What is the use of Milrinone (Amrinone)

From the Guidelines

Milrinone should be used with caution in patients with acute heart failure, particularly those with coronary artery disease, due to potential increased medium-term mortality, and its administration should be guided by the most recent evidence-based guidelines 1.

Key Considerations

• Milrinone is a phosphodiesterase-3 inhibitor that increases intracellular cyclic adenosine monophosphate (cAMP) in cardiac and vascular smooth muscle cells, enhancing cardiac contractility and causing peripheral vasodilation.
• The typical dosing of milrinone begins with a loading dose of 25-75 mcg/kg administered intravenously over 10-20 minutes, followed by a continuous infusion of 0.375-0.75 mcg/kg/minute 1.
• Milrinone is particularly useful in patients with reduced cardiac output who also have elevated pulmonary capillary wedge pressure or systemic vascular resistance.
• Common side effects include hypotension, arrhythmias, and headaches, and continuous hemodynamic monitoring is essential during administration.
• The effects of milrinone are maintained during concomitant beta-blocker therapy, as its cellular site of action is distal to the beta-adrenergic receptors 1.

Clinical Use

• Milrinone may be preferred to dobutamine in patients on concomitant beta-blocker therapy and/or with an inadequate response to dobutamine, with a class of recommendation IIa, level of evidence C 1.
• However, the data regarding the effects of phosphodiesterase inhibitor administration on the outcome of patients with acute heart failure are insufficient and raise concerns about safety, particularly in patients with ischemic heart failure 1.
• Therefore, milrinone should be used judiciously, with careful consideration of the potential benefits and risks, and in accordance with the most recent evidence-based guidelines 1.

From the FDA Drug Label

INDICATIONS AND USAGE Milrinone Lactate Injection is indicated for the short-term intravenous treatment of patients with acute decompensated heart failure. WARNINGS Whether given orally or by continuous or intermittent intravenous infusion, milrinone lactate has not been shown to be safe or effective in the longer (greater than 48 hours) treatment of patients with heart failure The primary use of milrinone is for the short-term intravenous treatment of patients with acute decompensated heart failure 2.

• Key points:
  • It is not recommended for long-term treatment (greater than 48 hours) due to increased risk of hospitalization and death 2.
  • Patients should be closely monitored with electrocardiographic equipment due to the risk of ventricular arrhythmias 2 2.

From the Research

Milrinone Overview

• Milrinone is a phosphodiesterase 3 inhibitor with positive inotropic and vasodilator properties 3
• It is used in the treatment of acute decompensated heart failure and can be employed as a home infusion therapy or a bridge to cardiac transplant 4

Clinical Uses

• Milrinone is indicated for the short-term treatment of patients with acute decompensated heart failure 3
• It can be used as a destination therapy for cardiac transplant or as palliative therapy for cardiomyopathy in pediatric outpatients 3
• Milrinone is also used in the management of acute decompensated heart failure, particularly in patients with low output syndrome who require inotropic support 5

Comparison with Other Agents

• A meta-analysis comparing milrinone with dobutamine in acute decompensated heart failure found that milrinone was associated with a lower risk of mortality 6
• Another study compared nesiritide with milrinone in the treatment of acute decompensated heart failure and found that nesiritide led to improved patient hemodynamics and a trend toward decreases in length of stay and rehospitalization 7

Adverse Effects and Limitations

• Milrinone can cause adverse effects such as increased risk of arrhythmias and hypotension, which often limit the doses used in clinical practice 4
• It is primarily cleared by renal excretion, and its use is often avoided in patients with acute renal failure or end-stage renal disease 4