title: Protein C zymogen in adults with severe sepsis or septic shock.
abstract: BACKGROUND
  Activated protein C is associated with a risk of bleeding and its effects on survival in septic shock patients are questionable. Protein C zymogen has no risk of bleeding and improves the outcome of patients with septic shock. We hereby describe the largest published case series of adult patients receiving protein C zymogen.
  
  
  METHODS
  A prospective study on 23 adult patients with severe sepsis or septic shock, two or more organ failures and at high risk for bleeding, treated with protein C zymogen (50IU/kg bolus followed by continuous infusion of 3IU/kg/h for 72h).
  
  
  RESULTS
  The Z-test evidenced a significant reduction between the expected mortality (53%) and the observed mortality 30% (Z value=1.99, p=0.046) in our sample population. Protein C levels increased from 34±18% to 66±22% at 6h after PC bolus (p<0.001), and kept on increasing during 72h of administration (p<0.001 to baseline). Sequential Organ Failure Assessment (SOFA), score of organ dysfunction, decreased from baseline to 7 days after administration of protein C from 14±2 to 7±4 (p<0.001). No adverse event drug related was noted.
  
  
  CONCLUSIONS
  Protein C zymogen administration is safe and its use in septic patients should be investigated through a randomized controlled trial.
authors.affiliation: Department of Anesthesia and Intensive Care, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Crivellari
authors.affiliation: Department of Anesthesia and Intensive Care, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Silvetti
authors.affiliation: Department of Anesthesia and Intensive Care, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Gerli
authors.affiliation: Department of Anesthesia and Intensive Care, San Raffaele Scientific Institute, Milano, Italy. Electronic address: landoni.giovanni@hsr.it.
authors.forename: G
authors.initials: G
authors.lastname: Landoni
authors.affiliation: Department of Anesthesia and Intensive Care, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Franco
authors.affiliation: Department of Anesthesia and Intensive Care, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Bove
authors.affiliation: Department of Anesthesia and Intensive Care, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pappalardo
authors.affiliation: Department of Anesthesia and Intensive Care, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Zangrillo
mesh_terms: D000328:Adult; D000368:Aged; D004792:Enzyme Precursors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011486:Protein C / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy*; D012772:Shock, Septic / Q000188:drug therapy*
chemical_list: D004792:Enzyme Precursors; D011486:Protein C
keywords: Bleeding; Critical care; Cuidados críticos; Cuidados intensivos; Hemorragia; Intensive care; Protein C zymogen; Sepsis; Zimógeno de proteína C