Paracetamol Overdose

Question 1

Define paracetamol overdose.

Answer 1

Taking too much paracetamol which results in generation of hepatotoxic metabolites. Overdose may occur after an acute single ingestion of a large amount of paracetamol or paracetamol-containing medication, or repeated ingestion of an amount exceeding the recommended dosage.

Question 2

Explain the aetiology/risk factors of paracetamol overdose.

Answer 2

Paracetamol is usually metabolised by glucuronidation, however, when these enzymes are saturated, the paracetamol is metabolised by the CYP450 system (specifically CYP3A4 and CYP2E1) which generates NAPQI which is a toxic metabolite.

Paracetamol overdose can be a suicide method due to its accessibility, however it seems that a lot of people are unaware of its harmful effects so is not a popular method by people attempting suicide. Death comes in the form of liver failure a few weeks later.

Question 3

Summarise the epidemiology of paracetamol overdose.

Answer 3

Paracetamol is easily accessible and often people take too much by accident by taking paracetamol along with other medication containing paracetamol.

Question 4

Recognise the presenting symptoms of paracetamol overdose. Recognise the signs of paracetamol overdose on physical examination.

Answer 4

Patients are often asymptomatic or have only mild gastrointestinal symptoms at initial presentation. Untreated paracetamol poisoning may cause varying degrees of liver injury over the 2 to 4 days following ingestion, including fulminant hepatic failure.

Rarely, massive overdose may initially present with coma and severe metabolic acidosis. Presentation with coma may also occur if a combination preparation of paracetamol and opioid is taken in overdose, or after an overdose of multiple drugs.

Hepatotoxicity is extremely rare in patients treated with acetylcysteine within 8 hours of an acute paracetamol overdose. The efficacy of acetylcysteine decreases subsequent to the first 8 hours following an acute paracetamol overdose, with a corresponding stepwise increase in hepatotoxicity with increasing treatment delays between 8 and 16 hours.

Question 5

Identify appropriate investigations for paracetamol overdose and interpret the results.

Answer 5

Serum paracetamol level
Serum AST and ALT
Arterial pH and lactate level
Urea and electrolytes or tests of renal function
Serum prothrombin time and INR - Used to monitor extent of hepatotoxicity

Question 6

What is the management of paracetamol overdose?

Answer 6

NAC

Use treatment graph - if more than 30 tablets, give NAC anyway.