Abstract
A clinical syndrome including fever, leukocytosis, elevated cardiac output, and reduced systemic vascular resistance has been associated with severe infection (i.e., sepsis). However, during the last 15 years, many patients have demonstrated all of the findings that have traditionally been associated with "sepsis" but have not had demonstrated sources of infection. This led to the term "sepsis syndrome" to refer to that population of patients who appeared to have a physiologic and metabolic response associated with, but who did not have, severe infection. More commonly called the systemic inflammatory response syndrome (SIRS), the sepsis syndrome is now associated with the nonspecific systemic activation of the human inflammatory cascade by any of a number of clinical events. The management of the SIRS patient has been ineffective because of incomplete definition of the mechanisms responsible for the syndrome. It is argued that all of the biological mechanisms that are operative in a simple wound and are beneficial are negative for the host when activated systemically. Thus, SIRS is seen in three separate scenarios at present: (1) invasive infection; (2) dissemination of microbes secondary to failure of host defense mechanisms; and (3) severe activation of inflammation by injury, shock, severe soft tissue inflammation, and other noninfectious but proinflammatory events. Newer treatment strategies will need to focus not on the inciting event itself but on better control of the complex responses of the host.