title: Dobutamine reverses the vasopressin-associated impairment in cardiac index and systemic oxygen supply in ovine endotoxemia.
abstract: BACKGROUND
  Arginine vasopressin (AVP) is increasingly used to treat sepsis-related vasodilation and to decrease catecholamine requirements. However, AVP infusion may be associated with a marked decrease in systemic blood flow and oxygen transport. The purpose of the present study was to evaluate whether dobutamine may be titrated to reverse the AVP-related decrease in cardiac index (CI) and systemic oxygen delivery index (DO2I) in an established model of ovine endotoxemia.
  
  
  METHODS
  Twenty-four adult ewes were chronically instrumented to determine cardiopulmonary hemodynamics and global oxygen transport. All ewes received a continuous endotoxin infusion that contributed to a hypotensive-hyperdynamic circulation and death of five sheep. After 16 hours of endotoxemia, the surviving ewes (n = 19; weight 35.6 +/- 1.5 kg (mean +/- SEM)) were randomized to receive either AVP (0.04 Umin-1) and dobutamine (n = 8) or the vehicle (normal saline; n = 6) and compared with a third group treated with AVP infusion alone (n = 5). Dobutamine infusion was started at an initial rate of 2 microg kg-1min-1 and was increased to 5 and 10 microg kg-1 min-1 after 30 and 60 minutes, respectively.
  
  
  RESULTS
  AVP infusion increased mean arterial pressure (MAP) and systemic vascular resistance index at the expense of a markedly decreased CI (4.1 +/- 0.5 versus 8.2 +/- 0.3 l min-1 m-2), DO2I (577 +/- 68 versus 1,150 +/- 50 ml min-1 m-2) and mixed-venous oxygen saturation (SvO2; 54.5 +/- 1.8% versus 69.4 +/- 1.0%; all p < 0.001 versus control). Dobutamine dose-dependently reversed the decrease in CI (8.8 +/- 0.7 l min-1 m-2 versus 4.4 +/- 0.5 l min-1 m-2), DO2I (1323 +/- 102 versus 633 +/- 61 ml min-1 m-2) and SvO2 (72.2 +/- 1.7% versus 56.5 +/- 2.0%, all p < 0.001 at dobutamine 10 microg kg-1 min-1 versus AVP group) and further increased MAP.
  
  
  CONCLUSIONS
  This study provides evidence that dobutamine is a useful agent for reversing the AVP-associated impairment in systemic blood flow and global oxygen transport.
authors.affiliation: Department of Anesthesiology and Intensive Care, University Hospital of Muenster, Albert-Schweitzer-Strasse 33, 48149 Muenster, Germany. ertmerc@gmx.net
authors.forename: Christian
authors.initials: C
authors.lastname: Ertmer
authors.forename: Andrea
authors.initials: A
authors.lastname: Morelli
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Bone
authors.forename: Henning Dirk
authors.initials: HD
authors.lastname: Stubbe
authors.forename: Ralf
authors.initials: R
authors.lastname: Schepers
authors.forename: Hugo
authors.initials: H
authors.lastname: Van Aken
authors.forename: Matthias
authors.initials: M
authors.lastname: Lange
authors.forename: Katrin
authors.initials: K
authors.lastname: Bröking
authors.forename: Martin
authors.initials: M
authors.lastname: Lücke
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Traber
authors.forename: Martin
authors.initials: M
authors.lastname: Westphal
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology* / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects* / Q000502:physiology; D004280:Dobutamine / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects* / Q000502:physiology; D012756:Sheep
chemical_list: D001127:Arginine Vasopressin; D004280:Dobutamine