Despite therapeutic advances, sepsis and septic shock continue to be leading causes of morbidity and mortality in critically ill patients (1). Over the last decade, the incidence of sepsis in U.S. hospitals has increased dramatically, resulting in part from an aging patient population and increasing use of immunosuppressive therapies and life-sustaining treatments (2). Based on our current understanding, this syndrome appears to result from an infectious nidus which has successfully circumvented host defensive barriers (e.g., skin and mucous membranes) (3). Subsequently, due to unique aspects of a given pathogen’s virulence and the host’s immune response, local defenses become overwhelmed, leading to bloodstream invasion by the pathogen, and systemic release of pathogenic products (Fig. 1). The result is activation of systemic host defenses including plasma factors (complement, clotting cascades) and cellular components (neutrophils, monocytes, lymphocytes, macrophages, endothelial cells), which in turn release potentially toxic mediators (cytokines, kinins, eicosanoids, platelet-activating factor, nitric oxide, etc.) that potentiate the inflammatory response (Fig. 2). Unchecked, this escalating immune response, in concert with microbial toxins, leads to hemodynamic instability, organ dysfunction, and death.
|Title of host publication||Respiratory-Circulatory Interactions in Health and Disease|
|Number of pages||18|
|State||Published - Jan 1 2001|