Septic shock is the most common type of vasodilatory shock and leading cause of mortality in the United States. Currently cardiovascular support involves fluid administration, use of catecholamines, and potentially the use of inotropes, corticosteroids, or vasopressin. Vasopressin is an endogenous hormone essential for both osmotic and cardiovascular homeostasis synthesized in the hypothalamus and released in conditions such as hyperosmolality, hypotension and hypovolemia. Studies have shown that in acute shock states, serum vasopressin levels increase rapidly and then decreases in prolonged shock states leading to a relative deficiency of vasopressin. Endogenous vasopressin levels are significantly lower in adult patients with severe sepsis which is thought to contribute to the hypotension of shock. The rationale for the use of vasopressin is its relative deficiency in circulation and the increased sensitivity to its vasopressor effects seen during septic shock. Various studies have suggested that exogenous administration of vasopressin may be an effective adjunctive therapy to traditional catecholamines for the management of hypotension during septic shock.
Vasopressin induces constriction of vascular smooth muscle cells through action on specific renal (V-2) and vascular (V-1) receptors. Vasopressin produces vasoconstriction in non-vital circulations by activation of V-1 receptors which leads to increased levels of the second messengers inositol phosphate and diacylglycerol, which in turn activate voltage-gated calcium channels. This results in increased intracellular calcium levels, causing vasoconstriction. Secondly, vasopressin inhibits the inflammatory cytokine interleukin 1 which is released in response to trauma or infection and produces vasodilation by stimulating vascular endothelial NO production. Vasopressin decreases nitric oxide–mediated vasodilation, the common pathophysiology of septic shock.
Patients with septic shock is sensitive to vasopressin administration. Very low doses of vasopressin (from 0.01 to 0.05 units/min) have been shown to improve mean arterial pressure. In addition, doses above 0.04 units/minute did not consistently improve hemodynamics. Studies of vasopressin in adults with vasodilatory shock have used infusion rates of 0.01 to 0.1 units/min. In a retrospective review of high versus conventional vasopressin doses showed no additional benefit from doses greater than 0.08 units/min.
The results of the Vasopressin and Septic Shock Trial (VASST), reported by Russell et al. didn’t fully support the conclusion that low-dose vasopressin did not reduce mortality. Survival effects in the subgroups of patients in VASST appear to support hypothesis that “larger amounts of vasopressin may be needed in patients with more severe septic shock.
Because vasopressin is a potent vasopressor, infusions of vasopressin in patients with several forms of shock have led to improved organ perfusion, increased mean arterial pressure, improved blood pressure and neurologic function. Vasopressin produces vasodilation and increased blood flow in the cardiac, renal, pulmonary, mesenteric and especially in the cerebral vascular beds by stimulating endothelial NO release. It then reduces blood flow to the skin, small bowel and fat, thereby the blood flow is diverted from non-critical to critical organ beds. Therefore, vasopressin represents an attractive adjunct to the management of septic shock especially when catecholamines such as norepinephrine and dopamine are ineffective.