Hemodynamic effects of terlipressin (a synthetic analog of vasopressin) in healthy and endotoxemic sheep

Abstract

Objective: Hypotension, vasodilation, and vasoplegia are characteristic signs of septic shock. The vasoconstrictive response to catecholamines typically is reduced. A decreased vasopressive effect of catecholamines can be observed in the late phase of hemorrhagic shock. Interestingly, an unaltered vasopressive response to vasopressin can be demonstrated in hemorrhagic shock. In this study, we investigated the vasoconstrictive response to an agonist of the vasopressin receptor, terlipressin, in healthy sheep as well as in ovine hyperdynamic endotoxemia.

Design: Prospective controlled trial.

Setting: University research laboratory.

Subjects: Six female adult sheep.

Interventions: Healthy sheep, instrumented for chronic study, received terlipressin (15 microg/kg) as a bolus; 30 mins later, norepinephrine was continuously given for 30 mins. Three hours later, a continuous infusion of endotoxin (Salmonella typhosa, 10 ng x kg(-1) x min(-1)) was started in the same sheep and given for the next 23 hrs. After 20 hrs of endotoxemia, terlipressin and norepinephrine were given as described previously.

Measurements and main results: Hemodynamic parameters were measured before and 30 mins after application of terlipressin and after 30 mins of continuous infusion of norepinephrine. Terlipressin significantly increased systemic vascular resistance index in healthy and endotoxemic sheep (p <.05). The increase was higher in endotoxemic compared with healthy animals (p <.05). Only during endotoxemia, terlipressin increased pulmonary vascular resistance index. This was accompanied by a significant decrease in cardiac index, whereas mean pulmonary arterial pressure did not change after application of terlipressin. Additional treatment with norepinephrine did not further increase systemic vascular resistance index or pulmonary vascular resistance index.

Conclusions: Terlipressin reversed the hemodynamic changes in ovine endotoxemia. However, its pulmonary vasopressive effect might limit its therapeutic use in septic shock.