Levosimendan for ECLS Weaning: A Strategy in Need of Validation

The Effectiveness of Levosimendan on Veno-Arterial Extracorporeal Membrane Oxygenation Management and Outcome: A Systematic Review and Meta-Analysis

“…[5] VA-ECMO weaning is usually facilitated by the use of beta-adrenergic agonists, such as dobutamine, dopamine and epinephrine, or phosphodiesterase inhibitors such as milrinone and enoximone. [6] Prolonged use of beta-adrenergic agonists may cause tachyarrhythmias and myocardial ischemia, [7,8] increase myocardial oxygen demand, and impair myocardial relaxation that leads to increasing left ventricular (LV) myocardial strain. [6] Moreover, the undesirable impact on the overall outcome as a result of metabolic acidosis and vasoconstriction, impairs the microcirculation and triggers a systemic inflammatory response.…”

“…[6] Prolonged use of beta-adrenergic agonists may cause tachyarrhythmias and myocardial ischemia, [7,8] increase myocardial oxygen demand, and impair myocardial relaxation that leads to increasing left ventricular (LV) myocardial strain. [6] Moreover, the undesirable impact on the overall outcome as a result of metabolic acidosis and vasoconstriction, impairs the microcirculation and triggers a systemic inflammatory response. [9] Phosphodiesterase inhibitors may have some advantages over the catecholamines in facilitating VA-ECMO weaning as they augment myocardial contractility through increasing intracellular calcium levels, reducing afterload, and decreasing LV strain.…”

“…Consequently, the risk of arrhythmias and cardiotoxicity remain an issue. [6] While the pharmacologic support in VA-ECMO weaning is limited to beta-adrenergic agonists and phosphodiesterase inhibitors, the calcium-sensitizing inotropic agent, levosimendan, is gaining popularity.…”

“…[6,10] It increases cardiac output and stroke volume, and reduces peripheral vascular resistance, [11] without increasing myocardial oxygen consumption; thus there is no increased risk of serious arrhythmogenic effects. [6,10,11] Furthermore, it has a long therapeutic effect that may last for weeks, due to the long half-life of one of its active metabolites (e.g., OR-1896, OR-1855). [5,10] OR-1896 is probably the clinically relevant metabolite.…”

“…[10] Additionally, levosimendan possesses anti-inflammatory and cardioprotective effects, [11] and has been successfully used in patients with post-cardiotomy myocardial dysfunction. [6,11] Potassium adenosine triphosphate channels, which are present in systemic, pulmonary, and coronary vascular smooth muscles, are also activated by levosimendan. The resultant smooth muscle relaxation improves coronary perfusion and decreases systemic and pulmonary vascular resistance; thus, unloading both ventricles.…”