Biomarkers of sepsis.

Sepsis is a highly heterogeneous clinical disorder currently characterized almost exclusively by the use of physiologic variables. A burgeoning interest in the potential descriptive role of biomarkers in sepsis holds the promise of transforming the diagnosis from a clinical one to a biologic one, and so permitting better evaluation and use of a spectrum of adjuvant therapies. Biomarkers provide information in one of three domains: diagnosis, prognosis, and monitoring of response to treatment. Their primary prognostic utility, however, is not in forecasting outcome, but in identifying patients who are more likely to benefit from (or be harmed by) a particular intervention. A proposed template for staging sepsis in a manner analogous to systems used in oncology provides a framework for evaluating sepsis biomarkers. The model stratifies patients on the basis of predisposition, insult, response, and organ dysfunction, generating the acronym PIRO. This brief review considers the methodologic basis for biomarker development and validation and situates some emerging sepsis biomarkers within the framework of the PIRO model.