title: Improved short-term survival with polyethylene glycol modified hemoglobin liposomes in critical normovolemic anemia.
abstract: OBJECTIVE
  To investigate the efficacy of a polyethylene glycol (PEG) modified formulation of liposome-encapsulated hemoglobin (LEH) as an oxygen-carrying blood substitute in the treatment of critical normovolemic anemia.
  
  
  METHODS
  Prospective, controlled, randomized experimental study in a university research facility.
  
  
  METHODS
  14 anesthetized and mechanically ventilated beagle dogs.
  
  
  METHODS
  Animals were splenectomized and hemodiluted by exchange of whole blood for iso-oncotic hetastarch (HES). Target parameter of the hemodilution protocol was the individual critical hemoglobin concentration (Hb(crit)) corresponding with the onset of O(2) supply dependency of total body O(2) consumption. At Hb(crit) animals were randomized to receive a bolus infusion (20[Symbol: see text]ml/kg) of either LEH (n = 7) or normal saline (NS; n = 7). Subsequently animals were observed without further intervention.
  
  
  RESULTS
  The primary endpoint was survival time after the completion of treatment; secondary endpoints were parameters of central hemodynamics, O(2) transport and tissue oxygenation. Animals in the LEH group survived significantly longer after completion of treatment (149 +/- 109 vs. 43+/- 56 min). Immediately after treatment LEH-treated animals presented with a more stable cardiovascular condition. After 30 min tissue O(2) tension on the surface of a skeletal muscle was significantly higher in the LEH group (23+/-8 vs. 9 +/- 2 mmHg). Nevertheless, treatment with LEH did not decrease mortality within the observation period.
  
  
  CONCLUSIONS
  In this present experimental study the infusion of a PEG-modified LEH provided adequate tissue oxygenation, hemodynamic stability, and a prolongation of survival time after critical anemia. However, these effects were sustained for only a short period of time.
authors.affiliation: Clinic of Anesthesiology, Intensive Care Medicine and Pain Management, J.W. Goethe University Hospital, Theodor Stern Kai 7, 60590, Frankfurt/Main, Germany. a.pape@em.uni-frankfurt.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Pape
authors.forename: Harry
authors.initials: H
authors.lastname: Kertscho
authors.forename: Jens
authors.initials: J
authors.lastname: Meier
authors.forename: Oliver
authors.initials: O
authors.lastname: Horn
authors.forename: Mohamed
authors.initials: M
authors.lastname: Laout
authors.forename: Max
authors.initials: M
authors.lastname: Steche
authors.forename: Mischa
authors.initials: M
authors.lastname: Lossen
authors.forename: Alf
authors.initials: A
authors.lastname: Theisen
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zwissler
authors.forename: Oliver
authors.initials: O
authors.lastname: Habler
mesh_terms: D000740:Anemia / Q000628:therapy*; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D004337:Drug Carriers; D005260:Female; D006439:Hemodynamics; D006454:Hemoglobins / Q000008:administration & dosage*; D008081:Liposomes; D008297:Male; D010101:Oxygen Consumption; D011092:Polyethylene Glycols
chemical_list: D004337:Drug Carriers; D006454:Hemoglobins; D008081:Liposomes; D011092:Polyethylene Glycols