Benefits of Preoperative and Intraoperative Intravenous Levosimendan for patients with Low Left Ventricular Ejection Fraction Undergoing Coronary Artery Bypass Grafting: A Literature Review
Research Question
In patients with a documented medical diagnosis of left ventricular systolic dysfunction who are undergoing procedures such as coronary artery bypass or off-pump coronary artery bypass, with and or without valve replacement, how does prophylactic and or intraoperative administration of levosimendan compared to other pharmacologic agents such as dobutamine and epinephrine, and or mechanical assist devices such as an intra-aortic balloon pump, prevent or reduce postoperative complications?
Review of Literature
The literature review was conducted by searching for terms such as: levosimendan, beta adrenergic agonists, cardiac surgery, coronary artery bypass grafting (CABG), left ventricular systolic dysfunction, low left ventricular ejection fraction (LVEF), intra-aortic balloon pump (IABP), inotropes, postoperative complications, intensive care unit (ICU), low cardiac output syndrome (LCOS); filtering included: randomized controlled trials (RCTs) and meta-analysis.
Patients with left ventricular systolic dysfunction and low LVEF who are undergoing CABG procedures with or without valve replacement are associated with a higher risk of complications compare to patients with normal left ventricular systolic function and often require inotropic support to maintain or increase myocardial contractility. However, conventional treatment modalities such as beta adrenergic agonists and phosphodiesterase inhibitors further increase myocardial oxygen consumption, and intra-aortic balloon pumps are associated with increased postoperative complications (Lomivorotov et. al, 2012). Levosimendan is a calcium sensitizer with inodilator properties that enhances myocardial contractility without causing the unwanted increases in myocardial oxygen consumption (Bozhinovska, Taleska, Fabian, & Šoštarič, 2016). The purpose of this literature review is to determine the possible advantages of preoperative and intraoperative levosimendan in patients with low LVEF undergoing extensive cardiac surgical procedures.
Levosimendan is considered a more recently developed calcium sensitizer compared to the traditional medications that are used to enhance myocardial contractility during CABG procedures such as dobutamine, norepinephrine, and epinephrine, and there are controversies as to whether this drug provides particular advantages of patient outcomes such as: cardioprotective mechanisms, more stable hemodynamic status, and decreased incidence of postoperative complications.
In the following literature reviews, Levosimendan has been administered either preoperatively or intraoperatively, to patients undergoing various CABG procedures with a known history of decreased LVEF, and compared to the following placebos: other medications that were made up of multivitamin solutions, dobutamine, and or epinephrine, and or norepinephrine, and intra-aortic balloon pumps. Jiménez-Rivera et. al (2020) performed a cohort study to evaluate the preconditioning effects of levosimendan in patients with moderate to severe systolic dysfunction with a low EF (<40%), on its ability to decrease postoperative complications, specifically in preventing postoperative LCOS compared to dobutamine; and performed numerous Monte Carlo simulations and probabilistic analyses in order to assess the cost-effectiveness of levosimendan (Jiménez-Rivera et. al, 2020). The patients who received preconditioning with levosimendan demonstrated the following statistically significant findings: no incidences of cardiogenic shock, decreased lactate levels, less mechanical respiratory support, decreased occurrences of new-onset atrial fibrillation, postoperative renal failure, and decreased amount of time in the ICU; lower occurrences of LCOS; and the probabilistic analysis demonstrated that these patients who received levosimendan had overall lower hospital bills due to the decreased incidence of postoperative complications (Jiménez-Rivera et. al, 2020). The authors who wrote Prophylactic preoperative levosimendan for off-pump coronary artery bypass grafting in patients with left ventricular dysfunction: Single-centered randomized prospective study, found that the levosimendan group had increases in cardiac index (CI) which suggests overall enhanced myocardial contractility, decreased pulmonary capillary wedge pressures (PCWPs) and lactate levels, as well as a decrease in occurrences of POAF, LCOS, and AKI (Desai, Sarkar, and Umbarkar, 2018). Lomivorotov et. al (2012) performed a randomized control trial in order to compare three separate groups who received one of the following: preoperative IABP, IABP with concomittment administration of levosimendan, and levosimendan alone, in which they found statistically significant hemodynamic parameters, decreases in cardiac troponin 1 levels, and decreased ICU stay (Lomivorotov et. al, 2012).
Conclusion
Levosimendan has been compared to various placebos and among groups of patients undergoing various CABG procedures. Overall, based on the findings on utilizing levosimendan in the preoperative and intraoperative periods to patients with decreased LVEF suggest that this new calcium sensitizer provides hemodynamically stable outcomes that are associated with a decreased need to use other inotropic support measures as well as an overall decreased incidence of multiple postoperative complications such as LCOS, acute kidney injury, mechanical ventilation, ICU stay and hospital stay. More evidence-based research studies are needed to determine the definitive answer on whether the cost-to-benefit ratio of using levosimendan offers a more cost-effective plan than previously used medications. There is also a need for more research studies to determine an exact dose range and time frame to administer levosimendan that would offer the best patient outcomes.
References
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