Paracetamol overdose

• What percentage of paracetamol ingested undergoes glucuronidation to create water-soluble paracetamol conjugate that is eliminated in urine?

  95%
• What percentage of paracetamol is metabolised using cytochrome P450 enzymes into NAPQI?

  5%
• What is the pathophysiology of paracetamol overdose?

  Normally, NAPQI binds to glutathione to become non-toxic and is excreted in urine but when paracetamol is outside of therapeutic doses the production of NAPQI can exceed the body's detoxification capacity due to finite amounts of glutathione available. Excess NAPQI binds to hepatocytes causing mitochondrial injury which could lead to liver failure and death.
• What are the three types of overdose?

  1. Acute overdose
  2. Staggered overdose
  3. Therapeutic excess
• What is the definition of an acute overdose?

  The overdose is ingested in less than 1 hour.
• What is the definition of staggered overdose?

  The overdose is ingested over longer than 1 hour.
• What is the definition of therapeutic excess overdose?

  There is no intent of self harm. Have to have consumed 75mg/kg in 24 hours.
• Give 3 examples of cytochrome P450 inducers which increase the risk of Liver injury and severity of toxicity in a paracetamol overdose patient

  Phenytoin

  Phenobarbital

  Rifampicin
• What would put an overdose patient more at risk of severe toxicity?

  Glutathione deficiency. Seen in those with eating disorders and alcohol use.
• What clinical features may you see within 12 hours of ingestion?

  May be asymptomatic

  Nausea and vomiting

  Mild/moderate abdominal pain and tenderness
• What clinical features may you see within 12-36 hours of ingestion?

  Moderare/severe abdominal pain

  Metabolic acidosis

  Jaundice

  AKI

  Hepatic encephalotpathy

  Coma

  Bruising or systemic haemorrhage - coagulopathy
• What investigations would you like to do in a paracetamol overdose?

  Paracetamol concentration

  LFTs

  INR

  U&Es

  Bicarbonate

  FBC

  Glucose
• What are 3 important areas of the history to cover in an overdose patient?

  1. Preparation ingested - combination and strength
  2. Length of time the products were ingested over
  3. Time since ingestion
• When can a paracetamol treatment graph be used?

  Provided the time interval since ingestion has been greater than 4 hours.
• What do you use to treat paracetamol overdose?

  IV acetylcysteine
• Within how many hours is IV acetylcysteine most effective?

  Within 8 hours of ingestion
• What are the two treatment regimens used in paracetamol overdose?

  1. Standard 21 hour regimen
  2. Modified 12 hour SNAP regimen
• What does the standard 21 hour treatment regimen consist of?

  150mg/kg in 1 hour

  50mg/kg in 4 hours

  100mg/kg in 16 hours
• What does the SNAP regimen consist of?

  100mg/kg in 2 hours

  200mg/kg in 10 hours
• Which criteria is used to identify which patients with hepatic failure should be referred for liver transplantation by weighing out poor prognosis versus benefit?

  Kings college criteria