The Microcirculation as a Therapeutic Target in the Treatment of Sepsis and Shock

Largely ignored throughout the history of clinical medicine, the microcirculation has recently been recognized at the bedside as the center of several pathophysiological processes. Normal microcirculatory function is critical for adequate tissue oxygenation and organ function, but it has a poorly understood and highly heterogeneous structure that is related to the diversity of functions that it accomplishes. The most important function of the microcirculation is the regulation and distribution of oxygen carrying red blood cells within the different organs. The determinants of oxygen delivery, blood flow regulation, tissue oxygen tension, and mitochondrial well-being are not fully understood; however, it is clear that insight into the function of the microcirculation is key in this respect. In fact, it is clear that the origin of circulatory failure in critical illness unresponsive to therapy is not represented in systemic hemodynamic variables but rather in the dysfunction of the microcirculation. The introduction of bedside techniques into clinical practice that allow the evaluation of the microcirculation has opened up a new field of functional hemodynamic monitoring, identified the microcirculatory failure as the most sensitive indicator of circulatory failure associated with adverse outcome, and has provided the promise of identifying new therapeutic targets. Clinical research has identified various conventional and new therapeutic approaches that are successful in modifying the microcirculation. Current research must determine whether some of these approaches are successful in improving the outcome of critically ill patients by recruiting the microcirculation.