MILRINONE

 

Milrinone is a phosphodiesterase-3 (PDE-3) inhibitor that has positive inotropic (increasing the strength of heart muscle contractions) and vasodilatory effects. It is primarily used for the management of acute and chronic heart failure. In the context of anesthesia, milrinone has several important roles:

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1. Management of heart failure patients: Patients with heart failure undergoing surgery may have impaired cardiac function and may not tolerate the hemodynamic changes associated with anesthesia and surgery. Milrinone, with its inotropic and vasodilatory properties, can help maintain cardiac output and systemic perfusion during the perioperative period.

2. Cardiac surgery: Milrinone is often used during cardiac surgery, especially in patients with pre-existing ventricular dysfunction or those at risk for low cardiac output syndrome postoperatively. By improving myocardial contractility and decreasing systemic vascular resistance, milrinone can help maintain adequate cardiac function and tissue perfusion during and after surgery.

3. Pulmonary hypertension: Milrinone can also be used to manage patients with pulmonary hypertension undergoing surgery. It has vasodilatory effects on the pulmonary vasculature, which can help reduce pulmonary arterial pressure and improve right ventricular function.

4. Weaning from cardiopulmonary bypass: In cardiac surgeries that require cardiopulmonary bypass (CPB), milrinone can be used to support the heart during the transition from CPB back to the patient's own circulation. This can help facilitate weaning from CPB and prevent complications related to low cardiac output.

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Here are the main steps in milrinone's mechanism of action:

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1. Inhibition of phosphodiesterase-3: Milrinone selectively inhibits PDE-3 enzymes, which are responsible for breaking down cAMP in cardiac and smooth muscle cells.

2. Increased cAMP levels: By inhibiting PDE-3, milrinone prevents the degradation of cAMP, leading to increased intracellular cAMP levels in both cardiac and vascular smooth muscle cells.

3. Cardiac muscle effects: Elevated cAMP levels in cardiac muscle cells activate protein kinase A (PKA), which in turn phosphorylates several target proteins. This phosphorylation leads to increased calcium influx during the action potential and increased calcium release from the sarcoplasmic reticulum. The net result is an increase in the strength of cardiac muscle contractions, which enhances cardiac output.

4. Vascular smooth muscle effects: In vascular smooth muscle cells, increased cAMP levels activate PKA, which phosphorylates target proteins that ultimately reduce intracellular calcium levels. This leads to relaxation of vascular smooth muscle, causing vasodilation, particularly in the arterial system.

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                                                                                         Key points about Milrinone

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• Inhibits cAMP specific phosphodiesterase (PDE) type 3 primarily in myocardium and vascular smooth muscle.

 

• Phosphodiesterase is an enzyme that hydrolyzes the second messenger cyclic adenosine monophosphate (cAMP) and guanosine monophosphate (cGMP), terminating their effects in tissues.

 

• In myocardial cells, it increases intracellular calcium leading to + inotropy and + lusitropy and + chronotropy.

 

• Enhanced myocardial relaxation (lusitropy) improves diastolic function.

 

• Vasculature: It causes vascular smooth muscle relaxation which decreases afterload (SVR and PVR) and preload.

 

• Beneficial cardiac effects: decreases wall tension and has minimal effect on MVO2 consumption.

 

• Increased cardiac output (CO) from increased contractility.

 

• Decreased Pulmonary Artery Occlusive Pressure (PAOP).

 

• Minimal effect on HR and MVO2 consumption.

 

• Indications: cardiac support in patients with acute heart failure, pulmonary hypertension, or chronic heart failure.

 

• Milrinone is commonly used in right heart failure by increasing ventricular contractility and decreasing pulmonary vascular resistance.

 

• Adverse effects: ventricular dysrhythmias, hypotension, hypokalemia.

 

• Contraindicated in severe aortic or pulmonic valvular heart disease and hypertrophic subaortic stenosis.

 

• Excretion: 80–90% excreted unchanged by the kidneys.

 

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