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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