Abstract

Microcirculatory dysfunction has been recently recognized as a key pathophysiologic process in the evolution of sepsis. In the present review, we discuss fundamental aspects of microcirculatory abnormalities during septic shock, including pathogenic mechanisms, technological assessment, clinical correlates and potential therapies. The most important function of the microcirculation is the regulation and distribution of flow within the different organs. In septic shock, microcirculatory dysfunction may arise as a result of several factors such as endothelial dysfunction, leukocyte-endothelium interactions, coagulation and inflammatory disorders, hemorheologic abnormalities, and functional shunting. Severity and persistence of these microcirculatory abnormalities are associated with bad prognosis and are not necessarily predicted by systemic variables. The introduction of bedside techniques that allow evaluation of the microcirculation into clinical practice has opened up a new field of functional hemodynamic monitoring. Recent data suggest that microcirculatory abnormalities can be staged in severity. Some microcirculatory indices are more accurately related to morbidity and mortality, and thus a definition of clinically relevant microcirculatory abnormalities is feasible. On the other hand, although several systemic variables do not predict microcirculatory status, high norepinephrine (NE) requirements and hyperlactatemia are associated with a much higher prevalence of relevant microcirculatory derangements. Therefore, severe septic shock patients could represent a more precise target for interventions, particularly in microcirculation-oriented clinical trials. Clinical research has identified various therapeutic approaches that are successful in modifying the microcirculation. Future research must determine whether some of these approaches are successful in improving outcome of critically ill patients by recruiting the microcirculation.