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

Judith Martini, Pedro Cabrales, K. Ananda, Seetharama A. Acharya, Marcos Intaglietta, Amy G. Tsai

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Introduction: 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. Conclusion: 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.

Original languageEnglish (US)
Article numberR54
JournalCritical Care
Volume12
Issue number2
DOIs
StatePublished - Apr 18 2008

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Hydroxyethyl Starch Derivatives
Hemodilution
Hemorrhagic Shock
Serum Albumin
Starch
Survival
Albumins
Hemorrhage
Arterial Pressure
Blood Volume
Shock
Maintenance
Surgical Blood Loss
Acid-Base Equilibrium
Austria
Hematocrit
Cricetinae
Membrane Proteins
Therapeutics
Heart Rate

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Medicine(all)

Cite this

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. / Martini, Judith; Cabrales, Pedro; Ananda, K.; Acharya, Seetharama A.; Intaglietta, Marcos; Tsai, Amy G.

In: Critical Care, Vol. 12, No. 2, R54, 18.04.2008.

Research output: Contribution to journalArticle

Martini, Judith ; Cabrales, Pedro ; Ananda, K. ; Acharya, Seetharama A. ; Intaglietta, Marcos ; Tsai, Amy G. / 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. In: Critical Care. 2008 ; Vol. 12, No. 2.
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abstract = "Introduction: 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. Conclusion: 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.",
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AU - Martini, Judith

AU - Cabrales, Pedro

AU - Ananda, K.

AU - Acharya, Seetharama A.

AU - Intaglietta, Marcos

AU - Tsai, Amy G.

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AB - Introduction: 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. Conclusion: 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.

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