title: Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure.
abstract: OBJECTIVE
  We sought to define the therapeutic dose range of levosimendan in patients with New York Heart Association class II-IV heart failure of ischemic origin.
  
  
  BACKGROUND
  Levosimendan is a calcium sensitizer for treatment of acute decompensated heart failure.
  
  
  METHODS
  A double-blind, placebo-controlled, randomized, multicenter, parallel-group study included 151 adult patients. Levosimendan was given as a 10-min intravenous bolus of 3, 6, 12, 24 or 36 microg/kg, followed by a 24-h infusion of 0.05, 0.1, 0.2, 0.4 or 0.6 microg/kg/min, respectively. Dobutamine, for comparative purposes, was given as an open-label infusion (6 microg/kg/min). The primary efficacy variable was the proportion of patients achieving in each treatment group at least one of the following: 1) a > or =15% increase in stroke volume (SV) at 23 h to 24 h; 2) a > or =25% decrease in pulmonary capillary wedge pressure (PCWP) (and > or =4 mm Hg) at 23 h to 24 h; 3) a > or =40% increase in cardiac output (CO) (with change in heart rate [HR] <20%); 4) a > or =50% decrease in PCWP during two consecutive measurements.
  
  
  RESULTS
  The response rate to levosimendan ranged from 50% at the lowest dose to 88% at the highest dose (compared with placebo 14%, dobutamine 70%). A dose-response relationship was demonstrated for levosimendan on increases in CO and SV, and reductions in PCWP during the infusion (for all, p< or =0.001). Headache (9%), nausea (5%) and hypotension (5%) were the most frequently reported adverse events at higher dosages.
  
  
  CONCLUSIONS
  Dosing of levosimendan with a 10-min bolus of 6 to 24 microg/kg followed by an infusion of 0.05 to 0.2 microg/kg/min is well tolerated and leads to favorable hemodynamic effects.
authors.affiliation: Helsinki University, Finland. markku.nieminen@hus.fi
authors.forename: M S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: J
authors.initials: J
authors.lastname: Akkila
authors.forename: G
authors.initials: G
authors.lastname: Hasenfuss
authors.forename: F X
authors.initials: FX
authors.lastname: Kleber
authors.forename: L A
authors.initials: LA
authors.lastname: Lehtonen
authors.forename: V
authors.initials: V
authors.lastname: Mitrovic
authors.forename: O
authors.initials: O
authors.lastname: Nyquist
authors.forename: W J
authors.initials: WJ
authors.lastname: Remme
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D009320:Atrial Natriuretic Factor / Q000032:analysis; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011724:Pyridazines / Q000008:administration & dosage*; D000077464:Simendan
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D009320:Atrial Natriuretic Factor; D009638:Norepinephrine