Clonidine Overdose Presentation
Clonidine overdose classically presents with CNS depression, bradycardia, hypotension, and miosis—a constellation that can mimic opioid toxicity but with the key distinguishing feature of profound cardiovascular depression. 1
Primary Clinical Features
The typical presentation develops within 30 minutes to 2 hours after exposure and includes: 1
- CNS depression: Ranging from drowsiness and sedation to coma, with decreased or absent reflexes 1, 2
- Bradycardia: Heart rates as low as 30-40 beats/min have been documented 3
- Hypotension: Follows the initial presentation in most cases 1, 2
- Miosis: Pinpoint pupils that mimic opioid overdose 2, 4
- Respiratory depression: Can progress to apnea in severe cases 1, 5
Biphasic Cardiovascular Response
A critical pitfall is the biphasic blood pressure response that occurs with larger overdoses: 1, 6
- Initial hypertension: At doses >7 mg/day, clonidine's peripheral alpha-1 and alpha-2 adrenergic receptor stimulation causes vasoconstriction and paradoxical hypertension 6
- Subsequent hypotension: As central alpha-2 agonist effects predominate, blood pressure drops, often accompanied by bradycardia 1, 4
- Hypertensive crisis: Massive overdoses (e.g., 12.24 mg subcutaneously) can produce sustained hypertensive emergency with associated complications including myocardial infarction 6
This biphasic pattern is dose-dependent and distinguishes clonidine from pure opioid toxicity. 4
Additional Clinical Manifestations
Beyond the classic triad, patients may exhibit: 1, 3
- Hypothermia 1
- Weakness and hypotonia 1, 3
- Irritability (particularly in children) 1
- Seizures: Reported with large overdoses, including tonic-clonic activity 1, 6
- Cardiac conduction defects: Reversible dysrhythmias and premature ventricular contractions 1
- Hallucinations: Documented in massive ingestions 1
Pediatric Considerations
Children are exceptionally sensitive to clonidine toxicity—as little as 0.1 mg has produced signs of toxicity in pediatric patients. 1 The frequency of CNS depression is higher in children than adults, making this population particularly vulnerable. 1, 5 Compounding pharmacy errors have resulted in concentrations up to eight times higher than labeled, leading to severe toxicity even with "prescribed" doses. 3
Distinguishing from Opioid Overdose
While clonidine overdose mimics opioid toxicity with the triad of CNS depression, respiratory depression, and miosis, key differentiating features include: 2, 4
- Prominent bradycardia and hypotension: More severe cardiovascular depression than typical opioid overdose 3, 2
- Possible initial hypertension: Not seen with opioids 6, 4
- Incomplete response to naloxone: While naloxone may help with respiratory depression and CNS depression, it does not fully reverse clonidine toxicity and can paradoxically worsen hypertension 1, 2
Dose-Response Relationship
The clinical presentation correlates with dose: 1, 6
- Therapeutic doses (0.2-2 mg/day): Central hypotensive effects predominate 6
- Moderate overdose: Classic presentation with sedation, bradycardia, hypotension 2, 4
- Massive overdose (>7 mg): Peripheral alpha-adrenergic effects cause initial hypertension, followed by severe CNS and cardiovascular depression 1, 6
The largest reported overdose involved 100 mg, resulting in hypertension followed by hypotension, bradycardia, apnea, hallucinations, semicoma, and premature ventricular contractions, with plasma levels reaching 370 ng/mL. 1
Common Pitfalls
- Assuming opioid overdose: The miosis and CNS depression can lead to misdiagnosis; always consider clonidine in patients with profound bradycardia and hypotension alongside these features 3, 2
- Aggressive naloxone administration: While naloxone may be useful for respiratory depression, it can cause paradoxical hypertension and should be used cautiously with blood pressure monitoring 1, 2
- Missing compounding errors: Always investigate medication sources when presentation is inconsistent with reported dosing 3
- Treating initial hypertension aggressively: The hypertension may be transient and followed by profound hypotension; overly aggressive treatment can worsen subsequent hypotensive phase 6, 4