Paracetamol (acetaminophen) poisoning
Overview
Paracetamol overdose is the commonest self‑poisoning presentation to emergency departments. Early identification and timely administration of intravenous N‑acetylcysteine (NAC) prevents most cases of hepatotoxicity.
This section summarises pathophysiology, clinical course, indications for antidote, practical IV NAC administration, recognition and management of adverse reactions, monitoring, escalation and key prognostic thresholds.
Pathophysiology
- Normal metabolism: hepatic glucuronidation and sulfation produce non‑toxic metabolites. A small fraction is oxidised by cytochrome P450 to NAPQI.
- Toxic mechanism: NAPQI is detoxified by glutathione. In overdose, conjugation pathways become saturated, more paracetamol is converted to NAPQI, glutathione is depleted and NAPQI binds cellular proteins, causing hepatocyte necrosis and sometimes renal tubular injury.
- Antidote action: NAC is a glutathione precursor that restores hepatic glutathione and limits further covalent binding by NAPQI; efficacy is time‑dependent-earlier administration is better.
Typical clinical course
- 0-24 h: often asymptomatic or has mild GI symptoms (nausea, vomiting, anorexia, malaise).
- 24-72 h: rising transaminases, right‑upper‑quadrant pain and jaundice as hepatic necrosis becomes apparent.
- 72-96 h: possible progression to hepatic failure with coagulopathy, hypoglycaemia, encephalopathy and renal impairment.
- Recovery usually follows prompt treatment; severe cases may progress to fulminant liver failure requiring transplantation.