title: Levosimendan reduces mortality in patients with severe sepsis and septic shock: A meta-analysis of randomized trials.
abstract: OBJECTIVE
  There is controversy about the use of inotropes in the treatment of severe sepsis and septic shock. The objective of this study was to evaluate if levosimendan, as compared with standard inotropic therapy (eg, dobutamine), reduces mortality in septic patients.
  
  
  METHODS
  BioMedCentral, PubMed, EMBASE, and the Cochrane Central Register were searched for pertinent studies, up to 1st May 2015. Randomized trials on the use of levosimendan in patients with severe sepsis and septic shock were included if reporting mortality data. The primary outcome was mortality, whereas secondary outcomes were blood lactate, cardiac index, total fluid infused, norepinephrine dosage, and mean arterial pressure.
  
  
  RESULTS
  Seven studies for a total of 246 patients were included in the analysis. Levosimendan was associated with significantly reduced mortality compared with standard inotropic therapy (59/125 [47%] in the levosimendan group and 74/121 [61%] in the control group; risk difference = -0.14, risk ratio = 0.79 [0.63-0.98], P for effect = .03, I(2) = 0%, numbers needed to treat = 7). Blood lactate was significantly reduced in the levosimendan group, whereas cardiac index and total fluid infused were significantly higher in the levosimendan group. No difference in mean arterial pressure and norepinephrine usage was noted.
  
  
  CONCLUSIONS
  In patients with severe sepsis and septic shock, levosimendan is associated with a significant reduction in mortality compared with standard inotropic therapy. A large ongoing multicenter randomized trial will have to confirm these findings.
authors.affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University of Milan, Milan, Italy. Electronic address: zangrillo.alberto@hsr.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zangrillo
authors.affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: alessandroputzu@ymail.com.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Putzu
authors.affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: monaco.fabrizio@hsr.it.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Monaco
authors.affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: oriani.alessandro@hsr.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Oriani
authors.affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: frau.giovanna@hsr.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Frau
authors.affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: monica.deluca@libero.it.
authors.forename: Monica
authors.initials: M
authors.lastname: De Luca
authors.affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: noramed@hotmail.it.
authors.forename: Nora
authors.initials: N
authors.lastname: Di Tomasso
authors.affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: bignami.elena@hsr.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Bignami
authors.affiliation: Department of Anesthesiology and Intensive Care, State Research Institute of Circulation Pathology, Novosibirsk, Russia. Electronic address: vvlom@mail.ru.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lomivorotov
authors.affiliation: Anesthesiology & Intensive Care Department, Moscow Regional Clinical & Research Institute, Moscow, Russia. Electronic address: lik0704@gmail.com.
authors.forename: Valery
authors.initials: V
authors.lastname: Likhvantsev
authors.affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University of Milan, Milan, Italy. Electronic address: landoni.giovanni@hsr.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Landoni
mesh_terms: D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004280:Dobutamine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000627:therapeutic use; D011724:Pyridazines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D012772:Shock, Septic / Q000188:drug therapy / Q000401:mortality / Q000628:therapy; D000077464:Simendan
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D004280:Dobutamine; D009638:Norepinephrine
keywords: Anesthesia; Dobutamine; Intensive care; Levosimendan; Septic shock; Severe sepsis