Levosimendan for resuscitating the microcirculation in patients with septic shock: a randomized controlled study
Andrea Morelli, Abele Donati, Christian Ertmer, Sebastian Rehberg, Matthias Lange, Alessandra Orecchioni, Valeria Cecchini, Giovanni Landoni, Paolo Pelaia, Paolo Pietropaoli, Hugo Van Aken, Jean-Louis Teboul, Can Ince and Martin Westphal
Critical Care 2010, 14:R232doi:10.1186/cc9387 Published: 23 December 2010.
Abstract (provisional)
Introduction
The purpose of the present study was to investigate microcirculatory blood flow in patients with septic shock treated with levosimendan as compared to an active comparator drug (i.e. dobutamine). The primary end point was a difference of [greater than or equal to] 20% in the microvascular flow index of small vessels (MFIs) among groups. Methods. The study was designed as a prospective, randomized, double blind clinical trial and performed in a multidisciplinary intensive care unit. After achieving normovolemia and a mean arterial pressure of at least 65 mmHg, 40 septic shock patients were randomized to receive either levosimendan 0.2 ugkg-1min-1 (n=20) or an active comparator (dobutamine 5 ugkg-1min-1; control; n=20) for 24 hours. Sublingual micro-circulatory blood flow of small and medium vessels was assessed by sidestream dark-field imaging. Microcirculatory variables and data from right heart catheterization were obtained at baseline and 24 hours after randomization. Baseline and demographic data were compared by the means of Mann-Whitney rank sum test or chi-square test, as appropriate. Microvascular and hemodynamic variables were analyzed using the Mann-Whitney rank sum test. Results. Microcirculatory flow index of small and medium vessels increased over time and were significantly higher in the levosimendan group as compared to the control group (24 hrs: MFIm 3.0 (3.0; 3.0) vs. 2.9 (2.8; 3.0); P = .02; MFIs 2.9 (2.9; 3.0) vs. 2.7 (2.3; 2.8); P < .001). The relative increase of perfused vessel density vs. baseline was significantly higher in the levosimendan group than in the control group (dMFIm 10 (3; 23) % vs. 0 (-1; 9) %; P = .007; dMFIs 47 (26; 83) % vs. 10 (-3; 27); P < .001). In addition, the heterogeneity index decreased only in the levosimendan group (dHI -93 (-100; -84) % vs. 0 (-78; 57) %; P < .001). There was no statistically significant correlation between systemic and microcirculatory flow variables within each group (each P > .05). Conclusions. Compared to a standard dose of 5 ug * kg-1 * min-1 of dobutamine, levosimendan at 0.2 ugkg-1min-1 improved sublingual microcirculatory blood flow in patients with septic shock, as reflected by changes in microcirculatory flow indices of small and medium vessels. Trial registration: NCT00800306
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