Cardiac, Circulatory, and Microvascular Changes in Sepsis and Multiorgan Dysfunction Syndrome

Most patients who die of sepsis develop a mul-tiorgan dysfunction syndrome (MODS), and outcome from sepsis is strongly related to the number of organs that fail. MODS has varied etiologies, including sepsis, trauma, hemorrhage, burns, myocardial infarction, acute pancreatitis, ischemia-reperfusion injury, and fulminant liver failure. Usually, it follows an overly severe or prolonged systemic inflammatory insult involving activation of components of peripheral blood, complement, and fibrinolytic pathways, leading to the production of a vast array of proinflamma-tory mediators, such as cytokines, nitric oxide (NO), and endothelins (see Figure 6.1). Concomitant exhaustion of protective, endogenous defence mechanisms (e.g., activated protein C and anti-thrombin III) is thought to exaggerate the predominance of the proinflammatory environment. This inflammatory state may dissipate within days, but the resultant injury to organ systems can persist, predisposing to organ failure.

In clinical terms, the mainstay of current therapy is centered on ensuring maintenance of global cardiac output and regional organ perfu-sion in an attempt to prevent secondary organ system injury after the initial inflammatory insult. This approach requires an understanding of the pathophysiology within the cardiovascular system (CVS) during sepsis and the influence of current therapies on such changes.