title: Non-Adrenergic Vasopressors in Patients with or at Risk for Vasodilatory Shock. A Systematic Review and Meta-Analysis of Randomized Trials.
abstract: BACKGROUND
  Hypotensive state is frequently observed in several critical conditions. If an adequate mean arterial pressure is not promptly restored, insufficient tissue perfusion and organ dysfunction may develop. Fluids and catecholamines are the cornerstone of critical hypotensive states management. Catecholamines side effects such as increased myocardial oxygen consumption and development of arrhythmias are well known. Thus, in recent years, interest in catecholamine-sparing agents such as vasopressin, terlipressin and methylene blue has increased; however, few randomized trials, mostly with small sample sizes, have been performed. We therefore conducted a meta-analysis of randomized trials to investigate the effect of non-catecholaminergic vasopressors on mortality.
  
  
  METHODS
  PubMed, BioMed Central and Embase were searched (update December 31st, 2014) by two independent investigators. Inclusion criteria were: random allocation to treatment, at least one group receiving a non-catecholaminergic vasopressor, patients with or at risk for vasodilatory shock. Exclusion criteria were: crossover studies, pediatric population, non-human studies, studies published as abstract only, lack of data on mortality. Studied drugs were vasopressin, terlipressin and methylene blue. Primary endpoint was mortality at the longest follow-up available.
  
  
  RESULTS
  A total of 1,608 patients from 20 studies were included in our analysis. The studied settings were sepsis (10/20 studies [50%]), cardiac surgery (7/20 [35%]), vasodilatory shock due to any cause (2/20 [19%]), and acute traumatic injury (1/20 [5%]). Overall, pooled estimates showed that treatment with non-catecholaminergic agents improves survival (278/810 [34.3%] versus 309/798 [38.7%], risk ratio = 0.88, 95% confidence interval = 0.79 to 0.98, p = 0.02). None of the drugs was associated with significant reduction in mortality when analyzed independently. Results were not confirmed when analyzing studies with a low risk of bias.
  
  
  CONCLUSIONS
  Catecholamine-sparing agents in patients with or at risk for vasodilatory shock may improve survival. Further researches on this topic are needed to confirm the finding.
authors.affiliation: Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Belletti
authors.affiliation: Department of Medical Sciences "M. Aresu", Cagliari University, Cagliari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Musu
authors.affiliation: Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Silvetti
authors.affiliation: Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Omar
authors.initials: O
authors.lastname: Saleh
authors.affiliation: Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pasin
authors.affiliation: Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Monaco
authors.affiliation: Surgical Intensive Care Unit, Department of Cardiopneumology, University of São Paulo, São Paulo, Brazil.
authors.forename: Ludhmila A
authors.initials: LA
authors.lastname: Hajjar
authors.affiliation: Department of Anaesthesiology and Intensive Care, Academician EN Meshalkin Novosibirsk State Budget Research Institute of Circulation Pathology, Novosibirsk, Russia.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Fominskiy
authors.affiliation: Department of Medical Sciences "M. Aresu", Cagliari University, Cagliari, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Finco
authors.affiliation: Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.|Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zangrillo
authors.affiliation: Department of Anaesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.|Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Landoni
mesh_terms: D016208:Databases, Factual; D006801:Humans; D008236:Lypressin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D008751:Methylene Blue / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018805:Sepsis / Q000188:drug therapy; D012769:Shock / Q000209:etiology*; D000077585:Terlipressin; D014662:Vasoconstrictor Agents / Q000009:adverse effects* / Q000627:therapeutic use; D014667:Vasopressins / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D014662:Vasoconstrictor Agents; D014667:Vasopressins; D008236:Lypressin; D000077585:Terlipressin; D008751:Methylene Blue