Introduction
The use of low-dose vasopressin infusions has become an accepted alternative for the management of vasodilatory shock refractory to catecholamines. While a growing number of publications describe the use of vasopressin in adults, there are only a small number of reports of its use in children. This issue of Pediatric Pharmacotherapy will review the available studies supporting the use of vasopressin infusions in pediatric patients and provide information on administration and monitoring.
Mechanism of Action
Vasopressin is an endogenous hormone produced in the parvocellular and magnocellular neurons within the supraoptic and paraventricular nuclei of the hypothalamus. It is stored and released by the posterior pituitary gland in response to increases in plasma osmolality or as a baroreflex response to decreases in blood pressure and/or blood volume.
Vasopressin acts on at least four different receptor sites, all of which appear to contribute to its effects in shock. The vasoconstrictive effects of vasopressin are mediated through vascular V1 receptors. Activity at these receptors produces activation of phospholipase C and blocks K-sensitive adenosine triphosphate channels allowing release of intracellular calcium into vascular smooth muscle and counteracting the effects of nitric oxide or atrial natriuretic peptide. The resulting vasoconstriction occurs predominately in the small vessels of the skin, skeletal muscle, small intestine, and fat.
Blood flow within the coronaries, as well as the cerebral, pulmonary, and renal vascular beds, is preserved, promoting shunting to those areas. This regional vasodilation is likely the result of a complex interplay of vasopressin activity at V1 and endothelial V3 and oxytocin receptor sites producing an increase in nitric oxide release.
The antidiuretic effects of vasopressin are mediated through V2 receptors, which are coupled to adenylyl cyclase and generate increases in cyclic adenosine monophosphatase (cAMP). As a result of this activity, capillary permeability in the distal tubules and collecting ducts is altered, producing increased reabsorption of water and augmenting systemic blood volume.
In addition to these direct effects, vasopressin may also enhance or restore catecholamine sensitivity. Synthetic vasopressin (8-arginine vasopressin) acts at the same receptor sites as endogenous vasopressin, producing an identical physiologic response.