title: Norepinephrine increases tolerance to acute anemia.
abstract: OBJECTIVE
  Extreme anemia threatens myocardial oxygen supply by 1) a decline of arterial oxygen content and 2) by a decline of mean aortic pressure (MAP) and thus coronary perfusion pressure. Standard treatment of low arterial oxygen content includes ventilation with pure oxygen and the transfusion of red blood cells. However, it is unknown whether the stabilization of MAP and coronary perfusion pressure with norepinephrine as the sole therapeutic modality may also increase tolerance to extreme anemia and thus improve outcome.
  
  
  METHODS
  Prospective, randomized, controlled study.
  
  
  METHODS
  Experimental animal laboratory of a university hospital.
  
  
  METHODS
  A total of 28 anesthetized, mechanically ventilated pigs.
  
  
  METHODS
  In the first protocol, 14 anesthetized pigs were hemodiluted by exchange of whole blood for 6% hydroxyethyl starch (200,000:0.5) until the individual critical hemoglobin concentration was reached. For the next 6 hrs, animals were either observed without any further intervention (control group) or their MAP was maintained by adapted infusion of norepinephrine (norepinephrine group). The main outcome variable of this protocol was the 6-hr mortality in both groups. In the second protocol, 14 anesthetized pigs received hemodilution until death. In seven animals, no intervention was performed during the hemodilution procedure, whereas in the other seven animals, MAP was maintained at >60 mm Hg by adapted infusion of norepinephrine. The main outcome variable of this protocol was the maximum exchangeable blood volume until death.
  
  
  RESULTS
  MAP stabilization with norepinephrine reduced the 6-hr mortality at the critical hemoglobin concentration from 100% to 14%. Maintaining MAP by adapted norepinephrine infusion during the hemodilution procedure allowed for the exchange of 125 (110/126) (median [quartile 1/quartile 3]) mL/kg blood (163% of blood volume) in the norepinephrine group, whereas only 76 (73/91) mL/kg blood (104% of blood volume) could be exchanged in the control group.
  
  
  CONCLUSIONS
  Application of norepinephrine can be judged a first-line intervention to bridge acute anemia via a stabilization of MAP and coronary perfusion pressure. However, due to the relevant side effects of norepinephrine, its sole long-term use during extreme anemia without concomitant transfusion of erythrocytes is not advised.
authors: Department of Anesthesiology, Intensive Care Medicine, and Pain Control, J. W. Goethe-University Hospital, Frankfurt, Germany. Meier@em.uni-frankfurt.de
authors: Jens
authors: J
authors: Meier
authors: Andreas
authors: A
authors: Pape
authors: Daria
authors: D
authors: Loniewska
authors: Patrick
authors: P
authors: Lauscher
authors: Harry
authors: H
authors: Kertscho
authors: Bernhard
authors: B
authors: Zwissler
authors: Oliver
authors: O
authors: Habler
mesh_terms: D000208:Acute Disease; D000740:Anemia / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006438:Hemodilution; D006454:Hemoglobins; D006895:Hydroxyethyl Starch Derivatives; D008297:Male; D009638:Norepinephrine / Q000627:therapeutic use*; D010101:Oxygen Consumption; D011897:Random Allocation; D012121:Respiration, Artificial; D013552:Swine; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
chemical_list: D006454:Hemoglobins; D006895:Hydroxyethyl Starch Derivatives; D014662:Vasoconstrictor Agents; D009638:Norepinephrine