Use of Levosimendan in Intensive Care Unit Settings: An Opinion Paper

Abstract

Levosimendan is an inodilator that promotes cardiac contractility primarily through calcium sensitization of cardiac troponin C and vasodilatation via opening of adenosine triphosphate-sensitive potassium (KATP) channels in vascular smooth muscle cells; the drug also exerts organ-protective effects through a similar effect on mitochondrial KATP channels. This pharmacological profile identifies levosimendan as a drug that may have applications in a wide range of critical illness situations encountered in intensive care unit medicine: hemodynamic support in cardiogenic or septic shock; weaning from mechanical ventilation or from extracorporeal membrane oxygenation; and in the context of cardiorenal syndrome. This review, authored by experts from 9 European countries (Austria, Belgium, Czech republic, Finland, France, Germany, Italy, Sweden, and Switzerland), examines the clinical and experimental data for levosimendan in these situations and concludes that, in most instances, the evidence is encouraging, which is not the case with other cardioactive and vasoactive drugs routinely used in the intensive care unit. The size of the available studies is, however, limited and the data are in need of verification in larger controlled trials. Some proposals are offered for the aims and designs of these additional studies.

FIGURE 1.

Changes in CPO during infusion of levosimendan () and dobutamine () in patients with AMI revascularized by percutaneous coronary intervention and who developed cardiac shock. Data points are mean ± SD. *P < 0.05 (Student's t-test). Data from the study by García-González et al.

FIGURE 2.

Confounder-adjusted long-term survival (levosimendan vs. control, P = 0.04) in 240 patients weaned from extracorporeal membrane oxygenation. Levosimendan was administered within the first 24 hours after initiation of ECMO therapy, at a standard dose of 12.5 mg in 24 hours. Data from the study by Distelmaier et al.

FIGURE 3.

Differential effects of levosimendan (0.1 µg/kg/min) and dopamine (2 µg/kg/min) on RBF and GFR in 30 postcardiac surgery patients. The experimental procedure started 4–6 hours after surgery in the ICU during propofol sedation and mechanical ventilation. Cardiac index (CI) was increased by ≈20% by both drugs. Data from the study by Bragadottir et al.