Levosimendan Enhances Cardiac Performance After Cardiopulmonary Bypass: A Prospective, Randomized Placebo-Controlled Trial

Abstract

Levosimendan is a new myofilament calcium (Ca2+) sensitizer that increases myocardial contractility by stabilizing the Ca2+-bound conformation of troponin C. We tested the hypothesis that levosimendan enhances cardiac performance after cardiopulmonary bypass (CPB). Anesthesia was induced and maintained with midazolam, sufentanil, and vecuronium in 18 patients randomly assigned to receive levosimendan (18 or 36 microg/kg loading dose and 0.2 or 0.3 microg/kg/min infusion, respectively) or placebo 15 min before and continued for 6 h after CPB. Significant (p < 0.05) increases in heart rate (HR) and decreases in systemic vascular resistance (SVR) occurred 15 min after CPB in patients receiving placebo. Later increases in mean arterial pressure (MAP) and cardiac output (CO) and decreases in stroke volume (SV) and pulmonary vascular resistance also were observed. HR was greater in patients receiving high- but not low-dose levosimendan versus placebo immediately after CPB. MAP also was lower in patients treated with either dose of levosimendan compared with placebo after CPB. Levosimendan increased CO and decreased SVR (4.2 +/- 0.4 to 7.9 +/- 0.4 L/min and 1,150 +/- 99 to 512 +/- 42 dyn/s/cm5, respectively, 15 min after CPB; mean +/- SEM). CO and SV were higher and SVR was lower in patients receiving levosimendan versus placebo after CPB. No differences in arterial oxygenation and perioperative arrhythmias (Holter analysis) were observed between groups. The results indicate that levosimendan enhances cardiac performance after CPB in humans.

Comparative Hemodynamic Effects of Levosimendan Alone and in Conjunction with 4-Aminopyridine or Calcium Chloride in a Rodent Model of Severe Verapamil Poisoning

“…It has a short half-life of about an hour but is metabolized to an active metabolite, OR-1896, with an elimination half-life of 70-80 h. Levosimendan is currently used for treatment of decompensated heart failure caused by chronic cardiac failure, acute myocardial infarction, and post-cardiac bypass surgery [3,9]. Several studies have demonstrated the benefits of levosimendan in patients after cardiopulmonary bypass to enhance their cardiac performance [10]. Levosimendan is also a vascular smooth muscle ATP-potassium channels agonist, which reduces after load and peripheral vascular resistance [11].…”

Part 14: Pediatric Advanced Life Support

“…In animal studies after resuscitation from cardiac arrest 418,419,[421][422][423][424] and post-cardiac surgical experience in children 352 and adults, [425][426][427][428] hemodynamic improvement was associated with administration of selected vasoactive agents. Each drug and dose must be tailored to the patient because clinical response is variable.…”

European Experience on the Practical Use of Levosimendan in Patients with Acute Heart Failure Syndromes

“…In a small randomized study, Nijhawan and colleagues 27 compared the hemodynamic effects of 2 doses of levosimendan (0.2 or 0.3 g/kg per min infused for 6 hours) with that of placebo after cardiopulmonary bypass. At 15 minutes after the end of cardiopulmonary bypass, levosimendan increased cardiac output and reduced systemic vascular resistance without hypotension or tachycardia.…”