title: C1-esterase inhibitor infusion increases survival rates for patients with sepsis*.
abstract: OBJECTIVE
  Systemic inflammatory response variability displays differing degrees of organ damage and differing outcomes of sepsis. C1-esterase inhibitor, an endogenous acute-phase protein, regulates various inflammatory and anti-inflammatory pathways, including the kallikrein-kinin system and leukocyte activity. This study assesses the influence of high-dose C1-esterase inhibitor administration on systemic inflammatory response and survival in patients with sepsis.
  
  
  METHODS
  Open-label randomized controlled study.
  
  
  METHODS
  Surgical and medical intensive care units of nine university and city hospitals.
  
  
  METHODS
  : Sixty-one patients with sepsis.
  
  
  METHODS
  Patients were randomized to receive either 12,000 U of C1-esterase inhibitor infusions in addition to conventional treatment or conventional treatment only (n = 41 C1-esterase inhibitor, 20 controls). Blood samples for measurement of C1-esterase inhibitor, complement components C3 and C4, and C-reactive protein concentrations were drawn on days 1, 3, 5, 7, 10, and 28.
  
  
  RESULTS
  Quartile analysis of C1-esterase inhibitor activity in sepsis subjects revealed that the lowest quartile subgroup had similar activity levels (0.7-1.2 U/L), when compared to healthy volunteers (p > .05). These normal-level C1-esterase inhibitor sepsis patients nevertheless displayed increased C-reactive protein (p = .04) production and higher likelihoods of a more severe sepsis (p = .001). Overall, infusion of C1-esterase inhibitor increased C1-esterase inhibitor (p < .005 vs. control on days 2, 3, and 5) functional activity, resulted in higher C3 levels (p < .05 vs. control on days 2 and 3), followed by decreased C-reactive protein (p < .05 vs. control on days 3 and 10). Simultaneously, C1-esterase inhibitor infusion in sepsis patients was associated with reduced all-cause mortality (12% vs. 45% in control, p = .008) as well as sepsis-related mortality (8% vs. 45% in control, p = .001) assessed over 28 days. The highest absolute reduction risk of 70% was achieved in sepsis patients with Simplified Acute Physiology Score II scores >27.
  
  
  CONCLUSIONS
  In the present study, patients in the lowest quartile of C1-esterase inhibitor activity in combination with high C-reactive protein demonstrated a higher risk of developing severe sepsis. In general, high-dose C1-esterase inhibitor infusion down-regulated the systemic inflammatory response and was associated with improved survival rates in sepsis patients, which could have important treatment and survival implications for individuals with C1-esterase inhibitor functional deficiency.
authors.affiliation: Department of Clinical Pharmacology, Sechenov Moscow Medical University, Moscow, Russia.
authors.forename: Anton A
authors.initials: AA
authors.lastname: Igonin
authors.forename: Denis N
authors.initials: DN
authors.lastname: Protsenko
authors.forename: Gennadiy M
authors.initials: GM
authors.lastname: Galstyan
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Vlasenko
authors.forename: Nana N
authors.initials: NN
authors.lastname: Khachatryan
authors.forename: Igor V
authors.initials: IV
authors.lastname: Nekhaev
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Shlyapnikov
authors.forename: Natalya B
authors.initials: NB
authors.lastname: Lazareva
authors.forename: Paul
authors.initials: P
authors.lastname: Herscu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D050718:Complement C1 Inhibitor Protein / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D050718:Complement C1 Inhibitor Protein