title: The epidemiology of severe sepsis syndrome and its treatment with recombinant human activated protein C.
abstract: Severe sepsis syndrome has important consequences to healthcare systems as the incidence is increasing, there is significant attributed morbidity and mortality and there is a substantial cost for in-hospital and post-discharge care. Current treatment includes the use of antimicrobials, local source control and aggressive physiological support, usually in an intensive care unit setting. Drotrecogin-alpha (activated) or recombinant human activated protein C (rhAPC) is the only biological agent approved for use in severe sepsis syndrome that has demonstrated efficacy in reducing 28-day all-cause mortality and new data suggests a trend towards longer term survival. However, given the evidence of a variable effect on survival rates in patient subgroups and its acquisition cost, controversy has arisen concerning its appropriate use. This review discusses the epidemiology of sepsis, preclinical and clinical evidence supporting the use of rhAPC use, controversies about the evidence of efficacy in severe sepsis syndrome and cost-effectiveness data.
authors.affiliation: Department of Critical Care Medicine, Faculty of Medicine, University of Calgary, Calgary AB, T2N 2T9, Canada. cdoig@ucalgary.ca
authors.forename: Christopher James
authors.initials: CJ
authors.lastname: Doig
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Laupland
authors.forename: David A
authors.initials: DA
authors.lastname: Zygun
authors.forename: Braden J
authors.initials: BJ
authors.lastname: Manns
mesh_terms: D000890:Anti-Infective Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D017327:Clinical Trials, Phase IV as Topic; D016527:Drug Costs; D006801:Humans; D011486:Protein C / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D012720:Severity of Illness Index; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated