DESCRIPTION

Sotalol (Betapace) is a class III antidysrhythmic medication.

FORMS AND USES

• Sotalol (Betapace, Sotacor) is used to treat high-risk ventricular dysrhythmia.
• Adult oral dosage is 120 to 480 mg/day.
• Adult intravenous dosage is 20 to 60 mg over 2 to 3 minutes.
• Pediatric oral dosage is 2 to 4 mg/kg/day in two divided doses.

TOXIC DOSE

A therapeutic dose has been associated with torsade de pointes, particularly in patients with predisposing conditions.

PATHOPHYSIOLOGY

• A noncardioselective beta-blocker, sotalol lacks significant intrinsic sympathomimetic activity and membrane-stabilizing properties.
• Sotalol lengthens the action potential duration, resulting in class III antidysrhythmic activity.
• The combined effects of bradycardia and lengthened action potential may produce torsade de pointes.

EPIDEMIOLOGY

• Poisoning is rare.
• Toxic effects following exposure are typically moderate.
• Death occurs in patients who have ingested a large quantity, who have underlying electrolyte disorders, or who have cardiovascular disease.

CAUSES

• Poisoning usually occurs as a suicidal ingestion in an adult.
• Child abuse or neglect should be considered if the patient is less than 1 year of age; suicide attempt in patients over 6 years of age.

RISK FACTORS

Patients with underlying heart disease, electrolyte abnormality (hyperkalemia, hypomagnesemia, hypocalcemia), renal insufficiency, or congenital QT prolongation are at increased risk of torsade de pointes.

DRUG AND DISEASE INTERACTIONS

Drugs that prolong QT interval (tricyclic antidepressants, type 1a antidysrhythmic agents) increase the risk of dysrhythmia.

PREGNANCY AND LACTATION

• US FDA Pregnancy Category B. Animal studies indicate no fetal risk and there are no controlled human studies, or animal studies show an adverse fetal effect but well-controlled studies in pregnant women do not.
• Sotalol is concentrated in breast milk, but there are no reports of infant toxicity.

Section Outline:

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

DIFFERENTIAL DIAGNOSIS

• Toxic agents that produce prolongation of QT interval include quinidine, disopyramide, procainamide, ibutilide, pentamidine, propoxyphene, thioridazine, and cyclic antidepressants.
• Other conditions that prolong QT interval include congenital QT prolongation, hyperkalemia, and ventricular dysrhythmia secondary to ischemia or other etiology.

SIGNS AND SYMPTOMS

An overdose may cause bradycardia, hypotension, syncope, ventricular dysrhythmia, or asystole.

Vital Signs

Mild bradycardia and hypotension are common and may become severe after a large ingestion.

Cardiovascular

Severe hypotension generally only develops with serious ventricular dysrhythmias (QT prolongation, torsade de pointes, premature ventricular contractions, ventricular tachycardia, or ventricular fibrillation).

Pulmonary

Respiratory depression may develop in severe cases.

Neurologic

Syncope, seizures, and altered mental status may occur in patients with ventricular dysrhythmia.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• Serum electrolytes, BUN, and creatinine are ordered to evaluate other causes of dysrhythmia.
• ECG with continuous cardiac monitoring is used to detect QT prolongation and ventricular dysrhythmia.

Recommended Tests

• Serum magnesium and calcium levels are assayed in patients with dysrhythmia to assess other causes.
• Serum acetaminophen and aspirin levels in overdose setting are tested to detect occult ingestion.

Section Outline:

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

• Treatment should focus on cardiac monitoring, supportive care, and treatment of ventricular dysrhythmia.
• The dose and time of exposure must be determined for all substances involved.

DIRECTING PATIENT COURSE

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

• Ventricular dysrhythmia, hypotension or other serious effects are present.
• Toxic effects are not consistent with sotalol ingestion.
• Coingestant, drug interaction, or underlying disease presents an unusual challenge.

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

• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Any symptoms develop.
• Coingestant, drug interaction, or underlying disease presents an unusual challenge.

Admission Considerations

Inpatient management is warranted for patients with prolonged QTc, dysrhythmia, hypotension, or a CNS complaint such as syncope.

DECONTAMINATION

Out of Hospital

Emesis should not be induced; coma or seizure may develop abruptly.

In Hospital

• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult patients (tube size 36-42 French) presenting within 1 hour of a large 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.

ANTIDOTES

There is no specific antidote available.

ADJUNCTIVE TREATMENT

An arterial line or Swan-Ganz catheterization may be needed to manage persistent hypotension and dysrhythmias.

Torsade de Pointes

• Electrolyte abnormalities should be corrected, if present.
• If the patient is hemodynamically unstable, electrical cardioversion should be performed immediately.
• The clinician should avoid quinidine, disopyramide, procainamide, amiodarone, or bretylium, or any other agents that prolong QT interval.
• Magnesium sulfate is the primary treatment.
  • Adult dose is 1 to 2 g, given as an intravenous push and repeated if needed in 10 to 15 minutes; intravenous infusion also should be initiated at a rate of 2 to 10 mg/min, titrated to antidysrhythmic effect.
  • Pediatric dosage is 25 to 50 mg/kg intravenously over 5 minutes followed by continuous infusion.
• If magnesium is not effective, isoproterenol (2 to 4 µg/ml) is administered at an initial rate of 0.5 to 1.0 µg/min, titrated to effect; pediatric dose is 0.1 µg/kg/min, titrated to effect.

Bradycardia

• If bradycardia is associated with hypotension, atropine is administered.
  • Adult dose is 0.5 to 1 mg intravenously, repeated in 5 minutes if necessary to a maximum of 2 mg.
  • Pediatric dose is 0.02 mg/kg intravenously, repeated every 5 minutes as needed; the maximum dose is 1 mg for children, 2 mg for adolescents.
• If the patient is unresponsive to atropine, isoproterenol may be added; adult infusion is 5.0 µg/min, titrated to effect; pediatric infusion is 0.1 µg/kg/min, titrated to effect.
• The unresponsive patient should undergo cardiac pacing.

Hypotension

• In patients with hypotension and no evidence of volume overload, intravenous 0.9% saline is administered at 10 to 20 ml/kg; volume overload must be avoided because many agents that cause bradycardia are also myocardial depressants.
• Dopamine may be administered for persistent hypotension at 2 to 5 µg/kg/min by intravenous infusion, titrated to effect; doses above 20 mg/kg/min are unlikely to have further effect.
• If the patient is unresponsive to dopamine, norepinephrine is added, 0.1 to 0.2 µg/kg/min in a continuous infusion, and titrated to effect.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT
  • Torsade de Pointes
  • Bradycardia
  • Hypotension

PATIENT MONITORING

Electrolytes as well as cardiac rhythm and respiratory function should be monitored throughout the patient's hospitalization.

EXPECTED COURSE AND PROGNOSIS

• Survival and full recovery are expected if the patient receives appropriate aggressive care before anoxic injury intercedes.
• Permanent neurologic injury from sustained hypotension, seizures, or hypoxia may result.

PATIENT EDUCATION

Patients with renal insufficiency should avoid sotalol.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. If electrolytes are normal and no dysrhythmia or QTc prolongation develops for 6 hours after ingestion, the patient may be discharged after gastrointestinal decontamination and psychiatric evaluation, if needed.
• From the hospital. Patient may be discharged approximately 24 hours after QTc and dysrhythmia normalize and after a psychiatric evaluation, if needed.

Section Outline:

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

DIAGNOSIS

Toxicity can occur at therapeutic doses in a patient who has an electrolyte disorder or who uses drugs that prolong the QT interval.

TREATMENT

High doses of magnesium may be required to control torsade de pointes.

Section Outline:

• DIAGNOSIS
• TREATMENT

Poisoning by agents primarily affecting the cardiovascular system.

See Also: SECTION II, Hypotension and Ventricular Dysrhythmia chapters; and SECTION III, Atropine and Magnesium Sulfate chapters.

RECOMMENDED READING

Neuvonen PJ, Elonen E, Vuorenmaa T, et al. Prolonged Q-T interval and severe tachyarrhythmias, common features of sotalol intoxication. Eur J Clin Pharmacol 1981;20:85-89.

Author: Katherine M. Hurlbut

Reviewer: Richard C. Dart