Acetaminophen Toxicity

Rumack Matthew Nomogram

Note: Use for single time-point ingestion only. Does not predict toxicity in chronic ingestion.

Background

Acetaminophen

• Metabolized through cytochrome P450 system to form toxic NAPQI metabolite, which requires glutathione to detoxify.
• Toxic ingestion dose = 150 mg/kg

Clinical Stages of Acetaminophen Overdose

• Stage 1 (< 24 hr): Abd pain, N/V, anorexia, lethargy, diaphoresis; normal labs
• Stage 2 (24-72 hr): RUQ abdominal pain, jaundice, rising AST/ALT/INR values
• Stage 3 (72-96 hr): Peak hepatotoxicity, renal insufficiency, and death vs. mild symptoms if treated
• Stage 4 (4 days-2 wk): 70% survive acute liver failure; resolution of symptoms

Workup and Treatment

Lab: Draw serum acetaminophen level at 4 hours post-ingestion.

Treatment

Activated charcoal

• Of benefit < 1 hour of ingestion and possible benefit beyond 1 hour

N-acetylcysteine (PO or IV) Start within 8-10 hours if:

• Above “possible hepatic toxicity” line
• Estimated single ingestion of acetaminophen > 150 mg/kg
• Time of ingestion unknown and serum level > 10 mcg/mL
• Lab evidence of hepatotoxicity and history of excessive ingestion
• Repeated ingestion and a serum level > 10 mcg/mL

PO:

• First dose 140 mg/kg
• Then 70 mg/kg every 4 hours
• Typically treat for 20 hours for uncomplicated overdose

IV:

• First dose 150 mg/kg over 1 hour to minimize anaphylactoid reaction
• Then 50 mg/kg over first 4 hours
• Then 100 mg/kg over next 16 hours
• Total Dose = 300 mg/kg over 20 hours

References

• Larson AM. Acetaminophen hepatotoxicity. Clin Liver Dis. 2007;11(3):525-48 [PubMed]