Clinical review: Vasopressin and terlipressin in septic shock patients

Abstract

Vasopressin (antidiuretic hormone) is emerging as a potentially major advance in the treatment of septic shock. Terlipressin (tricyl-lysine-vasopressin) is the synthetic, long-acting analogue of vasopressin, and has comparable pharmacodynamic but different pharmacokinetic properties. Vasopressin mediates vasoconstriction via V1 receptor activation on vascular smooth muscle. Septic shock first causes a transient early increase in blood vasopressin concentrations; these concentrations subsequently decrease to very low levels as compared with those observed with other causes of hypotension. Infusions of 0.01-0.04 U/min vasopressin in septic shock patients increase plasma vasopressin concentrations. This increase is associated with reduced need for other vasopressors. Vasopressin has been shown to result in greater blood flow diversion from nonvital to vital organ beds compared with adrenaline (epinephrine). Of concern is a constant decrease in cardiac output and oxygen delivery, the consequences of which in terms of development of multiple organ failure are not yet known. Terlipressin (one or two boluses of 1 mg) has similar effects, but this drug has been used in far fewer patients. Large randomized clinical trials should be conducted to establish the utility of these drugs as therapeutic agents in patients with septic shock.

Figure 1

Pituitary secretion of vasopressin. The main hypothalamic nuclei release vasopressin and corticotrophin-releasing hormone (CRH), which stimulates the secretion of adrenocorticotrophic hormone (ACTH) via the anterior pituitary gland (AP). Magnocellular neurones (MCN) and supraoptic neurones release vasopressin, which is stored in the posterior pituitary gland (PP) before its release into the circulation. CNS, central nervous system; PCN, parvocellular neurones; PVN, paraventricular nucleus of hypothalamus; SON, supraoptic nucleus of hypothalamus. Modified from Holmes and coworkers [8].

Figure 2

Influence of plasma osmolality and hypotension on vasopressin secretion.