Current Vascular Pharmacology

Dimitri P. Mikhailidis  
Academic Head, Deptartment of Clinical Biochemistry
Royal Free Hospital Campus
University College London Medical School
University College London (UCL)
Pond Street
London, NW3 2QG
UK

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Mechanisms of Vascular Hyporesponsiveness in Septic Shock

Author(s): Antoine Kimmoun, Nicolas Ducrocq and Bruno Levy

Affiliation: Groupe CHOC, Equipe Avenir INSERM U961 Universite de Lorraine, Faculte de medecine de Nancy, 9 Avenue de la Foret de Haye, 54500 Vandoeuvre les Nancy, France.

Keywords: Septic shock, vasopressor, nitric oxide, potassium channels, catecholamine, adrenoreceptors, illness-related

Abstract:

Purpose: To define some of the most common characteristics of vascular hyporesponsiveness to catecholamines during septic shock and outline current therapeutic approaches and future perspectives.

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: NO and peroxynitrite are mainly responsible for vasoplegia and vascular hyporeactivity while COX 2 enzyme is responsible for the increase in PGI2, which also contributes to hyporeactivity. Moreover, K+ATP and BKCa channels are over-activated during septic shock and participate in hypotension. Finally, other mechanisms are involved in vascular hyporesponsiveness such as critical illness-related corticosteroid insufficiency, vasopressin depletion, dysfunction and desensitization of adrenoreceptors as well as inactivation of catecholamines by oxidation.

Conclusion: In animal models, several therapeutic approaches, targeted on one particular compound have proven their efficacy in preventing or reversing vascular hyporesponsiveness to catecholamines. Unfortunately, none have been successfully tested in clinical trials. Nevertheless, very high doses of catecholamines (>5 μg/kg/min), hydrocortisone, terlipressin or vasopressin could represent an alternative for the treatment of refractory septic shock.

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Article Details

VOLUME: 11
ISSUE: 2
Page: [139 - 149]
Pages: 11
DOI: 10.2174/1570161111311020004