ICU · toxicology

Acute Paracetamol (Acetaminophen) Overdose — Comprehensive ICU Management

Also known as Paracetamol overdose · Acetaminophen overdose · Acetaminophen toxicity · NAPQI toxicity · N-acetylcysteine (NAC) protocol · Rumack-Matthew nomogram · King's College criteria for transplant · Paracetamol-induced acute liver failure

Acute paracetamol (acetaminophen) overdose — the commonest cause of acute liver failure in the developed world. Most of an absorbed dose is safely conjugated by glucuronidation and sulphation; a minor fraction is oxidised by cytochrome P450 (mainly CYP2E1) to a toxic intermediate metabolite (NAPQI) that is normally detoxified by glutathione — in overdose glutathione is overwhelmed and the metabolite binds covalently to hepatic enzymes and proteins, causing hepatocellular necrosis. The Rumack-Matthew nomogram: single timed 4-hour level against a treatment line starting at 150 mg/L at 4 h (half-life 4 h to 24 h) in North America and Australasia; the UK has used a single 100 mg/L line for all patients since September 2012, alongside treating all staggered or uncertain-time ingestions and extending the initial acetylcysteine infusion from 15 to 60 minutes. The 21-hour three-bag IV NAC regimen (150 mg/kg over 15-60 min, 50 mg/kg over 4 h, 100 mg/kg over 16 h), the two-bag 200 mg/kg plus 100 mg/kg regimen, anaphylactoid reactions (8.2 per cent of courses, 75 per cent cutaneous, 95 per cent within the first 5 hours), NACSTOP early cessation, modified-release and massive (40 g or more) overdose management, the King's College criteria for transplant referral (arterial pH under 7.30, prothrombin time over 100 s, creatinine over 300 micromol/L, grade 3-4 encephalopathy), arterial lactate for risk stratification, and cerebral oedema management in paracetamol-induced acute liver failure.

Checked against its sources on 5 Oct 2026