Optimum treatment of severe sepsis and septic shock: Evidence in support of the recommendations

Severe sepsis and septic shock are among the most common causes of death in noncoronary intensive care units. The incidence of sepsis has been increasing over the past two decades, and is predicted to continue to rise over the next 20 years. While our understanding of the complex pathophysiologic alterations that occur in severe sepsis and septic shock has increased greatly as a result of recent clinical and preclinical studies, mortality associated with the disorder remains unacceptably high. Despite these new insights, the cornerstone of therapy continues to be early recognition, prompt initiation of effective antibiotic therapy, and source control, and goal-directed hemodynamic, ventilatory, and metabolic support as necessary. To date, attempts to reduce mortality with innovative, predominantly anti-inflammatory therapeutic strategies have been extremely disappointing. Observations of improved outcomes with physiologic doses of corticosteroid replacement therapy and activated protein C (drotrecogin alfa [activated]) have provided new adjuvant therapies for severe sepsis and septic shock in selected patients. This article reviews the components of sepsis management and discusses the available evidence in support of these recommendations. In addition, there is a discussion of some promising new strategies.