New medication for the treatment of sepsis: Is there a rationale for the use of these novel substances?

Sepsis, septic shock, and sepsis-related multiple organ failure are the most frequent causes of death in surgical intensive care units. Triggered by infection, a cascade of complicated interactions between the inflammatory system and the coagulation system induces tissue hypoperfusion and hypoxia leading to organ dysfunction. Therapeutic approaches to interfere with this intricate network of inflammatory and coagulation processes or to directly affect tissue perfusion may therefore be expected to evolve as beneficial strategies in the treatment of sepsis. Although many of these approaches have been evaluated both in experimental and clinical studies, drotrecogin alfa (activated) is the only substance so far which has been proven successful in a large clinical trial and which is currently available for clinical use. Unfortunately, various contraindications have to be strictly considered due to the associated severe side effects on the coagulation system. Moreover, the use of drotrecogin alfa (activated) is very expensive and the beneficial effect has only been demonstrated in septic patients with failure of at least two organs.