title: Effects of titrated arginine vasopressin on hemodynamic variables and oxygen transport in healthy and endotoxemic sheep.
abstract: OBJECTIVE
  To determine the effects of titrated arginine vasopressin (AVP) alone or in combination with norepinephrine (NE) on hemodynamics and oxygen transport in healthy and endotoxemic sheep.
  
  
  METHODS
  Prospective controlled trial.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Six adult ewes.
  
  
  METHODS
  Healthy sheep received AVP as a titrated infusion, initiated with 0.6 units/hr and increased by 0.6 units/hr every 15 mins, either until mean arterial pressure was increased by 20 mm Hg vs. baseline or a maximum of 3.6 units/hr was administered. After 90 mins, AVP infusion was continued with the investigated dosage, and NE (0.2 microg x kg(-1) x min(-1)) was also infused for 90 mins. After a 24-hr period of recovery, endotoxemia was induced and maintained (Salmonella typhosa endotoxin, 10 ng x kg(-1) x min(-1)) in the same sheep for the next 19 hrs. After 16 hrs of endotoxemia, AVP and NE were administered as described previously.
  
  
  RESULTS
  Hemodynamics were obtained at baseline, every 15 mins during the titration period, and 60 and 90 mins after additional NE infusion. Variables of oxygen transport were calculated before and after the titration period. In healthy and endotoxemic sheep, AVP reduced heart rate and cardiac index (p <.001) and compromised oxygen delivery (p <.001) and oxygen consumption (healthy sheep, p =.003; endotoxemic sheep, p <.001). Vasopressin infusion did not alter mean pulmonary arterial pressure but increased pulmonary vascular resistance index in both groups (p <.001). Additional infusion of NE further augmented mean arterial pressure and increased cardiac index during endotoxemia (p <.001). This was accompanied by an increase in oxygen delivery and consumption (p <.05 each).
  
  
  CONCLUSIONS
  During ovine endotoxemia, AVP decreased cardiac index, compromised oxygen delivery, and increased pulmonary vascular resistance index. These side effects may limit its use as a sole vasopressor during sepsis. Potentially, a simultaneous infusion of AVP and NE could represent a useful therapeutic option.
authors.affiliation: Department of Anaesthesiology and Intensive Care, University of Muenster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Westphal
authors.forename: Henning
authors.initials: H
authors.lastname: Stubbe
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Sielenkämper
authors.forename: Christian
authors.initials: C
authors.lastname: Ball
authors.forename: Hugo
authors.initials: H
authors.lastname: Van Aken
authors.forename: Reka
authors.initials: R
authors.lastname: Borgulya
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Bone
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D019446:Endotoxemia / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D009638:Norepinephrine / Q000494:pharmacology / Q000627:therapeutic use; D010101:Oxygen Consumption / Q000187:drug effects*; D011446:Prospective Studies; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D015657:Respiratory Transport / Q000187:drug effects*; D012756:Sheep; D014435:Typhoid Fever / Q000188:drug therapy* / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D009638:Norepinephrine