Acetaminophen (APAP) overdose is the leading cause of liver failure in the U.S. and Europe. Large APAP ingestion can result in hepatotoxicity despite the early initiation of n-acetylcysteine (NAC). 

A recently published study from Austrialia investigated the effect of activate charcoal and increasing the NAC dose for large APAP overdose patients (3rd bag: 100 to 200 mg/kg over 16 hours) during first 21 hours of NAC therapy

acetaminophen ratio (first APAP level taken between 4 to 16 hour post ingestion / APAP level on the Rumack nomogram line at that time point) was determined to compare APAP levels at different time points among study sample

e.g.  

first APAP level at 4 hour post ingestion = 400

APAP level on the Rumack APAP nomogram at 4 hour post ingestion = 150

APAP ratio = 400/150 = 2.67

 

Findings:

1. Activated charcoal (AC): if given within 4 hours, AC significantly decreased the APAP ratio (OR: 1.4 vs. 2.2)
2. Increased dose of NAC during the first 21 hour significantly decreased the risk of hepatotoxicity (OR: 0.27; 95% CI: 0.08 - 0.94).

 

Conclusion: 

1. Administration of AC in patients with history of large APAP overdose (>=40 gm) within 4 hour of ingestion can still be beneficial.
2. Increasing NAC dosing (3rd bag in first 21 hour thearpy) may decrease the risk of hepatotoxicity. 

Note: Any increase in NAC dosing from the standard 21 hour therapy should be performed after consulting your regional poison center.

References

Chiew AL et al. Massive paracetamol overdose: an obsevational study of the effect of activated charcoal and increased acetylcysteine dose (ATOM-2). Clin Toxicol 2017;55:1055-1065. PMID: 28644687.