Vasopressin and its Analogues in the Therapy of Shock

Overview

Hemodynamic support during the circulatory failure with vasodilation, most frequently during the septic shock, isbased on volume recovery and administration of inotropic drugs. If such therapy is not sufficient, vasoconstrictiondrugs are subsequently or parallely added to maintain the perfusion pressure. As a standard therapy, norepinephrineor other catecholamines with alpha-adrenergic effect are used in rising doses. Some patients do not respond to suchtherapy with desired hemodynamic changes – they develop catecholamine resistant shock. Because of serious sideeffects of high doses of catecholamines, alternative vasopressors are necessary. Vasopressin, antidiuretic hormone,has in physiological conditions only minimal effect of the vascular tone. During hypovolemia its concentration risesand it may significantly contribute to the maintenance of arterial pressure by vasoconstriction. Contrary to it, duringseptic shock the levels of vasopressine are very low and vasodilation clinically dominates. At the same time, theseptic shock is accompanied by an increased sensitivity to vasopressin administration. In a critical shock a seriousdeficit of endogenous vasopressin is expected. At present several pilot studies with vasopressine administration inseptic shock exist in literature describing beneficial effect of vasopressin on hemodynamic parameters. Suchcomparatively lowdoses have no side effects on perfusion and function of body organs. Terlipressin,which is availablein Czech Republic, is a synthetic analogue of vasopressin with extended effect. Its intermittent administration isused for the treatment of portal hypertension complications. Terlipressin in animalmodel of septic shock has similarlybeneficial effects as vasopressin. High doses of Terlipressin have, similarly to vasopressin, adverse effects onpulmonary circulation and other systems. Till present, only casuistic experience has been published with low dosesof Terlipressin in the treatment of septic shock resistant to catecholamines, which has shown similar effects tovasopressin. In shock states with the deficit of endogenous vasopressin, which are resistant to high doses ofcatecholamines, administration of vasopressin analogues represents a new perspective therapy. The treatment shouldbe studied from the point of morbidity and mortality. A careful approach has to be used in septic patients withpre-existing obliterative vassal disease.

Key words:
shock, sepsis, vasopressin, nitric oxide, terlipressin, therapy.