Critical care : the official journal of the Critical Care Forum
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Sepsis is characterized by systemic microvascular dysfunction. Endothelial progenitor cells (EPCs) are critically involved in maintaining vascular homeostasis under both physiological and pathological conditions. The aim of the present study was to analyze the endothelial progenitor cell system in patients suffering from sepsis with acute renal dysfunction. ⋯ Sepsis significantly affects the endothelial progenitor cell system, as reflected by increased EPC numbers, increased concentrations of proangiogenic mediators, and reduced proliferative capacity of the cells. This occurs independently from the frequency of dialysis and from patient survival. Increased serum levels of uric acid are possibly responsible for stronger EPC mobilization in sepsis patients with higher average creatinine levels.
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Hemodynamic resuscitation should be aimed at achieving not only adequate cardiac output but also sufficient mean arterial pressure (MAP) to guarantee adequate tissue perfusion pressure. Since the arterial pressure response to volume expansion (VE) depends on arterial tone, knowing whether a patient is preload-dependent provides only a partial solution to the problem. The objective of this study was to assess the ability of a functional evaluation of arterial tone by dynamic arterial elastance (Ea(dyn)), defined as the pulse pressure variation (PPV) to stroke volume variation (SVV) ratio, to predict the hemodynamic response in MAP to fluid administration in hypotensive, preload-dependent patients with acute circulatory failure. ⋯ Functional assessment of arterial tone by Ea(dyn), measured as the PVV to SVV ratio, predicted arterial pressure response after volume loading in hypotensive, preload-dependent patients under controlled mechanical ventilation.
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Thromboelastometry (TEM)-guided haemostatic therapy with fibrinogen concentrate and prothrombin complex concentrate (PCC) in trauma patients may reduce the need for transfusion of red blood cells (RBC) or platelet concentrate, compared with fresh frozen plasma (FFP)-based haemostatic therapy. ⋯ TEM-guided haemostatic therapy with fibrinogen concentrate and PCC reduced the exposure of trauma patients to allogeneic blood products.
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Activated protein C (APC), a physiological coagulation inhibitor, has been shown to reduce mortality in patients with severe sepsis. APC exerts pleiotropic cytoprotection by a mechanism that requires its interaction with endothelial cell protein C receptor and protease-activated receptor-1 on target cells. In the previous issue, Pérez-Casal and colleagues elegantly demonstrate that APC, using its recombinant form (rhAPC), can communicate to target cells through release of microparticles (MPs), small membrane vesicles released from activated cells, to induce anti-apoptotic and anti-inflammatory properties that might participate in the improvement of patient outcome. ⋯ These MPs bear the endothelial cell protein C receptor/APC molecules and can transfer the message to target cells including those of origin to induce cytoprotection. The long-range APC signal can thus be mediated by MPs in vivo upon pharmacological treatment using rhAPC in severe septic patients. A novel pharmacological approach targeting MP production and properties could therefore be used to treat severe sepsis in addition to other well-known actions of APC via direct interaction with the cells of interest.
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Down-regulation of ex-vivo cytokine production is a specific feature in patients with sepsis. Cytokine downregulation was studied focusing on caspase-1 activation and conversion of pro-interleukin-1β into interleukin-1β (IL-1β). ⋯ These data demonstrate that the inhibition of caspase-1 and defective IL-1 β production is an important immunological feature in sepsis.