Paracetamol poisoning

Overview & Definition

Paracetamol (acetaminophen) poisoning is the most common paediatric poisoning presentation worldwide and remains a leading, preventable cause of acute liver failure. At therapeutic doses paracetamol is safely conjugated by the liver, but after an overdose the conjugation pathways saturate and a greater fraction is metabolised by cytochrome P450 2E1 into the reactive intermediate N-acetyl-p-benzoquinone imine (NAPQI). NAPQI is normally detoxified by glutathione, but once glutathione is depleted it binds hepatocytes and causes centrilobular necrosis. The antidote, N-acetylcysteine (NAC), works by restoring glutathione and by directly conjugating NAPQI, and it is most effective when given early. [1] [2]

The decisive clinical skill is therefore not memorising doses but taking an accurate time-of-ingestion history and using the Rumack-Matthew nomogram correctly. The nomogram relates the serum paracetamol concentration to the time after a single acute ingestion, and the treatment line decides whether NAC is indicated. It is valid only for a single acute ingestion with a known time, and only for a level drawn at four hours or later. A staggered ingestion (multiple doses over hours), an unknown-time ingestion, a repeated supratherapeutic dosing history, or a level drawn before four hours cannot be plotted on the nomogram and demand a different decision rule. [1] [4]

The modern approach treats paracetamol poisoning as a protocolised, region-dependent pathway. The treatment line, the NAC regimen and the threshold to treat staggered ingestions differ between guidelines, and the local poisons information centre or toxicology service should be consulted early. The principles, however, are universal: estimate risk from the history, measure the level at the right time, give NAC when indicated, monitor the liver and coagulation trend, and escalate when liver failure develops. [2] [4]