Managing Paracetamol Overdose

A 25-year-old woman with a long history of depression has taken an overdose of paracetamol. She took the overdose 10 hours ago and cannot recall how many tablets she has taken. She is complaining of abdominal pain and nausea.
1. What is the mechanism of liver damage caused by paracetamol?
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Paracetamol overdose is the most common overdose in the U.K. and is also the commonest cause of acute liver failure.

The liver damage is caused by a metabolite of paracetamol, N-acetyl-p-benzoquinoneimine (NAPQI), which depletes the livers stores of glutathione and directly damages liver cells. An overdose of greater than 12 g or > 150 mg/kg body weight may cause severe liver damage and death.

2. What are the clinical features associated with paracetamol overdose?
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The clinical features of paracetamol overdose occur in 4 stages:

Stage 1 (0-24 hours):
Patients can be asymptomatic.
Nausea, vomiting and abdominal discomfort are common

Stage 2 (24-48 hours):
Right upper quadrant pain and tenderness develop
Hypoglycaemia and reduced conscious level can occur

Stage 3 (48-96 hours):
Hepatic failure starts (jaundice, coagulopathy, encephalopathy)
Loin pain, haematuria, and proteinuria suggest incipient renal failure

Stage 4 (> 96 hours)
Progressively worsening hepatic failure
Cerebral oedema, DIC and death

3. Which blood test is the earliest and most sensitive indicator of liver damage?
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The earliest and most sensitive indicator of liver damage is a prolonged INR, which starts to rise at around 24 hours after overdose. LFTs are usually normal until 18 hours after overdose. AST and ALT levels then sharply rise and can reach > 10,000 units/L by 72-96 hours after overdose. Bilirubin levels rise more slowly and reach their maximum at around 5 days.
4. How is a paracetamol overdose managed?
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The mainstay of treatment of paracetamol overdose is acetylcysteine. Acetylcysteine is a very effective antidote but its effectiveness declines rapidly if started > 8 hours after a significant ingestion. All ingestions > 75 mg/kg are considered to be significant.

Acetylcysteine should be administered based on a 4 hour level or given empirically if presentation is > 8 hours after a significant overdose. If the overdose is staggered or the timing is uncertain the patient should also be treated empirically. The treatment line is shown below:

eipcodtreatmentline

Acetylcysteine is administered as follows:

  • 1st dose 150 mg/kg in 200 mL 5% glucose over 1 hour
  • 2nd dose 50 mg/kg in 500 mL 5% glucose over 4 hours
  • 3rd dose 100 mg/kg in 1000 mL 5% glucose over 16 hours

 

Methionine is a useful alternative in patients who refuse treatment. It is given orally 2.5 g every 4 hours to a total dose of 10 g.