Acetaminophen poisoning: contemporary intravenous acetylcysteine regimens and early discharge pathways

Acetaminophen (paracetamol, APAP) overdose remains a leading cause of drug-induced acute liver failure, yet N-acetylcysteine (NAC) prevents hepatic injury.

We conducted a narrative search of PubMed/MEDLINE, Embase, and Google Scholar (January 2000-August 2025) and reviewed NAC regimens, including the 3-bag protocol (21 h), the U.S. FDA-labeled 2-bag regimen (20 h), and the 12-h Scottish and Newcastle Acetylcysteine Protocol (SNAP), as well as early-stop pathways. Across regimens, efficacy is broadly similar, but simplified protocols reduce non non-immunoglobulin E reactions and dosing errors. SNAP delivers 300 mg/kg over 12 h and is extended only when stopping criteria are not met, whereas early-stop pathways (NACSTOP/SARPO) are restricted to selected low-risk patients. In most acute overdoses, NAC can be stopped when APAP is < 10 mg/L, ALT/AST are stable or falling, and INR is acceptable.

A protocolized NAC pathway with clear stop/extend rules is the most impactful way to improve care. Escalation (higher or prolonged dosing, early hepatology/transplant referral, and consideration of ECTR) should be reserved for high-risk cases. In low- and middle-income countries (LMICs), dose and timing history can guide empiric NAC when levels are delayed. Biomarkers and artificial intelligence remain useful adjuncts, not substitutes, for laboratory-based decisions.