Clonidine Toxicity

Clonidine is a centrally acting alpha-2 adrenergic agonist used for hypertension, attention deficit disorder, opioid withdrawal and tic disorders. Related imidazolines (oxymetazoline, tetrahydrozoline, naphazoline, found in nasal and eye drops) and guanfacine and dexmedetomidine produce similar toxicity. Stimulation of central alpha-2 receptors reduces sympathetic outflow, causing bradycardia, hypotension, sedation and respiratory depression. Peripheral alpha-2 stimulation causes transient hypertension early after ingestion.

A single tablet (0.1 to 0.3 mg) can cause toxicity in a toddler, and ingestion of over 0.01 mg/kg is significant. The effects begin within 30 to 90 minutes and last 12 to 36 hours (up to 72 hours with transdermal patches and extended-release products). Complications: apnea, hypothermia, severe bradycardia, hypotension, seizures and, in a child, prolonged coma with a presentation that mimics opioid poisoning.

• Drowsiness progressing to coma, hypotonia, small pupils (miosis) and respiratory depression or apnea
• Bradycardia, sinoatrial and atrioventricular block, hypotension (sometimes initial hypertension)
• Hypothermia, pallor, dry mouth, hyporeflexia
• Seizures (uncommon) and irritability on waking
• Rebound hypertension and agitation after abrupt withdrawal
• Red flags: apnea, heart rate under 50 beats a minute, systolic pressure under 80 mmHg, and any ingestion of a transdermal patch

1. Clinical diagnosis: the opioid-like picture (miosis, coma, respiratory depression) with bradycardia and hypotension that does not fully respond to naloxone.
2. 12-lead ECG and continuous monitoring (at least 6 hours, up to 24 hours for extended-release products and patches).
3. Glucose, electrolytes, creatinine, blood gases.
4. Paracetamol and salicylate levels, and toxicology screen for opioids and other sedatives.
5. Examination of the skin for transdermal patches.

Differentials: opioid poisoning, organophosphate poisoning, beta blocker and calcium channel blocker overdose, sedative-hypnotic overdose, brainstem lesion, hypothyroid crisis.

1. Airway, breathing and circulation: intubate and ventilate for apnea or depressed consciousness, and warm for hypothermia.
2. Remove patches and wash the skin.
3. Decontamination: activated charcoal 50 g orally (children 1 g/kg, maximum 50 g) within 1 hour if the patient is alert with a protected airway.
4. Bradycardia with hypotension: atropine 0.5 to 1 mg IV every 3 to 5 minutes up to 3 mg (children 20 micrograms/kg, minimum 0.1 mg, maximum 1 mg).
5. Hypotension: IV crystalloid 10 to 20 mL/kg, then norepinephrine 0.05 to 0.5 micrograms/kg/min or dopamine 5 to 20 micrograms/kg/min. Avoid vasodilators.
6. Naloxone: 0.4 to 2 mg IV (children 0.1 mg/kg, maximum 2 mg), repeated up to 10 mg total. Response is unpredictable, and a lack of response does not exclude clonidine.
7. Seizures: lorazepam 4 mg IV (children 0.1 mg/kg).
8. Hypertension (transient, early): usually requires no treatment. If severe, use phentolamine 1 to 5 mg IV (children 0.05 to 0.1 mg/kg).
9. Withdrawal rebound hypertension: restart clonidine (0.1 mg orally twice daily and taper over 1 to 2 weeks) or give phentolamine 1 to 5 mg IV or labetalol 20 mg IV bolus then 40 to 80 mg every 10 minutes. Avoid beta blockers alone, which worsen hypertension from unopposed alpha stimulation.
10. Haemodialysis is ineffective.

Observation for at least 6 hours in asymptomatic children (24 hours for patches and extended-release tablets), with fall precautions. Counsel on child-resistant storage and gradual withdrawal over 2 to 4 days.