Adrenergic downregulation in critical care: molecular mechanisms and therapeutic evidence

Abstract Catecholamines remain the mainstay of therapy of acute cardiovascular dysfunction. However, adrenergic receptors quickly undergo desensitization and downregulation following prolonged stimulation. Moreover, prolonged exposure to high circulating catecholamines levels is associated with several adverse effects on different organ systems. Unfortunately, in critically ill patients, adrenergic downregulation translates in progressive reduction of cardiovascular response to exogenous catecholamine administration, leading to refractory shock. Accordingly, there has been a growing interest in recent years towards use of non-catecholaminergic inotropes and vasopressors. Several studies investigating a wide variety of catecholamine-sparing strategies (e.g. levosimendan, vasopressin, beta-blockers steroids, and use of mechanical circulatory support) have been recently published. Use of these agents was associated to improvement in hemodynamics and decreased catecholamine use, but without a clear beneficial effect on major clinical outcomes. Accordingly, further research is needed to define the optimal management of catecholamine-resistant shock.