Pathophysiological Determinants of Cardiovascular Dysfunction in Septic Shock

Abstract

The International Sepsis Definitions consensus conference defined septic shock as the most severe clinical manifestation of sepsis [1]. Septic shock is characterized by sepsis-induced cardiovascular alterations that result in severe hypotension, tissue hypoperfusion and metabolic disorders [2]. Sepsis-induced arterial vasodilatation and the consequent loss of vascular tone are thought to be the main determinants of the altered hemodynamic state in septic shock. The introduction of echocardiography into clinical practice and the direct evaluation of heartmorphology and function in septic patients emphasized the role of myocardial depression as a pathophysiological mechanism underlying hemodynamic impairment [3, 4].

The Surviving Sepsis Campaign recommends that resuscitation of patients in septic shock should be performed early and tailored to restore adequate peripheral perfusion to prevent organ injury. International guidelines strongly recommend early therapy based on fluid administration to restore cardiac output, vasopressor drugs to sustain mean arterial pressure and inotropes when cardiac dysfunction limits blood flow under pressure [2]. The mortality rate of this severe clinical manifestation of sepsis remains high (up to 50% in critically ill patients) despite the recommended therapeutic strategies and the results of several studies to determine the pathophysiological mechanisms of the altered hemodynamics in septic shock [5–8].

Pathophysiological determinants of cardiovascular dysfunction are receiving increased interest, with the goal of tailoring treatment options based on novel understanding of the specific pathophysiology present. This review discusses the emergent pathophysiological issues related to cardiovascular alterations in septic shock and their possible influence on clinical management.