EComment. Preoperative levosimendan administration in cardiac surgery patients

Abstract

According to its dual mode of action, levosimendan is both a calcium sensitizer, hence enhancing myocardial contractility without increasing the concentration of intracellular calcium, and a potassium adenosine triphosphate(ATP)-dependent channel opener, leading to vasodilation, which reduces left ventricular afterload and improves blood flow to vital organs [1]. Levosimendan exerts vasodilatory and possible anti-ischaemic and cardioprotective effects by opening of the ATP-dependent potassium-channel. Levosimendan may facilitate weaning from cardiopulmonary bypass (CPB) by both its inotropic and lusitropic properties. It enhances both systolic and diastolic left and right ventricular performance [1]. Levosimendan has a half-life of 1 hour, meaning that it is quickly eliminated from plasma. However, it has an active metabolite (OR-1896), which is formed by intestinal bacteria. OR-1896 has a similar haemodynamic profile to its parent compound, but a longer half-life of 70-80 hours. These pharmacokinetic features provide plausible explanations for the prolonged haemodynamic effects of levosimendan metabolites, which last for up to 7-9 days after discontinuation of a 24-h infusion of levosimendan [2]. We read with great interest the paper by Angadi et al. [3], regarding levosimendan use in paediatric cardiac surgey patients. They suggest that levosimendan is beneficial in improving cardiac performance and reducing the left ventricular afterload. It is promising as a rescue drug on the named-patient basis for a potential clinical benefit in low cardiac ouput syndrome (LCOS) and postcardiac surgeries. We agree with their implications and also would like to add a short comment on preoperative levosimendan administration. Currently, the use of levosimendan in cardiac surgery has gradually increased and is studied more in adults than in children. In cardiac surgery patients, candidates to receive levosimendan include low preoperative left ventricular ejection fraction (LVEF)(<35%), high-risk patients (emergency operation, decompensated heart failure), weaning failure from CPB, scheduled for mechanical assist device (intra-aortic balloon pump/left ventricular assist device), or postoperative LCOS [1]. Levosimendan is often used to improve peri- and postoperative haemodynamics to reduce morbidity and hospital stay. Levosimendan may be administered preoperatively, intraoperatively (before, during, or after CPB), or postoperatively. The timing depends on the logistic utilities of the hospital and the haemodynamic target [1]. Current dosing regimes use levosimendan perioperatively. However, during CPB, there is hypoperfusion in the hepatosplenic region, which may affect intestinal function. Thus, patients receiving levosimendan perioperatively may not have the active metabolite OR-1896. In our retrospective study [4] we reported early results of 18 patients receiving preoperative levosimendan that underwent coronary artery bypass grafting (CABG) with LVEF of 35% or less. Levosimendan infusion was given at a rate of 0.2 microgram/kg/min without a loading dose. It started 12 h before surgey. There was no in-hospital mortality. Levosimendan infusion was tolerated well in all patients. There were significant amelioration in haemodynamic parameters and diuresis. All patients showed no stormy postoperative recovery. In the prospective randomized study by Leppikangas et al. [5], levosimendan improved haemodynamics during the 4 day postoperative period, when infused a day before surgery. The formation of metabolites was documented for this 4 day postoperative period. We think that preoperative levosimendan administration may improve haemodynamic function and clinical outcome in patients with poor left ventricular function undergoing CABG. Conflict of interest: none declared