Is Milrinone or Dobutamine more arrhythmogenic?

From the Guidelines

Dobutamine is more arrhythmogenic than milrinone, as evidenced by its higher incidence of atrial fibrillation in patients with low cardiac output after cardiac surgery. The arrhythmogenic potential of these two inotropes is a critical consideration in their use, particularly in patients with pre-existing heart conditions or those at high risk for rhythm disturbances.

Key Differences

• Dobutamine, a beta-adrenergic agonist, directly stimulates beta-1 receptors in the heart, increasing heart rate and contractility but also carrying a higher risk of triggering ventricular arrhythmias, as seen in a study where dobutamine was associated with a higher incidence of AF than milrinone (18% vs 5%; P < 0.04) 1.
• Milrinone, a phosphodiesterase-3 inhibitor, works by increasing intracellular cyclic AMP, improving contractility without the same degree of direct adrenergic stimulation, resulting in less arrhythmogenic potential.

Clinical Implications

• The choice between dobutamine and milrinone should consider the patient's individual risk factors for arrhythmias, with milrinone potentially being a safer option for those with a history of rhythm disturbances.
• Both medications require careful monitoring for hypotension due to vasodilation, which may necessitate concurrent vasopressor support.
• The longer half-life of milrinone means that any adverse effects, including arrhythmias, may persist longer after discontinuation, a factor to consider in treatment planning 1.

From the FDA Drug Label

In patients receiving milrinone lactate in Phase II and III clinical trials, ventricular arrhythmias were reported in 12.1%: Ventricular ectopic activity, 8.5%; nonsustained ventricular tachycardia, 2.8%; sustained ventricular tachycardia, 1% and ventricular fibrillation, 0. 2% Dobutamine is a direct-acting inotropic agent whose primary activity results from stimulation of the β receptors of the heart while producing comparatively mild chronotropic, hypertensive, arrhythmogenic, and vasodilative effects.

The information provided in the drug labels does not allow for a direct comparison of the arrhythmogenic potential of Milrinone and Dobutamine. Milrinone is reported to have caused ventricular arrhythmias in 12.1% of patients, while Dobutamine is described as producing "comparatively mild" arrhythmogenic effects, but no specific incidence is provided in the text.

• Key points:
  • Milrinone: 12.1% incidence of ventricular arrhythmias
  • Dobutamine: described as having "comparatively mild" arrhythmogenic effects, but no specific incidence provided Given the lack of direct comparison and specific incidence data for Dobutamine, no conclusion can be drawn about which drug is more arrhythmogenic 2 3.

From the Research

Arrhythmogenic Effects of Milrinone and Dobutamine

• The arrhythmogenic effects of milrinone and dobutamine have been studied in various clinical settings, including cardiogenic shock and acute decompensated heart failure 4, 5, 6.
• A study published in the Journal of Cardiovascular Pharmacology and Therapeutics found that arrhythmias were more common in patients treated with dobutamine than milrinone (62.9% vs 32.8%, P < 0.01) 5.
• Another study published in Cureus found that both dobutamine and milrinone can trigger ventricular and supraventricular tachyarrhythmias, but the mortality from dobutamine-induced arrhythmias led to an increase in all-cause mortality rates 4.
• A meta-analysis published in Current Problems in Cardiology found that milrinone was associated with a lower risk of mortality in patients with acute decompensated heart failure, but there was no difference between the two strategies for the outcome of arrhythmias 6.
• A study published in the American Journal of Therapeutics found that dobutamine infusion increased the incidence of ventricular arrhythmias, but the arrhythmogenic effect subsided on the day after the dobutamine infusion 7.
• A study published in Progress in Cardiovascular Diseases found that dobutamine increased sinoatrial node automaticity and decreased atrial and atrioventricular node refractoriness, which can lead to arrhythmias 8.
• Overall, the evidence suggests that dobutamine may be more arrhythmogenic than milrinone, but both agents can trigger arrhythmias and require careful monitoring and management 4, 8, 5, 6, 7.

Key Findings

• Dobutamine is associated with a higher incidence of arrhythmias compared to milrinone 5.
• Milrinone is associated with a lower risk of mortality in patients with acute decompensated heart failure 6.
• Both dobutamine and milrinone can trigger ventricular and supraventricular tachyarrhythmias 4.
• The arrhythmogenic effect of dobutamine subsides on the day after the dobutamine infusion 7.
• Careful monitoring and management are required when using either dobutamine or milrinone due to their potential to trigger arrhythmias 4, 8, 5, 6, 7.