PMID: 11918516Mar 29, 2002Paper

New and emerging therapies for sepsis

The Annals of Pharmacotherapy
Daniel P Healy

Abstract

To review the recent advances related to the pathophysiology of sepsis and the rationale for recombinant human-activated protein C (drotrecogin alfa) and other antisepsis agents currently in Phase III trials. A MEDLINE (1990-December 2001) search was performed to identify pertinent literature on the pathophysiology of sepsis and treatment strategies. The search was supplemented with AdisInsight (Adis International) using the search terms sepsis, severe sepsis, or septic shock combined with agents in Phase II or higher clinical development. Abstracts presented at infectious diseases and critical care meetings were also reviewed. Clinical efficacy studies were selected for drotrecogin alfa and other Phase III investigational agents. Our current understanding of the pathophysiology of sepsis underscores the contribution of increased coagulation and diminished fibrinolytic activity working in conjunction with an excessive and dysregulated inflammatory response. The loss of homeostatic balance among these systems results in a systemic inflammatory response with generalized coagulopathy, microvascular thrombosis, and, ultimately, acute organ failure and death. As a result of these advances, several compounds are now in various phases...Continue Reading

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