Physiology of vasopressin relevant to management of septic shock

Vasopressin is emerging as a rational therapy for the hemodynamic support o f septic shock and vasodilatory shock due to systemic inflammatory response syndrome. The goal of this review is to understand the physiology of vasop ressin relevant to septic shock in order to maximize its safety and efficac y in clinical trials and in subsequent therapeutic use. Vasopressin is both a vasopressor and an antidiuretic hormone. It also has hemostatic, GI, and thermoregulatory effects, and is an adrenocorticotropic hormone secretagog ue. Vasopressin is released from the axonal terminals of magnocellular neur ons in the hypothalamus. Vasopressin mediates vasoconstriction via VI-recep tor activation on vascular smooth muscle and mediates its antidiuretic effe ct via V2-receptor activation in the renal collecting duct system. In addit ion, vasopressin, at low plasma concentrations, mediates vasodilation in co ronary, cerebral, and pulmonary arterial circulations. Septic shock causes first a transient early increase in blood vasopressin concentrations that d ecrease later in septic shock to very low levels compared to other causes o f hypotension. Vasopressin infusion of 0.01 to 0.04 U/min in patients with septic shock increases plasma vasopressin levels to those observed in patie nts with hypotension from other causes, such as cardiogenic shock. Increase d vasopressin levels are associated with a lesser need for other vasopresso rs. Urinary output may increase, and pulmonary vascular resistance may decr ease. Infusions of > 0.04 U/min may lead to adverse, likely vasoconstrictio n-mediated events. Because clinical studies have been relatively small, foc used on physiologic end points, and because of potential adverse effects of vasopressin, clinical use of vasopressin should await a randomized control led trial of its effects on clinical outcomes such as organ failure and mor tality.