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

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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.

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