Paracetamol overdose
NAPQI depletes glutathione → hepatocellular necrosis
Overview
The commonest significant overdose. Toxic NAPQI accumulates once glutathione is depleted, causing delayed hepatic necrosis. Treatment is N-acetylcysteine, with the timed nomogram (or staggered-overdose rules) deciding who is treated.
Recognise
- Often asymptomatic early; later nausea/vomiting, then RUQ pain and jaundice
- Hepatic failure at 3–4 days: encephalopathy, coagulopathy, AKI, acidosis
- Staggered ingestion / unknown timing → treat without relying on the nomogram
Red flags
- Late presentation, staggered overdose, hepatic encephalopathy, raised INR/lactate, acidosis (pH <7.3) → liver-unit criteria (King’s College)
Differentials & how to tell them apart
Investigations
Paracetamol level at 4 hours post-ingestion (single acute); LFTs, INR, U&E, venous gas/lactate, glucose; plot on the treatment nomogram.
Management
N-acetylcysteine guided by the 4-hour level/nomogram (or empirically if staggered/late/unknown timing)
- 1Take a paracetamol level at 4 hours post-ingestion (single acute) and plot on the nomogram; activated charcoal if within 1 hour. Start NAC if above the treatment line.Gate: Staggered overdose, unknown timing, or presentation >8 h → start NAC EMPIRICALLY without waiting for/relying on the nomogram
- 2Monitor INR/LFTs/pH/creatinine; apply King’s College criteria for liver transplant referral (pH <7.3, or the INR/creatinine/encephalopathy triad).
Key points
NAC works best early but still helps late. The nomogram is only valid for a single acute ingestion with a known time ≥4 h ago. King’s College criteria flag transplant need.
Monitor & prognosis
Serial INR, LFTs, creatinine, pH/lactate, glucose, GCS.
Excellent if NAC given early; severe hepatotoxicity if delayed.
Source: TOXBASE / MHRA; King’s College criteria