Paracetamol Overdose

Question 1

Define paracetamol overdose

Answer 1

Excessive ingestion of paracetamol >150 mg/kg
12g can be fatal

Acute: excessive amount <1 hr
Staggered: excessive amount >1 hr
Therapeutic excess: smaller amounts and cumulative dosage due to pain, no intent of self harm

Question 2

Aetiology of paracetamol overdose

Answer 2

Usually as a self-harm attempt or therapeutic error

Question 3

Pathophysiology of paracetamol overdose

Answer 3

NAPQI produced from CYP2E1 (Cyt p450) exceeds glutathione stores and causes mitochondrial injury and hepatocyte death -> acute liver failure

Question 4

Epidemiology of paracetamol overdose

Answer 4

Most frequently used drugs in intentional overdoses
Accounts for 48% of poisoning admission in the UK
100-200 deaths per year
Incidence has decreased

Question 5

Presenting symptoms of paracetamol overdose according to time (<24h, 24-72h, >72h)

Answer 5

<24h: asymptomatic OR mild N+V, lethargy, malaise

24-72h: RUQ pain, vomiting

> 72h: acute liver failure -> increasing confusion (encephalopathy), jaundice

Question 6

Signs of paracetamol overdose according to time (<24h, 24-72h, >72h)

Answer 6

<24h: none

24-72h: hepatomegaly, tenderness

> 72h: jaundice, coagulopathy, hypoglycaemia, renal angle pain

Question 7

Investigations for paracetamol overdose

Answer 7

Paracetamol levels: >700mg/L -> critical care (Done 4h post ingestion) -> normogram

Urinalysis: ?Kidney failure
LFTs: elevated/deranged esp. ALT
PT and INR: prolongation 
Glucose: ?liver injury (hypoglycaemia)
U+Es: Cr may be elevated (?AKI)
FBC: leukocytosis, anaemia, thrombocytopenia

Question 8

Management for paracetamol overdose

Answer 8

IV N-acetyl cysteine (NAC) if below certain level using the paracetamol normogram

Liver transplant

Question 9

Risk factors for paracetamol overdose

Answer 9

History of frequent or repeated use of medications for pain relief
Glutathione deficiency
Drugs that induce liver enzymes (Cytochrome P450 inducers) e.g. anticonvulsants, anti-TB
Chronic abusers