title: Comparative Effectiveness of Second Vasoactive Agents in Septic Shock Refractory to Norepinephrine.
abstract: OBJECTIVE
  We aim to identify the appropriate vasoactive agent in patients with septic shock who are refractory to optimal doses of norepinephrine.
  
  
  METHODS
  In this retrospective observational cohort study over a 4-year period, patients who received norepinephrine within 24 hours of ICU admission and a second agent within 48 hours were enrolled.
  
  
  RESULTS
  Among 2640 patients screened, 234 patients were enrolled, aged 60.8 ± 17.8 years, Acute Physiology and Chronic Health Evaluation IV 98.3 ± 27.5, 81.6% mechanically ventilated, and 65.8% in-hospital mortality. Within 96 hours, 2.8 ± 1.0 vasoactive agents were administered. Fifty, 50, 66, and 68 patients received dobutamine, dopamine, phenylephrine, and vasopressin as the second agent, with crude in-hospital mortality 40.0%, 66.0%, 74.2%, and 76.5%, respectively, P < .001. Survival analysis showed a statistically significant difference in survival time by second vasoactive agent, P < .001. After adjusting for confounding variables, dobutamine showed significant decreased odds ratio (OR) for mortality compared to vasopressin: OR 0.34 (95% confidence interval 0.14-0.84, P = .04). The relative risk of dying was 55.8% lower in patients receiving dobutamine versus vasopressin, P < .01.
  
  
  CONCLUSIONS
  Dobutamine is associated with decreased mortality compared to other second vasoactive agents in septic shock when norepinephrine is not sufficient. A prospective randomized trial examining the outcome impact of the second vasoactive agent is needed.
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine, Loma Linda University, Loma Linda, CA, USA.|2 Department of Medicine, Loma Linda University, Loma Linda, CA, USA.|3 Department of Emergency Medicine, Loma Linda University, Loma Linda, CA, USA.
authors.forename: H Bryant
authors.initials: HB
authors.lastname: Nguyen
authors.affiliation: 4 School of Medicine, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Lu
authors.affiliation: 2 Department of Medicine, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Isabella
authors.initials: I
authors.lastname: Possagnoli
authors.affiliation: 4 School of Medicine, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Stokes
mesh_terms: D000368:Aged; D057186:Comparative Effectiveness Research; D004280:Dobutamine / Q000008:administration & dosage; D004298:Dopamine / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine; D010656:Phenylephrine / Q000008:administration & dosage; D012189:Retrospective Studies; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*; D014667:Vasopressins / Q000008:administration & dosage*
chemical_list: D014662:Vasoconstrictor Agents; D014667:Vasopressins; D010656:Phenylephrine; D004280:Dobutamine; D004298:Dopamine; D009638:Norepinephrine
keywords: dobutamine; dopamine; norepinephrine; phenylephrine; septic shock; vasoactive agent; vasopressin