2. Academic Validation
  3. The selective vasopressin type 1a receptor agonist selepressin (FE 202158) blocks vascular leak in ovine severe sepsis*

The selective vasopressin type 1a receptor agonist selepressin (FE 202158) blocks vascular leak in ovine severe sepsis*

  • Crit Care Med. 2014 Jul;42(7):e525-e533. doi: 10.1097/CCM.0000000000000300.
Marc O Maybauer # 1 2,  Dirk M Maybauer # 1 2,  Perenlei Enkhbaatar # 1,  Régent Laporte # 3,  Halina Wiśniewska 3,  Lillian D Traber 1,  ChiiDean Lin 4,  Juanjuan Fan 4,  Hal K Hawkins 5,  Robert A Cox 5,  Kazimierz Wiśniewski 3,  Claudio D Schteingart 3,  Donald W Landry 6,  Pierre J-M Rivière 3,  Daniel L Traber 1
Affiliations

Affiliations

  • 1 Investigational Intensive Care Unit, Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, United States of America.
  • 2 Department of Anaesthesia and Intensive Care, Philipps University of Marburg, Marburg, Germany.
  • 3 Ferring Research Institute, Inc., San Diego, California, United States of America.
  • 4 Department of Mathematics and Statistics, San Diego State University, San Diego, California, United States of America.
  • 5 Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
  • 6 Department of Medicine, Columbia University, New York City, New York, United States of America.
  • # Contributed equally.
PMID: 24674922 DOI: 10.1097/CCM.0000000000000300
Abstract

Objective: To determine if the selective vasopressin type 1a receptor agonist selepressin (FE 202158) is as effective as the mixed vasopressin type 1a receptor/vasopressin V2 receptor agonist vasopressor hormone arginine vasopressin when used as a titrated first-line vasopressor therapy in an ovine model of Pseudomonas aeruginosa pneumonia-induced severe sepsis.

Design: Prospective, randomized, controlled laboratory experiment.

Setting: University animal research facility.

Subjects: Forty-five chronically instrumented sheep.

Interventions: Sheep were anesthetized, insufflated with cooled cotton smoke via tracheostomy, and P. aeruginosa were instilled into their airways. They were then placed on assisted ventilation, awakened, and resuscitated with lactated Ringer's solution titrated to maintain hematocrit ± 3% from baseline levels. If, despite fluid management, mean arterial pressure fell by more than 10 mm Hg from baseline level, an additional continuous IV infusion of arginine vasopressin or selepressin was titrated to raise and maintain mean arterial pressure within no less than 10 mm Hg from baseline level. Effects of combination treatment of selepressin with the selective vasopressin V2 receptor agonist desmopressin were similarly investigated.

Measurements and main results: In septic sheep, MAP fell by ~30 mm Hg, systemic vascular resistance index decreased by ~50%, and ~7 L of fluid were retained over 24 hours; this fluid accumulation was partially reduced by arginine vasopressin and almost completely blocked by selepressin; and combined infusion of selepressin and desmopressin increased fluid accumulation to levels similar to arginine vasopressin treatment.

Conclusions: Resuscitation with the selective vasopressin type 1a receptor agonist selepressin blocked vascular leak more effectively than the mixed vasopressin type 1a receptor/vasopressin V2 receptor agonist arginine vasopressin because of its lack of agonist activity at the vasopressin V2 receptor.

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