What is the effect of Isoproterenol (Isoprenaline)?

From the Guidelines

Isoproterenol should be used with caution in patients with bradycardia, particularly those with coronary artery disease, due to its potential to increase myocardial oxygen demand and worsen ischemia, as evidenced by the 2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay 1.

Key Points

• Isoproterenol is a non-selective beta-adrenergic agonist medication that stimulates both beta-1 receptors in the heart and beta-2 receptors in the lungs.
• The typical dosage for adults ranges from 2-10 mcg/min as an IV infusion, titrated according to heart rate response, as recommended by the 2018 ACC/AHA/HRS guideline 1.
• Isoproterenol has largely been replaced by other medications with more selective actions and better safety profiles, such as dopamine or epinephrine for bradycardia, but remains valuable in specific clinical scenarios where both chronotropic and inotropic effects are desired without alpha-adrenergic vasoconstriction.
• Continuous cardiac monitoring is essential when administering isoproterenol, as it can cause significant tachycardia, arrhythmias, and hypotension, as noted in the 2018 ACC/AHA/HRS guideline 1.

Clinical Considerations

• Isoproterenol should be avoided in settings where there is concern for coronary ischemia, as it increases myocardial oxygen demand through beta-1 effects while decreasing coronary perfusion attributable to beta-2 effects, as stated in the 2018 ACC/AHA/HRS guideline 1.
• The medication has a second-line role in the treatment of bradycardia in the setting of resuscitation, and two RCTs of isoproterenol as adjunctive therapy in the setting of cardiac arrest did not show improved return of spontaneous circulation or survival to hospital discharge, as reported in the 2018 ACC/AHA/HRS guideline 1.
• In patients who have undergone heart transplant, atropine at standard clinical doses resulted in paradoxical heart block or less commonly sinus arrest in 20%, highlighting the need for caution when using isoproterenol in this population, as noted in the 2018 ACC/AHA/HRS guideline 1.

From the FDA Drug Label

Isoproterenol is a potent nonselective beta-adrenergic agonist with very low affinity for alpha-adrenergic receptors. Intravenous infusion of isoproterenol in man lowers peripheral vascular resistance, primarily in skeletal muscle but also in renal and mesenteric vascular beds. Diastolic pressure falls. Renal blood flow is decreased in normotensive subjects but is increased markedly in shock. Systolic blood pressure may remain unchanged or rise, although mean arterial pressure typically falls Cardiac output is increased because of the positive inotropic and chronotropic effects of the drug in the face of diminished peripheral vascular resistance.

The effect of Isoproterenol (Isoprenaline) is to:

• Lower peripheral vascular resistance
• Decrease diastolic pressure
• Increase cardiac output due to positive inotropic and chronotropic effects
• Relax smooth muscle, particularly bronchial and gastrointestinal smooth muscle
• Prevent or relieve bronchoconstriction 2, 2 Key effects include increased heart rate, decreased blood pressure, and relaxation of smooth muscle. Main uses are for bronchospasm and heart block. Side effects may include tachycardia, nervousness, and headache.

From the Research

Effects of Isoproterenol

• Isoproterenol has been shown to have a rapid effect in reducing the modified pulmonary index score (MPIS) in pediatric patients with severe acute exacerbation of asthma, with fewer adverse events compared to salbutamol 3.
• In adult patients with severe acute asthma, continuous inhalation therapy using l-isoproterenol has been found to be a safe and possibly useful option, especially in patients who do not respond to conventional therapy 4.
• The cardiovascular effects of isoproterenol can be influenced by hypoxemia and hypercapnia, which can increase myocardial oxygen demand and potentially be detrimental in severe asthma 5.
• Isoproterenol is used in pharmacological testing for the diagnosis of arrhythmias, including supraventricular and ventricular tachycardia, and is required in exercise-related arrhythmias, arrhythmogenic right ventricular cardiomyopathy, and idiopathic ventricular tachycardia 6.
• The pulmonary and extrapulmonary effects of inhaled beta-agonists, including isoproterenol, have been compared in patients with asthma, showing that isoproterenol results in greater positive inotropic stimulation and a fall in plasma potassium levels 7.

Cardiovascular Effects

• Isoproterenol increases heart rate, systolic blood pressure, QTc interval, cardiac index, ejection fraction, and fractional shortening 5.
• The changes in cardiovascular measurements after isoproterenol administration are additive to those caused by hypoxemia-hypercapnia 5.
• Isoproterenol can cause positive inotropic stimulation, which can be greater than that caused by other beta-agonists such as albuterol 7.

Respiratory Effects

• Isoproterenol has a bronchodilating effect, which is similar to that of other beta-agonists such as fenoterol and albuterol 7.
• Isoproterenol can improve the modified pulmonary index score (MPIS) in pediatric patients with severe acute exacerbation of asthma 3.
• Continuous inhalation therapy using l-isoproterenol can improve PaO2/FiO2 and reduce PaCO2 in adult patients with severe acute asthma 4.