Paracetamol (acetaminophen) overdose is one of the commonest causes of acute liver failure in the UK and a frequent ICU admission diagnosis. In therapeutic doses, paracetamol is conjugated in the liver by glucuronidation and sulphation and excreted safely. In overdose, these pathways are saturated and the remaining paracetamol is metabolised by CYP2E1 to the toxic metabolite NAPQI (N-acetyl-p-benzoquinone imine). Normally, NAPQI is rapidly conjugated by glutathione; in overdose, glutathione stores are depleted and NAPQI accumulates, causing hepatocellular necrosis.

The clinical course of paracetamol poisoning is characterised by initially mild symptoms (nausea, vomiting, abdominal pain in the first 24 hours), followed by a period of apparent improvement, and then liver failure developing at 48–72 hours if untreated. The deceptive early improvement is dangerous because it can lead to delayed presentation or failure to treat.

Treatment with N-Acetylcysteine (NAC)

NAC is the antidote for paracetamol overdose. It works by replenishing glutathione stores, providing an alternative substrate for NAPQI conjugation, and having direct antioxidant effects. Its efficacy is greatest when given within 8 hours of ingestion but it should be given at any time after overdose if there is evidence of hepatotoxicity. The indication for NAC is determined by the paracetamol level measured at 4 hours or more after ingestion, plotted against the treatment nomogram.

The standard NAC regimen is a 3-bag IV infusion: 150 mg/kg over 1 hour, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours. The most common adverse effect is an anaphylactoid reaction (urticaria, angioedema, bronchospasm) occurring during the first bag — this is treated by stopping the infusion temporarily, giving chlorphenamine, and restarting at a slower rate. True anaphylaxis to NAC is extremely rare.

Staggered and Late Presentations

Staggered overdose — multiple doses taken over a period of time rather than a single large ingestion — cannot be plotted on the standard nomogram. All patients with staggered paracetamol overdose should receive NAC treatment regardless of the serum level. Similarly, patients presenting more than 24 hours after overdose who have any evidence of hepatotoxicity (raised transaminases, jaundice, coagulopathy) should receive NAC and be referred to a specialist liver unit.