Paracetamol Overdose

Question 1

What are the steps in paracetamol breakdown causing overdose complications?

Answer 1

1. Sulphate and glucuronide pathways become saturated.
2. More paracetamol is shunted to cytochrome p450 system to produce NAPQI (toxic).
3. Glutathione enables NAPQI to be excreted, but itself becomes saturated too.
4. In the liver NAPQI causes hepatocyte damage and death, leading to acute liver necrosis.

Question 2

What is the definition of a single acute dose of paracetamol?

Answer 2

Ingestion of >4g (75mg/kg) in <1 hour.

Question 3

What is the definition of a staggered overdose of paracetamol?

Answer 3

Ingestion of multiple doses of paracetamol over >1 hour.

Question 4

What are the signs and symptoms of paracetamol overdose in these time frames?

1. First 24 hours
2. > 24 hours
3. > 3 days

Answer 4

1. Asymptomatic
2. Vomiting, RUQ pain
3. Jaundice, encephalopathy, AKI

Question 5

How is a suspected paracetamol overdose investigated?

Answer 5

1. Blood paracetamol and salicylate levels STAT
2. Plot against ‘treatment line’
3. Paracetamol takes 4 hours to metabolise and show on bloods.
4. LFTs, U&Es, INR, glucose, ABG, lactate.

Question 6

What is the treatment paracetamol overdose?

Answer 6

1. <1 hour since OD - activated charcoal

2. >1 hour + if concentration of plasma paracetamol is above the treatment line - IV ACETYLCYSTEINE

Question 7

What is the King’s College Hospital criteria for a paracetamol induced liver failure?

Answer 7

Arterial pH <7.3 24hrs after ingestion, or all of the following:

1. PT >100s
2. Creatinine >300umol/L
3. Grade III/IV encephalopathy