Colchicine toxicity

Colchicine toxicity is rare but any intention overdose with colchicine is potentially lethal. Although resuscitation is a priority as with all toxicities, colchicine requires urgent decontamination due to the limited therapies we have once toxic serum levels develop.

Toxic Mechanism:

Colchicine is used to treat gout, Mediterranean fever and pericarditis. It is a natural alkaloid (found in autumn crocus) and it binds tubulin, preventing microtubule formation thus inhibiting mitosis. Therefore any tissues with a high cellular turnover are affected (Gastrointestinal tract, bone marrow).

Toxicokinetics: 

• Rapid absorption
• Peak levels within 30-120 minutes
• It has an extensive first pass metabolism hence 45% bioavailability
• Extensively tissue bound with a volume of distribution 2L/kg
• Elimination is via hepatic mechanisms
• Elimination half life, up to 30 hours in overdose

Resuscitation:

• Hypovolaemic shock: Secondary to massive GI fluid loss. Patients will require large volumes of crystalloid and potentially vasopressors. Noradrenaline dose: 0.15mg/kg in 50ml D5W at 1-10ml/hr (0.05 – 0.5 mcg/kg/min)
• Respiratory insufficiency or cardia arrest: Both should be anticipated in the severely unwell colchicine patient with a low threshold for intubation and ventilation. If there is a compensatory respiratory alkalosis then pre-intubation  bolus of sodium bicarbonate 1-2 mmol/kg followed by hyperventilation and further boluses of sodium bicarbonate to prevent cardiovascular collapse is best practice.
• Activated Charcoal: Administer 50 g (1 g/kg in children) as soon as possible in any patient who has ingested > 0.5 mg/kg of colchicine as any reduction in absorption maybe lifesaving.

Risk Assessment

• Dose related risk:
  • <0.5 mg/kg            Gastrointestinal symptoms
  • 0.5 – 0.8 mg/kg     Systemic toxicity (10% mortality)
  • >0.8 mg/kg            Cardiovascular collapse, coagulopathy, acute renal failure (close to 100% mortality)
• Clinical progression:
  • 2 – 24 hours: GI (nausea, vomiting, diarrhoea), severe fluid loss resulting in hypotension. Peripheral leucocytosis seen on blood film.
  • 2 – 7 days: Bone marrow suppression and pancytopenia, rhabdomyolysis, renal failure, metabolic acidosis, respiratory failure, ARDS, cardiac dysrhythmias.
  • > 7 days: Rebound leucocytosis and transient alopecia. Complete recovery is expected if the patient survives to this stage.
• Children: One or two tablets are not problematic. Any child who has a large ingestion or develops GI symptoms needs evaluation.

Supportive Care

• General supportive measures
• Meticulous fluid balance monitoring
• Correction of electrolyte and acid-base status
• Treat infectious complications
• Severe toxicity will require invasive monitoring

Investigations

• Screening: 12 lead ECG, BSL, Paracetamol level
• Specific:
  • Colchicine levels are not routinely available
  • Will needs baseline bloods (EUC, LFTs, FBC, VBG/ABG, Lactate, Coagulation) to monitor for end organ damage
  • CXR/USS to help assess fluid status or the development of ARDS.

Decontamination:

• Administer activated charcoal 50 g (1 g/kg in children) as soon as possible in any patient who has ingested > 0.5 mg/kg of colchicine as any reduction in absorption maybe lifesaving.

Enhanced Elimination

• Multiple-dose activated charcoal in theory may enhance elimination but it is difficult in the vomiting patient and it has not been shown to affect outcome.

Antidote

• Not currently available (although colchicine-specific antibodies do exist)

Disposition

• All adults of deliberate self poisoning are admitted for observation
• If there are no gastrointestinal symptoms by 24 hours the patients can be medically cleared.
• Anyone with significant toxicity requires intensive care monitoring

References and Additional Resources:

Additional Resources:

• Tox Conundrum – Colchicine
• CCC – Plant toxicity

References:

• Harris R, Gillet M. Colchicine poisoning – overview and new directions. Emergency Medicine 1998; 10:161-167
• Jayaprakash V, Ansell G, Galler D. Colchicine overdose: the devil is in the detail. New Zealand Medical Journal 2007; 120(1248):81-88
• Murray L et al. Toxicology Handbook 3rd Edition. Elsevier Australia 2015. ISBN 9780729542241