LEVOSIMENDAN ENHANCES CARDIAC PERFORMANCE IN PATIENTS UNDERGOING CARDIAC SURGERY

Abstract

Introduction Levosimendan (L) is a new myofilament calcium sensitizer that has been shown to enhance left ventricular (LV) systolic and diastolic function and produce arterial and venous vasodilation in vivo. This investigation was designed to assess the safety and efficacy of L in enhancing cardiac performance after cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery. Methods The hemodynamic and electrophysiologic effects of L were characterized in 18 patients undergoing cardiac surgery including CPB. After Institutional Review Board approval, the trial was carried out in a randomized, double-blind manner. Patients gave written, informed consent and were then randomized to receive either intravenous placebo, or low dose L (18 ug/kg bolus followed by a 0.2 ug/kg/min infusion), or high dose L (36 ug/kg bolus followed by a 0.3 ug/kg/min infusion). Placebo or L boluses were administered 15 min prior to separation from CPB and infusions were maintained for a total of 6 hours. Systemic and pulmonary hemodynamics were recorded at selected intervals before and after CPB. Pulmonary capillary wedge pressure was maintained between 10-15 mmHg with the infusion of intravenous crystalloid. Arterial blood gas tensions and plasma concentrations of L were obtained at selected intervals. ECG was continuously recorded by Holter monitoring (8 hrs preoperative to 30 hrs postoperative). Changes between placebo and experimental groups were assessed with Two-way ANOVA analysis with p<0.05 constituting statistical significance. Results Demographics, preoperative hemodynamics, type of surgery, and durations of aortic crossclamp and CPB were equivalent between groups. L significantly increased cardiac output in a dose dependent fashion (mean +/- SD data, Figure 1) Heart rate was not significantly increased while stroke volume increased with L. Systemic and pulmonary pressures and vascular resistances were reduced by L. Myocardial oxygen demand was not increased relative to control for low or high dose L. Blood gas tensions and shunt fraction were similar between groups. No significant alteration in the frequency of supra-ventricular and ventricular ectopy were observed.Figure 1Conclusion Levosimendan improves cardiac performance in patients undergoing cardiac surgery and CPB. It also appears safe by virtue of not causing dysrhythmias or tachycardia. Future trials will compare L to other therapies for hemodynamic support after CPB.