title: Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial.
abstract: BACKGROUND
  International guidelines for management of septic shock recommend that dopamine or norepinephrine are preferable to epinephrine. However, no large comparative trial has yet been done. We aimed to compare the efficacy and safety of norepinephrine plus dobutamine (whenever needed) with those of epinephrine alone in septic shock.
  
  
  METHODS
  This prospective, multicentre, randomised, double-blind study was done in 330 patients with septic shock admitted to one of 19 participating intensive care units in France. Participants were assigned to receive epinephrine (n=161) or norepinephrine plus dobutamine (n=169), which were titrated to maintain mean blood pressure at 70 mm Hg or more. The primary outcome was 28-day all-cause mortality. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00148278.
  
  
  RESULTS
  There were no patients lost to follow-up; one patient withdrew consent after 3 days. At day 28, there were 64 (40%) deaths in the epinephrine group and 58 (34%) deaths in the norepinephrine plus dobutamine group (p=0.31; relative risk 0.86, 95% CI 0.65-1.14). There was no significant difference between the two groups in mortality rates at discharge from intensive care (75 [47%] deaths vs 75 [44%] deaths, p=0.69), at hospital discharge (84 [52%] vs 82 [49%], p=0.51), and by day 90 (84 [52%] vs 85 [50%], p=0.73), time to haemodynamic success (log-rank p=0.67), time to vasopressor withdrawal (log-rank p=0.09), and time course of SOFA score. Rates of serious adverse events were also similar.
  
  
  CONCLUSIONS
  There is no evidence for a difference in efficacy and safety between epinephrine alone and norepinephrine plus dobutamine for the management of septic shock.
authors.affiliation: Raymond Poincaré Hospital (AP-HP), University of Versailles Saint Quentin, PRES UniverSud, Paris, France. djillali.annane@rpc.aphp.fr
authors.forename: Djillali
authors.initials: D
authors.lastname: Annane
authors.forename: Philippe
authors.initials: P
authors.lastname: Vignon
authors.forename: Alain
authors.initials: A
authors.lastname: Renault
authors.forename: Pierre-Edouard
authors.initials: PE
authors.lastname: Bollaert
authors.forename: Claire
authors.initials: C
authors.lastname: Charpentier
authors.forename: Claude
authors.initials: C
authors.lastname: Martin
authors.forename: Gilles
authors.initials: G
authors.lastname: Troché
authors.forename: Jean-Damien
authors.initials: JD
authors.lastname: Ricard
authors.forename: Gérard
authors.initials: G
authors.lastname: Nitenberg
authors.forename: Laurent
authors.initials: L
authors.lastname: Papazian
authors.forename: Elie
authors.initials: E
authors.lastname: Azoulay
authors.forename: Eric
authors.initials: E
authors.lastname: Bellissant
mesh_terms: D000322:Adrenergic Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D004280:Dobutamine / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage* / Q000009:adverse effects; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012772:Shock, Septic / Q000188:drug therapy*; D014662:Vasoconstrictor Agents / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000322:Adrenergic Agonists; D014662:Vasoconstrictor Agents; D004280:Dobutamine; D009638:Norepinephrine; D004837:Epinephrine