Continuous versus bolus infusion of terlipressin in ovine endotoxemia.

Abstract

In patients with sepsis, hemodynamic support is often complicated by a tachyphylaxis against conventional vasopressor agents. Bolus infusion of terlipressin, a vasopressin analog, has been reported to increase mean arterial pressure in patients with catecholamine-resistant septic shock. However, bolus infusion of terlipressin may be associated with severe side effects, including pulmonary vasoconstriction and impairment of oxygen delivery. We hypothesized that continuous low-dose infusion of terlipressin may reverse sepsis-related systemic arterial hypotension with reduced side effects as compared with the traditional concept of bolus administration. Twenty-seven adult sheep were instrumented for chronic study. After a baseline measurement, Salmonella typhosa endotoxin (10 ng.kg-1.min-1) was continuously administered for the next 40 h. After 16 h of endotoxemia, the surviving sheep (n = 24) were randomly assigned to be treated with either a continuous infusion of terlipressin (2 mg for 24 h), bolus injections of terlipressin (1 mg every 6 h), or placebo (normal saline; each n = 8). Continuous infusion of terlipressin permanently reversed endotoxin-induced systemic arterial hypotension (P < 0.001) and improved left ventricular stroke work index in all sheep (P < 0.05). Intermittent bolus injections of terlipressin were linked to decreases in heart rate and cardiac index and increases in pulmonary vascular resistance index (each, P < 0.001). These unwanted side effects were prevented by continuous low-dose infusion of the drug. In conclusion, continuous infusion of terlipressin stabilized hemodynamics and improved myocardial performance in endotoxemic ewes without obvious side effects. Continuous low-dose terlipressin infusion may represent a useful alternative treatment of arterial hypotension related to sepsis and systemic inflammatory response syndrome.

• Authors: Matthias Lange, Andrea Morelli, Christian Ertmer, Gabriele Koehler, Katrin Bröking, Christoph Hucklenbruch, Hans-Georg Bone, Hugo Van Aken, Daniel L Traber, Martin Westphal
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 28 Issue 5 Pg. 623-9 (Nov 2007) ISSN: 1073-2322 [Print] United States
• PMID: 17589382 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Catecholamines
• Endotoxins
• Vasoconstrictor Agents
• Lypressin
• Terlipressin

Topics

• Animals
• Catecholamines (metabolism)
• Disease Models, Animal
• Endotoxemia (chemically induced, drug therapy, metabolism, physiopathology)
• Endotoxins (chemistry, toxicity)
• Female
• Heart Rate (drug effects)
• Hemodynamics (drug effects)
• Humans
• Hypotension (drug therapy, metabolism, physiopathology)
• Lypressin (adverse effects, analogs & derivatives, pharmacology)
• Myocardium (metabolism)
• Random Allocation
• Salmonella typhi (chemistry)
• Sheep
• Tachyphylaxis
• Terlipressin
• Vasoconstriction (drug effects)
• Vasoconstrictor Agents (adverse effects, pharmacology)