Low-Dose Vasopressin in the Treatment of Septic Shock in Sheep

• Published in: American journal of respiratory and critical care medicine 2003-08, Vol.168 (4), p.481-486
• Main Authors: Sun, Qinghua, Dimopoulos, George, Nguyen, Duc Nam, Tu, Zizhi, Nagy, Nathalie, Hoang, Anh Dung, Rogiers, Peter, De Backer, Daniel, Vincent, Jean-Louis
• Format: Article
• Language: English
• Subjects: Animals; Blood Pressure - drug effects; Carbon Dioxide - blood; Cecum - injuries; Ileum - blood supply; Intestinal Perforation - complications; Isotonic Solutions; Lactates - blood; Mesenteric Arteries - drug effects; Norepinephrine - administration & dosage; Norepinephrine - therapeutic use; Proportional Hazards Models; Random Allocation; Sheep; Shock, Septic - drug therapy; Shock, Septic - urine; Splanchnic Circulation - drug effects; Statistics, Nonparametric; Survival Rate; Vasoconstrictor Agents - administration & dosage; Vasoconstrictor Agents - therapeutic use; Vasopressins - administration & dosage; Vasopressins - therapeutic use
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200205-447OC

After induction of cecal perforation, 20 anesthetized sheep were randomized to be treated, when arterial blood pressure fell below 75 mm Hg, with vasopressin (fixed dose of 0.02 U/minute), norepinephrine (0.5-5 microg/kg/minute titrated to maintain mean arterial pressure between 75 and 85 mm Hg), vasopressin + norepinephrine (vasopressin at fixed dose 0.01 U/minute plus norepinephrine titrated as for norepinephrine only group), or no vasopressor (Ringer's lactate [control]). Mean arterial pressure was well maintained in all treatment groups. Superior mesenteric arterial blood flow was significantly lower in the vasopressin + norepinephrine group than in the vasopressin group. Vasopressin alone or combined with norepinephrine limited the increase in blood lactate concentration and ileal PCO2-gap compared with control and norepinephrine groups. Urine output was higher in the vasopressin group than in control and norepinephrine groups. Survival time was longer in the vasopressin (30 +/- 6 hours) and vasopressin + norepinephrine (30 +/- 3 hours) groups than in the norepinephrine group (20 +/- 1 hours, p < 0.05) and in all treatment groups than in the control group (17 +/- 2 hours, p < 0.05). Tissue injury was less severe in the vasopressin and vasopressin + norepinephrine groups than in the others. In this clinically relevant model of septic shock due to peritonitis, vasopressin administration (alone or with norepinephrine) can prolong survival.