Microcirculatory dysfunction in sepsis: a pathogenetic basis for therapy? (original) (raw)

2000, The Journal of Pathology

Abnormal microvascular perfusion, including decreased functional capillary density and increased blood flow heterogeneity, is observed in early stages of the systemic inflammatory response to infection and appears to have prognostic significance in human sepsis. It is known that improvements in systemic hemodynamics are weakly correlated with the correction of microcirculatory parameters, despite an appropriate treatment of macrohemodynamic abnormalities. Furthermore, conventional hemodynamic monitoring systems available in clinical practice fail to detect microcirculatory parameter changes and responses to treatments, as they do not evaluate intrinsic events that occur in the microcirculation. Fortunately, some bedside diagnostic methods and therapeutic options are specifically directed to the assessment and treatment of microcirculatory changes. In the present review we discuss fundamental aspects of septic microcirculatory abnormalities, including pathophysiology, clinical monitoring, and potential therapies. microcirculation; sepsis; microcirculatory monitoring; microvascular resuscitation IN EARLY STAGES OF SEPSIS, proinflammatory cytokines are released in an attempt to eliminate the offending agent, generating an intense response that impairs the microcirculation (24, 69). Nearly every cellular component of the microcirculation, including endothelial cells, smooth muscle cells, platelets, leukocytes, red blood cells, and adjacent parenchymal cells, is affected (59). The resulting microcirculatory dysfunction is characterized by an increased number of capillaries with stopped flow and maldistribution of microvascular blood flow (15, 40, 68). These microcirculatory changes have been observed in different models of sepsis, organs, and species (5, 31, 42, 68, 78, 95, 101, 111) and appear to have prognostic significance in human sepsis, as the severity of initial microcirculatory derangements in the early resuscitation phase of therapy and their persistence over time have been associated with lower survival rates (5, 7, 93, 105). This review of fundamental aspects of septic microcirculatory abnormalities includes pathophysiological mechanisms, available techniques for clinical monitoring, and potential therapies to rescue the microcirculation. The Microcirculation The microcirculation consists of Ͻ100-m-diameter vessels (arterioles, capillaries, venules, and microlymphatics). It is the major site of blood oxygen release to tissues and works as an integrated system that ensures tissue oxygen delivery adequate to meet cell oxygen demand. Main cell types in the microvasculature are endothelial cells (which line the inside of blood vessels), smooth muscle cells (which are present mainly in arterioles), red blood cells, leukocytes, and platelets (59). Endothelial cells play a central role in control of microcirculatory function, regulating microvascular thrombosis and fibrinolysis, leukocyte adhesion and migration, vasomotor tone, trafficking of cells and nutrients, and capillary permeability and recruitment (1). Pathophysiology of Microcirculatory Changes in Sepsis Local distribution of blood flow to tissues is regulated by the microcirculation. This is possible because, under physiological conditions, endothelial cells sense metabolic and physical signs and respond by regulating microvascular flow through local