When is milrinone (phosphodiesterase 3 inhibitor) indicated?

From the Guidelines

Milrinone is indicated for the short-term treatment of acute decompensated heart failure, particularly in patients with reduced cardiac output, pulmonary congestion, and elevated pulmonary capillary wedge pressure, as stated in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.

Key Considerations

• The typical dosing regimen includes a loading dose of 50 mcg/kg administered over 10 minutes, followed by a continuous infusion of 0.125-0.75 mcg/kg/min, which should be adjusted based on hemodynamic response and renal function, as outlined in the guideline 1.
• Milrinone works as a phosphodiesterase-3 inhibitor that increases cardiac contractility and causes vasodilation, thereby improving cardiac output without significantly increasing myocardial oxygen demand.
• Patients receiving milrinone require close monitoring for hypotension, arrhythmias, and electrolyte imbalances, especially hypokalemia, as noted in the guideline 1.
• Dose reduction is necessary in patients with renal impairment as the drug is primarily eliminated by the kidneys, as stated in the guideline 1.

Clinical Context

• The 2022 AHA/ACC/HFSA guideline for the management of heart failure recommends the use of milrinone in patients with acute decompensated heart failure who are refractory to conventional therapy 1.
• The guideline also notes that there is a lack of robust evidence to suggest the clear benefit of one inotrope over another, and that the choice of agent may need to be changed during longer periods of support 1.
• The European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure also recommend the use of inotropic agents, including milrinone, in patients with hypotension and/or signs of peripheral hypoperfusion 1.

From the FDA Drug Label

Milrinone Lactate Injection is indicated for the short-term intravenous treatment of patients with acute decompensated heart failure. Milrinone is indicated for the short-term intravenous treatment of patients with acute decompensated heart failure 2.

• The treatment should be done with close observation and appropriate equipment.
• It is mostly used in patients who are already on digoxin and diuretics.

From the Research

Indications for Milrinone

• Milrinone is indicated for the treatment of end-stage heart failure patients who are refractory to optimal medical therapy 3
• It is also used in the treatment of acute decompensated heart failure 3, 4, 5
• Milrinone can be employed as a home infusion therapy or a bridge to cardiac transplant 3, 4
• It is used as a destination therapy for cardiac transplant or as palliative therapy for cardiomyopathy in pediatric outpatients 4
• Milrinone is indicated for the short-term treatment of patients with acute decompensated heart failure 4

Specific Patient Populations

• In patients with acute decompensated heart failure (AHF), milrinone is associated with a lower risk of mortality compared to dobutamine 5
• In patients with AHF with destination therapy, milrinone is also associated with improved mortality 5
• However, in patients with ischemic heart failure etiology, milrinone may have a deleterious effect, whereas in nonischemic cardiomyopathy, it may be neutral to beneficial 6

Important Considerations

• Milrinone is primarily cleared by renal excretion, and its use is often limited or avoided in patients with acute renal failure or end-stage renal disease 3
• The drug can cause adverse effects such as an increased risk of arrhythmias and hypotension, which often limit the doses used in clinical practice 3