Paracetamol Overodose

Question 1

How many tablets of paracetamol may become fatal? What is the dose?

Answer 1

Each tablet = 500mg

12g (=24 tablets) may be fatal

• Or 150mg/kg in adults
• If the patient weighs >110kg, calculate ingested dose using a body weight of 110kg to avoid underestimating toxicity.
• If the patient is malnourished then 75mg/kg can kill.

Question 2

What is the recommended daily dose of paracetamol?

Answer 2

The recommended dose of paracetamol is 4 g (or 75 mg/kg) in 24 hours for an adult patient.

Any ingestion exceeding this is regarded as an overdose. However, toxicity is extremely unlikely if <75 mg/kg paracetamol has been ingested within a 24-hour period.

Question 3

What is the pathophysiology of paracetamol overdose?

Answer 3

• Usually occurs as self-harm/therapeutic error
• Paracetamol undergoes sulfation and glucuronidation –> non toxic urine metabolites excreted
• 4% metabolised by CYP450 (CYP2E1 mainly) –> intermediate toxic metabolise of NAPQI –> NAPQI is combined with glutathione –> non-toxic mercapturate derivative –> urinary excretion
• After overdose, CYP2E1 pathway becomes important
• Glutathione becomes saturated –> perivenular/zone 3 hepatocyte damage (as this is where highest conc of CYP2E1 is located in centrilobular hepatocytes)
• Hepatocyte damage –> acute liver failure

Question 4

What are the risk factors for paracetamol overdose?

Answer 4

• history of self-harm
• history of frequent use of pain relief meds
• glutathione deficiency e.g. malnourished, AIDs, alcoholism
• drugs that induce liver enzymes - e.g., phenobarbital, isoniazid or long-standing alcohol abuse may increase the risk of liver damage following paracetamol overdose

Question 5

What are the signs and symptoms of paracetamol overdose?

Answer 5

None initially/vomiting +/- RUQ pain

Later: jaundice, encephalopathy from liver damage (main danger) +/- AKI

Question 6

What investigations would you do for paracetamol overdose?

Answer 6

Bloods:

• Toxicology screen - serum paracetamol level 4hrs after ingestion
• Serum AST/ALT - elevated but depends on time of presentation
• ABG - lactate raised and pH (acidaemia)
• U&Es - may show renal impairment
• Clotting - prolonged PT, increased INR if severe

Question 7

How do you manage paracetamol overdose? (not on Sofia)

Answer 7

• GI decontamination if <4hr after overdose, giver 1g/kg activated charcoal max 50.
• Check Glucose, U&E, LFT, INR, ABG, FBC, HCO3−; blood paracetamol level at 4h post-ingestion.
• If <10–12h since overdose, not vomiting, and plasma paracetamol is above the line on the graph , start acetylcysteine.
• If >8–24h and suspicion of large overdose (>7.5g) err on the side of caution and start acetylcysteine, stopping it if level below treatment line and inr/alt normal.
• Next day do inr, u&e, lft. If inr rising, continue acetylcysteine until <1.4.
• If continued deterioration, discuss with the liver team. Don’t hesitate to get help.
• Consider referral to specialist liver unit guided by eg King’s College criteria

Question 8

What is the antidote to paracetamol?

Answer 8

Acetylcysteine - IV acetylcysteine is the antidote to treat paracetamol overdose and is virtually 100% effective in preventing liver damage when given within 8 hours of the overdose