What is the preferred inotropic agent, levosimendan (Calcium Sensitizer) or milrinone (Phosphodiesterase Inhibitor), in minimal invasive Coronary Artery Bypass Grafting (CABG)?

Levosimendan vs Milrinone in Minimally Invasive CABG

Levosimendan is the preferred inotropic agent over milrinone in minimally invasive CABG due to its superior effects on myocardial protection, hemodynamic parameters, and clinical outcomes. 1, 2

Mechanisms of Action

• Levosimendan works through calcium sensitization by binding to cardiac troponin-C, increasing myocardial contractility without raising intracellular calcium concentrations 1
• Levosimendan provides vasodilation through ATP-sensitive potassium channels in vascular smooth muscle and has mild phosphodiesterase III inhibitory effects 1, 3
• Milrinone acts primarily as a phosphodiesterase inhibitor, increasing cyclic AMP levels which leads to increased contractility and vasodilation 4

Comparative Advantages of Levosimendan

• Levosimendan increases cardiac output and stroke volume while decreasing pulmonary wedge pressure, systemic vascular resistance, and pulmonary vascular resistance more effectively than milrinone 2
• Levosimendan demonstrates lower coronary sinus lactate levels compared to milrinone, indicating better myocardial metabolism and less ischemia 2
• Levosimendan is associated with less hypotension (46.7% of patients on milrinone required norepinephrine vs. fewer in levosimendan group) 2

Clinical Benefits in CABG

• Preoperative administration of levosimendan (24 μg/kg over 10 minutes) before cardiopulmonary bypass reduces time to tracheal extubation, ICU length of stay, and postoperative troponin I concentrations 1, 5
• Levosimendan shows evidence of myocardial preconditioning when administered before CABG, resulting in lower postoperative troponin I levels and higher cardiac index 5
• Elective preoperative initiation of levosimendan 12 hours before operation provides better improvement in cardiac function, lower mortality and complication rates, and reduced need for additional inotropic support 6

Optimal Timing and Dosing

• For best outcomes, levosimendan should be administered 12 hours before surgery at 0.2 μg/kg/min 6
• Alternative effective timing includes administration just before cardiopulmonary bypass at a dose of 24 μg/kg over 10 minutes 5
• When used during surgery, a loading dose of 10 μg/kg over 10 minutes followed by infusion at 0.1 μg/kg/min is effective 2

Special Considerations

• Levosimendan is particularly beneficial in patients with reduced left ventricular ejection fraction undergoing CABG 1
• Levosimendan has an active metabolite (OR-1896) with a half-life of approximately 80 hours, providing prolonged hemodynamic effects for up to 2 weeks after a 24-hour infusion 3
• Unlike dobutamine, levosimendan's hemodynamic effects are not attenuated with concomitant beta-blocker use, making it ideal for patients on beta-blocker therapy 3

Monitoring Parameters

• Key monitoring parameters for levosimendan use include cardiac output, stroke volume, systemic and pulmonary vascular resistance, heart rate, and blood pressure 1
• Coronary sinus lactate levels can be monitored as an indicator of myocardial metabolism and ischemia 2
• Pulmonary artery catheter measurements are valuable for monitoring the effects of levosimendan on pulmonary pressures and cardiac output 4

Clinical Outcomes

• Levosimendan reduces the need for intraaortic balloon pump support compared to conventional treatment (10% vs 50%) 6
• Levosimendan decreases the incidence of postoperative atrial fibrillation, myocardial infarction, and ventricular arrhythmias compared to dobutamine 1
• Levosimendan is associated with improved survival rates and reduced complications in cardiogenic shock compared to traditional inotropes 7