Abstract
Despite interesting and unique pharmacological properties, levosimendan has not proven a clear superiority to placebo in the patient populations that have been enrolled in the various recent multicenter randomized controlled trials. However, the pharmacodynamic effects of levosimendan are still considered potentially very useful in a number of specific situations.Patients with decompensated heart failure requiring inotropic support and receiving beta-blockers represent the most widely accepted indication. Repeated infusions of levosimendan are increasingly used to facilitate weaning from dobutamine and avoid prolonged hospitalizations in patients with end-stage heart failure, awaiting heart transplantation or left ventricular assist device implantation. New trials are under way to confirm or refute the potential usefulness of levosimendan to facilitate weaning from veno-arterial ECMO, to treat cardiogenic shock due to left or right ventricular failure because the current evidence is mostly retrospective and requires confirmation with better-designed studies. Takotsubo syndrome may represent an ideal target for this non-adrenergic inotrope, but this statement also relies on expert opinion. There is no benefit from levosimendan in patients with septic shock. The two large trials evaluating the prophylactic administration of levosimendan (pharmacological preconditioning) in cardiac surgical patients with poor left ventricular ejection fraction could not show a significant reduction in their composite endpoints reflecting low cardiac output syndrome with respect to placebo. However, the subgroup of those who underwent isolated CABG appeared to have a reduction in mortality. A new study will be required to confirm this exploratory finding.Levosimendan remains a potentially useful inodilator agent in a number of specific situations due to its unique pharmacological properties. More studies are needed to provide a higher level of proof regarding these indications.
Highlights
Levosimendan was developed in the early 1990s in Finland and became available for prescription starting in 2001
Cholley et al Critical Care (2019) 23:385 comparing levosimendan with placebo on top of standard care in cardiac surgical patients failed to reach statistical significance. Two of these studies addressed the question of the effectiveness of levosimendan as a prophylactic treatment for the prevention of postoperative low cardiac output syndrome (LCOS) in patients with poor left ventricular ejection fraction (LVEF) undergoing on-pump cardiac surgery [7, 8], and one study evaluated its effectiveness in reducing mortality at day 30 in patients developing post-bypass LCOS [9]
In a small number (n = 52) of patients with acute or chronic heart failure and treated with beta-blockers, a prospective randomized doubleblind international study found that levosimendan, as opposed to dobutamine, increased cardiac index and decreased pulmonary capillary wedged pressure, but failed to improve clinical symptoms and mixed venous oxygen saturation [33]
Summary
Levosimendan was developed in the early 1990s in Finland and became available for prescription starting in 2001. In a small number (n = 52) of patients with acute or chronic heart failure and treated with beta-blockers, a prospective randomized doubleblind international study found that levosimendan, as opposed to dobutamine, increased cardiac index and decreased pulmonary capillary wedged pressure, but failed to improve clinical symptoms and mixed venous oxygen saturation [33]. Prophylactic Levosimendan in cardiac surgical patients with low LVEF two large randomized controlled trials failed to show a reduction in composite endpoints reflecting low cardiac output syndrome and mortality in a mixed population of CABG, valvular, or combined surgery with LVEF< 40% [7, 8], a recent meta-analysis suggested that there could be a greater benefit in the isolated CABG population [74].
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