Milrinone: Indications, Side Effects, Mechanism of Action and Precautions

It is a medicine used in patients with heart failure.

Milrinone is an inhibitor of phosphodiesterase three that works to increase the contractility of the heart and decrease pulmonary vascular resistance. Milrinone also works to vasodilate, which helps relieve the increased pressures (afterload) on nature, thus improving its pumping action.


Although it has been used in people with heart failure for many years, recent studies suggest that milrinone may have some adverse side effects that have caused some debate about its clinical use.

In general, milrinone is compatible with the ventricular function of the heart by decreasing the degradation of cAMP and, therefore, increasing the levels of phosphorylation of many components in the heart that contribute to contractility and heart rate.

The use of milrinone after cardiac surgery has been debated due to the possible increased risk of postoperative atrial arrhythmias.

However, in the short term, milrinone has been considered beneficial for those who experience heart failure and an effective therapy to maintain cardiac function after cardiac surgeries.

There is no evidence of any long-term beneficial effect on survival. In critically ill patients with evidence of cardiac dysfunction, there is limited evidence of good quality to recommend its use.


Side effects

Headaches can occur. If this effect persists or worsens, inform your doctor immediately.

Tell your doctor immediately if you have any severe side effects, such as:

  • Pain.
  • Redness
  • Swelling at the injection site.
  • Accelerated heart rate.
  • Dizziness
  • Fainting.
  • Chest pain.

Seek medical attention immediately if you notice any symptoms of a severe allergic reaction, which include: rash, itching/swelling (especially of the face, tongue, or throat), severe dizziness, and trouble breathing.

This is not a complete list of possible side effects. Contact your doctor or pharmacist if you notice other effects not mentioned above.

Mechanism of action

Cyclic adenosine monophosphate (cAMP) causes increased protein kinase A (PKA) activation. PKA is an enzyme that phosphorylates many elements of the contractile machinery within the cardiac cell. In the short term, this leads to a greater force of contraction.

Phosphodiesterases are enzymes responsible for the decomposition of cAMP. Therefore, when phosphodiesterases decrease the cAMP level in the cell, they also decrease the active fraction of PKA within the cell and reduce the force of contraction.

Milrinone is an inhibitor of phosphodiesterase-3. This drug inhibits the action of phosphodiesterase-3 and therefore prevents the degradation of cAMP.

With the increase in cAMP levels, there is an increase in the activation of PKA. This PKA will phosphorylate many components of the cardiomyocyte, such as calcium channels and myofilament components.

Phosphorylation of calcium channels allows an increase in calcium entry into the cell. This increase in calcium influx results in greater contractility. PKA also phosphorylates potassium channels promoting its action.

Potassium channels are responsible for the repolarization of cardiomyocytes, which increases the rate at which cells can depolarize and generate contraction.

PKA also phosphorylates components in myofilaments, which allows actin and myosin to interact more efficiently and, therefore, increases the contractility and inotropic state of the heart.

Milrinone allows the stimulation of cardiac function independently of the β-adrenergic receptors that appear to be negatively regulated in those with heart failure.


If you are allergic, tell your doctor before using milrinone. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Consult your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history:

  • Heart valve disease
  • Kidney disease
  • Mineral imbalance (low level of potassium in the blood)
  • Irregular heartbeat (such as atrial fibrillation )

Milrinone should only be used strictly if necessary during pregnancy. Consult your doctor before breastfeeding.