Skip to main content
Top
Published in: Critical Care 2/2008

Open Access 01-04-2008 | Research

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

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

Published in: Critical Care | Issue 2/2008

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Shander A, Goodnough LT: Objectives and limitations of bloodless medical care. Curr Opin Hematol 2006, 13: 462-470.PubMedCrossRef Shander A, Goodnough LT: Objectives and limitations of bloodless medical care. Curr Opin Hematol 2006, 13: 462-470.PubMedCrossRef
2.
go back to reference Goodnough LT, Shander A, Spence R: Bloodless medicine: clinical care without allogeneic blood transfusion. Transfusion 2003, 43: 668-676.PubMedCrossRef Goodnough LT, Shander A, Spence R: Bloodless medicine: clinical care without allogeneic blood transfusion. Transfusion 2003, 43: 668-676.PubMedCrossRef
3.
go back to reference Messmer K, Sunder-Plassman L, Klövekorn WP, Holper K: Circulatory significance of hemodilution: rheological changes and limitations. In Advances in Microcirculation. Volume 4. Basel: Karger; 1972:1-77. Messmer K, Sunder-Plassman L, Klövekorn WP, Holper K: Circulatory significance of hemodilution: rheological changes and limitations. In Advances in Microcirculation. Volume 4. Basel: Karger; 1972:1-77.
4.
go back to reference Suttner S, Boldt J: Volume replacement with hydroxyethyl starch: is there an influence on kidney function? [in German]. Anasthesiol Intensivmed Notfallmed Schmerzther 2004, 39: 71-77.PubMedCrossRef Suttner S, Boldt J: Volume replacement with hydroxyethyl starch: is there an influence on kidney function? [in German]. Anasthesiol Intensivmed Notfallmed Schmerzther 2004, 39: 71-77.PubMedCrossRef
5.
go back to reference Treib J, Baron JF, Grauer MT, Strauss RG: An international view of hydroxyethyl starches. Intensive Care Med 1999, 25: 258-268.PubMedCrossRef Treib J, Baron JF, Grauer MT, Strauss RG: An international view of hydroxyethyl starches. Intensive Care Med 1999, 25: 258-268.PubMedCrossRef
6.
go back to reference Grocott M, Mythen M: Fluid Rherapy. London, UK: Harcourt; 1999. Grocott M, Mythen M: Fluid Rherapy. London, UK: Harcourt; 1999.
7.
go back to reference Halljamae H: Crystalloids vs. colloids. Mölndal, Sweden: Pharmacia Upjohn Sverige AB; 1996. Halljamae H: Crystalloids vs. colloids. Mölndal, Sweden: Pharmacia Upjohn Sverige AB; 1996.
8.
go back to reference Hangai-Hoger N, Intaglietta M: Polyethylene glycol conjugated albumin: a new generation plasma expander. Artificial Blood 2006, 14: 230-240. Hangai-Hoger N, Intaglietta M: Polyethylene glycol conjugated albumin: a new generation plasma expander. Artificial Blood 2006, 14: 230-240.
9.
go back to reference Acharya SA, Manjula BN: Surface decoration of hemoglobin with polyethylene glycol. In Blood Substitutes. Edited by: Winslow RM. Elsevier; 2006:460-469.CrossRef Acharya SA, Manjula BN: Surface decoration of hemoglobin with polyethylene glycol. In Blood Substitutes. Edited by: Winslow RM. Elsevier; 2006:460-469.CrossRef
11.
go back to reference Cabrales P, Tsai AG, Winslow RM, Intaglietta M: Extreme hemodilution with PEG-hemoglobin vs. PEG-albumin. Am J Physiol 2005, 289: H2392-H2400. Cabrales P, Tsai AG, Winslow RM, Intaglietta M: Extreme hemodilution with PEG-hemoglobin vs. PEG-albumin. Am J Physiol 2005, 289: H2392-H2400.
12.
go back to reference Winslow RM, Lohman J, Malavalli A, Vandegriff KD: Comparison of PEG-modified albumin and hemoglobin in extreme hemodilution in the rat. J Appl Physiol 2004, 97: 1527-1534.PubMedCrossRef Winslow RM, Lohman J, Malavalli A, Vandegriff KD: Comparison of PEG-modified albumin and hemoglobin in extreme hemodilution in the rat. J Appl Physiol 2004, 97: 1527-1534.PubMedCrossRef
13.
go back to reference Cabrales P, Nacharaju P, Manjula BN, Tsai AG, Acharya SA, Intaglietta M: Early difference in tissue pH and microvascular hemodynamics in hemorrhagic shock resuscitation using polyethylene glycol-albumin- and hydroxyethyl starch-based plasma expanders. Shock 2005, 24: 66-73.PubMedCrossRef Cabrales P, Nacharaju P, Manjula BN, Tsai AG, Acharya SA, Intaglietta M: Early difference in tissue pH and microvascular hemodynamics in hemorrhagic shock resuscitation using polyethylene glycol-albumin- and hydroxyethyl starch-based plasma expanders. Shock 2005, 24: 66-73.PubMedCrossRef
14.
go back to reference Hangai-Hoger N, Nacharaju P, Manjula BN, Cabrales P, Tsai AG, Acharya SA, Intaglietta M: Microvascular effects following treatment with polyethylene glycol-albumin in lipopolysaccharide-induced endotoxemia. Crit Care Med 2006, 34: 108-117.PubMedCrossRef Hangai-Hoger N, Nacharaju P, Manjula BN, Cabrales P, Tsai AG, Acharya SA, Intaglietta M: Microvascular effects following treatment with polyethylene glycol-albumin in lipopolysaccharide-induced endotoxemia. Crit Care Med 2006, 34: 108-117.PubMedCrossRef
15.
go back to reference Molineux G: Pegylation: engineering improved pharmaceuticals for enhanced therapy. Cancer Treat Rev 2002,28(suppl A):13-16.PubMedCrossRef Molineux G: Pegylation: engineering improved pharmaceuticals for enhanced therapy. Cancer Treat Rev 2002,28(suppl A):13-16.PubMedCrossRef
16.
go back to reference Veronese FM, Harris JM: Introduction and overview of peptide and protein pegylation. Adv Drug Deliv Rev 2002, 54: 453-456.PubMedCrossRef Veronese FM, Harris JM: Introduction and overview of peptide and protein pegylation. Adv Drug Deliv Rev 2002, 54: 453-456.PubMedCrossRef
17.
go back to reference Scott MD, Murad KL: Cellular camouflage: fooling the immune system with polymers. Curr Pharm Des 1998, 4: 423-438.PubMed Scott MD, Murad KL: Cellular camouflage: fooling the immune system with polymers. Curr Pharm Des 1998, 4: 423-438.PubMed
18.
go back to reference Olsen H, Andersen A, Nordbo A, Kongsgaard UE, Bormer OP: Pharmaceutical-grade albumin: impaired drug-binding capacity in vitro. BMC Clin Pharmacol 2004, 4: 4.PubMedPubMedCentralCrossRef Olsen H, Andersen A, Nordbo A, Kongsgaard UE, Bormer OP: Pharmaceutical-grade albumin: impaired drug-binding capacity in vitro. BMC Clin Pharmacol 2004, 4: 4.PubMedPubMedCentralCrossRef
19.
go back to reference Endrich B, Asaishi K, Götz A, Messmer K: Technical report: a new chamber technique for microvascular studies in unanaesthetized hamsters. Res Exp Med 1980, 177: 125-134.CrossRef Endrich B, Asaishi K, Götz A, Messmer K: Technical report: a new chamber technique for microvascular studies in unanaesthetized hamsters. Res Exp Med 1980, 177: 125-134.CrossRef
20.
go back to reference Colantuoni A, Bertuglia S, Intaglietta M: Effects of anesthesia on the spontaneous activity of the microvasculature. Int J Microcirc Clin Exp 1984, 3: 13-28.PubMed Colantuoni A, Bertuglia S, Intaglietta M: Effects of anesthesia on the spontaneous activity of the microvasculature. Int J Microcirc Clin Exp 1984, 3: 13-28.PubMed
21.
go back to reference Intaglietta M, Silverman NR, Tompkins WR: Capillary flow velocity measurements in vivo and in situ by television methods. Microvasc Res 1975, 10: 165-179.PubMedCrossRef Intaglietta M, Silverman NR, Tompkins WR: Capillary flow velocity measurements in vivo and in situ by television methods. Microvasc Res 1975, 10: 165-179.PubMedCrossRef
22.
go back to reference Lipowsky HH, Zweifach BW: Application of the 'two-slit' photometric technique to the measurement of microvascular volumetric flow rates. Microvasc Res 1978, 15: 93-101.PubMedCrossRef Lipowsky HH, Zweifach BW: Application of the 'two-slit' photometric technique to the measurement of microvascular volumetric flow rates. Microvasc Res 1978, 15: 93-101.PubMedCrossRef
23.
go back to reference Intaglietta M, Tompkins WR: On-line measurement of microvascular dimensions by television microscopy. J Appl Physiol 1972, 32: 546-551.PubMed Intaglietta M, Tompkins WR: On-line measurement of microvascular dimensions by television microscopy. J Appl Physiol 1972, 32: 546-551.PubMed
24.
go back to reference Winslow RM, Gonzales A, Gonzales ML, Magde M, McCarthy M, Rohlfs RJ, Vandegriff K: Vascular resistance and the efficacy of red cell substitutes in a rat hemorrhage model. J Appl Physiol 1998, 85: 993-1003.PubMed Winslow RM, Gonzales A, Gonzales ML, Magde M, McCarthy M, Rohlfs RJ, Vandegriff K: Vascular resistance and the efficacy of red cell substitutes in a rat hemorrhage model. J Appl Physiol 1998, 85: 993-1003.PubMed
25.
go back to reference Manjula BN, Tsai AG, Intaglietta M, Tsai CH, Ho C, Smith PK, Perumalsamy K, Kanika ND, Friedman JM, Acharya SA: Conjugation of multiple copies of polyethylene glycol to hemoglobin facilitated through thiolation: influence on hemoglobin structure and function. Protein J 2005, 24: 133-146.PubMedCrossRef Manjula BN, Tsai AG, Intaglietta M, Tsai CH, Ho C, Smith PK, Perumalsamy K, Kanika ND, Friedman JM, Acharya SA: Conjugation of multiple copies of polyethylene glycol to hemoglobin facilitated through thiolation: influence on hemoglobin structure and function. Protein J 2005, 24: 133-146.PubMedCrossRef
26.
go back to reference Grassetti DR, Murray JF: Conjugation of multiple copies of polyethylene glycol to hemoglobin facilitated through thiolation: influence on hemoglboin structure and function. Protein J 2005, 24: 133-146.CrossRef Grassetti DR, Murray JF: Conjugation of multiple copies of polyethylene glycol to hemoglobin facilitated through thiolation: influence on hemoglboin structure and function. Protein J 2005, 24: 133-146.CrossRef
27.
go back to reference Sander O, Reinhart K, Meier-Hellmann A: Equivalence of hydroxyethyl starch HES 130/0. 4 and HES 200/0. 5 for perioperative volume replacement in major gynaecological surgery. Acta Anaesthesiol Scand 2003, 47: 1151-1158.PubMedCrossRef Sander O, Reinhart K, Meier-Hellmann A: Equivalence of hydroxyethyl starch HES 130/0. 4 and HES 200/0. 5 for perioperative volume replacement in major gynaecological surgery. Acta Anaesthesiol Scand 2003, 47: 1151-1158.PubMedCrossRef
28.
go back to reference Kerger H, Saltzman DJ, Menger MD, Messmer K, Intaglietta M: Systemic and subcutaneous microvascular pO 2 dissociation during 4-h hemorrhagic shock in conscious hamsters. Am J Physiol 1996, 270: H827-H836.PubMed Kerger H, Saltzman DJ, Menger MD, Messmer K, Intaglietta M: Systemic and subcutaneous microvascular pO 2 dissociation during 4-h hemorrhagic shock in conscious hamsters. Am J Physiol 1996, 270: H827-H836.PubMed
29.
go back to reference Tsai AG, Friesenecker B, McCarthy M, Sakai H, Intaglietta M: Plasma viscosity regulates capillary perfusion during extreme hemodilution in hamster skin fold model. Am J Physiol 1998, 275: H2170-H2180.PubMed Tsai AG, Friesenecker B, McCarthy M, Sakai H, Intaglietta M: Plasma viscosity regulates capillary perfusion during extreme hemodilution in hamster skin fold model. Am J Physiol 1998, 275: H2170-H2180.PubMed
30.
go back to reference Boldt J: The balanced concept of fluid resuscitation. Br J Anesth 2007, 99: 312-315.CrossRef Boldt J: The balanced concept of fluid resuscitation. Br J Anesth 2007, 99: 312-315.CrossRef
31.
go back to reference Boldt J, Mengistu A, Seyfert UT, Vogt A, Hellstern P: The impact of a medium molecular weight, low molar substitution hydroxyethyl starch dissolved in a physiologically balanced electrolyte solution on blood coagulation and platelet function in vitro. Vox Sang 2007, 93: 139-144.PubMedCrossRef Boldt J, Mengistu A, Seyfert UT, Vogt A, Hellstern P: The impact of a medium molecular weight, low molar substitution hydroxyethyl starch dissolved in a physiologically balanced electrolyte solution on blood coagulation and platelet function in vitro. Vox Sang 2007, 93: 139-144.PubMedCrossRef
32.
go back to reference Wilkes NJ, Woolf RL, Powanda MC, Gan TJ, Machin SJ, Webb A, Mutch M, Bennett-Guerrero E, Mythen M: Hydroxyethyl starch in balanced electrolyte solution (Hextend): pharmacokinetic and pharmacodynamic profiles in healthy volunteers. Anesth Analg 2002, 94: 538-544.PubMedCrossRef Wilkes NJ, Woolf RL, Powanda MC, Gan TJ, Machin SJ, Webb A, Mutch M, Bennett-Guerrero E, Mythen M: Hydroxyethyl starch in balanced electrolyte solution (Hextend): pharmacokinetic and pharmacodynamic profiles in healthy volunteers. Anesth Analg 2002, 94: 538-544.PubMedCrossRef
33.
go back to reference Tsai AG, Intaglietta M: High viscosity plasma expanders: volume restitution fluids for lowering the transfusion trigger. Biorheology 2001, 38: 229-237.PubMed Tsai AG, Intaglietta M: High viscosity plasma expanders: volume restitution fluids for lowering the transfusion trigger. Biorheology 2001, 38: 229-237.PubMed
34.
go back to reference Cabrales P, Tsai AG: Plasma viscosity regulates systemic and microvascular perfusion during acute extreme anemic conditions. Am J Physiol 2006, 291: H2445-H2452. Cabrales P, Tsai AG: Plasma viscosity regulates systemic and microvascular perfusion during acute extreme anemic conditions. Am J Physiol 2006, 291: H2445-H2452.
35.
go back to reference Cabrales P, Tsai AG, Intaglietta M: Alginate plasma expander maintains perfusion and plasma viscosity during extreme hemodilution. Am J Physiol 2005, 288: H1708-H1716. Cabrales P, Tsai AG, Intaglietta M: Alginate plasma expander maintains perfusion and plasma viscosity during extreme hemodilution. Am J Physiol 2005, 288: H1708-H1716.
36.
go back to reference Tsai AG, Acero C, Nance PR, Cabrales P, Frangos JA, Buerk DG, Intaglietta M: Elevated plasma viscosity in extreme hemodilution increases perivascular nitric oxide concentration and microvascular perfusion. Am J Physiol Heart Circ Physiol 2005, 288: H1730-H1739.PubMedCrossRef Tsai AG, Acero C, Nance PR, Cabrales P, Frangos JA, Buerk DG, Intaglietta M: Elevated plasma viscosity in extreme hemodilution increases perivascular nitric oxide concentration and microvascular perfusion. Am J Physiol Heart Circ Physiol 2005, 288: H1730-H1739.PubMedCrossRef
37.
go back to reference Tsai AG, Cabrales P, Acharya AS, Intaglietta M: Resuscitation from hemorrhagic shock: recovery of oxygen carrying capacity or perfusion? Efficacy of new plasma expanders. Transfus Altern Transfus Med 2007, 9: 246-253.CrossRef Tsai AG, Cabrales P, Acharya AS, Intaglietta M: Resuscitation from hemorrhagic shock: recovery of oxygen carrying capacity or perfusion? Efficacy of new plasma expanders. Transfus Altern Transfus Med 2007, 9: 246-253.CrossRef
38.
go back to reference Minamiyama Y, Takemura S, Inoue M: Albumin is an important vascular tonus regulator as a reservoir of nitric oxide. Biochem Biophys Res Commun 1996, 225: 112-115.PubMedCrossRef Minamiyama Y, Takemura S, Inoue M: Albumin is an important vascular tonus regulator as a reservoir of nitric oxide. Biochem Biophys Res Commun 1996, 225: 112-115.PubMedCrossRef
39.
go back to reference Wettstein R, Tsai AG, Erni D, Lukyanov AN, Torchilin VP, Intaglietta M: Improving microcirculation is more effective than substitution of red blood cells to correct metabolic disorder in experimental hemorrhagic shock. Shock 2004, 21: 235-240.PubMedCrossRef Wettstein R, Tsai AG, Erni D, Lukyanov AN, Torchilin VP, Intaglietta M: Improving microcirculation is more effective than substitution of red blood cells to correct metabolic disorder in experimental hemorrhagic shock. Shock 2004, 21: 235-240.PubMedCrossRef
40.
go back to reference Assaly RA, Azizi M, Kennedy D, Amuro C, Zaher A, Houts FW, Habib RH, Shapiro JI, Dignam JD: Plasma expansion by polyethylene-glycol-modified-albumin. Clin Sci 2004, 107: 263-272.PubMedCrossRef Assaly RA, Azizi M, Kennedy D, Amuro C, Zaher A, Houts FW, Habib RH, Shapiro JI, Dignam JD: Plasma expansion by polyethylene-glycol-modified-albumin. Clin Sci 2004, 107: 263-272.PubMedCrossRef
41.
go back to reference Wettstein R, Cabrales P, Erni D, Tsai AG, Winslow RM, Intaglietta M: Resuscitation from hemorrhagic shock with MalPEG-albumin: comparison with MalPEG-hemoglobin. Shock 2004, 22: 351-357.PubMedCrossRef Wettstein R, Cabrales P, Erni D, Tsai AG, Winslow RM, Intaglietta M: Resuscitation from hemorrhagic shock with MalPEG-albumin: comparison with MalPEG-hemoglobin. Shock 2004, 22: 351-357.PubMedCrossRef
42.
go back to reference Gladwin MT, Crawford JH, Patel RP: The biochemistry of nitric oxide, nitrite, and hemoglobin: role in blood flow regulation. Free Radic Biol Med 2004, 36: 707-717.PubMedCrossRef Gladwin MT, Crawford JH, Patel RP: The biochemistry of nitric oxide, nitrite, and hemoglobin: role in blood flow regulation. Free Radic Biol Med 2004, 36: 707-717.PubMedCrossRef
Metadata
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
Authors
Judith Martini
Pedro Cabrales
Ananda K
Seetharama A Acharya
Marcos Intaglietta
Amy G Tsai
Publication date
01-04-2008
Publisher
BioMed Central
Published in
Critical Care / Issue 2/2008
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc6874

Other articles of this Issue 2/2008

Critical Care 2/2008 Go to the issue