What is the effect of Milrinone (Amrinone) on afterload?

From the Guidelines

Milrinone should be used with caution in patients with heart failure, as it can reduce afterload and increase cardiac output, but its use is not recommended for long-term treatment due to concerns about toxicity and lack of evidence for efficacy 1.

Key Points

• Milrinone is a phosphodiesterase-3 inhibitor that causes vasodilation in both arterial and venous vessels, reducing systemic vascular resistance and pulmonary vascular resistance 1.
• The typical dosing of milrinone includes a loading dose of 50 mcg/kg administered over 10 minutes, followed by a continuous infusion of 0.375-0.75 mcg/kg/min 1.
• Milrinone has positive inotropic effects, increasing cardiac contractility, which provides additional benefit in heart failure management 1.
• Careful monitoring of blood pressure is essential when administering milrinone, as excessive vasodilation can lead to hypotension 1.
• The medication should be used cautiously in patients with renal impairment, as it is primarily eliminated by the kidneys, and dose adjustments may be necessary in these patients 1.

Considerations

• The use of milrinone is not recommended for long-term treatment of heart failure due to concerns about toxicity and lack of evidence for efficacy 1.
• Intermittent infusions of positive inotropic agents, including milrinone, should not be used in the long-term treatment of heart failure, even in its advanced stages 1.
• The choice of inotropic agent may need to be changed during longer periods of support, and the ongoing need for inotropic support and the possibility of discontinuation should be regularly assessed 1.

From the FDA Drug Label

Milrinone lactate is a positive inotrope and vasodilator, with little chronotropic activity different in structure and mode of action from either the digitalis glycosides or catecholamines Clinical studies in patients with congestive heart failure have shown that milrinone lactate produces dose-related and plasma drug concentration-related increases in the maximum rate of increase of left ventricular pressure Milrinone lactate also produces dose-related and plasma concentration-related increases in forearm blood flow in patients with congestive heart failure, indicating a direct arterial vasodilator activity of the drug.

The use of milrinone after a load is not explicitly mentioned in the provided drug label. However, it can be inferred that milrinone is administered as an infusion, and the label mentions that single-dose vials require preparation of dilutions prior to administration to patients intravenously.

• The label does mention that milrinone lactate produces dose-related and plasma drug concentration-related increases in the maximum rate of increase of left ventricular pressure, which may be relevant to its use after a load.
• The therapeutic range of plasma milrinone concentrations is 100 ng/mL to 300 ng/mL.
• No direct information is provided about the use of milrinone after a load, and caution should be exercised when administering this medication 2.

From the Research

Milrinone Afterload Reduction

• Milrinone is a phosphodiesterase inhibitor that increases intracellular cyclic adenosine monophosphate, resulting in a positive inotropic effect on the heart and vasodilatation in the periphery 3.
• The hemodynamic consequences of milrinone action produce left ventricular afterload reduction, with an increase in cardiac output and a reduction in total peripheral resistance 3.
• Milrinone has been shown to decrease pulmonary vascular resistance, which is a distinct advantage over sympathomimetic amines 3.

Clinical Utility of Milrinone

• Milrinone has been demonstrated to be safe and efficacious in the treatment of decompensated heart failure, with significant decreases in left ventricular end-diastolic pressure, pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance 4.
• Long-term intravenous milrinone therapy has been shown to be safe and well tolerated, with sustained long-term hemodynamic effects and significant improvements in systemic hemodynamics 5.
• Milrinone has been used in pediatric patients with heart diseases, with improvements in ejection fraction and fractional shortening of the left ventricle, and a low incidence of adverse events 6.

Safety and Efficacy of Milrinone

• The safety and efficacy of milrinone in critically ill adult patients with cardiac dysfunction have been evaluated in a systematic review, which found that the current evidence suffers from considerable risks of both bias and random error, and demonstrates no benefits 7.
• Milrinone has been shown to be effective in preventing low cardiac output after cardiac surgery, with a low incidence of adverse events such as hypotension and arrhythmia 6.
• The use of milrinone as primary inodilator therapy may be associated with less need for mechanical ventricular support, although mortality rates while awaiting transplantation were statistically similar 5.