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Colchicine overdose

Toxicity:

general features:

  • death from as little as 7mg, survival with ingestions as large as 350mg
  • survival usual with doses < 0.5mg/kg (ie. low therapeutic index!!)
  • death almost certain with doses > 0.8mg/kg

organ toxicity:

  • within hours:
    • GIT toxicity:
      • ⇒ nausea, vomiting & profuse watery diarrhoea +/- bloody diarrhoea
      • ⇒ burning throat pain
      • ⇒ ileus
    • other organ toxicity as below may occur
  • 24-48hrs:
    • cardiovascular collapse:
      • fluid loss - diarrhoea, third space
      • electrolyte, acid-base derangements
      • endotoxaemia from GIT mucosal dysfunction
      • direct cardiac toxicity:
        • impaired sarcoplasmic reticular function
        • decreased calcium myofilament sensitivity
        • altered cross-bridge kinetics
        • myothermal economy
        • cardiac conduction abnormalities:
          • bradycardia
          • varying degrees of AV block
          • sinus arrest
        • elevated cardiac enzymes in severe cases
    • renal dysfunction:
      • haematuria is almost invariable +/- oliguria, resulting from:
        • hypotension
        • sepsis
        • myoglobinuria
        • direct nephrotoxicity
    • respiratory failure (30% pts, & may occur suddenly) which may be due to:
      • aspiration
      • cardiac failure
      • massive transfusion
      • direct pulmonary vascular injury
      • resp. muscle weakness
    • metabolic disturbances:
    • neuromuscular:
      • muscle weakness
      • depressed tendon reflexes
      • papilloedema, transverse myelitis, ascending paralysis, altered mental state (incl. coma)
  • several days - 1 week:
    • bone marrow failure - the major cause of late fatalities
    • alopecia (mat persist for several months)

management of poisoning:

  • ABC's
  • IV line, fluids to prevent hypovolaemia
  • bloods taken for: FBE, clotting, U&Es, LFTs (repeat all at 6hrs)
  • bloods for se paracetamol level if co-ingestion possible (otherwise urinary drug screen)
  • activated charcoal if no ileus
  • if presentation within 1hr with substantial ingestion or symptomatic
    • ⇒ consider gastric lavage
    • ⇒ repeat activated charcoal 4hrly if no ileus in view of enterohepatic circulation
    • ⇒ consider early central/arterial lines to assist monitoring of BP, CVP
  • supportive care as indicated
  • Rx haematologic toxicity as indicated:
  • Rx consumptive coagulopathy with:
    • blood component replacement
    • consider:
      • DDAVP to improve platelet release reaction
      • aminocaproic acid as an antifibrinolytic
    • Rx bone marrow hypoplasia:
      • G-CSF
    • take precautions to minimise infection risk
  • theoretically, Fab fragments specific for colchicine may be of help but are still not available, & the French researchers who developed it have recently abandoned plans to make them commercially available
  • NOT USEFUL:
    • forced urine alkaline diuresis
    • haemodialysis/heamoperfusion

disposition:

  • adults asymptomatic (ie. no GIT toxicity) for 8hrs post-ingestion & normal repeat laboratory tests at 6hrs, can be medically cleared, otherwise admit +/- ICU

References:

  • Harris RD Gillett MJ Colchicine poisoning - overview & new directions Emergency Medicine June 1998 10(2):161-7
odcolchicine.txt · Last modified: 2008/09/30 11:10 by 127.0.0.1

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