TY - JOUR
T1 - Adrenergic Downregulation in Critical Care
T2 - Molecular Mechanisms and Therapeutic Evidence
AU - Belletti, Alessandro
AU - Landoni, Giovanni
AU - Lomivorotov, Vladimir V.
AU - Oriani, Alessandro
AU - Ajello, Silvia
N1 - Funding Information:
The authors do not have any conflicts of interest to declare.
Publisher Copyright:
© 2019 Elsevier Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/4
Y1 - 2020/4
N2 - Catecholamines remain the mainstay of therapy for acute cardiovascular dysfunction. However, adrenergic receptors quickly undergo desensitization and downregulation after 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 into progressive reduction of cardiovascular response to exogenous catecholamine administration, leading to refractory shock. Accordingly, there has been a growing interest in recent years toward use of noncatecholaminergic inotropes and vasopressors. Several studies investigating a wide variety of catecholamine-sparing strategies (eg, levosimendan, vasopressin, β-blockers, steroids, and use of mechanical circulatory support) have been published recently. Use of these agents was associated with improvement in hemodynamics and decreased catecholamine use but without a clear beneficial effect on major clinical outcomes. Accordingly, additional research is needed to define the optimal management of catecholamine-resistant shock.
AB - Catecholamines remain the mainstay of therapy for acute cardiovascular dysfunction. However, adrenergic receptors quickly undergo desensitization and downregulation after 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 into progressive reduction of cardiovascular response to exogenous catecholamine administration, leading to refractory shock. Accordingly, there has been a growing interest in recent years toward use of noncatecholaminergic inotropes and vasopressors. Several studies investigating a wide variety of catecholamine-sparing strategies (eg, levosimendan, vasopressin, β-blockers, steroids, and use of mechanical circulatory support) have been published recently. Use of these agents was associated with improvement in hemodynamics and decreased catecholamine use but without a clear beneficial effect on major clinical outcomes. Accordingly, additional research is needed to define the optimal management of catecholamine-resistant shock.
KW - adrenergic downregulation
KW - adrenergic receptors
KW - catecholamines
KW - critical care
KW - inotropes
KW - molecular mechanisms
KW - therapeutic evidence
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U2 - 10.1053/j.jvca.2019.10.017
DO - 10.1053/j.jvca.2019.10.017
M3 - Review article
C2 - 31839459
AN - SCOPUS:85076562925
VL - 34
SP - 1023
EP - 1041
JO - Journal of Cardiothoracic and Vascular Anesthesia
JF - Journal of Cardiothoracic and Vascular Anesthesia
SN - 1053-0770
IS - 4
ER -