Terlipressin dose response in healthy and endotoxemic sheep: impact on cardiopulmonary performance and global oxygen transport

Abstract

Objective. To determine whether a goal-directed terlipressin infusion increases mean arterial pressure without causing a pulmonary vasopressive effect and whether this response impacts on key parameters of oxygen transport in healthy and endotoxemic sheep.

Design and setting. Prospective controlled trial in a university research laboratory.

Animals and interventions. Six conscious adult ewes instrumented for chronic study received terlipressin as titrated infusion started with 10 µg kg^–1 h^–1 and increased by 5 µg kg^–1 h^–1 every 15 min, either until mean arterial pressure was increased by 15 mmHg from baseline, or a maximum of 40 µg kg^–1 h^–1 was given. Following 24 h of recovery sepsis was induced and maintained in the same ewes by a continuous infusion of endotoxin (Salmonella typhosa, 10 ng kg^–1 min^–1). After 16 h of endotoxemia the sheep were again treated with terlipressin.

Measurements and results. Systemic oxygen delivery and consumption were calculated before and after the titration period; hemodynamic parameters were measured every 15 min. The increase in mean arterial pressure was greater during endotoxemia than in healthy controls. In both states terlipressin administration decreased cardiac index and diminished oxygen delivery and consumption. While mean pulmonary arterial pressure remained constant, terlipressin increased the pulmonary vascular resistance index in endotoxemic sheep.

Conclusions. During ovine endotoxemia titrated terlipressin reversed hypotension but impaired the pulmonary circulation. The observed decrease in oxygen delivery may carry the risk of tissue hypoxia especially in sepsis, where oxygen demand is typically increased.