title: 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.affiliation: Department of Anesthesiology and Intensive Care, University Hospital of Muenster, Muenster, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lange
authors.forename: Andrea
authors.initials: A
authors.lastname: Morelli
authors.forename: Christian
authors.initials: C
authors.lastname: Ertmer
authors.forename: Gabriele
authors.initials: G
authors.lastname: Koehler
authors.forename: Katrin
authors.initials: K
authors.lastname: Bröking
authors.forename: Christoph
authors.initials: C
authors.lastname: Hucklenbruch
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Bone
authors.forename: Hugo
authors.initials: H
authors.lastname: Van Aken
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Traber
authors.forename: Martin
authors.initials: M
authors.lastname: Westphal
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004731:Endotoxins / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007022:Hypotension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008236:Lypressin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D011897:Random Allocation; D012485:Salmonella typhi / Q000737:chemistry; D012756:Sheep; D013618:Tachyphylaxis; D000077585:Terlipressin; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D002395:Catecholamines; D004731:Endotoxins; D014662:Vasoconstrictor Agents; D008236:Lypressin; D000077585:Terlipressin