Low-dose terlipressin during long-term hyperdynamic porcine ... : Critical Care Medicine (original) (raw)

Laboratory Investigations

Low-dose terlipressin during long-term hyperdynamic porcine endotoxemia: Effects on hepatosplanchnic perfusion, oxygen exchange, and metabolism*

Asfar, Pierre MD, PhD; Hauser, Balázs MD; Iványi, Zsolt MD; Ehrmann, Ulrich MD; Kick, Jochen MD; Albicini, Maura MD; Vogt, Josef PhD; Wachter, Ulrich BSc; Brückner, Uwe Bernd MD, PhD; Radermacher, Peter MD, PhD; Bracht, Hendrik MD

From Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Ulm, Germany (PA, BH, ZI, UE, JK, MA, JV, UW, PR, HB); Service de Réanimation Médicale, CHU, Angers, France (PA); Aneszteziológiai és Intenzív Terαpiαs Klinika, Semmelweis Egyetem, Budapest, Hungary (BH, ZI); Abteilung Thorax- und Gefäßchirurgie, Universitätsklinikum, Ulm, Germany (JK); Istituto di Anestesiologia e Rianimazione dell’Universita degli Studi di Milano: Azienda Ospedaliera, Polo Universitario San Paolo, Milano, Italy (MA); and Sektion Chirurgische Forschung, Universitätsklinikum, Ulm, Germany (UBB).

Drs. Asfar and Hauser contributed equally to this work.

Supported, in part, by a Roman Herzog research fellowship of the Alexander von Humboldt Stiftung and the Gemeinnützige Hertie Stiftung (BH); by the Centre Hospitalo-Universitaire, Angers, France (PA); by a grant from Ferring France; and by Prof. K.-D. Döhler, Curatis Pharma GmbH, Hannover (Germany), who provided terlipressin (Haemopressin).

Abstract

Objective:

To investigate whether the vasopressin analog terlipressin might induce hepatosplanchnic ischemia during long-term, hyperdynamic, volume-resuscitated porcine endotoxemia.

Design:

Prospective, randomized, controlled experimental study with repeated measures.

Setting:

Investigational animal laboratory.

Subjects:

Eighteen pigs were divided into two groups receiving either endotoxin alone (control group, n = 10) or endotoxin and terlipressin (n = 8).

Interventions:

Pigs were anesthetized, mechanically ventilated, and instrumented and received a continuous intravenous infusion of Escherichia coli endotoxin. Animals were resuscitated with hydroxyethyl starch targeted to maintain mean arterial pressure >60 mm Hg. Twelve hours after the start of the endotoxin infusion, terlipressin (5–15 μg·kg−1·hr−1 titrated to maintain mean arterial pressure at preendotoxin levels) or its vehicle was administered for 12 hrs.

Measurements and Main Results:

Terlipressin increased mean arterial pressure and systemic vascular resistances, which was affiliated with a decrease in cardiac output and global oxygen consumption. Terlipressin restored the hepatic artery buffer response, which led to an increase in hepatic artery flow, ultimately resulting in well-maintained liver oxygen delivery, oxygen uptake, and all other variables of regional metabolism and organ function. Terlipressin markedly attenuated the hepatosplanchnic venous acidosis but was associated with pronounced hyperlactatemia.

Conclusions:

During long-term hyperdynamic porcine endotoxemia, the well-known vasoconstrictor properties of terlipressin blunted the progressive decrease in mean arterial pressure without any detrimental effect on hepatosplanchnic perfusion, oxygen exchange, and metabolism. The marked terlipressin-induced hyperlactatemia did not originate from the hepatosplanchnic organs but from extrasplanchnic tissues, possibly muscle and skin.