title: Timing of drotrecogin alfa (activated) initiation in treatment of severe sepsis: a database cohort study of hospital mortality, length of stay, and costs.
abstract: BACKGROUND
  For patients with critical conditions including severe sepsis, minimizing the time from presentation to treatment is important to improving outcomes. Understanding the factors influencing high hospital mortality and resource utilization in severe sepsis continues to interest clinicians and researchers. This study examined the associations between timing of drotrecogin alfa (activated) (DrotAA) initiation and hospital mortality, length-of-stay, and costs.
  
  
  METHODS
  We conducted a cohort study of adult patients (N = 1179) with intensive care unit stays from November 2001 to June 2003 who received DrotAA in US hospitals with data in the Solucient ACTracker database. We defined evident severe sepsis (ESS) as concurrent antibiotic plus ventilator and/or vasopressor use. We characterized the interval between ESS and DrotAA initiation as Same-day, Next-day, or Day 2+. We compared group characteristics and created multivariate models of hospital mortality, length-of-stay, and costs.
  
  
  RESULTS
  Forty-three percent of patients received Same-day DrotAA, 30% Next-day, and 27% Day 2+. Same-day and Next-day patients had more organ dysfunctions at ICU admission than Day 2+ patients (1.1 +/- 0.9 and 1.2 +/- 0.8 vs. 1.0 +/- 0.8; p = 0.021 and p < 0.001, respectively), but from ESS to DrotAA initiation, organ dysfunctions for Day 2+ patients had increased more (+0.0 and +0.4 vs. +0.6, respectively; all p < 0.0001). Increased mortality was observed with administration later than Same-day, although only for the Day 2+ group did the association remain significant (p < 0.05) after adjusting for clinical and demographic factors. Only Next-day initiation was associated with significantly decreased costs (p = 0.0145).
  
  
  CONCLUSIONS
  Timing of DrotAA initiation is associated with clinical and economic outcomes in severe sepsis. The potential impact of this timing on hospital mortality, length-of-stay, and costs deserves further study.
authors.affiliation: Premier Inc, Pharmaceutical Research Services, Charlotte, NC 28266-8800, USA. frank_ernst@premierinc.com
authors.forename: F R
authors.initials: FR
authors.lastname: Ernst
authors.forename: J A
authors.initials: JA
authors.lastname: Johnston
authors.forename: S
authors.initials: S
authors.lastname: Pulgar
authors.forename: J
authors.initials: J
authors.lastname: He
authors.forename: D E
authors.initials: DE
authors.lastname: Ball
authors.forename: J K
authors.initials: JK
authors.lastname: Young
authors.forename: L M
authors.initials: LM
authors.lastname: Cooper
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D016208:Databases, Factual; D005260:Female; D017721:Hospital Costs / Q000706:statistics & numerical data*; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay / Q000706:statistics & numerical data*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010351:Patient Discharge; D011486:Protein C / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated