Drugs That Increase Cardiac Contractility
The primary drugs that increase cardiac contractility (positive inotropes) include beta-adrenergic agonists (dobutamine, dopamine, epinephrine, norepinephrine), phosphodiesterase inhibitors (milrinone), and calcium sensitizers (levosimendan). Each medication has distinct mechanisms of action and clinical applications.
Beta-Adrenergic Agonists
Dobutamine: Primarily stimulates β1-receptors to increase myocardial contractility with comparatively mild chronotropic, hypertensive, arrhythmogenic, and vasodilative effects 1. It increases cardiac output through enhanced cardiac contractility 1.
Dopamine: At infusion rates of 2-15 μg/kg/min, stimulates β1-receptors to increase myocardial contractility, though this may cause tachycardia and increased risk of arrhythmias 1. At higher doses (>5 μg/kg/min), it has more pronounced α-adrenergic effects 1.
Epinephrine: At low doses (<0.3 mcg/kg/min), produces β-adrenergic effects (increased contractility) while higher doses (>0.3 mcg/kg/min) cause α-adrenergic vasoconstriction 1. It increases blood pressure, coronary artery pressure, and ventricular contractility 2.
Norepinephrine: Primarily a vasopressor that increases blood pressure and enhances ventricular contractility through sympathetic nervous system activation 1.
Phosphodiesterase Inhibitors
Milrinone: A phosphodiesterase-3 inhibitor that increases myocardial contractility and provides vasodilation 1, 3. It works by inhibiting peak III cAMP phosphodiesterase isozyme in cardiac and vascular muscle, leading to increased intracellular calcium and contractile force 3. Unlike adrenergic agents, it doesn't directly stimulate adrenergic receptors 3.
Enoximone: Similar to milrinone, inhibits phosphodiesterase-3, increasing cAMP and producing inotropic and peripheral vasodilating effects 1.
Calcium Sensitizers
- Levosimendan: Increases cardiac contractility by sensitizing cardiac myofibrils to calcium 4, 5. It also has vasodilatory effects through opening ATP-sensitive potassium channels 4, 5. Unlike conventional inotropes, levosimendan doesn't significantly increase myocardial oxygen consumption and has been shown to be effective in the presence of beta-blockers 4.
Clinical Applications
Cardiogenic Shock: Inotropes are indicated when persistent low cardiac output and hypotension are related to left ventricular systolic dysfunction 1.
Acute Heart Failure: Inotropes are used for temporary support in patients with myocardial depression to improve cardiac output through enhanced contractility 1.
Post-Cardiac Surgery: Inotropes help manage low cardiac output syndrome following cardiopulmonary bypass 6, 7.
Comparative Effects
Hemodynamic Effects: Dobutamine typically produces stronger inotropic effects than milrinone, while levosimendan has been shown to be comparable to dobutamine in increasing cardiac index 5, 7.
Vascular Effects: Milrinone and levosimendan cause more vasodilation than dobutamine, which may result in more pronounced hypotension 5, 7.
Arrhythmogenic Potential: Epinephrine and dopamine have higher risks of tachycardia and arrhythmias compared to other inotropes 1.
Important Considerations and Cautions
Inotropes should be used at the lowest effective dose for the shortest duration possible due to potential adverse effects 1.
All positive inotropes can increase myocardial oxygen demand, potentially worsening ischemia in patients with coronary artery disease 1.
Common adverse effects include tachycardia, arrhythmias, hypotension (especially with phosphodiesterase inhibitors), and increased myocardial oxygen consumption 1.
Levosimendan may offer advantages in certain situations due to its calcium-sensitizing properties and lower impact on myocardial oxygen consumption 4, 6.
Careful monitoring of hemodynamic parameters is essential when using any inotropic agent 1.