What are inotropes and chronotropes?

Inotropes and Chronotropes: Definition and Clinical Applications

Inotropes are medications that increase myocardial contractility (force of heart contraction), while chronotropes are medications that affect heart rate. Both classes of medications play crucial roles in managing cardiovascular conditions, particularly in shock and heart failure.

Inotropic Medications

Inotropic agents increase the force of myocardial contraction through various mechanisms:

Catecholamines/Adrenergic Agents

• Dobutamine: Primary inotropic agent working through β1-receptor stimulation to produce dose-dependent positive inotropic effects. Dosing range: 2-20 μg/kg/min without loading dose 1.
• Dopamine: Stimulates β-adrenergic receptors both directly and indirectly. Effects are dose-dependent 2:
  • Low doses (2-3 μg/kg/min): Primarily renal effects
  • Medium doses (5-9 μg/kg/min): Inotropic effects
  • High doses (10-20 μg/kg/min): Vasopressor effects through α-receptor stimulation
• Epinephrine: Non-selective agent with powerful inotropic properties at doses of 0.05-0.3 μg/kg/min 2.
• Norepinephrine: Primarily a vasopressor with some inotropic properties, used in cardiogenic shock with hypotension 2.

Phosphodiesterase Inhibitors

• Milrinone: Increases intracellular calcium levels and myocardial contractility (0.375-0.75 μg/kg/min). Causes arterial and venous vasodilation without directly stimulating adrenergic receptors 3.
• Enoximone: Similar mechanism to milrinone (1.25-7.5 μg/kg/min) 1.

Calcium Sensitizers

• Levosimendan: Enhances cardiac contractility through calcium sensitization (0.1 μg/kg/min). Has vasodilatory properties 1.

Chronotropic Medications

Chronotropic agents specifically affect heart rate:

Positive Chronotropes (Increase Heart Rate)

• Dobutamine: Besides inotropic effects, produces dose-dependent positive chronotropic effects 2.
• Dopamine: Increases heart rate, especially at higher doses 2.
• Epinephrine: Powerful positive chronotropic effect 2.
• Isoproterenol: Primarily used for its chronotropic effects in bradyarrhythmias 1.

Negative Chronotropes (Decrease Heart Rate)

• Beta-blockers: Reduce heart rate by blocking β-adrenergic receptors 1.
• Ivabradine: Selective inhibitor of the cardiac pacemaker If current that controls spontaneous diastolic depolarization in the sinoatrial node, reducing heart rate without affecting contractility 4.
• Digoxin: Moderate negative chronotropic effect through increased vagal tone 1.

Clinical Applications

Heart Failure

• Inotropes are indicated in patients with low cardiac output, hypoperfusion, and dilated, hypokinetic ventricles 2.
• Short-term use to stabilize patients with acute decompensated heart failure 1.
• Bridge therapy to more definitive treatment (mechanical circulatory support, transplantation) 2.

Cardiogenic Shock

• Dobutamine is first-line for low cardiac output with normal blood pressure 2.
• Norepinephrine is preferred when hypotension is present 2.
• Combination therapy may be necessary in refractory cases 2.

Septic Shock

• Norepinephrine is first-line for fluid-refractory vasodilated septic shock 2.
• Dobutamine may be added when cardiac dysfunction is present 2.

Important Considerations

• Preload Assessment: Ensure adequate preload before administering inotropes 1.
• Monitoring: Continuous clinical and ECG monitoring is required due to risk of arrhythmias 2.
• Duration: Use at the lowest effective dose for the shortest duration possible 1.
• Weaning: Gradual tapering is essential, particularly with dobutamine (decrease by steps of 2 μg/kg/min) 2.

Risks and Adverse Effects

• Most inotropes increase myocardial oxygen demand 2.
• Increased risk of atrial and ventricular arrhythmias 2.
• Tachycardia and potential myocardial ischemia 5.
• Long-term use associated with increased mortality 1.
• Tachyphylaxis may develop, especially with continuous administration 2.

Inotropes and chronotropes are powerful tools in managing cardiovascular conditions, but their use requires careful consideration of benefits versus risks, with close monitoring and a plan for timely discontinuation once clinical stability is achieved.