Adrenergic Downregulation in Critical Care: Molecular Mechanisms and Therapeutic Evidence

Alessandro Belletti, Giovanni Landoni, Vladimir V. Lomivorotov, Alessandro Oriani, Silvia Ajello

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Pages (from-to)1023-1041
Number of pages19
JournalJournal of Cardiothoracic and Vascular Anesthesia
Issue number4
Publication statusPublished - Apr 2020


  • adrenergic downregulation
  • adrenergic receptors
  • catecholamines
  • critical care
  • inotropes
  • molecular mechanisms
  • therapeutic evidence

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Anesthesiology and Pain Medicine


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