratherapeutic ingestion (RSI):

   • Initiate NAC if there is a detectable acetaminophen level or elevated transaminases (AST/ALT >50 IU/L) 1

5. Massive overdose (>30g or >500 mg/kg):

   • Consider increased NAC dosing
   • Continue NAC beyond standard protocol if evidence of ongoing liver injury 1

Special Considerations

• NAC is most effective when administered within 8-10 hours of ingestion but still beneficial up to 24 hours 1
• For patients with hepatic failure due to acetaminophen, NAC reduces mortality, cerebral edema, and need for inotropic support 4
• Monitor for NAC-related adverse effects, particularly hypersensitivity reactions (10-15% of patients) 1
• For IV NAC-related anaphylactoid reactions: temporarily discontinue infusion, administer antihistamines, and restart at a slower rate 5

Monitoring and Supportive Care

• Repeat liver function tests, coagulation parameters, and renal function daily if acetaminophen level is in the potentially toxic range 1, 2
• Provide IV fluids, correction of coagulopathy, and treatment of metabolic acidosis as needed 1
• Consider fresh frozen plasma and vitamin K for coagulopathy 1
• For severe acidosis with altered mental status, consider intubation and mechanical ventilation 1

Liver Transplantation Considerations

• If no response after approximately 1 week of NAC therapy, consider hepatic transplantation 1
• In cases of persistent severe coagulopathy and/or encephalopathy, transplantation considerations may need to begin after only 2-3 days 1

Common Pitfalls and Caveats

• Do not delay NAC administration while awaiting acetaminophen levels if overdose is suspected
• Do not rely solely on patient history regarding time and amount of ingestion as these are often unreliable 5
• Remember that patients can present in liver failure days after ingestion with undetectable serum acetaminophen concentrations 5
• Activated charcoal can reduce NAC efficacy if administered simultaneously - ensure proper timing 2
• Patients with chronic excessive acetaminophen ingestion are more likely to develop renal failure 5