Effects of two different dosing regimens of terlipressin on organ functions in ovine endotoxemia

Abstract

To test the hypothesis that a continuous infusion of the vasopressin analog terlipressin is associated with less organ dysfunction as compared to intermittent bolus infusion in an ovine sepsis model. Twenty-seven adult female sheep. All sheep were subjected to a Salmonella typhosa endotoxin infusion (10 ng/kg/min). After 16 h of endotoxemia, the surviving animals (n = 24) were randomized to (1) an untreated control group, (2) a continuous terlipressin group (2 mg/24 h), or (3) a terlipressin bolus group (1 mg/6 h). Hemodynamic variables were measured and blood was withdrawn at specific time points for the assessment of organ functions. Continuous terlipressin infusion was associated with improved surrogate parameters of myocardial, renal, and hepatic function as compared with terlipressin bolus infusion. Reduced vascular hyperpermeability was evidenced by an attenuated decrease in plasma protein concentrations in sheep treated with continuous terlipressin infusion as compared to bolus injection or no treatment. Continuous infusion of low-dose terlipressin preserved several surrogate parameters of organ function better than intermittent bolus injections in sheep with systemic inflammation.