Paracetamol Overdose Flashcards
What is the recommended therapeutic dose of paracetamol for an adult?
24 hours is 4 g
What is another name for paracetamol commonly used in other countries?
Acetaminophen
The National Poisons Information Service (NPIS) in the UK defines different types of paracetamol overdose (acute, staggered and therapeutic)
Briefly describe each one
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
Briefly describe the pathophysiology of paracetamol overdose
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.
What are the risk factors for paracetamol overdose?
- 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)
What are the signs of paracetamol overdose?
Examination can be normal unless signs of acute liver failure are present
- Jaundice
- Tender hepatomegaly
- Altered conscious level (hepatic encephalopathy)
- Asterixis
What are the symptoms of paracetamol overdose?
- Nausea and vomiting
- RUQ abdominal pain
What investigations should be ordered for paracetamol overdose?
- Serum paracetamol concentration
- LFTs
- Prothrombin time and INR
- Blood glucose
- Urea, creatinine and electrolytes
- Venous or arterial blood gas
- FBC
Why investigate serum paracetamol concentration? And what may this show?
- Use serum paracetamol concentration to risk-stratify the likelihood of liver injury and to determine whether treatment with acetylcysteine is needed
- May be positive
Why investigate LFTs? And what may this show?
- Suspect acute liver injury if alanine aminotransferase (ALT) is above the upper limit of normal
- May be elevated
Why investigate prothrombin time and INR? And what may this show?
- May indicate acute liver injury as prothrombin is produced by the liver
- Prothrombin time may be prolonged; INR may be increased
Why investigate blood glucose? And what may this show?
- If hypoglycaemia is present as this may indicate acute liver injury
- <3.3 mmol/L
Why investigate urea, creatinine and electrolytes? And what may this show?
- Creatinine will be raised in acute kidney injury, this may occur as part of acute liver injury (hepatorenal syndrome)
- Creatinine may be acutely elevated
Why investigate venous or arterial blood gas? And what may this show?
- 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
Why investigate FBC? And what may this show?
- This may show leukocytosis, anaemia, or thrombocytopenia
What signs would warrant discussion of the patient urgently with a senior following a paracetamol overdose?
- 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
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?
Activated charcoal
What treatment is given in paracetamol overdose?
Acetylcysteine
Briefly describe the mechanism of action of acetylcysteine
Liver damage is minimised with acetylcysteine
Acetylcysteine restores levels of glutathione, which detoxifies the hepatotoxic metabolite of paracetamol N-acetyl-p-benzoquinone imine (NAPQI)
What database can be used to guide treatment in paracetamol overdose?
National Poisons Information Service (NPIS)
What complications are associated with paracetamol overdose?
- Oral acetylcysteine-related nausea and vomiting
- IV acetylcysteine-related coagulopathy
- IV acetylcysteine-related anaphylactoid reaction
What differentials should be considered for paracetamol overdose?
- Ischemic hepatitis
- Acute hepatitis A
- Acute hepatitis B
- Other hepatotoxins
How does paracetamol overdose and ischemic hepatits differ?
- 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
How does paracetamol overdose and acute hepatitis A differ?
- 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
How does paracetamol overdose and acute hepatitis B differ?
- 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
Give examples of other heptotoxins
- 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
