Clonidine toxicity

Clonidine has a vast array of uses including anxiety, ADHD, hypertension, withdrawal (opitates, alcohol and smoking), migraines, menopausal flushing, diarrhoea and finally pain. It causes the classic triad of drowsiness, miosis and bradycardia in overdose.

Toxic Mechanism:

Centrally acting alpha 2 adrenergic agonist. It act as a sympathoplegic agent and also increases endothelial nitric oxide levels and decreases renin activity.

Toxicokinetics: 

• Rapid absorption
• Peak serum concentration 1 – 3 hours
• Large volume of distribution 3 – 6 L/kg
• Metabolised by the live and exerted by the urine (although 50% is excreted unchanged)
• Half life 6 – 24 hours

Resuscitation:

• CNS depression: Intubation and ventilation is usually only required in large overdoses.
•  Hypotension:
  • 20ml/kg crystalloid bolus
• Bradycardia:
  • Is usually well tolerated and adjunctive therapy should only be considered if the patient is symptomatic with hypotension
  • Atropine 0.01 – 0.03 mg/kg IV (usually 600 microgram boluses to a maximum of 1.8 mg)
  • Isoprenaline 1 – 10 micrograms/min IV infusion (0.05-1.0 microgram/kg/min in children)
  • Adrenaline infusion: 0.15mg/kg in 50ml D5W at 1-10ml/hr (0.05 – 0.5 mcg/kg/min)

Risk Assessment

• Clinical effects are not entirely dose related. As little as 20 micrograms/kg can cause significant CNS depression in some while higher doses are tolerated well in others.
• Onset of symptoms is usually within 2 hours and definitely by 6.
• The onset of toxicity can be rapid
• Children: 2 tablets is potentially lethal
  • >10 micrograms/kg: bradycardia and hypotension
  • >20 micrograms/kg: respiratory depression and apnoea
• Clinical effects:
  • Lethargy, miosis, slurred speech and ataxia.
  • Classically the patient will be deep asleep but can be roused, only to quickly fall back to sleep again
  • HR as low as 30 can be common
  • Hypotension is less common
  • Respiratory depression and apnoea are rare
  • Symptoms usually resolve within 24 hours

Supportive Care

• Hypotension normally responds to IV fluids
• If intubated see FASTHUGSINBED for further supportive care.

Investigations

• Screening: 12 lead ECG, BSL, Paracetamol level
• Specific:
  • Serial ECGs

Decontamination:

• Contraindicated due to the risk of CNS depression

Enhanced Elimination

• Not clinical useful

Antidote

• Naloxone – gives transient improvement in GCS and respiratory rate, however if it is required intubation is recommended as this is more reliable than repeated doses of naloxone.

Disposition

• Patients who are asymptomatic and have a normal ECG at 6 hours are medically cleared (not for discharge at night)
• Patients with significant features of toxicity and CNS depression require HDU/ICU level care

References and Additional Resources

Additional Resources:

• CCC – Sedative toxidrome
• CCC – Sympatholytic toxidrome
• Tox conundrum 041 – A Toxic Slumber

References:

• Erickson SJ, Duncan A. Clonidine poisoning-an emerging problem: epidemiology, clinical features, management and preventative strategies. Journal of Paediatrics & Child Health 1998; 34(3):280-282.
• Fiser DH, Moss MM, Walker W. Critical care for clonidine poisoning in toddlers. Critical Care Medicine 1990; 18(10):1124-1128.
• Murray L et al. Toxicology Handbook 3rd Edition. Elsevier Australia 2015. ISBN 9780729542241
• Seger DL. Clonidine toxicity revisited. Journal of Toxicology Clinical Toxicology 2002; 40:145-155.