title: Timing of vasopressor initiation and mortality in septic shock: a cohort study.
abstract: BACKGROUND
  Despite recent advances in the management of septic shock, mortality remains unacceptably high. Earlier initiation of key therapies including appropriate antimicrobials and fluid resuscitation appears to reduce the mortality in this condition. This study examined whether early initiation of vasopressor therapy is associated with improved survival in fluid therapy-refractory septic shock.
  
  
  METHODS
  Utilizing a well-established database, relevant information including duration of time to vasopressor administration following the initial documentation of recurrent/persistent hypotension associated with septic shock was assessed in 8,670 adult patients from 28 ICUs in Canada, the United States of America, and Saudi Arabia. The primary endpoint was survival to hospital discharge. Secondary endpoints were length of ICU and hospital stay as well as duration of ventilator support and vasopressor dependence. Analysis involved multivariate linear and logistic regression analysis.
  
  
  RESULTS
  In total, 8,640 patients met the definition of septic shock with time of vasopressor/inotropic initiation documented. Of these, 6,514 were suitable for analysis. The overall unadjusted hospital mortality rate was 53%. Independent mortality correlates included liver failure (odds ratio (OR) 3.46, 95% confidence interval (CI), 2.67 to 4.48), metastatic cancer (OR 1.63, CI, 1.32 to 2.01), AIDS (OR 1.91, CI, 1.29 to 2.49), hematologic malignancy (OR 1.88, CI, 1.46 to 2.41), neutropenia (OR 1.78, CI, 1.27 to 2.49) and chronic hypertension (OR 0.62 CI, 0.52 to 0.73). Delay of initiation of appropriate antimicrobial therapy (OR 1.07/hr, CI, 1.06 to 1.08), age (OR 1.03/yr, CI, 1.02 to 1.03), and Acute Physiology and Chronic Health Evaluation (APACHE) II Score (OR 1.11/point, CI, 1.10 to 1.12) were also found to be significant independent correlates of mortality. After adjustment, only a weak correlation between vasopressor delay and hospital mortality was found (adjusted OR 1.02/hr, 95% CI 1.01 to 1.03, P <0.001). This weak effect was entirely driven by the group of patients with the longest delays (>14.1 hours). There was no significant relationship of vasopressor initiation delay to duration of vasopressor therapy (P = 0.313) and only a trend to longer duration of ventilator support (P = 0.055) among survivors.
  
  
  CONCLUSIONS
  Marked delays in initiation of vasopressor/inotropic therapy are associated with a small increase in mortality risk in patients with septic shock.
authors.forename: Vance
authors.initials: V
authors.lastname: Beck
authors.forename: Dan
authors.initials: D
authors.lastname: Chateau
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Bryson
authors.forename: Amarnath
authors.initials: A
authors.lastname: Pisipati
authors.forename: Sergio
authors.initials: S
authors.lastname: Zanotti
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parrillo
authors.forename: Anand
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000368:Aged; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D012189:Retrospective Studies; D012772:Shock, Septic / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*
chemical_list: D014662:Vasoconstrictor Agents