Selecting patients with severe sepsis for drotrecogin alfa (activated) therapy.
Selecting patients for drotrecogin alfa (activated) (Xigris; Eli Lilly and Company, Indianapolis, IN) therapy outside of a clinical trial setting requires knowledge of the rationale that led the Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) investigators to select the various entry criteria for the trial. Enrollment criteria for the study included a known or suspected infection, presence of at least 3 systemic inflammatory response syndrome (SIRS) criteria, and dysfunction of > or =1 organ or system. The infection criteria used in PROWESS were designed to be straightforward and were based on common clinical and radiological data. Although previous definitions of sepsis required only 2 SIRS criteria, the PROWESS trial investigators required the presence of > or =3 SIRS criteria to improve the sensitivity and specificity of these criteria for the diagnosis of sepsis. Acute organ dysfunction, the diagnostic criterion for severe sepsis, was used to define the study population because it identifies patients at significant risk of death. Characteristics of drotrecogin alfa (activated)-treated patients, including infection, modified SIRS criteria, and organ dysfunction, were similar to those of the placebo group and the general sepsis population. Proper clinical judgment and use of the these inclusion criteria as a guide will help clinicians select and treat sepsis patients with drotrecogin alfa (activated).
Sollet
Jean-Pierre
JP
Réanimation Polyvalente, Centre Hospitalier Victor Dupouy, 69 rue du Lieutenant Colonel Prudhon, 95107 Argenteuil, France. jps@fc.horus-medical.fr
Garber
Gary E
GE
D018806:APACHE; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000628:therapy; D002493:Central Nervous System Diseases / Q000175:diagnosis; D002986:Clinical Trials as Topic / Q000379:methods; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D009102:Multiple Organ Failure / Q000150:complications / Q000188:drug therapy; D018579:Patient Selection; D011486:Protein C / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality
D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005343:Fibrinolytic Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated