Investigational Intensive Care Unit, Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, United States of America.
Department of Anaesthesia and Intensive Care, Philipps University of Marburg, Marburg, Germany.
Crit Care Med. 2014 Jul;42(7):e525-e533. doi: 10.1097/CCM.0000000000000300.
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.
Prospective, randomized, controlled laboratory experiment.
University animal research facility.
Forty-five chronically instrumented sheep.
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.
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.
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.
在绵羊铜绿假单胞菌肺炎诱发严重脓毒症模型中，比较选择性血管加压素 1a 型受体激动剂 selepressin（FE 202158）与混合血管加压素 1a 型受体/血管加压素 V2 受体激动剂血管升压素激素精氨酸血管升压素作为一线血管加压药物滴定治疗的效果。
前瞻性、随机、对照实验室实验。
大学动物研究设施。
45 只慢性仪器化绵羊。
羊被麻醉，通过气管切开术用冷却的棉烟充气，并将铜绿假单胞菌注入其气道。然后，它们被置于辅助通气下，苏醒，并通过乳酸林格氏液复苏，滴定以维持血细胞比容±从基线水平下降 3%。如果尽管进行了液体管理，平均动脉压仍比基线水平下降超过 10mmHg，则另外连续静脉输注精氨酸血管升压素或 selepressin，以将平均动脉压提高并维持在不低于基线水平 10mmHg。同样研究了 selepressin 与选择性血管加压素 V2 受体激动剂去氨加压素联合治疗的效果。
在脓毒症绵羊中，MAP 下降约 30mmHg，全身血管阻力指数下降约 50%，24 小时内保留约 7L 液体；精氨酸血管升压素和 selepressin 部分减少了这种液体积累，而 selepressin 几乎完全阻断了这种积累；联合输注 selepressin 和去氨加压素使液体积累增加到与精氨酸血管升压素治疗相似的水平。
与混合血管加压素 1a 型受体/血管加压素 V2 受体激动剂精氨酸血管升压素相比，用选择性血管加压素 1a 型受体激动剂 selepressin 复苏更有效地阻断了血管渗漏，因为其缺乏血管加压素 V2 受体的激动剂活性。
