Paracetamol / Acetaminophen Poisoning – At A Glance

Paracetamol poisoning is a commonly encountered case in Toxicology.

Toxic dose of PCM – More than 150 mg/kg

Usually 24 tablets are considered to be toxic for a healthy individual. 

Incidence – 150 to 200 deaths and 15 to 20 liver transplants each year in UK  

Pathophysiology Of PCM Poisoning

Intake of PCM in large doses

Metabolized into NAQI by the liver
(NAPQI – N-acetyl-p-benzoquinone imine)
NAPQI is a toxic metabolite
Normally, NAPQI is conjugated by glutathione into a non toxic metabolite
But there are not enough glutathione reserves to completely inactivate these toxic NAPQI
NAPQI accumulate in the liver and react with P450
Leading to hepatic damage

Patients At High Risk Of Developing Hepatotoxicity

  • Chronic alcoholics
  • CLCD
  • Patients on cytochrome p450 inducers
    • Rifampicin
    • Phenytoin
    • Carbamazepine
  • Anorexia nervosa
    • Reduced glutathione stores
  • HIV

Clinical Features Of PCM Toxicity

There are four stages of PCM toxicity

  • Stage I 
    • Within 24 hours of ingestion 
    • Nausea, vomiting
    • Pallor
    • LFTs are normal
  • Stage II 
    • After 24 hours of ingestion 
    • Tenderness at right hypochondriac region 
    • Hepatic enzymes starts to rise
  • Stage III
    • After 48 hours of ingestion 
    • Jaundice
    • Tender hepatomegaly
    • After 72 hours 
      • Coagulopathy 
      • Acute hepatic failure
      • Hepatic encephalopathy
      • Multi-organ failure
    • AST peaks at 72 hours 
    • Prolong prothrombin time
    • Acidosis
  • Stage IV
    • After 5 days of ingestion
    • Recovery
    • Normalizing LFTs 

PCM Poisoning Management Protocol (UK Guidelines)
 Management Of PCM Poisoning

Download the above figure from here
Staggered ingestion means intake of PCM at separate intervals
Antidote is N-acetyl cysteine (NAC)
Methionine is an alternative to NAC

Dosage of NAC

  • 150 mg/kg of NAC + 200 ml of 5% dextrose, IV infusion over 15 mins  
  • 50 mg/kg of NAC + 500 ml of 5% dextrose, IV infusion over 4 hours
  • 100 mg/kg of NAC + 1000 ml of 5% dextrose, IV infusion over 16 hours

Side effects of NAC

  • Flushing
  • Hypotension
  • Wheezing
  • Anaphylactoid reaction 

Haemodialysis and haemoperfusion has a role in extreme PCM levels
Liver transplantation should be done in case of fulminant hepatitis

Criteria For Liver Transplantation

  • Arterial pH is less than 7.3 after 24 hrs of ingestion OR
  • Should present all of the following
    • Prothrombin time more than 100s
    • Serum creatinine is more than 300μmol/L
    • Grade III or grade IV hepatic encephalopathy
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