in the previous issue of critical care , a european group made a new contribution to the terlipressin literature . for the first time , terlipressin , vasopressin , and norepinephrine were compared among patients with septic shock . because vasopressin is not available in most european countries , terlipressin , a vasopressin analog , terlipressin is initially indicated in patients with hepatorenal syndrome and bleeding esophageal varices . in 2001 , a british group treated eight patients with norepinephrine - resistant septic shock by repeated bolus administration of terlipressin . in 2004 , studies from france , spain , and italy confirmed the feasibility of terlipressin in septic shock [ 4 - 6 ] . vasopressin and its analogs act on three subtypes of receptors : v1 , v2 , and v3 . v1 receptors are found on various cells , including vascular smooth muscle cells , causing vasoconstriction . v3 receptors are found on cells within the central nervous system and modulate corticotrophin secretion . in septic shock , treatment is aimed to stimulate v1 receptors , and the vascular selectivity ( v1/v2 ) of terlipressin is 2.2/1.0 compared with 1.0/1.0 for vasopressin . the half - life of terlipressin is 6 hours compared with 20 minutes for vasopressin . because of the prolonged half - life of terlipressin , patients with septic shock received repeated boluses ( 1 mg ) of the drug . after intravenous injection , terlipressin works as a prodrug that slowly metabolizes to lysinevasopressin and in this way provides prolonged biological effect . nevertheless , a recent paper shows that terlipressin is not only a prodrug of vasopressin but also a strong vasoconstrictor per se . with regard to vasopressin , terlipressin may by itself have certain specific properties . because of its strong vasopressive effects , excessive vasoconstriction and a decrease in cardiac index are associated with bolus injection of terlipressin [ 3 - 6 ] . it was therefore hypothesized that low - dose continuous infusion may reverse sepsis - related systemic arterial hypotension with reduced side effects . in an ovine model , continuous infusion of terlipressin permanently reversed endotoxin - induced systemic arterial hypotension and improved left ventricular stroke work , whereas bolus injections were associated with a decrease in cardiac index and increases in pulmonary resistance . the purpose of the study by morelli and colleagues   was to test this hypothesis in humans . they used a fixed low dose of continuous infusion of terlipressin ( 1.3 g / kg per hour , which is approximately equal to 2 mg / day ) . this treatment was associated with a reduced norepinephrine infusion rate as compared with a control group . this result was not found in the vasopressin group ( 0.03 u / minute ) . however , as the fixed dosages were compared , this suggests that vasopressin at 0.03 u / minute probably reduces vasoconstriction less than terlipressin at 1.3 g / kg per hour . however , the persistent low levels of mixed venous oxygen saturation ( svo2 ) in all groups were quite unusual in septic shock . this would indirectly show that the management of these patients did not follow recent published guidelines . the investigators should not be blamed for not following international guidelines , but a local effect may have a role in their findings . at variance , low - dose terlipressin seems to have beneficial effects on regional hemodynamics . although vasopressin and analogs are recommended in patients with refractory septic shock , the investigators chose to introduce them as first - line treatment . this strategy may in fact be supported by several lines of evidence . in the vasopressin and septic shock trial ( vasst ) , low - dose vasopressin plus norepinephrine was compared with norepinephrine among patients with septic shock . although low - dose vasopressin did not reduce overall mortality rates , the mortality rate in patients with less severe septic shock was lower in the vasopressin group than in the norepinephrine group . these results are consistent with findings in isolated arteries , in which the ' beneficial ' synergistic effect of low - dose vasopressin ( on norepinephrine responsiveness ) was preserved in conditions mimicking less severe septic shock but was eliminated in a model of more severe shock . hence , one can hypothesize that a strategy using an early and multimodal approach to counteract the vascular dysfunction in septic shock may pay off . already , we are waiting for the results of the subsequent study , entitled terlipressin in septic shock trial ( tesst-1 ) . this randomized study , a european translation of vasst , was initiated to assess the safety and efficacy of continuous low - dose terlipressin infusion to treat patients with septic shock .
use of terlipressin in septic shock relies on a series of european studies resulting in a better knowledge of this vasopressive agent . 
 additional studies demonstrate that this agent appears to have attractive properties when administered properly . in comparison to prior reports , 
 continuous infusion of low - dose terlipressin seems superior when administered to septic animals . for the first time in humans , morelli and 
 colleagues compared this mode of administration with other vasopressors .