Acetaminophen Toxicity

1. Risk Factors: Serious to lethal hepatotoxicity
   1. Acetaminophen Overdosage
      1. Adults: 7.5 grams in 24 hours (or 150-250 mg/kg)
   2. Concurrent interacting factors: Lowers the threshold for N-Acetylcysteine use
      1. Dehydration, fasting or malnutrition
      2. Alcohol Abuse
      3. Cirrhosis
      4. Concurrent use of other medications
         1. Isoniazid (reports of hepatotoxicity with concurrent Acetaminophen 3.2 grams)
         2. Zidovudine
         3. Barbiturate
         4. Phenytoin
         5. Acarbose
2. Symptoms and Signs
   1. Anorexia
   2. Nausea and Vomiting
   3. Lethargy
   4. Elevated Liver Function Tests to Jaundice and liver failure
   5. Pallor
3. Course: Stages
   1. Stage 1 (0-24 hours): Asymptomatic with normal Liver Function Tests
   2. Stage 2 (24-48 hours): Liver Function Tests begin to rise
   3. Stage 3 (48-72 hours): Liver Function Tests peak, and symptoms and signs evident
      1. Jaundice
      2. Metabolic Acidosis
      3. Acute Renal Failure
   4. Stage 4 (>72 hours): Fulminant liver failure and death or Survival
4. Labs
   1. Acetaminophen Level
      1. First level at 4 hours: >150 indicates treatment as below
         1. Concurrent interacting factors above lower the threshold for treatment
      2. Consider obtaining at 2 hours: <50 is reassuring
   2. Liver Function Tests
5. Management: N-Acetylcysteine (NAC)
   1. Indications
      1. See Acetaminophen level as above
   2. Preparations
      1. Mucomyst oral or nebulized
      2. Acetadote intravenous
   3. Dosing
      1. See N-Acetylcysteine (Mucomyst)
      2. As directed by Rumack-Matthew Acetaminophen nomogram
         1. http://www.ars-informatica.ca/toxicity_nomogram.php?calc=acetamin
   4. Duration
      1. Standard Course is 72 hours
      2. Abbreviated course of 24 hours and until Acetaminophen level <10
         1. Appears safe and effective
         2. Woo (2000) Ann Emerg Med