What is the use of milrinone (phosphodiesterase 3 inhibitor) in patients after heart surgery?

Milrinone After Heart Surgery

Milrinone is beneficial for the prevention and treatment of low cardiac output syndrome following cardiac surgery, particularly in pediatric patients undergoing biventricular repair, though clinicians must balance its hemodynamic benefits against an increased risk of postoperative atrial fibrillation.

Primary Indication and Evidence

Milrinone is specifically recommended for preventing and treating low cardiac output syndrome (LCOS) after cardiac surgery. 1 The strongest evidence comes from a Level 1 pediatric placebo-controlled trial demonstrating effectiveness in preventing LCOS in infants and children following biventricular cardiac repair. 1

Hemodynamic Benefits

Milrinone functions as a phosphodiesterase III inhibitor, providing both positive inotropic and vasodilatory effects through distinct mechanisms from catecholamines or digitalis glycosides. 2

Key hemodynamic improvements include:

• Rapid and sustained increases in cardiac index across all dosing regimens (low 0.375, mid 0.5, high 0.75 mcg/kg/min), with patients showing 27-54% increases depending on baseline cardiac function 3, 4
• Significant reductions in pulmonary capillary wedge pressure and filling pressures 3, 5, 4
• Decreased pulmonary and systemic vascular resistance, making it particularly valuable for right ventricular failure or pulmonary hypertension 1, 6
• Improved cardiac index in neonates with low cardiac output following surgery 1

Comparative Advantages Over Other Inotropes

Milrinone demonstrates several advantages over catecholamines in the post-cardiac surgery setting:

• Lower arrhythmia risk than dobutamine: In patients with low cardiac output after cardiac surgery, dobutamine caused atrial fibrillation in 18% versus only 5% with milrinone (p < 0.04) 7
• Reduced myocardial oxygen consumption compared to catecholamines, as phosphodiesterase III inhibitors decrease left ventricular wall tension despite increasing contractility 1
• Lower postoperative myocardial infarction rates: Amrinone (same drug class) showed 0% MI incidence versus 40% with dobutamine 1
• Better outcomes in specific populations: Children receiving milrinone after tetralogy of Fallot repair had better hemodynamic parameters and shorter ICU stays compared to low-dose epinephrine plus nitroglycerin 1, 7

Critical Safety Considerations and Arrhythmia Risk

The major limitation of milrinone is an increased risk of postoperative atrial fibrillation, which must be carefully weighed against its benefits. In patients undergoing elective cardiac surgery, perioperative milrinone was associated with a 2-4 fold increased risk of postoperative atrial fibrillation (58.2% vs. 26.1% in non-users). 7 Patients who develop atrial fibrillation after receiving milrinone have longer hospital stays (p < 0.001) and higher mortality (p = 0.02). 7

Additional safety concerns include:

• Vasodilation-induced hypotension: Blood pressure and heart rate must be monitored continuously, with infusion rate adjusted or stopped if excessive hypotension occurs 2
• Increased ventricular response in atrial flutter/fibrillation: Milrinone slightly shortens AV node conduction time, potentially increasing ventricular rates in uncontrolled atrial arrhythmias 2
• Contraindication in severe valvular obstruction: Should not be used in severe obstructive aortic or pulmonic valvular disease, and may worsen outflow tract obstruction in hypertrophic subaortic stenosis 2

Dosing Strategy

Standard dosing regimen:

• Loading dose: 50 mcg/kg administered over 10 minutes 3, 5, 4
• Maintenance infusion: 0.375-0.75 mcg/kg/min for minimum 12 hours 3, 5, 4
• Therapeutic plasma concentration range: 100-300 ng/mL 2

The therapeutic response is partially determined by pretreatment hemodynamics: patients with lower baseline cardiac index (1.59 L/min/m²) showed 54% increases versus 27% in those with higher baseline values (2.2 L/min/m²). 8 Patients with high pulmonary vascular resistance (>200 dynes·sec·cm⁻⁵) demonstrated greater PVR reductions (26% fall) compared to others (9% fall). 8

Patient Selection and Monitoring

Ideal candidates for milrinone include:

• Pediatric patients undergoing biventricular cardiac repair 1, 7
• Patients with right ventricular failure or pulmonary hypertension complicating cardiac surgery 6
• Patients with low cardiac output despite adequate filling pressures (PCWP 8-20 mmHg, CI <2.5 L/min/m²) 3, 5, 4
• Patients with single-ventricle physiology requiring reduced systemic vascular resistance 7

Essential monitoring parameters:

• Continuous blood pressure and heart rate monitoring 2
• Cardiac output and stroke volume 9
• Pulmonary capillary wedge pressure and filling pressures 3, 4
• Continuous ECG telemetry for arrhythmia detection 7, 2
• Infusion site monitoring to avoid extravasation 2

Common Pitfalls and How to Avoid Them

Hypovolemia mismanagement: If vigorous diuretic therapy has caused significant decreases in cardiac filling pressure, milrinone should be administered cautiously with close monitoring, as its vasodilatory effects may cause profound hypotension. 2

Electrolyte disturbances: Improvement in cardiac output with resultant diuresis may necessitate diuretic dose reduction. Hypokalemia from excessive diuresis predisposes digitalized patients to arrhythmias and should be corrected before or during milrinone use. 2

Drug incompatibility: Immediate chemical precipitation occurs when furosemide is injected into IV lines containing milrinone—furosemide must never be administered through the same line. 2

Duration limitations: No controlled trial experience exists for infusions exceeding 48 hours; prolonged use should be approached with caution. 2

Alternative Considerations

While levosimendan has shown advantages over milrinone in some contexts (decreased time to extubation, reduced postoperative atrial fibrillation, myocardial infarction, ICU length of stay, acute renal dysfunction, and mortality compared to dobutamine) 1, 9, milrinone remains the guideline-recommended phosphodiesterase III inhibitor with the strongest evidence base specifically for post-cardiac surgery LCOS prevention and treatment. 1

The American Heart Association emphasizes that catecholamine dosing for inotropic support must be individually titrated due to wide variability in clinical response, and milrinone represents a reasonable option alongside epinephrine, levosimendan, dopamine, or dobutamine for cardiogenic shock in pediatric patients. 1, 7