UMEM Educational Pearls

Title: Is standard NAC dosing adequate for "massive" acetaminophen overdose.

Category: Toxicology

Keywords: massive acetaminophen overdose, standard NAC, hepatotoxicity (PubMed Search)

Posted: 3/4/2021 by Hong Kim, MD
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Recently, there has been questions if standard n-acetylcysteine (NAC) dose is adequate for massive acetaminophen (APAP) overdose (ingestion of > 32 gm or APAP >300 mcg/mL).

A retrospective study from a single poison center (1/1/2010 to 12/31/2019) investigated the clinical outcome of massive APAP overdose (APAP > 300 mcg/mL at 4 hour post ingestion) treated with standard dosing of NAC.

Results

1425 cases of APAP overdose identified; 104 met the criteria of massive APAP overdose. 

  • 300-449 mcg/mL: 59.6% (n=62)
  • 450-599 mcg/mL: 14.4% (n=15)
  • >600 mcg/mL: 25.9% (n=27)

 

  • No acute liver injury/hepatotoxicity: 76% (n=79)
  • Hepatotoxicity: 24% (n=25)

Among cases that received NAC within 8 hours post ingestion (n=44)

  • Only 9% (n=4) cases developed hepatotoxicity

Among cases that received NAC > 8 hours post ingestion (n=60)

  • 35% (n=21) developed hepatotoxicity 

Odds of hepatotoxicity

  • 5.5 If NAC initiated > 8 hours post ingestion
  • 3.8 if 4 h post ingestion APAP level >600 mcg/mL  

Conclusion

  • Cohort: no acute liver injury/hepatotoxicity in 76% (n=79)
  • Standard NAC dosing initiated within 8 hours prevented hepatotoxicity in 91% (n=40/44)