Matthias Lange1, Christian Ertmer, Martin Westphal. 1. Department of Anesthesiology and Intensive Care, University of Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany. lange-m@anit.uni-muenster.de
Abstract
BACKGROUND: Arginine vasopressin (AVP) and terlipressin (TP) are increasingly used as adjunct vasopressors in the treatment of septic shock. Despite important pharmacological differences between the two drugs (e.g., receptor selectivity, effective half-life) the use of either substance is determined mainly by local availability and institutional inventory. We briefly describe the pathophysiology and pharmacology of septic shock relevant to the treatment with vasopressin analogues. In addition, differences in pharmacokinetics and pharmacodynamics between AVP and TP are discussed. DISCUSSION: The current literature suggests that neither AVP nor TP should be administered in high doses in patients with septic shock. Furthermore, increasing evidence indicates that early administration of vasopressin analogues may improve outcome as compared to a last-resort treatment. Low-dose infusion of AVP (0.6-2.4 U/h) has been demonstrated to be a safe adjunct in the management of septic shock. The V2 agonistic effects of AVP may exert favorable effects on hepatosplanchnic, renal, pulmonary, and coronary perfusion. However, the higher V1 receptor selectivity of TP may prove more potent in restoring arterial blood pressure and avoiding rebound hypotension, while carrying the risk of sustained global and regional vasoconstriction after bolus injection. CONCLUSIONS: Evidence from experimental studies and initial clinical reports suggests that continuous low-dose infusion of TP may stabilize hemodynamics in septic shock with reduced side effects. However, randomized, controlled trials are necessary to determine the role of bolus or continuous infusion of TP in the treatment of septic shock before this approach can be recommended for routine clinical use.
BACKGROUND:Arginine vasopressin (AVP) and terlipressin (TP) are increasingly used as adjunct vasopressors in the treatment of septic shock. Despite important pharmacological differences between the two drugs (e.g., receptor selectivity, effective half-life) the use of either substance is determined mainly by local availability and institutional inventory. We briefly describe the pathophysiology and pharmacology of septic shock relevant to the treatment with vasopressin analogues. In addition, differences in pharmacokinetics and pharmacodynamics between AVP and TP are discussed. DISCUSSION: The current literature suggests that neither AVP nor TP should be administered in high doses in patients with septic shock. Furthermore, increasing evidence indicates that early administration of vasopressin analogues may improve outcome as compared to a last-resort treatment. Low-dose infusion of AVP (0.6-2.4 U/h) has been demonstrated to be a safe adjunct in the management of septic shock. The V2 agonistic effects of AVP may exert favorable effects on hepatosplanchnic, renal, pulmonary, and coronary perfusion. However, the higher V1 receptor selectivity of TP may prove more potent in restoring arterial blood pressure and avoiding rebound hypotension, while carrying the risk of sustained global and regional vasoconstriction after bolus injection. CONCLUSIONS: Evidence from experimental studies and initial clinical reports suggests that continuous low-dose infusion of TP may stabilize hemodynamics in septic shock with reduced side effects. However, randomized, controlled trials are necessary to determine the role of bolus or continuous infusion of TP in the treatment of septic shock before this approach can be recommended for routine clinical use.
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