Paracetamol Poisoning
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Direct answer
Paracetamol poisoning causes centrilobular hepatic necrosis when its toxic metabolite NAPQI overwhelms hepatic glutathione, and it is treated with N-acetylcysteine. The Rumack-Matthew nomogram uses a serum paracetamol level taken four hours or more after a single acute ingestion to decide whether N-acetylcysteine is needed. Treatment is most effective when started early, and it is never delayed for the result if the time of ingestion is unknown and the patient is at risk.
What you must remember
- Toxic threshold: A single ingestion above about 150 mg/kg is potentially hepatotoxic, with lower thresholds in chronic users, heavy alcohol users and those taking enzyme-inducing drugs.
- Nomogram: Applies only to a single acute ingestion of known time, with levels taken from four to 24 hours; the treatment line starts at 150 µg/mL at four hours and halves every four hours.
- IV NAC: Three bags: 150 mg/kg over one hour, 50 mg/kg over four hours, then 100 mg/kg over 16 hours.
- Oral NAC: A loading dose of 140 mg/kg, then 70 mg/kg every four hours for 17 doses.
- Early treatment: NAC is most effective within eight hours, and it is still given later if transaminases are raised.
- Liver failure: King's College criteria are arterial pH below 7.30 after resuscitation, or prothrombin time above 100 seconds with creatinine above 300 µmol/L and grade III or IV encephalopathy.
A worked scenario at six hours
A 19-year-old woman presents six hours after ingesting an unknown quantity of tablets during an argument. Her paracetamol level is 180 µg/mL.
- Read the line: On the original North American line, the treatment threshold at six hours is near 105 µg/mL, because the line halves every four hours from 150 µg/mL at four hours.
- Start NAC: Her level is well above the line, so N-acetylcysteine is started without waiting for liver function results, using the three-bag intravenous regimen.
- Monitor serially: Liver function, prothrombin time, creatinine, glucose and lactate are checked serially, since hepatotoxicity typically peaks around 72 to 96 hours.
- Treat an unknown time: If the time of ingestion were unknown and the level detectable, treatment would also start, because the nomogram cannot be applied.
- Do not plot early levels: Suppose instead she presents at two hours with a level of 200 µg/mL. The nomogram cannot be used, because the level is drawn before four hours.
- Repeat the level: The correct action is to repeat the level at four hours and compare it with the line, while starting NAC if there is clinical concern. This is the common error the examiner tests, and it is why timing is recorded at presentation.
Where the exam tries to catch you
Four traps recur in examiner questions.
- Trap: applying the nomogram at the wrong time Correct: it is not valid before four hours, for staggered or repeated ingestion, or when the time is unknown.
- Trap: taking reassurance from normal enzymes at 24 hours Correct: liver injury may still be evolving and transaminases typically rise later, so normal early values do not exclude toxicity.
- Trap: treating the toxic dose as a fixed line Correct: chronic overdose, alcohol use, malnutrition and concurrent isoniazid or rifampicin can cause serious injury at lower total doses.
- Trap: choosing N-acetylcysteine for other poisons Correct: it is the antidote for paracetamol specifically, and examiners often offer it as a distractor in questions about other poisons.
Frequently asked questions
At what time after ingestion is the paracetamol level used in the nomogram?
The Rumack-Matthew nomogram uses a paracetamol level taken four hours or more after a single acute ingestion of known timing. Levels drawn earlier than four hours cannot be plotted reliably and should be repeated.
What is the intravenous N-acetylcysteine regimen for paracetamol poisoning?
The standard intravenous regimen is 150 mg/kg over one hour, then 50 mg/kg over four hours, then 100 mg/kg over 16 hours. This 21-hour regimen replaces glutathione and is given with weight-based dosing in adults and children.
Which criteria define acute liver failure in paracetamol poisoning?
King's College criteria define paracetamol-induced acute liver failure: arterial pH below 7.30 after resuscitation, or prothrombin time above 100 seconds with creatinine above 300 µmol/L and grade III or IV encephalopathy. Meeting these criteria prompts urgent transplant referral.
Why is N-acetylcysteine most effective within eight hours of paracetamol ingestion?
N-acetylcysteine is most effective within eight hours of paracetamol ingestion, because hepatocyte damage from NAPQI has not yet progressed. Treatment is still given after eight hours when the nomogram or liver enzymes indicate risk.