The small amounts of NAPQI produced after therapeutic doses are detoxified by irreversible glutathione-dependent conjugation reactions to two non-toxic metabolites. It is a highly reactive toxic metabolite formed by cytochrome P450 2E1 and is responsible for the hepatocellular injury that occurs with paracetamol toxicity.
NAPQI, is formed in small amounts following a therapeutic dose of paracetamol. In adults taking therapeutic doses, paracetamol is metabolised into two major non-toxic metabolites – sulphate and glucuronide conjugates – which account for 30% and 55% of paracetamol metabolism. The main toxicity following paracetamol poisoning is acute liver injury which results from the formation of a toxic metabolite of paracetamol, N-acetyl-p-benzoquinone imine (NAPQI). Equally do not discharge the symptomatic patient, you may have mis-timed the point of ingestion or the patient may have lied to you (about time or co-ingestants). Beyond 24 hours, symptoms should be evident (nausea, vomiting, abdominal pain or encephalopathy). Screening and testing for paracetamol in the first 24 hours is necessary as patients are asymptomatic with toxic doses.anticholinergic agents that decrease gastric emptying) and is close to the line. In these cases, start or continue NAC until the risk assessment can be refined using further biochemical parameters and paracetamol concentrations. When in doubt, conservative management is recommended, particular if the patient co-ingested substances that might prolong absorption (i.e.Extrapolation beyond 15-24 hours and modified release preparations are not validated.Always check the units – mg/L vs µmol/L.The nomogram has only be validated for acute (single) immediate-release paracetamol ingestions where an accurate time of ingestion is know.There is no standard definition of “massive” paracetamol ingestion but those with an initial paracetamol concentration greater than double the 150mg at 4 h nomogram line are at higher risk of acute liver injury and require higher doses of acetylcysteine.So, 10g is the toxic dose for all those heavier than 50kg. Most patients will present following a single immediate-release paracetamol ingestion of 10g or >200 mg/kg (whichever is less) within 24 hours.
The majority of paracetamol overdoses/ poisoning are straight forward, and standard treatment protocols can be applied. Guest Post Dr Angela Chiew – Australian Clinical Toxicologist and Emergency Staff Specialist
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