Reducing Mortality in Severe Sepsis and Septic Shock

Andrew T. Levinson, M.D., M.P.H.; Brian P. Casserly, M.D.; Mitchell M. Levy, M.D.


Semin Respir Crit Care Med. 2011;32(2):195-205. 

In This Article

Methods of Reducing Mortality


Severe sepsis and septic shock are initially characterized by components of hypovolemic, cardiogenic, and distributive shock.[24,25] In the early phases of sepsis, increased capillary leakage and decreased vasomotor tone result in a decrease in venous return to the heart.[26] This results in a decrease in cardiac output.[27,28] The normal hemodynamic response would be increased sympathetic tone resulting in tachycardia and restoration of mean arterial blood pressure (MAP) toward normal values by reducing unstressed circulatory blood and increased arterial vasomotor tone.[29] Complete restoration in arterial vasomotor tone does not typically occur in sepsis because of a loss of vascular responsiveness.[30] Therefore, normotension can be preserved only by a significant increase in cardiac output and, importantly, the presence of normotension does not ensure hemodynamic stability.[31] This is further compounded by global systemic vasodilation of the resistance vessels of various organ beds further impairing autoregulated blood flow induced by hypotension. The host's ability to respond to the septic insult to maintain homeostasis with an increase in cardiac output is further impeded by cytokines released secondary to the inflammatory response to sepsis directly causing myocardial depression.[26] The end result of these changes is an imbalance between systemic oxygen delivery and oxygen demand, resulting in global tissue hypoxia or shock.[32] An indicator of serious illness, global tissue hypoxia is a key development preceding multiorgan failure and death.[32] Rapid restoration of fluid deficits not only modulates inflammation but also decreases the need for vasopressor therapy and inotrope support by restoring cardiac output.[25,33,34]


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