title: Efficacy of therapy with recombinant human activated protein C of critically ill surgical patients with infection complicated by septic shock and multiple organ dysfunction syndrome.
abstract: BACKGROUND
  Septic shock causing or complicating critical surgical illness results in high mortality. Drotrecogin alfa (activated), known also as recombinant human activated protein C (rhAPC) has become controversial as therapy, owing to persisting questions of efficacy and safety. We hypothesized rhAPC to be effective therapy for critically ill surgical patients with septic shock.
  
  
  METHODS
  Open-label therapy with rhAPC (by predefined criteria) of 108 critically ill surgical patients. Treated patients were matched individually in prospect for age, gender, Acute Physiology and Chronic Health Evaluation (APACHE)-II and -III scores, site of infection, and organism (0-2 points each, maximum 12 points) with 108 patients from our 15,000-patient surgical intensive care unit database who did not receive rhAPC. No match was accepted if <6 points. Multiple organ dysfunction (MOD) scores and data regarding cortisol concentrations, bleeding complications, and transfusion requirements were collected. The primary endpoint was 28-day mortality, with mortality for hospitalization and resolution of organ dysfunction as secondary endpoints. Statistical analyses included ANOVA, c statistic, binary logistic regression, and Kaplan-Meier time-to-event and Cox proportional hazards analyses; α=0.05.
  
  
  RESULTS
  The mean match score was 9.2±0.1 points (range, 6-12 points). Patients were well matched by all criteria, including baseline MOD score (9.5±0.7 vs. 9.8±0.3 points, p=0.66). Mean age was 68.1±1.1 years (p=0.49), Mean APACHE-III score was 99.6±1.5 points (p=0.87). Mean time to rhAPC administration was 25±3 h. Survival at 28 days after rhAPC was 71.3% vs. 49.1% (p=0.001); hospital survival was 57.4% vs. 40.7% (p=0.02). By logistic regression, rhAPC therapy resulted in improved 28-day survival (OR 2.57, 95% CI 1.46-4.52, p=0.001) (model χ2 11.244, p=0.001); and hospital survival (OR 1.96, 95% CI 1.14-3.36, p=0.015) (model χ2 6.03, p=0.014). The MOD score decreased significantly (p=0.012) during rhAPC therapy.
  
  
  CONCLUSIONS
  Therapy with rhAPC appeared to improve survival in surgical ICU patients with life-threatening infection characterized by septic shock and organ dysfunction.
authors.affiliation: Division of Burns, Critical Care, and Trauma, Department of Surgery, Weill Cornell Medical College, New York, New York, USA. pbarie@med.cornell.edu
authors.forename: Philip S
authors.initials: PS
authors.lastname: Barie
authors.forename: Lynn J
authors.initials: LJ
authors.lastname: Hydo
authors.forename: Jian
authors.initials: J
authors.lastname: Shou
authors.forename: Soumitra R
authors.initials: SR
authors.lastname: Eachempati
mesh_terms: D000368:Aged; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001803:Blood Transfusion / Q000706:statistics & numerical data; D016022:Case-Control Studies; D016638:Critical Illness; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009102:Multiple Organ Failure / Q000150:complications / Q000188:drug therapy*; D019106:Postoperative Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D057216:Propensity Score; D011486:Protein C / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012772:Shock, Septic / Q000150:complications / Q000188:drug therapy*; D016037:Single-Blind Method; D013530:Surgical Wound Infection / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated