title: The effect of vasoactive drugs on mortality in patients with severe sepsis and septic shock. A network meta-analysis of randomized trials.
abstract: Inotropes and vasopressors are cornerstone of therapy in septic shock, but search for the best agent is ongoing. We aimed to determine which vasoactive drug is associated with the best survival.
  
  
  
  PubMed, BioMedCentral, Embase, and the Cochrane Central Register were searched. Randomized trials performed in septic patients with at least 1 group allocated to an inotrope/vasopressor were included. Network meta-analysis with a frequentist approach was performed.
  
  
  
  The 33 included studies randomized 3470 patients to 16 different comparators. As compared with placebo, levosimendan (odds ratio [OR], 0.17, 95%; confidence interval [CI], 0.05-0.60), dobutamine (OR, 0.30; 95% CI, 0.09-0.99), epinephrine (OR, 0.35; 95% CI, 0.13-0.96), vasopressin (OR, 0.37; 95% CI, 0.16-0.89), and norepinephrine plus dobutamine (OR, 0.4; 95% CI, 0.11-0.96) were significantly associated with survival. Norepinephrine improved survival compared with dopamine (OR, 0.81; 95% CI, 0.66-1.00). Rank analysis showed that levosimendan had the highest probability of being the best treatment.
  
  
  
  Among several regimens for pharmacological cardiovascular support in septic patients, regimens based on inodilators have the highest probability of improve survival.
authors.affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: belletti.ale@gmail.com.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Belletti
authors.affiliation: University of Bristol, School of Clinical Sciences, Bristol Heart Institute, Bristol, United Kingdom. Electronic address: umberto.benedetto@bristol.ac.uk.
authors.forename: Umberto
authors.initials: U
authors.lastname: Benedetto
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy. Electronic address: giuseppe.biondizoccai@uniroma1.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biondi-Zoccai
authors.affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: leggieri.carlo@hsr.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Leggieri
authors.affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: silvani.paolo@hsr.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Silvani
authors.affiliation: University of Bristol, School of Clinical Sciences, Bristol Heart Institute, Bristol, United Kingdom. Electronic address: g.d.angelini@bristol.ac.uk.
authors.forename: Gianni D
authors.initials: GD
authors.lastname: Angelini
authors.affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, 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; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: landoni.giovanni@hsr.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Landoni
mesh_terms: D001127:Arginine Vasopressin / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004280:Dobutamine / Q000627:therapeutic use; D004298:Dopamine / Q000627:therapeutic use; D004837:Epinephrine / Q000627:therapeutic use; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use; D009638:Norepinephrine / Q000627:therapeutic use; D016017:Odds Ratio; 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; D000077464:Simendan; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*; D014667:Vasopressins / Q000627:therapeutic use
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D001127:Arginine Vasopressin; D000077464:Simendan; D004280:Dobutamine; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine
keywords: Inotropes; Intensive care; Microcirculation; Mortality; Sepsis; Vasopressors