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.