Vasoplegia in patients with sepsis and septic shock: pathways and mechanisms

Abstract

At intensive care units sepsis is still one of the most frequent reasons for death. In the past years lots of therapeutic strategies have been checked out without desired success. One of the key factors for death is hypotension due to vasodilatation with vascular hyposensitivity. The underlying pathways, however, are not sufficiently explained. Endotoxemia induces inflammatory mediators, which is followed by vasoplegia and decreased cardiac contractility. Inhibition of these mediators is described to diminish mortality rates in animal models but without confirmation in humans. Further on a downregulation of vasoconstrictive receptors like angiotensin-, adrenergic- and vasopressin-receptors is seen in sepsis, which is associated with a hyporesponsiveness to vasoconstrictive mediators. Animal studies verify that receptor-downregulation is linked to the inflammatory mediators mentioned above. Anti-inflammatory therapy with glucocorticoids is described to improve responsiveness to catecholamins with higher survival in rats though there is no clinical significance in humans. Hence there is the urgent need for in-depth studies investigating the underlying mechanisms of vasoplegia in order to develop effective therapeutic strategies for the treatment of septic patients.