Levosimendan Versus Milrinone in the Management of Impaired Left Ventricular Function in Patients Undergoing Coronary Artery Bypass Graft Surgery
Authors: Amin Sheta W. , Abd-Elgalil Sallam M. , Mohamed Shafeek A. , Ahmed Mahran M. , Hamawy Tamer Y. , Fathi Lotfy M. 
Published: September 2019

Background:
Patients undergoing cardiac surgery are at risk of postcardiotomy myocardial dysfunction. This condition causes delayed recovery, organ failure, prolonged intensive care unit and hospital stays, and an increased risk of mortality; these patients often require inotropic agent support. Levosimendan is a calcium sensitizer with a unique mechanism of action, binding to cardiac troponin C and enhancing myofilament responsiveness to calcium, increasing myocardial contraction without increasing myocardial oxygen consumption. Phosphodiesterase III inhibitors such as milrinone provide an alternative means of inotropic support by increasing the concentration of cyclic AMP and intracellular calcium. They also have vasodilatory effects.

Objective:
The aim of this study was the comparison between levosimendan versus milrinone regarding their effects on the hemodynamics, need for additional mechanical (intra aortic balloon pump) or pharmacological support to the heart, weaning from mechanical ventilation and duration of intensive care unit stay for patients after Off-Pump Coronary Artery Bypass Graft (OPCABG) surgery suffering from impaired left ventricular function (preoperative ejection fraction ≤ 40%).

Methods:
60 patients between 40 and 70 years of both sexes with impaired left ventricular function (ejection fraction ≤ 40%), New York Heart Association (NYHA III & IV), undergoing elective Off-Pump Coronary Artery Bypass Graft (OPCABG) surgery were selected for this study. After induction of anesthesia, patients were randomly assigned to one of two equal groups each containing 30 patients:
Group L (Levosimendan group) included patients who received levosimendan 0.1- 0.2 µg/kg/min. Started immediately with the induction of anesthesia.
Group M (Milrinone group) included patients who received milrinone 0.4-0.6 µg/kg/min. Started immediately with the induction of anesthesia.
In both groups, norepinephrine was titrated (8 mg norepinephrine in 50 ml saline) to keep mean arterial pressure MAP ≥ 70 mmHg.
Hemodynamic findings included Preoperative and post ICU discharge ejection fraction, systemic and pulmonary artery pressures, systemic and pulmonary vascular resistance, cardiac output and stroke volume. Also laboratory findings included Serum lactate and Troponin I., in addition, to post operative findings were: Need for intra aortic balloon pump, time of weaning from the ventilator, days of ICU stay and appearance of drug allergy compared in both groups.

Results:
There was a significant increase in the ejection fraction in both groups that was greater in the levosimendan group. The decrease in pulmonary pressure in the levosimendan group was more significant than milrinone group. There was a gradual decrease in pulmonary and systemic vascular resistance in both groups with a more significant decrease in the levosimendan group. There was a gradual increase in cardiac output and stroke volume in both groups that was greater in the levosimendan group. Serum lactate gradually decreased in both groups with an insignificant difference; there was an increase in serum troponin I level in both groups which was more significant in the milrinone group. Weaning from mechanical ventilation and length of ICU stay was shown to be significantly shorter in time in the levosimendan group.

Conclusion:
Both levosimendan and milrinone caused a significant increase in cardiac output, stroke volume and ejection fraction, with a decrease in pulmonary and systemic vascular resistance. These effects improved cardiac performance by decreasing afterload and increasing cardiac inotropism. It was noticed that these effects were more significant with levosimendan than milrinone. Also, there was a decrease in ICU stay, mechanical ventilation timing and hospital stay with levosimendan than milrinone which decreased the costs of treatment for the patients.