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  • Title: Continuous versus bolus infusion of terlipressin in ovine endotoxemia.
    Author: Lange M, Morelli A, Ertmer C, Koehler G, Bröking K, Hucklenbruch C, Bone HG, Van Aken H, Traber DL, Westphal M.
    Journal: Shock; 2007 Nov; 28(5):623-9. PubMed ID: 17589382.
    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.
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