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Am J Crit Care. 2003 Nov;12(6):518-24; quiz 525-6.

Role of activated protein C in the pathophysiology of severe sepsis.

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Division of Pulmonary, Critical Care, and Occupational Medicine, St. Louis University School of Medicine, St. Louis, Mo., USA.


Sepsis is a complex syndrome that can lead to multiple organ failure and death. Severe sepsis has been associated with mortality rates ranging from 28% to 50% and is the most common cause of death in the noncardiac intensive care unit. Despite advances in both antibiotic therapy and supportive care, the mortality rate due to severe sepsis has remained fundamentally unchanged in the past several decades. With increased understanding of the pathophysiology of sepsis, particularly the intricate interplay between activation of coagulation and inflammation, novel therapeutic agents that may improve clinical outcomes are being researched and developed. The epidemiology, pathophysiology, and treatment of severe sepsis are reviewed. Also discussed are the recently published results from a multicenter, randomized, placebo-controlled phase 3 clinical trial of drotrecogin alfa (activated), a recombinant form of human activated protein C, in patients with severe sepsis. The nursing implications of this new approved therapy are discussed.

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