title: Survival time in severe hemorrhagic shock after perioperative hemodilution is longer with PEG-conjugated human serum albumin than with HES 130/0.4: a microvascular perspective.
abstract: BACKGROUND
  Preoperative hemodilution is an established practice that is applied to reduce surgical blood loss. It has been proposed that polyethylene glycol (PEG) surface decorated proteins such as PEG-conjugated human serum albumin may be used as non-oxygen-carrying plasma expanders. The purpose of this study was to determine whether there is any difference in survival time after severe hemorrhagic shock following extreme hemodilution using a conventional hydroxyethyl starch (HES)-based plasma expander or PEG-albumin.
  
  
  METHODS
  Experiments were performed using the hamster skinfold window preparation. Human serum albumin that was surface decorated with PEG was compared with Voluven 6% (Fresenius Kabi, Austria; a starch solution that is of low molecular weight and has a low degree of substitution; HES). These plasma expanders were used for a 50% (blood volume) exchange transfusion to simulate preoperative hemodilution. Exchange transfusion was followed by a 60% (blood volume) hemorrhage to reproduce a severe surgical bleed over a 1 hour period. Observation of the animal was continued for another hour during the shock phase.
  
  
  RESULTS
  The PEG-albumin group exhibited significantly greater survival rate than did the HES group, in which none of the animals survived the hemorrhage phase of the experiment. Among the treatment groups there were no changes in mean arterial pressure and heart rate from baseline after hemodilution. Both groups experienced gradual increases in arterial oxygen tension and disturbance in acid-base balance, but this response was more pronounced in the HES group during the shock period. Mean arterial pressure remained elevated after the initial hemorrhage period in the PEG-albumin group but not in the HES group. Maintenance of a greater mean arterial pressure during the initial stages of hemorrhage is proposed to be in part due to the improved volume expansion with PEG-albumin, as indicated by the significant decrease in systemic hematocrit compared with the HES group. PEG-albumin treatment yielded higher functional capillary density during the initial stages of hemorrhage as compared with HES treatment.
  
  
  CONCLUSIONS
  The ability of PEG-albumin to prolong maintenance of microvascular function better than HES is a finding that would be significant in a clinical setting involving preoperative blood management and extreme blood loss.
authors.affiliation: Department of Bioengineering, University of California, San Diego, Gilman Dr, La Jolla, California 92093, USA. judith.martini@uki.at
authors.forename: Judith
authors.initials: J
authors.lastname: Martini
authors.forename: Pedro
authors.initials: P
authors.lastname: Cabrales
authors.forename: Ananda
authors.initials: A
authors.lastname: K
authors.forename: Seetharama A
authors.initials: SA
authors.lastname: Acharya
authors.forename: Marcos
authors.initials: M
authors.lastname: Intaglietta
authors.forename: Amy G
authors.initials: AG
authors.lastname: Tsai
mesh_terms: D000418:Albumins / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D016063:Blood Loss, Surgical / Q000517:prevention & control; D001809:Blood Viscosity / Q000187:drug effects; D006224:Cricetinae; D006438:Hemodilution / Q000379:methods*; D006439:Hemodynamics / Q000187:drug effects; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation; D010952:Plasma Substitutes / Q000008:administration & dosage / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D018709:Statistics, Nonparametric; D016019:Survival Analysis
chemical_list: D000418:Albumins; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D011092:Polyethylene Glycols