title: The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock.
abstract: BACKGROUND
  Despite abundant experimental studies of biomarker patterns in early severe sepsis and septic shock, human data are few. Further, the impact of the severity of global tissue hypoxia resulting from resuscitative strategies on these early biomarker patterns remains unknown.
  
  
  METHODS
  The temporal patterns of interleukin-1 receptor antagonist, intercellular adhesion molecule-1, tumor necrosis factor-alpha, caspase-3, and interleukin-8 were serially examined over the first 72 hrs of hospitalization after early hemodynamic optimization strategies of early goal-directed vs. standard therapy for severe sepsis and septic shock patients. The relationship of these biomarker patterns to each hemodynamic optimization strategy, severity of global tissue hypoxia (reflected by lactate and central venous oxygen saturation), organ dysfunction, and mortality were examined.
  
  
  RESULTS
  Abnormal biomarker levels were present upon hospital presentation and modulated to distinct patterns within 3 hrs based on the hemodynamic optimization strategy. The temporal expression of these patterns over 72 hrs was significantly associated with the severity of global tissue hypoxia, organ dysfunction, and mortality.
  
  
  CONCLUSIONS
  In early severe sepsis and septic shock, within the first 3 hrs of hospital presentation, distinct biomarker patterns emerge in response to hemodynamic optimization strategies. A significant association exists between temporal biomarker patterns in the first 72 hrs, severity of global tissue hypoxia, organ dysfunction, and mortality. These findings identify global tissue hypoxia as an important contributor to the early inflammatory response and support the role of hemodynamic optimization in supplementing other established therapies during this diagnostic and therapeutic "window of opportunity."
authors.affiliation: Department of Emergency Medicine, Henry Ford Hospital, Wayne State University, Detroit, MI, USA. erivers1@hfhs.org
authors.forename: Emanuel P
authors.initials: EP
authors.lastname: Rivers
authors.forename: James A
authors.initials: JA
authors.lastname: Kruse
authors.forename: Gordon
authors.initials: G
authors.lastname: Jacobsen
authors.forename: Kant
authors.initials: K
authors.lastname: Shah
authors.forename: Manisha
authors.initials: M
authors.lastname: Loomba
authors.forename: Ronny
authors.initials: R
authors.lastname: Otero
authors.forename: Ed W
authors.initials: EW
authors.lastname: Childs
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D053148:Caspase 3 / Q000097:blood; D005260:Female; D006801:Humans; D007118:Immunoassay; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D016209:Interleukin-8; D008297:Male; D008875:Middle Aged; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D018805:Sepsis / Q000503:physiopathology* / Q000628:therapy*; D012772:Shock, Septic / Q000503:physiopathology* / Q000628:therapy*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D016209:Interleukin-8; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D053148:Caspase 3