Paracetamol Overdose Flashcards

1
Q

What is the recommended therapeutic dose of paracetamol for an adult?

A

24 hours is 4 g

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2
Q

What is another name for paracetamol commonly used in other countries?

A

Acetaminophen

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3
Q

The National Poisons Information Service (NPIS) in the UK defines different types of paracetamol overdose (acute, staggered and therapeutic)

Briefly describe each one

A

Acute overdose: excessive amounts of paracetamol ingested over a period of less than 1 hour; usually in the context of self-harm

Staggered overdose: excessive amounts of paracetamol ingested over longer than 1 hour; usually in the context of self-harm

Therapeutic excess: excessive paracetamol taken with intent to treat pain or fever and without self-harm intent

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4
Q

Briefly describe the pathophysiology of paracetamol overdose

A

When the production of NAPQI exceeds the capacity to detoxify it, the excess NAPQI binds to cellular components, causing mitochondrial injury and ultimately the death of the hepatocyte. If a sufficient dose is taken, hepatocyte death may be massive and produce acute liver failure.

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5
Q

What are the risk factors for paracetamol overdose?

A
  • History of self-harm
  • History of frequent or repeated use of medications for pain relief
  • Glutathione deficiency
  • Long-term treatment with drugs that induce liver enzymes (cytochrome P450 inducers)
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6
Q

What are the signs of paracetamol overdose?

A

Examination can be normal unless signs of acute liver failure are present

  • Jaundice
  • Tender hepatomegaly
  • Altered conscious level (hepatic encephalopathy)
  • Asterixis
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7
Q

What are the symptoms of paracetamol overdose?

A
  • Nausea and vomiting
  • RUQ abdominal pain
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8
Q

What investigations should be ordered for paracetamol overdose?

A
  • Serum paracetamol concentration
  • LFTs
  • Prothrombin time and INR
  • Blood glucose
  • Urea, creatinine and electrolytes
  • Venous or arterial blood gas
  • FBC
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9
Q

Why investigate serum paracetamol concentration? And what may this show?

A
  • Use serum paracetamol concentration to risk-stratify the likelihood of liver injury and to determine whether treatment with acetylcysteine is needed
  • May be positive
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10
Q

Why investigate LFTs? And what may this show?

A
  • Suspect acute liver injury if alanine aminotransferase (ALT) is above the upper limit of normal
  • May be elevated
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11
Q

Why investigate prothrombin time and INR? And what may this show?

A
  • May indicate acute liver injury as prothrombin is produced by the liver
  • Prothrombin time may be prolonged; INR may be increased
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12
Q

Why investigate blood glucose? And what may this show?

A
  • If hypoglycaemia is present as this may indicate acute liver injury
  • <3.3 mmol/L
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13
Q

Why investigate urea, creatinine and electrolytes? And what may this show?

A
  • Creatinine will be raised in acute kidney injury, this may occur as part of acute liver injury (hepatorenal syndrome)
  • Creatinine may be acutely elevated
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14
Q

Why investigate venous or arterial blood gas? And what may this show?

A
  • A blood gas may show lactic acidosis in 2 scenarios:
    • Early- lactic acidosis is commonly severe and associated with coma, most patients do not develop liver damage if treated with acetylcysteine
    • Late- elevated lactate in these patients strongly predicts high mortality
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15
Q

Why investigate FBC? And what may this show?

A
  • This may show leukocytosis, anaemia, or thrombocytopenia
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16
Q

What signs would warrant discussion of the patient urgently with a senior following a paracetamol overdose?

A
  • Clinical signs of liver injury
  • Significant acute kidney injury
  • Arterial pH <7.3
  • Hypoglycaemia
  • International normalised ratio (INR) >1.3 or prothrombin time >30 seconds
  • Serum lactate >3.5 mmol/L on admission OR >3.0 mmol/L post-paracetamol ingestion or after fluid resuscitation
17
Q

What treatment can be given if the patient presents within 1 hour of paracetamol ingestion and has ingested more than 150 mg/kg of paracetamol?

A

Activated charcoal

18
Q

What treatment is given in paracetamol overdose?

A

Acetylcysteine

19
Q

Briefly describe the mechanism of action of acetylcysteine

A

Liver damage is minimised with acetylcysteine

Acetylcysteine restores levels of glutathione, which detoxifies the hepatotoxic metabolite of paracetamol N-acetyl-p-benzoquinone imine (NAPQI)

20
Q

What database can be used to guide treatment in paracetamol overdose?

A

National Poisons Information Service (NPIS)

21
Q

What complications are associated with paracetamol overdose?

A
  • Oral acetylcysteine-related nausea and vomiting
  • IV acetylcysteine-related coagulopathy
  • IV acetylcysteine-related anaphylactoid reaction
22
Q

What differentials should be considered for paracetamol overdose?

A
  1. Ischemic hepatitis
  2. Acute hepatitis A
  3. Acute hepatitis B
  4. Other hepatotoxins
23
Q

How does paracetamol overdose and ischemic hepatits differ?

A
  • Differentiating signs and symptoms: ischaemic hepatitis occurs in the setting of sustained hypotension or low-flow state in the liver, which is unusual in paracetamol overdose
  • Differentiating investigations: serum paracetamol level will be negative
24
Q

How does paracetamol overdose and acute hepatitis A differ?

A
  • Differentiating signs and symptoms: there may be a history of travel to an endemic region, foodborne outbreak, close contact with an infected person, or men who have sex with men
  • Differentiating investigations: hepatitis A IgM positive
25
Q

How does paracetamol overdose and acute hepatitis B differ?

A
  • Differentiating signs and symptoms: there may be a history of travel to an endemic region, intravenous drug use, contact with an infected person, or men who have sex with men
  • Differentiating investigations: hepatitis B core antigen positive
26
Q

Give examples of other heptotoxins

A
  • Mushrooms (e.g., Amanita phalloides)
  • Herbal preparations (e.g., cascara, chaparral, comfrey, kava, ma-huang)
  • Anaesthetic agents (e.g., halothane)
  • Industrial chemicals (e.g., carbon tetrachloride, trichloroethylene, paraquat)
  • ACE inhibitors
  • Anabolic steroids
  • Aspirin
  • Calcium-channel blockers
  • Ibuprofen
  • Ioniazid
  • Methotrexate
  • Naproxen
  • Phenytoin
  • Statins