VHIR Seminar led by Daniel De Backer, PhD., from the Dpt of Intensive Care Erasme University Hospital Brussels - Belgium. Abstract: Multiple studies have shown that alterations in microcirculatory perfusion are frequently observed in patients with septic shock. These alterations are characterized by heterogeneity of perfusion with capillaries with stop flow in close vicinity to well perfused capillaries. What are the consequences of these alterations? The presence of stop flow capillaries favours development of zones of tissue hypoxia, even though total perfusion to the organ is preserved. In addition, the heterogeneity in perfusion is associated with inadequate matching of flow to metabolism and is hence less well tolerated by tissues than an homogeneous decrease in perfusion. In patients with septic shock, the severity of the microvascular alterations was associated with development of organ dysfunction and an increase risk of death. Different mechanisms have been implicated in the development of these alterations including loss of communication between vascular segments, impaired endothelial reactivity, alterations in red and white blood cells rheology, alteration in endothelial glycocalyx, platelet aggregation and microthrombosis. In view of the various mechanisms implicated in the development of these alterations, it is unlikely that therapies used in usual hemodynamic resuscitation. Novel therapies should aim at improving the matching of perfusion to metabolism rather than further increasing flow in the already perfused vessels or non selectively dilating microvessels.