DESCRIPTION

Clonidine, an alpha-₂-receptor agonist, is available as Catapres (0.1-, 0.2-, and 0.3-mg tablets); Catapres-TTS (2.5-, 5.0-, and 7.5-mg transdermal patches); and Combipres (0.1-, 0.2-, and 0.3-mg tablets).

FORMS AND USES

• Hypertension. 0.1 mg by mouth twice a day to a maximum of 2.4 mg/day; clonidine transdermal 1 patch/wk; 0.1 to 0.3 mg/day.
• Opiate and nicotine withdrawal. As much as 25 µg/kg/day in divided doses.
• Also used for prophylaxis of migraine headache, and the flushing associated with menopause and dysmenorrhea.

TOXIC DOSE

• Adults have survived doses greater than 10 mg.
• Children have become symptomatic after ingestion of 1 tablet (0.1 mg) clonidine.
• Deaths have been reported from children sucking on discarded clonidine patches.

PATHOPHYSIOLOGY

• Clonidine is an alpha-₂-receptor agonist that inhibits sympathetic outflow by presynaptic alpha-₂ stimulation in the brainstem and medulla; it causes peripheral alpha-receptor stimulation as well.
• The precise mechanisms of action or toxicity are unknown.

EPIDEMIOLOGY

• Poisoning is uncommon.
• Toxic effects following exposure are typically mild to moderate, with death occurring in cases of large overdose where medical intervention is not immediately available.

CAUSES

• Toxic ingestion is usually intentional.
• Child neglect or abuse should be considered if the patient is less than 1 year of age, suicide attempt if the patient is over 6 years of age.

DRUG AND DISEASE INTERACTIONS

Sedating agents may enhance CNS depression caused by clonidine; other antihypertensive agents may increase the hypotensive effect.

PREGNANCY AND LACTATION

• US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.
• Clonidine is secreted in breast milk in clinically significant amounts.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

DIFFERENTIAL DIAGNOSIS

• Toxicologic causes of CNS depression include anticonvulsants, alcohols, benzodiazepines, barbiturates, narcotics, other imidazolines, gamma-hydroxybutrate and many others.
• Nontoxicologic causes of CNS depression include metabolic changes such as hypoglycemia, hyponatremia, hypoxia, hypothermia, hypothyroidism, and postictal states; infectious causes such as meningitis or sepsis; space-occupying lesions; trauma; and tumors.

SIGNS AND SYMPTOMS

Sedation, apnea, hypotension, bradycardia, and miosis are characteristic. The toxic effects of clonidine are often mistaken for a narcotic overdose.

Vital Signs

• Initial transient hypertension (usually occurs before reaching health care) can be followed by hypotension, bradycardia, hypothermia, and hypoventilation.
• Apnea may develop; patients will respond to stimulation (such as stroking foot) by resuming normal breathing pattern but revert to hypoventilation or even apnea when not touched or otherwise stimulated.

HEENT

Miosis and dry mucous membranes are characteristic.

Dermatologic

Pallor is common.

Cardiovascular

• Bradycardia is common; atrioventricular nodal blocks occur rarely.
• Cardiac ischemia may develop in hypotensive patients.

Pulmonary

Respiratory depression may progress to apnea.

Neurologic

• CNS depression ranges from lethargy to coma; ataxia, hyporeflexia, and hypotonia may occur.
• Seizures occur rarely.

Endocrine

Weight gain, gynecomastia, and interference with the renin-angiotensin-aldosterone system are infrequent physiologic effects.

PROCEDURES AND LABORATORY TESTS

Essential Tests

No tests are usually needed in asymptomatic patients

Recommended Tests

• ECG and cardiac monitoring should be performed to assess bradycardia and atrioventricular nodal blocks. Cardiac ischemia may develop in hypotensive patients.
• Serum electrolytes, BUN, and creatinine are assayed to assess electrolyte causes of altered mental status or hypotension.
• Arterial blood gas or pulse oximetry is performed for assessment of altered mental status.
• Head CT, lumbar puncture, bacterial cultures are obtained to assess altered mental status.
• Serum acetaminophen and aspirin levels are determined in an overdose setting to assess occult ingestion.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Neurologic
  • Endocrine
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• Treatment should focus on airway management and general supportive care.
• The dose and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care professional should call the poison control center when:

• Hypotension or altered mental status develops.
• Toxic effects are not consistent with clonidine.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

The patient should be referred to a health-care facility when:

• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Toxic effects develop.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient management is warranted for:

• Small children with a history of clonidine ingestion
• Adults who develop toxic effects

DECONTAMINATION

Out of Hospital

Emesis should not be induced because CNS depression may develop quickly.

In Hospital

• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients for large ingestion presenting within 1 hour of ingestion or if serious effects are present.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.
• In cases of suspected ingestion of clonidine patches, whole-bowel irrigation is recommended.

ANTIDOTES

• There is no specific antidote for clonidine poisoning.
• Naloxone is typically used to treat patients with depressed mental status of unknown etiology; however, its role in clonidine overdose is unclear (some studies suggest efficacy in reversing opioid-like effects and cardiovascular depression, but it is likely that body stimulation is responsible).
  • Patients with coma and respiratory depression are treated with 2 mg intravenously initially and observed for clinical improvement.
  • Dose may be doubled to 4 mg intravenously; if no improvement is seen, more naloxone is unlikely to have an effect

ADJUNCTIVE TREATMENT

• Hypotension. The patient should be treated with isotonic fluid infusion, the Trendelenburg position, and, if needed, vasopressors. Dopamine is preferred, and norepinephrine is added for refractory hypotension.
• Hypertension. If end-organ damage develops (rare), treatment with a titratable antihypertensive such as nitroprusside should be initiated.
• Bradycardia should be treated initially according to Advanced Cardiac Life Support guidelines; but if bradycardia persists, cardiac pacing could be effective.
• Hemodialysis, multiple-dose activated charcoal, and urinary alkalinization have not been demonstrated to be effective.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT

PATIENT MONITORING

Respiratory function and cardiac rhythm should be monitored continuously.

EXPECTED COURSE AND PROGNOSIS

• Toxic effects typically peak soon after ingestion of tablets, but may be delayed after ingestion of a patch.
• Complete recovery occurs if adequate airway management is maintained.
• Bradycardia, hypotension, and apnea may persist for more than 24 hours following severe overdose.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Asymptomatic patients may be discharged following cardiac monitoring during a minimum 4- to 6-hour observation period and after psychiatric evaluation, if needed.
• From the hospital. Patients may be discharged when CNS, respiratory, and cardiovascular effects have resolved or stabilized, and after psychiatric evaluation, if needed.

PATIENT EDUCATION

• Adults should be instructed to keep clonidine pills and patches out of reach of children.
• Clonidine patches should be disposed of in childproof containers; when discarded, patches may contain up to 75% of their original content.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS
• PATIENT EDUCATION

The toxic effects of clonidine are often mistaken for a narcotic overdose.

TREATMENT

• Treatment of the initial transient hypertensive event with a long-acting antihypertensive may complicate management of subsequent clonidine-induced hypotension.
• Sequelae of hypoxia may occur if airway control is not achieved early.

Poisoning by agents primarily affecting the cardiovascular system: other antihypertensive agents.

See Also: SECTION II, Hypertension and Hypotension chapters; and Section III, Naloxone and Nalmephene chapter.

RECOMMENDED READING

Anderson RJ, Hart GR. Clonidine overdose. Ann Emerg Med 1981;10:107-112.

Caravati EM. Clonidine. In: Tintinalli JE, et al., eds. Emergency medicine: a comprehensive study guide, 4th ed. New York: McGraw-Hill, 1996:805-807.

Wiley JF, Wiley CC, Torrey SB, et al. Clonidine poisoning in young children. J Pediatr 1990;116:654.

Authors: Lada Kokan and Gerald F. O'Malley

Reviewer: Richard C. Dart