Current vascular pharmacology
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Curr Vasc Pharmacol · Mar 2013
Historical ArticleMechanisms of vascular hyporesponsiveness in septic shock.
To define some of the most common characteristics of vascular hyporesponsiveness to catecholamines during septic shock and outline current therapeutic approaches and future perspectives. ⋯ In animal models, several therapeutic approaches, targeted on one particular compound have proven their efficacy in preventing or reversing vascular hyporesponsiveness to catecholamines. Unfortunately, none have been successfully tested in clinical trials. Nevertheless, very high doses of catecholamines ( > 5 μg/kg/min), hydrocortisone, terlipressin or vasopressin could represent an alternative for the treatment of refractory septic shock.
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Brain dysfunction is a frequent complication of sepsis, usually defined as "sepsis-associated encephalopathy" (SAE). Its pathophysiology is complex and related to numerous processes and pathways, while the exact mechanisms producing neurological impairment in septic patients remain incompletely elucidated. Alterations of the cerebral blood flow (CBF) may represent a key component for the development of SAE. ⋯ Brain perfusion can further become inadequate due to cerebral microcirculatory dysfunction, as evidenced in the experimental setting. Microvascular alterations can be implicated in the development of electrophysiological abnormalities observed during sepsis and contribute to neurological alterations in septic animals. The aim of this review is to provide an update on the pathophysiology of brain perfusion in sepsis, with a particular focus on human clinical investigation and novel tools for CBF monitoring in septic patients.
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Cardiovascular failure in sepsis involves a combination of hypovolemia, decreased vascular tone, myocardial depression and microcirculatory alterations. Fluids represent the first line therapeutic intervention, with controversy regarding the type of fluid. Recent data indicate that albumin is safe and might even be beneficial in specific subgroups. ⋯ In one large trial, no significant difference in outcome was observed, and the exact role of vasopressin still needs clarification. Finally, various inotropic agents can counteract septic myocardial depression. So far, no study supports their routine use, but these may be justified on an individual basis.
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Curr Vasc Pharmacol · Mar 2013
ReviewThe heart in sepsis: from basic mechanisms to clinical management.
Septic shock is characterized by circulatory compromise, microcirculatory alterations and mitochondrial damage, which all reduce cellular energy production. In order to reduce the risk of major cell death and a diminished likelihood of recovery, adaptive changes appear to be activated. As a result, cells and organs may survive in a non-functioning hibernation-like condition. ⋯ Beta-blockers additionally reduce local and systemic inflammation. Advances may also come from metabolic interventions such as pyruvate, succinate or high dose insulin substitutions. All these potentially advantageous concepts require rigorous testing before implementation in routine clinical practice.
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The endothelium takes part in the regulation of numerous physiological functions and lies at the interface of circulating blood and the vessel wall. Under physiological conditions, it is responsible for anticoagulant and anti-adhesive properties, and it regulates vasomotor tone and vascular homeostasis. Endothelial dysfunction has been associated with many pathophysiological processes, such as inflammation and oxidative and nitrosative stresses. ⋯ Thus, early detection of endothelial dysfunction could be of great interest to adapt treatment in initial stage of sepsis. Current therapeutics used in sepsis mostly aim at controlling inflammation, vascular function and coagulation. Fluid administration, vasopressors, vasodilators and recombinant human activated protein C are also part of the treatments with the ultimate goal to exert beneficial effects on organ function and survival.