Impact of Terlipressin on Hepatosplanchnic Perfusion: “Only the Dose Makes a Thing Not a Poison” (Paracelsus)
Treschan, Tanja A. M.D.*; Peters, Jürgen M.D.
We appreciate the comments of Dr. Roth regarding the use of vasopressin to restore blood pressure after pheochromocytoma resection. This case certainly adds an interesting experience to the few published cases discussed in our recent review.1
The use of a very small vasopressin bolus dose (0.4 U) is a reasonable approach to evaluate the patient's reaction toward the drug. Dr. Roth used a vasopressin infusion (4 U/h ≈ 0.07 U/min) for blood pressure maintenance. This dose is consistent with the recommendations for continuous vasopressin infusion when used as an adjunct vasopressor in septic shock (1–4 U/h ≈ 0.01–0.07 U/min).2
Use of vasopressin during pheochromocytoma resection has been described in a few patients with very different preoperative conditions (well-controlled blood pressure vs.
), treated with different anesthetic regimens (intraoperative use of thoracic epidural vs.
general anesthesia only3,4
), and intraoperative complications (e.g.
, severe blood loss4
). Therefore, data are not comparable, and it is much too early to provide treatment recommendations. Undoubtedly, the role of the vasopressin system is of greatest interest in patients with pheochromocytoma and stresses the importance of the vasopressin system as an important backup system for blood pressure control.1
We agree with Dr. Roth that some patients may have a specific need for treatment with exogenous vasopressin, due to down-regulation and/or preoperative pharmacologic blockade of adrenoceptors, down-regulation of vasopressin receptors, and/or “inadequately low” vasopressin release during acute hypotension. Further studies are needed to address these issues.
We thank Drs. Lange, van Aken, and Westphal for their comments on the impact of the long-acting vasopressin analog terlipressin on hepatosplanchnic perfusion. Westphal et al.5
investigated the effects of arginine vasopressin on gut mucosal microcirculation in septic rats. In fact, their study provides evidence for severe abnormalities in mucosal blood flow after vasopressin infusion, adding to a number of studies that showed jeopardized splanchnic microcirculation due to vasopressin agonist activity at intestinal V1 receptors. In addition, both agents, arginine vasopressin and the specific vasopressin V1 agonist terlipressin, have been shown to significantly reduce the oxygen content of the gastric mucosa, suggesting malperfusion of the intestinal mucosa.6,7
Furthermore, Westphal et al.8
themselves summarized similar results as “data suggest that, in sepsis, vasopressin and terlipressin infusion may decrease gastrointestinal mucosal blood flow.” In our recent review,1
we concluded that “terlipressin is a potent intestinal vasoconstrictor, and evidence suggests decreased intestinal perfusion with terlipressin infusion.”
We agree with Dr. Lange et al.
that this conclusion can be discussed further by taking into account also the role of fluid management and the dose itself. Asfar et al.9
used studies in animals to investigate the influence of terlipressin on splanchnic perfusion, and results obtained in pigs show that a continuous low-dose infusion of terlipressin (5–15 μg · kg−1
) does not have detrimental effects on hepatosplanchnic perfusion, oxygen exchange, and metabolism. However, to our knowledge, this regimen has not been used in clinical trials in humans. Rather, terlipressin is usually administered in intravenous boluses of 1–2 mg. Bolus doses have been used by Asfar et al.10
in their study on endotoxic rats. The bolus of 6 μg/kg used in this study, however, is only 25–50% of the dose reported to be used in humans, and lower boluses have not been studied in clinical trials with humans so far. Even with their low bolus doses, Asfar et al.
found a high mortality in endotoxic animals treated with terlipressin alone. Only when terlipressin was administered after adequate fluid resuscitation, ileal microcirculation improved, as expected. Therefore, these latter results support the importance of early and aggressive fluid resuscitation in sepsis11
and also warrant further research on dosing of terlipressin in sepsis. However, until these results are available, terlipressin can not be recommended for routine use in septic patients because of its potentially detrimental intestinal vasoconstrictor activities. That is, what dose it takes to make this drug not a poison is unsettled.
Tanja A. Treschan, M.D.*
Jürgen Peters, M.D.
*Universitätsklinikum Essen, Essen, Germany. firstname.lastname@example.org
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11. Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004; 32:858–73
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