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

Abstract

Sepsis is one of the most frequent causes of death among patients in intensive care units. Many therapeutic strategies have been assessed without the desired success rates. A key risk factor for death is hypotension due to vasodilatation with vascular hyposensitivity. However, the pathways underlying this process remain unclear. Endotoxemia induces inflammatory mediators, and this is followed by vasoplegia and decreased cardiac contractility. Although inhibition of these mediators diminishes mortality rates in animal models, this phenomenon has not been confirmed in humans. Downregulation of vasoconstrictive receptors such as angiotensin receptors, adrenergic and vasopressin receptors is seen in sepsis, which is associated with a hyporesponsiveness to vasoconstrictive mediators. Animal studies have verified that receptor downregulation is linked to the above-mentioned inflammatory mediators. Anti-inflammatory therapy with glucocorticoids reportedly improves responsiveness to catecholamines with higher survival in rats, although this has not been shown to be clinically significant in humans. Hence, there is an urgent need for in-depth studies investigating the underlying mechanisms of vasoplegia to allow for development of effective therapeutic strategies for the treatment of sepsis.