title: A prospective, multicenter derivation of a biomarker panel to assess risk of organ dysfunction, shock, and death in emergency department patients with suspected sepsis.
abstract: OBJECTIVE
  To define a biomarker panel to predict organ dysfunction, shock, and in-hospital mortality in emergency department (ED) patients with suspected sepsis.
  
  
  METHODS
  Prospective observational study.
  
  
  METHODS
  EDs of ten academic medical centers.
  
  
  METHODS
  There were 971 patients enrolled.
  
  
  METHODS
  1) ED patients age > 18; 2) suspected infection or a serum lactate level > 2.5 mmol/L; and 3) two or more systemic inflammatory response syndrome criteria.
  
  
  METHODS
  pregnancy, do-not-resuscitate status, or cardiac arrest.
  
  
  RESULTS
  Nine biomarkers were assayed from blood draws obtained on ED presentation. Multivariable logistic regression was used to identify an optimal combination of biomarkers to create a panel. The derived formula for weighting biomarker values was used to calculate a "sepsis score," which was the predicted probability of the primary outcome of severe sepsis (sepsis plus organ dysfunction) within 72 hrs. We also assessed the ability of the sepsis score to predict secondary outcome measures of septic shock within 72 hrs and in-hospital mortality. The overall rates of each outcome were severe sepsis, 52%; septic shock, 39%; and in-hospital mortality 7%. Among the nine biomarkers tested, the optimal 3-marker panel was neutrophil gelatinase-associated lipocalin, protein C, and interleukin-1 receptor antagonist. The area under the curve for the accuracy of the sepsis score derived from these three biomarkers was 0.80 for severe sepsis, 0.77 for septic shock, and 0.79 for death. When included in multivariate models with clinical variables, the sepsis score remained highly significant (p < 0.001) for all the three outcomes.
  
  
  CONCLUSIONS
  A biomarker panel of neutrophil gelatinase-associated lipocalin, interleukin-1ra, and Protein C was predictive of severe sepsis, septic shock, and death in ED patients with suspected sepsis. Further study is warranted to prospectively validate the clinical utility of these biomarkers and the sepsis score in risk-stratifying patients with suspected sepsis.
authors.affiliation: Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. nshapiro@bidmc.harvard.edu
authors.forename: Nathan I
authors.initials: NI
authors.lastname: Shapiro
authors.forename: Stephen
authors.initials: S
authors.lastname: Trzeciak
authors.forename: Judd E
authors.initials: JE
authors.lastname: Hollander
authors.forename: Robert
authors.initials: R
authors.lastname: Birkhahn
authors.forename: Ronny
authors.initials: R
authors.lastname: Otero
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Osborn
authors.forename: Eugene
authors.initials: E
authors.lastname: Moretti
authors.forename: H Bryant
authors.initials: HB
authors.lastname: Nguyen
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Gunnerson
authors.forename: David
authors.initials: D
authors.lastname: Milzman
authors.forename: David F
authors.initials: DF
authors.lastname: Gaieski
authors.forename: Munish
authors.initials: M
authors.lastname: Goyal
authors.forename: Charles B
authors.initials: CB
authors.lastname: Cairns
authors.forename: Long
authors.initials: L
authors.lastname: Ngo
authors.forename: Emanuel P
authors.initials: EP
authors.lastname: Rivers
mesh_terms: D000209:Acute-Phase Proteins; D015415:Biomarkers / Q000097:blood; D004636:Emergency Service, Hospital; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007375:Interleukin-1 / Q000097:blood*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000453:epidemiology* / Q000209:etiology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011486:Protein C / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000097:blood*; D018570:Risk Assessment / Q000379:methods; D018805:Sepsis / Q000097:blood* / Q000150:complications*; D012772:Shock, Septic / Q000453:epidemiology* / Q000209:etiology*
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D007375:Interleukin-1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011486:Protein C; D011518:Proto-Oncogene Proteins