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


METHODS
Prospective controlled trial in a university research laboratory.


METHODS
Six conscious adult ewes instrumented for chronic study received terlipressin as titrated infusion started with 10 microg x kg(-1) x h(-1) and increased by 5 microg x kg(-1) x h(-1) every 15 min, either until mean arterial pressure was increased by 15 mmHg from baseline, or a maximum of 40 microg x kg(-1) x 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 x kg(-1) min(-1)). After 16 h of endotoxemia the sheep were again treated with terlipressin.


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.
Westphal
Martin
M
Department of Anesthesiology and Intensive Care, University of Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany. mwestpha@uni-muenster.de
Stubbe
Henning
H
Sielenkämper
Andreas Wilhelm
AW
Borgulya
Reka
R
Van Aken
Hugo
H
Ball
Christian
C
Bone
Hans-Georg
HG
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D019446:Endotoxemia / Q000150:complications*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D008236:Lypressin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects*; D011446:Prospective Studies; D011652:Pulmonary Circulation / Q000187:drug effects; D015657:Respiratory Transport / Q000187:drug effects*; D012756:Sheep; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D000077585:Terlipressin; D014435:Typhoid Fever / Q000150:complications*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D008236:Lypressin; D000077585:Terlipressin