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, Martin Westphal

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

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 ≥ 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 μg·kg-1·min-1 (n = 20) or an active comparator (dobutamine 5 μg·kg-1·min-1; control; n = 20) for 24 hours. Sublingual microcirculatory 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 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 indices 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 μg·kg-1·min-1 of dobutamine, levosimendan at 0.2 μg·kg-1·min-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.

Original languageEnglish
Article numberR232
JournalCritical Care
Volume14
Issue number6
DOIs
Publication statusPublished - Dec 23 2010

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Microcirculation
Septic Shock
Dobutamine
Nonparametric Statistics
Chi-Square Distribution
Cardiac Catheterization
Random Allocation
Intensive Care Units
Arterial Pressure
Hemodynamics
Demography
Clinical Trials
Control Groups
simendan
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Medicine(all)

Cite this

Morelli, A., Donati, A., Ertmer, C., Rehberg, S., Lange, M., Orecchioni, A., ... Westphal, M. (2010). Levosimendan for resuscitating the microcirculation in patients with septic shock: A randomized controlled study. Critical Care, 14(6), [R232]. https://doi.org/10.1186/cc9387

Levosimendan for resuscitating the microcirculation in patients with septic shock : A randomized controlled study. / Morelli, Andrea; Donati, Abele; Ertmer, Christian; Rehberg, Sebastian; Lange, Matthias; Orecchioni, Alessandra; Cecchini, Valeria; Landoni, Giovanni; Pelaia, Paolo; Pietropaoli, Paolo; Van Aken, Hugo; Teboul, Jean Louis; Ince, Can; Westphal, Martin.

In: Critical Care, Vol. 14, No. 6, R232, 23.12.2010.

Research output: Contribution to journalArticle

Morelli, A, Donati, A, Ertmer, C, Rehberg, S, Lange, M, Orecchioni, A, Cecchini, V, Landoni, G, Pelaia, P, Pietropaoli, P, Van Aken, H, Teboul, JL, Ince, C & Westphal, M 2010, 'Levosimendan for resuscitating the microcirculation in patients with septic shock: A randomized controlled study', Critical Care, vol. 14, no. 6, R232. https://doi.org/10.1186/cc9387
Morelli, Andrea ; Donati, Abele ; Ertmer, Christian ; Rehberg, Sebastian ; Lange, Matthias ; Orecchioni, Alessandra ; Cecchini, Valeria ; Landoni, Giovanni ; Pelaia, Paolo ; Pietropaoli, Paolo ; Van Aken, Hugo ; Teboul, Jean Louis ; Ince, Can ; Westphal, Martin. / Levosimendan for resuscitating the microcirculation in patients with septic shock : A randomized controlled study. In: Critical Care. 2010 ; Vol. 14, No. 6.
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T1 - Levosimendan for resuscitating the microcirculation in patients with septic shock

T2 - A randomized controlled study

AU - Morelli, Andrea

AU - Donati, Abele

AU - Ertmer, Christian

AU - Rehberg, Sebastian

AU - Lange, Matthias

AU - Orecchioni, Alessandra

AU - Cecchini, Valeria

AU - Landoni, Giovanni

AU - Pelaia, Paolo

AU - Pietropaoli, Paolo

AU - Van Aken, Hugo

AU - Teboul, Jean Louis

AU - Ince, Can

AU - Westphal, Martin

PY - 2010/12/23

Y1 - 2010/12/23

N2 - 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 ≥ 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 μg·kg-1·min-1 (n = 20) or an active comparator (dobutamine 5 μg·kg-1·min-1; control; n = 20) for 24 hours. Sublingual microcirculatory 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 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 indices 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 μg·kg-1·min-1 of dobutamine, levosimendan at 0.2 μg·kg-1·min-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.

AB - 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 ≥ 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 μg·kg-1·min-1 (n = 20) or an active comparator (dobutamine 5 μg·kg-1·min-1; control; n = 20) for 24 hours. Sublingual microcirculatory 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 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 indices 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 μg·kg-1·min-1 of dobutamine, levosimendan at 0.2 μg·kg-1·min-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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