Introduction

Sympathomimetic agent that acts directly on both β₁- and β₂-adrenergic receptors (nonselective β-agonist).

Uses for Isoproterenol

Cardiac Arrhythmias and Cardiac Arrest

Used for treatment of heart block and Adams-Stokes attacks. Also has been used for treatment of ventricular arrhythmias secondary to AV nodal block and carotid sinus hypersensitivity. However, evidence supporting benefit in patients with cardiac arrhythmias generally lacking; safer and more effective alternatives such as cardiac pacing and other drug therapies are available.

Has been used in the treatment of cardiac arrest until defibrillation or emergency pacemaker therapy could be employed. However, experts state that isoproterenol is not a drug of choice in ACLS and should only be considered in this setting for treatment of symptomatic bradycardia unresponsive to atropine or as a temporary measure until pacemaker therapy can be instituted. Should not be used for resuscitation in patients with cardiac arrest or hypotension because of potential deleterious effects (e.g., exacerbation of ischemia, arrhythmias, peripheral vasodilation).

Must not be administered to patients with acetylcholinesterase-induced bradycardias; however, may be beneficial at high doses in refractory bradycardia caused by β-adrenergic blocking agents.

Shock

Used as adjunctive therapy to produce cardiac stimulation and vasodilation in the treatment of shock.

The value of isoproterenol therapy in shock has been questioned because the drug increases oxygen demand in the myocardium and other tissues to levels that may not be met by increased blood flow. Efficacy in reducing mortality in refractory shock not demonstrated.

Vasopressors such as norepinephrine and epinephrine generally considered drugs of choice for effective hemodynamic management of shock.

Isoproterenol generally not recommended for cardiogenic shock; increases in myocardial oxygen consumption and cardiac workload usually outweigh benefits, and arrhythmias can occur more readily.

Should not be used in patients with drug-induced distributive shock; may worsen hypotension by further decreasing systemic vascular resistance.

Bronchospasm

IV isoproterenol may be useful in bronchospasm occurring during anesthesia but must be administered with extreme caution, if at all, in patients receiving cyclopropane or halogenated hydrocarbon general anesthetics.

Has been used as a bronchodilator in the symptomatic treatment of bronchial asthma and reversible bronchospasm that may occur in association with chronic bronchitis, pulmonary emphysema, bronchiectasis, and other chronic obstructive pulmonary disorders. However, oral, sublingual, and oral inhalation preparations of the drug no longer are commercially available in the US.

Pulmonary Embolism

Has been used by IV infusion to reverse decreases in cardiac output and circulating pulmonary blood volume and to reverse increases in pulmonary arterial pressure and pulmonary vascular resistance occurring during pulmonary embolism^{† [off-label]}.

Diagnosis of CAD and Other Cardiac Abnormalities

Has been used as an aid in the diagnosis of CAD^{† [off-label]}. Also has been used in the diagnosis of CAD by increasing myocardial oxygen consumption and intensifying symptoms of ischemia.

Has been used as an aid in diagnosing the etiology of mitral regurgitation^{† [off-label]}.

Isoproterenol Dosage and Administration

General

• Select dosage and method of administration according to patient response and specific clinical situation.

• Initiate therapy at lowest recommended dose and increase gradually, if necessary, while monitoring the patient.

• Adjust dosage according to clinical and hemodynamic parameters including heart rate, central venous pressure, systemic BP, and urine output.

Administration

Usually administer IV.

May administer by intracardiac injection in extreme emergencies (in adults). In less urgent situations, initial IM or sub-Q injection is preferred.

Dilute commercially available isoproterenol hydrochloride injection prior to IV administration. For IM, sub-Q, or intracardiac injection, administer injection solution undiluted.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by direct (“bolus”) IV injection or IV infusion.

Dilution

To prepare diluted solution for direct IV injection, add 1 mL of the injection containing isoproterenol hydrochloride 0.2 mg/mL to 9 mL of 0.9% sodium chloride injection or 5% dextrose injection.

To prepare diluted solution for IV infusion, add 10 mL of the injection containing isoproterenol hydrochloride 0.2 mg/mL to 500 mL of 5% dextrose injection.

Rate of Administration

When the drug is administered by IV infusion, especially as an adjunct in the treatment of shock, adjust rate of infusion based on patient’s heart rate, central venous pressure, systemic BP, and urine flow.

If heart rate >110 beats/minute or if premature heart beats or changes in ECG develop, consider slowing rate of infusion or temporarily discontinuing the infusion.

Dosage

Available as isoproterenol hydrochloride; dosage expressed in terms of the salt.

Pediatric Patients

Cardiac Arrhythmias and Cardiac Arrest

IV

No well-controlled studies have been conducted in pediatric patients to inform dosing; however, AHA recommends initial rate of 0.1 mcg/kg per minute in children^{† [off-label]} and subsequent rate generally ranging from 0.1–1 mcg/kg per minute.

For the management of complete heart block following closure of ventricular septal defects, IV doses of 0.01–0.03 mg have been administered in infants.

Adults

Cardiac Arrhythmias and Cardiac Arrest

Although manufacturer makes dosage recommendations for patients with cardiac arrest, most experts state that isoproterenol should not be used for cardiopulmonary resuscitation. (See Cardiac Arrhythmias and Cardiac Arrest under Uses.)

IV Infusion

Manufacturer recommends initial dosage of 5 mcg/minute (1.25 mL of the diluted solution per minute) for treatment of heart block, Adams-Stokes attacks, or cardiac arrest; adjust subsequent dosage based on patient response (generally ranges from 2–20 mcg/minute).

For treatment of symptomatic bradycardia unresponsive to atropine during ACLS, recommended dosage is 2–10 mcg/minute; adjust infusion rate according to heart rate and rhythm response.

IV injection

Manufacturer recommends initial dose of 0.02–0.06 mg (1–3 mL of the diluted solution) for treatment of heart block, Adams-Stokes attacks, or cardiac arrest; subsequent doses range from 0.01–0.2 mg (0.5–10 mL of the diluted solution).

For the management of complete heart block following closure of ventricular septal defects, IV doses of 0.04–0.06 mg have been used in adults.

IM

Manufacturer recommends initial dose of 0.2 mg (1 mL of the commercially available 0.2-mg/mL injection without dilution) for treatment of heart block, Adams-Stokes attacks, or cardiac arrest; subsequent doses range from 0.02–1 mg.

Sub-Q

Manufacturer recommends initial dose of 0.2 mg (1 mL of the commercially available 0.2-mg/mL injection without dilution) for treatment of heart block, Adams-Stokes attacks, or cardiac arrest; subsequent doses range from 0.15–0.2 mg.

Shock

IV Infusion

Manufacturer suggests 0.5–5 mcg (0.25–2.5 mL of the diluted solution) per minute. In advanced stages of shock, rates >30 mcg/minute have been used.

IV injection

Manufacturer recommends initial dose of 0.01–0.02 mg (0.5–1 mL of the diluted solution); dose may be repeated if necessary.

Bronchospasm

IV

Has been administered in IV doses of 0.01–0.02 mg, repeated as needed.

Diagnosis of CAD and Other Cardiac Abnormalities

IV Infusion

Has been administered by IV infusion at a rate of 1–3 mcg/minute in the diagnosis of CAD or lesions^{† [off-label]} or at a rate of 4 mcg/minute as an aid in diagnosing the etiology of mitral regurgitation^†.

Special Populations

Renal Impairment

No specific dosage recommendations. Administer with caution.

Geriatric Patients

Careful dosage selection recommended due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy; initiate therapy at low end of dosage range.

Contraindications

• Angina pectoris.

• Preexisting cardiac arrhythmias (particularly ventricular arrhythmias requiring inotropic therapy and tachyarrhythmias).

• Tachycardia or heart block caused by cardiac glycoside intoxication.

Warnings/Precautions

Warnings

Cardiovascular Effects

In patients with acute MI, isoproterenol may increase the extent of ischemic injury to the myocardium. Use of the drug as initial agent in the treatment of cardiogenic shock following MI is discouraged. May cause focal necrosis of myocardial cells.

Paradoxically, the drug may precipitate Adams-Stokes seizures in some patients with normal sinus rhythm or transient AV block. It has been suggested that these patients may have had organic disease of the AV node or its branches.

Evidence of transient myocardial ischemia (i.e., ECG changes and elevation of the cardiac [MB] fraction of creatine kinase [CK, creatine phosphokinase, CPK]) or myocardial dysfunction (i.e., abnormal ECG findings) has been reported with the use of isoproterenol IV infusion for the treatment of severe asthma exacerbation in children. In patients with asthma receiving isoproterenol infusion, administer oxygen concomitantly; monitor heart rate, BP, and arterial blood gases (maintaining arterial oxygen pressure [PaO₂ ] >60 mm Hg); and monitor ECG. Confirm ECG changes suggestive of myocardial ischemia by determining the MB fraction of CK.

Disturbances of cardiac rhythm and rate produced by isoproterenol may result in palpitation and VT. Isoproterenol can cause potentially fatal ventricular arrhythmias in doses sufficient to increase heart rate above 130 beats/minute.

Administration of isoproterenol to patients who are in shock is not a substitute for replacement of blood, plasma, fluids, and/or electrolytes.

Blood volume depletion must be corrected as fully as possible before the drug is administered.

Use with caution in patients with CAD, coronary insufficiency, diabetes, hyperthyroidism, and sensitivity to sympathomimetic amines.

Sensitivity Reactions

Sulfite Sensitivity

Some formulations contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.

General Precautions

Hypovolemia

Pressor therapy is not a substitute for replacement of blood, plasma, fluids, and/or electrolytes. Correct blood volume depletion as fully as possible before isoproterenol therapy is instituted.

Additional volume replacement also may be required during administration of isoproterenol; fluid administration must be adequate to compensate for isoproterenol-induced vasodilation, or shock may be worsened.

Detecting and treating hypovolemia: Monitor central venous pressure or left ventricular filling pressure; in addition, monitor central venous or pulmonary arterial diastolic pressure to avoid overloading the cardiovascular system, diluting serum electrolyte concentrations, and precipitating CHF.

Monitoring

Monitor ECG, BP, heart rate, urine flow, central venous pressure, blood pH, and blood PCO₂ or bicarbonate concentrations. (See Hypoxia, Hypercapnia, Acidosis, Electrolyte Disturbances under Cautions.) Measure cardiac output and circulation time to determine the patient’s condition and response to therapy. Ensure adequate ventilation. Carefully monitor patients who are in shock. Consider the possibility that isoproterenol may not produce improved capillary perfusion and oxygen delivery while increasing oxygen demand in the myocardium.

Hypoxia, Hypercapnia, Acidosis, and Electrolyte Disturbances

Must be identified and corrected prior to or during administration of the drug. May reduce the efficacy and/or increase the incidence of adverse effects of isoproterenol.

Disease States

Use with caution in geriatric patients, diabetics, patients with renal or cardiovascular disease (including hypertension, CAD, coronary insufficiency, or degenerative heart disease), hyperthyroidism, and/or those with a history of sensitivity to sympathomimetic amines.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether isoproterenol is distributed into human milk. Caution advised.

Pediatric Use

Safety and efficacy not established. Has been used in children^† for certain conditions (e.g., refractory asthma, bradycardia).

IV infusions of 0.05–2.7 mcg/kg per minute in pediatric patients with refractory asthma have caused clinical deterioration, myocardial necrosis, CHF, and death; the risk may be increased by acidosis, hypoxia, and/or concomitant use of other agents (e.g., xanthine derivatives, corticosteroids [see Specific Drugs under Interactions]) likely to be used in these children. If used in pediatric patients with refractory asthma, monitor vital signs continuously and ECG frequently, and determine cardiac-specific (MB) fraction of serum CK (CPK) daily.

Geriatric Use

Insufficient experience in patients >65 years of age to determine whether geriatric patients respond differently to isoproterenol hydrochloride than younger patients. Geriatric healthy individuals or hypertensive patients may be less responsive to β-adrenergic stimulation than younger adults. Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy. (See Geriatric Patients under Dosage and Administration.)

Renal Impairment

Use with caution.

Common Adverse Effects

Nervousness, headache, dizziness, restlessness, insomnia, anxiety, tension, blurring of vision, fear, excitement, tachycardia, palpitations, angina, Adam-Stokes syndrome, pulmonary edema, hypertension, hypotension, ventricular arrhythmias, tachyarrhythmias, flushing of the skin, diaphoresis, mild tremors, weakness.

General

• Select dosage and method of administration according to patient response and specific clinical situation.

• Initiate therapy at lowest recommended dose and increase gradually, if necessary, while monitoring the patient.

• Adjust dosage according to clinical and hemodynamic parameters including heart rate, central venous pressure, systemic BP, and urine output.

Administration

Usually administer IV.

May administer by intracardiac injection in extreme emergencies (in adults). In less urgent situations, initial IM or sub-Q injection is preferred.

Dilute commercially available isoproterenol hydrochloride injection prior to IV administration. For IM, sub-Q, or intracardiac injection, administer injection solution undiluted.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by direct (“bolus”) IV injection or IV infusion.

Dilution

To prepare diluted solution for direct IV injection, add 1 mL of the injection containing isoproterenol hydrochloride 0.2 mg/mL to 9 mL of 0.9% sodium chloride injection or 5% dextrose injection.

To prepare diluted solution for IV infusion, add 10 mL of the injection containing isoproterenol hydrochloride 0.2 mg/mL to 500 mL of 5% dextrose injection.

Rate of Administration

When the drug is administered by IV infusion, especially as an adjunct in the treatment of shock, adjust rate of infusion based on patient’s heart rate, central venous pressure, systemic BP, and urine flow.

If heart rate >110 beats/minute or if premature heart beats or changes in ECG develop, consider slowing rate of infusion or temporarily discontinuing the infusion.

Dosage

Available as isoproterenol hydrochloride; dosage expressed in terms of the salt.

Pediatric Patients

Cardiac Arrhythmias and Cardiac Arrest

IV

No well-controlled studies have been conducted in pediatric patients to inform dosing; however, AHA recommends initial rate of 0.1 mcg/kg per minute in children^{† [off-label]} and subsequent rate generally ranging from 0.1–1 mcg/kg per minute.

For the management of complete heart block following closure of ventricular septal defects, IV doses of 0.01–0.03 mg have been administered in infants.

Adults

Cardiac Arrhythmias and Cardiac Arrest

Although manufacturer makes dosage recommendations for patients with cardiac arrest, most experts state that isoproterenol should not be used for cardiopulmonary resuscitation. (See Cardiac Arrhythmias and Cardiac Arrest under Uses.)

IV Infusion

Manufacturer recommends initial dosage of 5 mcg/minute (1.25 mL of the diluted solution per minute) for treatment of heart block, Adams-Stokes attacks, or cardiac arrest; adjust subsequent dosage based on patient response (generally ranges from 2–20 mcg/minute).

For treatment of symptomatic bradycardia unresponsive to atropine during ACLS, recommended dosage is 2–10 mcg/minute; adjust infusion rate according to heart rate and rhythm response.

IV injection

Manufacturer recommends initial dose of 0.02–0.06 mg (1–3 mL of the diluted solution) for treatment of heart block, Adams-Stokes attacks, or cardiac arrest; subsequent doses range from 0.01–0.2 mg (0.5–10 mL of the diluted solution).

For the management of complete heart block following closure of ventricular septal defects, IV doses of 0.04–0.06 mg have been used in adults.

IM

Manufacturer recommends initial dose of 0.2 mg (1 mL of the commercially available 0.2-mg/mL injection without dilution) for treatment of heart block, Adams-Stokes attacks, or cardiac arrest; subsequent doses range from 0.02–1 mg.

Sub-Q

Manufacturer recommends initial dose of 0.2 mg (1 mL of the commercially available 0.2-mg/mL injection without dilution) for treatment of heart block, Adams-Stokes attacks, or cardiac arrest; subsequent doses range from 0.15–0.2 mg.

Shock

IV Infusion

Manufacturer suggests 0.5–5 mcg (0.25–2.5 mL of the diluted solution) per minute. In advanced stages of shock, rates >30 mcg/minute have been used.

IV injection

Manufacturer recommends initial dose of 0.01–0.02 mg (0.5–1 mL of the diluted solution); dose may be repeated if necessary.

Bronchospasm

IV

Has been administered in IV doses of 0.01–0.02 mg, repeated as needed.

Diagnosis of CAD and Other Cardiac Abnormalities

IV Infusion

Has been administered by IV infusion at a rate of 1–3 mcg/minute in the diagnosis of CAD or lesions^{† [off-label]} or at a rate of 4 mcg/minute as an aid in diagnosing the etiology of mitral regurgitation^†.

Special Populations

Renal Impairment

No specific dosage recommendations. Administer with caution.

Geriatric Patients

Careful dosage selection recommended due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy; initiate therapy at low end of dosage range.

Specific Drugs