Paracetamol Overdose

Question 1

Definition

Answer 1

> 75mg/kg

Question 2

Risk factors

Answer 2

History of self harm
History of frequent or repeated use of medication for pain relief
Glutathione deficiency
- infants
- elderly
- genetic condition
Drugs that induce liver enzymes (cytochrome P450 inducers)
Alcohol, malnutrition, anorexia

Question 3

Pathophysiology

Answer 3

Hepatocytes mainly metabolite acetaminophen by glucuronidation + sulfation to non-toxic metabolites = excreted in urine = phase II conjugation
Small amount metabolised by cytochrome P450 enzyme to a highly toxic metabolite N-acetyl-P-benzoquinamine (NAPQI) = phase I conjugation = inactivated by glutathione
Too much acetaminophen = cant all be broken down by hepatocytes = creates more NAPQI
Cell death + acute hepatic necrosis

Question 4

Signs

Answer 4

Jaundice
Reduced GCS
Evidence of self-harm

Question 5

Symptoms

Answer 5

Abdominal pain
Nausea and vomiting
Right upper quadrant pain
Confusion or coma

Question 6

Investigations

Answer 6

Serum paracetamol: levels should be measured at 4 hours post-ingestion. If presenting after 4 hours of ingestion, take levels immediately
LFT: deranged liver function
U+E: severe toxicity in renal failure
ABG: lactic acidosis

Question 7

Treatment

Answer 7

FIRST LINE: Activated charcoal: reduces intestinal absorption
- Administered if the patient presents within 1 hour of ingestion
N-acetylcysteine (NAC): replenishes glutathione stores which bind NAPQI, the toxic metabolite
- Infused over 1 hour to avoid side effects

Liver transplantation: indicated as per the King’s College Criteria if arterial pH < 7.3 after 24 hours of ingestion OR all three of the following are present:
- Prothrombin time > 100 seconds
- Creatinine > 300 µmol/l
- Grade III or IV encephalopathy

Question 8

Complication

Answer 8

Acute liver failure
Anaphylactoid reaction