Clonidine and Other Sympatholytics
GENERAL PRINCIPLES
• Clonidine belongs to the imidazoline class; these medications are also referred to as sympatholytics.
• Other commonly encountered members of this class include guanfacine, dexmedetomidine, tizanidine, and the topical nasal and ocular imidazolines (tetrahydrozoline, oxymetazoline, naphazoline, and brimonidine).
Pathophysiology
• Sympatholytics are centrally acting alpha-2 adrenergic agonists; they have a negative feedback effect
on catecholamine release and thus decrease heart rate, blood pressure, and CNS excitation.
• Sympatholytics also interact with the less-understood imidazoline (I) receptor system; this system also has CNS depressant and antihypertensive actions.
• When used as intended, the topical nasal and ocular imidazolines act primarily as alpha-1 adrenergic agonists, and thus induce local vasoconstriction.
In large overdose or when consumed by mouth, these agents act primarily as alpha-2 adrenergic agonists.
• Early in the course of sympatholytic poisoning, off-target effects on alpha-1 adrenoceptors may lead to peripheral vasoconstriction and transient hypertension.
DIAGNOSIS
Clinical Presentation
• Patients with sympatholytic poisoning present with bradycardia, normal or depressed blood pressure, miosis, and significantly depressed mental status.
° Mental status changes in sympatholytic poisoning are usually characterized by preserved response to physical stimulus and a waxing and waning course.
î In severe poisoning, mental status depression may be profound enough to impair respiration, producing apnea or ineffective respirations.
• Onset of toxicity and recovery are typically quite rapid.
Differential Diagnosis
• In patients with bradycardia and hypotension, consider BB/CCA poisoning, digoxin/cardioactive steroid poisoning, myxedema coma, hypothermia, high-grade heart block with cardiogenic shock, and shock with profound acidosis or hyperkalemia.
• In patients with profound mental status depression, ineffective respirations, and miosis, consider opioid poisoning.
Diagnostic Testing
LABORATORIES
Routine laboratory testing is not usually helpful.
ELECTROCARDIOGRAPHY
ECG will usually show sinus bradycardia.
TREATMENT
• In general, sympatholytic poisoning does not require treatment.
î While striking, the bradycardia does not typically lead to profound hypotension or end-organ malperfusion.
° The duration of sympatholytic poisoning is typically very short.
• Atropine will likely be effective in increasing the heart rate but is rarely truly indicated.
• In very severe cases, when effective respiration is impaired, intubation and mechanical ventilation may be necessary.
• Significant hypotension is unusual but will respond to low-dose norepinephrine.
• For patients with profound mental status changes, apnea, or hypotension, for whom critical care interventions such as intubation or vasopressors are being discussed, consider a trial of high-dose naloxone. 22
î A single dose of naloxone 10 mg IV may reverse sympatholytic poisoning.
#9632; Repeated bolus doses or an infusion may be necessary due to the relatively short duration of action of intravenous naloxone.
î Avoid high-dose naloxone in opioid-tolerant patients, in whom it may precipitate opioid withdrawal.
SPECIAL CONSIDERATIONS: SYMPATHOLYTIC WITHDRAWAL
• Patients who are chronically exposed to sympatholytics are at risk for withdrawal if sympatholytics are stopped abruptly.
î The withdrawal syndrome consists of tachycardia, severe hypertension, and anxiety and agitation.
î The profound “rebound hypertension” seen when patients miss a clonidine dose may represent early sympatholytic withdrawal.
î Treat withdrawal by reinstituting sympatholytics and tapering them off gradually.
• Patients on dexmedetomidine infusions for sedation in the intensive care unit may develop sympatholytic dependence in as little as 72-96 hours.
î Clonidine tapers may be helpful in preventing withdrawal when dexmedetomidine is discontinued.