title: Levosimendan for resuscitating the microcirculation in patients with septic shock: a randomized controlled study.
abstract: BACKGROUND
  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.
  
  
  BACKGROUND
  NCT00800306.
authors.affiliation: Department of Anesthesiology and Intensive Care, University of Rome, La Sapienza, Viale del Policlinico 155, Rome 00161, Italy. andrea.morelli@uniroma1.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Morelli
authors.forename: Abele
authors.initials: A
authors.lastname: Donati
authors.forename: Christian
authors.initials: C
authors.lastname: Ertmer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rehberg
authors.forename: Matthias
authors.initials: M
authors.lastname: Lange
authors.forename: Alessandra
authors.initials: A
authors.lastname: Orecchioni
authors.forename: Valeria
authors.initials: V
authors.lastname: Cecchini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Landoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelaia
authors.forename: Paolo
authors.initials: P
authors.lastname: Pietropaoli
authors.forename: Hugo
authors.initials: H
authors.lastname: Van Aken
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Teboul
authors.forename: Can
authors.initials: C
authors.lastname: Ince
authors.forename: Martin
authors.initials: M
authors.lastname: Westphal
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D009060:Mouth Floor / Q000098:blood supply*; D011446:Prospective Studies; D011724:Pyridazines / Q000627:therapeutic use*; D012151:Resuscitation / Q000379:methods*; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology; D000077464:Simendan
chemical_list: D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan