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Vascular hyporesponsiveness to vasopressors in septic shock: from bench to bedside

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Applied Physiology in Intensive Care Medicine 2

Abstract

Purpose: To delineate some of the characteristics of septic vascular hypotension, to assess the most commonly cited and reported underlying mechanisms of vascular hyporesponsiveness to vasoconstrictors in sepsis, and to briefly outline current therapeutic strategies and possible future approaches. Methods: Source data were obtained from a PubMed search of the medical literature with the following MeSH terms: Muscle, smooth, vascular/ physiopathology; hypotension/etiology; shock/physiopathology; vasodilation/physiology; shock/therapy; vasoconstrictor agents. Results: Nitric oxide (NO) and peroxynitrite are crucial components implicated in vasoplegia and vascular hyporeactivity. Vascular ATP-sensitive and calcium-activated potassium channels are activated during shock and participate in hypotension. In addition, shock state is characterized by inappropriately low plasma glucocorticoid and vasopressin concentrations, a dysfunction and desensitization of alpha-receptors, and an inactivation of catecholamines by oxidation. Numerous other mechanisms have been individualized in animal models, the great majority of which involve NO: MEK1/2–ERK1/2 pathway, H2S, hyperglycemia, and cytoskeleton dysregulation associated with decreased actin expression. Conclusions: Many therapeutic approaches have proven their efficiency in animal models, especially therapies directed against one particular compound, but have otherwise failed when used in human shock. Nevertheless, high doses of catecholamines, vasopressin and terlipressin, hydrocortisone, activated protein C, and non-specific shock treatment have demonstrated a partial efficiency in reversing sepsis-induced hypotension.

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Authors and Affiliations

  1. Groupe Choc, Contrat Avenir INSERM 2006, Faculté de Médecine, Nancy Université, Avenue de la Forêt de Haye, BP, Vandoeuvre-lés-Nancy Cedex, France

    B. Levy, S. Collin, N. Sennoun, A. Kimmoun & P. Perez

  2. Service de Réanimation Médicale, Institut du Coeur et des Vaisseaux, Hôpitaux de Brabois, CHU de Nancy, Rue du Morvan, Vandoeuvre-lès-Nancy, France

    B. Levy, N. Ducrocq & A. Kimmoun

  3. Groupe Choc, Contrat Avenir INSERM 2006, Faculté de Médecine, Nancy Université, Avenue de la Forêt de Haye, BP 184, Vandoeuvre-lès-Nancy Cedex, France

    N. Ducrocq

  4. Laboratoire HIFIH UPRES EA 3859, Université d’Angers, Angers, France

    P. Asfar

  5. Laboratoire HIFIH, IFR 132, Universitéd’ Angers et service de réanimation médicale et médecine hyperbare, CHU Angers, rue Larrey, Angers Cedex, France

    P. Asfar

  6. Laboratoire de Biophotonique et Pharmacologie, UMR 7213 CNRS, Faculté de Pharmacie, Université de Strasbourg, Illkirch, Strasbourg, France

    F. Meziani

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Editors and Affiliations

  1. Dept. of Critical Care Medicine, University of Pittsburgh Medical Center, Scaife Hall 606 3550 Terrace Street, Pittsburgh, PA, 15261, USA

    Michael R. Pinsky MD

  2. Dept. Intensive Care Medicine, Hôpital Henri Mondor, 51 av. Maréchal Lattre de Tassigny, 94010, Créteil, CX, France

    Laurent Brochard MD

  3. Dept. Intensive Care Medicine, Hospital de Sant Pau, Avda. S. Antonio M. Claret 167, 08025, Barcelona, Spain

    Jordi Mancebo MD

  4. General Intensive Care Unit, Università Cattolica des Sacro Cuore, Largo A. Gemelli 8, 00168, Rome, Italy

    Massimo Antonelli

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Levy, B. et al. (2012). Vascular hyporesponsiveness to vasopressors in septic shock: from bench to bedside. In: Pinsky, M.R., Brochard, L., Mancebo, J., Antonelli, M. (eds) Applied Physiology in Intensive Care Medicine 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28233-1_25

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