Bretylium

Indications

Bretylium is used for: Ventricular Arrhythmia

Adult Dose

Ventricular Arrhythmia Indicated for prophylaxis and treatment of ventricular fibrillation (VF); also indicated for treatment of life-threatening ventricular arrhythmias (eg, ventricular tachycardia [VT] unresponsive to first-line antiarrhythmic agents [eg, lidocaine]) Immediately life-threatening ventricular arrhythmias (eg, VF, unstable VT) Other usual cardiopulmonary resuscitative procedures, including electrical cardioversion, should be used prior to and following the injection in accordance with good medical practice Undiluted solution: 5 mg/kg IV by rapid injection; if arrhythmia persists, may increase dose to 10 mg/kg and repeat prn Diluted solution for continuous suppression: 1-2 mg/min IV; alternatively, 5-10 mg/kg IV over at least 8 min q6hr Other ventricular arrhythmias IV Use diluted solution 5-10 mg/kg IV over at least 8 min; may repeat dose at 1- to 2-hr intervals if arrhythmia persists Maintenance: 5-10 mg/kg IV over at least 8 min q6hr; alternatively, 1-2 mg/min IV continuous infusion IM Use undiluted solution 5-10 mg/kg IM; may repeat dose at 1- to 2-hr intervals if arrhythmia persists Maintenance: 5-10 mg/kg IM q6-8hr Switch of oral antiarrhythmic agent as soon as possible for continued maintenance therapy

Child Dose

Renal Dose

Renal impairment Primarily excreted via kidneys; increase dosage interval in patients with impaired renal function Removed by hemodialysis

Administration

IV Preparation Solution should appear clear; slight discoloration does not alter potency Rapid IV bolus: Do NOT dilute solution Continuous or intermittent IV infusion: Dilute 500 mg to a minimum of 50 mL with D52 or 0.9% NaCl IM Preparation Solution should appear clear; slight discoloration does not alter potency Do NOT dilute solution IV Administration Patients should remain in supine position until tolerance to the hypotensive effect of bretylium develops; tolerance occurs unpredictably but may be present after several days Immediately life-threatening ventricular arrhythmias Rapid IV bolus (undiluted drug): When used for immediately life-threatening ventricular arrhythmias (eg, VF, hemodynamically unstable VT), give rapid IV bolus and if continuous suppression needed, follow with continuous or intermittent IV infusion (dilute drug as described above) Continuous IV solution infusion: 1-2 mg/min Intermittent IV infusion: 5-10 mg/kg infused over at least 8 min q6hr Rapid infusion More rapid infusion may cause nausea and vomiting, and possibly provoke hypertensive crisis May increase orthostatic hypotension risk, especially in patients aged ?65 yr IM Administration Patients should be kept in supine position until tolerance to the hypotensive effect of bretylium develops; tolerance occurs unpredictably but may be present after several days Do not dilute for IM injection Do not inject directly into or near a major nerve Rotate injection site if repeated Do not exceed 5 mL/injection site As soon as possible, and when indicated, change to oral antiarrhythmic agent for maintenance therapy

Contra Indications

Digitalis-induced arrhythmias

Precautions

Hypotension Administration regularly results in postural hypotension, subjectively recognized by dizziness, lightheadedness, vertigo, or faintness Some degree of hypotension is present in ~50% of patients while they are supine Hypotension may occur at doses lower than those needed to suppress arrhythmias Keep patients in supine position until tolerance to hypotensive effect develops; tolerance occurs unpredictably, but may be present after several days Patients aged >65 years may be at increased risk of developing orthostatic hypotension, especially if recommended IV infusion exceeded Hypotension with supine systolic pressure >75 mm Hg need not be treated unless there are associated symptoms If supine systolic pressure falls below 75 mm Hg, dopamine or norepinephrine infusion may be used to raise blood pressure When catecholamines are administered, use a dilute solution and closely monitor blood pressure (pressor effects catecholamines enhanced by bretylium) Volume expansion with blood or plasma and correction of dehydration should be carried out where appropriate Transient hypertension Bretylium causes an initial norepinephrine release from adrenergic postganglionic nerve terminals Transient hypertension or increased frequency of premature ventricular contractions and other arrhythmias may occur in some patients, especially after too vigorous a dosing Hyperthermia Hyperthermia, characterized by temperature excess of 106°F, reported; temperature rise can begin within 1 hr or later after administration and peak within 1-3 days If suspected or diagnosed, discontinue bretylium and institute treatment immediately

Pregnancy-Lactation

Pregnancy Unknown whether bretylium can cause fetal harm when administered to pregnant women or can affect reproduction capacity Administer during pregnancy only if clearly needed Animal reproduction studies have not been conducted Lactation Data are not available

Interactions

Digoxin Initial release of norepinephrine caused by bretylium may aggravate digitalis toxicity When a life-threatening cardiac arrhythmia occurs in a digitalized patient, bretylium should be used only if the etiology of the arrhythmia does not appear to be digitalis toxicity and other antiarrhythmic drugs are not effective Avoid simultaneous initiation of therapy with digitalis glycosides and bretylium Monoamine oxidase inhibitors (MAOIs) Bretylium produces release of catecholamines from nerve endings This increased catecholamine release is potentiated by MAOIs Catecholamines If catecholamines (ie, dopamine, norepinephrine) are administered to treat systolic blood pressure <75 mm Hg, a dilute solution should be used and blood pressure monitored closely because the pressor effects of the catecholamines are enhanced by bretylium

Adverse Effects

Side effects of Bretylium : >10% Hypotension, some degree even while supine (50%) <1% ~0.7% Vertigo Dizziness Lightheadedness Syncope ~0.2% Increased frequency of premature ventricular contractions Transitory hypertension Initial increase in arrhythmias Precipitation of anginal attacks Sensation of substernal pressure ~0.1% Renal dysfunction Diarrhea, abdominal pain Hiccups Erythematous macular rash Flushing Hyperthermia Confusion, paranoid psychosis, emotional lability, anxiety Lethargy Generalized tenderness Shortness of breath, diaphoresis, nasal stuffiness Mild conjunctivitis

Mechanism of Action

Accumulates in sympathetic ganglia and their postganglionic adrenergic neurons when administered slowly or incrementally, where it inhibits norepinephrine release by depressing adrenergic nerve terminal excitability Also suppresses ventricular fibrillation (VF) and ventricular arrhythmias; mechanisms of antifibrillatory and antiarrhythmic actions are not established, although electrophysiologic actions have been described in animal studies Electrophysiologic effects observed in animal studies Increased VF threshold Increased action potential duration and effective refractory period without changes in heart rate Little effect on the rate of rise or amplitude of the cardiac action potential (Phase 0) or in resting membrane potential (Phase 4) in normal myocardium; however, when cell injury slows the rate of rise, decreases amplitude, and lowers resting membrane potential, bretylium transiently restores these parameters toward normal In canine hearts with infarcted areas, bretylium decreases disparity in action potential duration between normal and infarcted regions Increased impulse formation and spontaneous firing rate of pacemaker tissue, as well as increased ventricular conduction velocity