Evolving concepts in sepsis definitions.

Developing effective therapies for any disease process relies on the ability to clearly define the population of patients who will benefit from that intervention. Advances in our understanding of sepsis pathogenesis have made it clear that the global definition or concept of sepsis as a single, homogeneous disease process is inadequate. The idea that all patients who have severe sepsis will respond positively to any single therapeutic intervention is probably too simple, although some interventions may target more general pathways and be globally beneficial. For example, drotrecogin alfa (activated) was shown to be effective at reducing mortality in a clinical trial with a heterogeneous patient population,(28) although even here positive results were restricted to patients who had severe sepsis, highlighting the importance of being able to better characterize patients. Our approach to sepsis and its definition has evolved as we increasingly recognize the complex nature of the process and the importance of targeting treatments according to individual patients' characteristics. Clinical variables are too sensitive and nonspecific and improved biologic and biochemical tools need to be incorporated into current definitions to provide precise and accurate methods of diagnosis. Systems, such as PIRO, that can characterize patients according to their likely prognosis and response to a specific therapy need to be further developed so that treatments can be appropriately directed for individual patients.