Used in the treatment of Adams-Stokes syndrome (Stokes-Adams disease). May be used in ventricular arrythmias secondary to AV nodal block and treatment of carotid sinus hypersensitivity.
Has been used in the treatment of cardiac arrest until defibrillation or emergency pacemaker therapy could be employed. The drug may be used in ACLS only as a temporary measure until pacemaker therapy is instituted either for refractory atypical ventricular tachycardia (torsades de pointes) or for the immediate temporary control of hemodynamically significant bradycardia (e.g., in the denervated heart of patients undergoing heart transplantation).
Use of isoproterenol for temporary immediate control of hemodynamically significant bradycardia usually is limited to when atropine and dobutamine have failed and transcutaneous and transvenous pacing are not available.
Isoproterenol (at low doses and in patients with a pulse) should be used with extreme caution, if at all, in the management of symptomatic bradycardia since its potential beneficial chronotropic effect may be outweighed by possible deleterious effects on myocardial oxygen consumption and peripheral circulation.
Electrical cardiac pacemakers largely have replaced drug therapy in third-degree AV nodal block (complete heart block), but isoproterenol may be used temporarily until a pacemaker can be implanted or if the implanted pacemaker fails.
Electroshock may be required in the management of ventricular arrhythmias and usually is the treatment of choice.
Shock
Isoproterenol IV infusion is used as adjunct to correct hemodynamic imbalances in the treatment of shock characterized by low cardiac output and intense vasoconstriction that persists after adequate fluid replacement. The drug is not useful if the peripheral vascular bed is already dilated.
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. The efficacy of isoproterenol in reducing the incidence of mortality in refractory shock has not been convincingly demonstrated.
Isoproterenol appears to be less effective than norepinephrine or metaraminol in increasing coronary perfusion. Also, isoproterenol-induced increases in myocardial oxygen consumption and the work of the heart usually outweigh the beneficial effects of the drug, and arrhythmias occur more readily when the drug is administered to patients with cardiogenic shock.
Isoproterenol generally is not recommended in shock caused by AMI. Norepinephrine is considered by some clinicians to be the vasopressor of choice for this condition; however, this type of shock generally has a poor prognosis even when vasopressors are used. If peripheral vascular resistance is elevated, isoproterenol sometimes is used in conjunction with norepinephrine, but dosage of both drugs must be adjusted carefully according to the specific hemodynamic imbalances present.
The efficacy of isoproterenol may be reduced if CHF is present.
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†.
Diagnosis of CAD and Other Cardiac Abnormalities
Has been used as an aid in the diagnosis of CAD†. 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†.
Dosage and Administration
General
Generally, initiate therapy at the lowest recommmended dose.
Rate of administration may be gradually increased, if needed.
Dosage must be regulated by monitoring the ECG and by patient’s response.
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.
IV Administration
For solution and drug compatibility information, see Compatibility under Stability.
Administer by IV injection or infusion.
Dilution
For direct IV injection, diluted solutions containing isoproterenol hydrochloride 20 mcg/mL (1:50,000) are used; these solutions may be prepared by diluting 1 mL of the commercially available injection containing isoproterenol hydrochloride 0.2 mg/mL (1:5000) to a volume of 10 mL with 0.9% sodium chloride injection or 5% dextrose injection.
For IV infusion, solutions may be prepared by diluting 1–10 mL of the injection containing isoproterenol hydrochloride 0.2 mg/mL (1:5000) with 500 mL of 5% dextrose injection to provide infusion solutions containing 0.4–4 mcg/mL; solutions containing 2–4 mcg/mL are most commonly used.
The injection concentrate (1:5000) must be diluted in large-volume parenteral fluids in a single-use container and administered by slow IV infusion. As the injection concentrate contains no bacteriostatic or antimicrobial agent, each vial is intended for single use only; any unused solution should be discarded.
Rate of Administration
When the drug is administered by IV infusion, especially as an adjunct in the treatment of shock, the rate of infusion should be adjusted on the basis of the patient’s heart rate, central venous pressure, systemic BP, and urine flow.
If the heart rate exceeds 110 beats/minute or if premature heart beats or changes in the ECG develop, slowing the rate of infusion or discontinuing the infusion temporarily should be considered.
Dosage
Available as isoproterenol hydrochloride; dosage expressed in terms of the salt.
Pediatric Patients
Cardiac Arrhythmias and CPR
IV Injection and Infusion
Initial doses of isoproterenol hydrochloride in children† have been one-half of those in adults; 0.01–0.03 mg (0.5–1.5 mL of a 1:50,000 dilution) has been given as an IV bolus dose.
For IV infusion, the AHA recommends an initial rate of 0.1 mcg/kg per minute; subsequent dosage generally ranges from 0.1–1 mcg/kg per minute.
In the management of postoperative cardiac patients with bradycardia, children† have been given isoproterenol by IV infusion in a dosage of 0.029 mcg/kg per minute.
For the management of complete heart block following closure of ventricular septal defects, the drug has been administered to infants as an IV bolus in doses of 0.01–0.03 mg (0.5–1.5 mL of a 1:50,000 dilution).
Adults
Cardiac Arrhythmias and CPR
IV Injection and Infusion
Initially, 0.02–0.06 mg (1–3 mL of a 1:50,000 dilution) as an IV bolus dose; subsequent doses range from 0.01–0.2 mg (0.5–10 mL of a 1:50,000 dilution).
For IV infusion, the initial rate of administration is 5 mcg/minute (1.25 mL of a 1:250,000 dilution per minute); subsequent dosage generally ranges from 2–20 mcg/minute.
Doses of isoproterenol hydrochloride used for the treatment of cardiac arrhythmias also may be employed in the treatment of cardiac arrest; however, the drug usually should not be used for the treatment of cardiac arrest. (See Cardiac Arrhythmias and CPR under Uses.)
Until pacemaker therapy is instituted either for refractory atypical ventricular tachycardia (torsades de pointes) or for the immediate temporary control of hemodynamically significant bradycardia during ACLS, the suggested IV infusion rate is 2–10 mcg/minute. Higher dosages may be associated with increased myocardial oxygen consumption, increased infarct size, and malignant ventricular arrhythmias.
For the management of complete heart block following closure of ventricular septal defects, a dose of 0.04–0.06 mg (2–3 mL of a 1:50,000 dilution) has been used.
IM
Initially, 0.2 mg (1 mL of 1:5000 injection); subsequent doses range from 0.02–1 mg (0.1–5 mL of 1:5000 injection).
Sub-Q
Initially, 0.2 mg (1 mL of 1:5000 injection); subsequent doses range from 0.15–0.2 mg (0.75–1 mL of 1:5000 injection).
Shock
IV Infusion
Suggested infusion rate is 0.5–5 mcg (0.25–2.5 mL of a 1:500,000 dilution) per minute. In advanced stages of shock, rates >30 mcg/minute have been used. For septic shock, the drug usually should not be administered for longer than 1 hour.
Bronchospasm
IV
0.01–0.02 mg (0.5–1 mL of a 1:50,000 dilution); dose may be repeated as needed.
Diagnosis of CAD and Other Cardiac Abnormalities
IV Infusion
Isoproterenol hydrochloride has been administered by IV infusion at a rate of 1–3 mcg/minute in the diagnosis of CAD or lesions† or at a rate of 4 mcg/minute as an aid in diagnosing the etiology of mitral regurgitation†.
Prescribing Limits
For septic shock, the drug usually should not be administered for longer than 1 hour.
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.
Cautions
Contraindications
Angina pectoris.
Preexisting cardiac arrhythmias (particularly ventricular arrhythmias requiring inotropic therapy and tachyarrhythmias) other than those arrhythmias that may respond to treatment with isoproterenol.
Tachycardia or AV block caused by cardiac glycoside intoxication.
Warnings/Precautions
Warnings
Cardiovascular Effects
In patients with AMI, 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 if IV isoproterenol hydrochloride is used.
Pediatric Use
Safety and efficacy not established. Has been used IV in children† with asthma or in postoperative cardiac patients with bradycardia. Also has been used in the management of cardiac arrhythmias and CPR in children† and for the management of complete heart block following closure of ventricular septal defects in infants†.
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. Titrate dosage carefully. (See Special Populations under Dosage and Administration.)
Cardiac output usually is increased and may be accompanied by an increase in stroke volume.
Increases myocardial oxygen consumption and the work of the heart and decreases cardiac efficiency.
Lowers peripheral vascular resistance, mainly in skeletal muscle and also in renal and mesenteric vascular beds.
Decreases DBP by producing vasodilation. Mean BP usually is decreased slightly but it may remain unchanged or may be increased slightly if the vasculature already is maximally dilated.
Renal blood flow usually is decreased in normotensive patients, but is substantially increased in patients with shock.
SBP may be increased or remain unchanged.
In patients with AV block, isoproterenol shortens conduction time and the refractory period of the AV node and increases the rate and strength of ventricular contraction.
Inhibits antigen-induced release of histamine and the slow reacting substance of anaphylaxis.
Advice to Patients
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
