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Improved short-term survival with polyethylene glycol modified hemoglobin liposomes in critical normovolemic anemia

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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.

Design and setting

Prospective, controlled, randomized experimental study in a university research facility.

Subjects

14 anesthetized and mechanically ventilated beagle dogs.

Interventions

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 (Hbcrit) corresponding with the onset of O2 supply dependency of total body O2 consumption. At Hbcrit animals were randomized to receive a bolus infusion (20 ml/kg) of either LEH (n = 7) or normal saline (NS; n = 7). Subsequently animals were observed without further intervention.

Measurements and results

The primary endpoint was survival time after the completion of treatment; secondary endpoints were parameters of central hemodynamics, O2 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 O2 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.

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Acknowledgements

The authors gratefully thank Mr. W. Daut and his team's excellent performance of animal care and Mr. H. Winkelmeier's valuable technical assistance.

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Authors and Affiliations

  1. Clinic of Anesthesiology, Intensive Care Medicine and Pain Management, J.W. Goethe University Hospital, Theodor Stern Kai 7, 60590, Frankfurt/Main, Germany

    Andreas Pape, Harry Kertscho, Jens Meier, Oliver Horn, Mohamed Laout, Max Steche & Mischa Lossen

  2. Central Research Facility, J.W. Goethe University, Frankfurt/Main, Germany

    Alf Theisen

  3. Clinic of Anesthesiology, Ludwig Maximilian University Hospital, Munich, Germany

    Bernhard Zwissler

  4. Clinic of Anesthesiology, Surgical Intensive Care Medicine and Pain Management, Krankenhaus Nordwest, Frankfurt/Main, Germany

    Oliver Habler

Authors
  1. Andreas Pape
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  2. Harry Kertscho
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  3. Jens Meier
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  4. Oliver Horn
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  5. Mohamed Laout
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  7. Mischa Lossen
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  8. Alf Theisen
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  9. Bernhard Zwissler
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  10. Oliver Habler
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Corresponding author

Correspondence to Andreas Pape.

Additional information

The study was sponsored by a research grant from Terumo Inc., Kanagawa, Japan.

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Pape, A., Kertscho, H., Meier, J. et al. Improved short-term survival with polyethylene glycol modified hemoglobin liposomes in critical normovolemic anemia. Intensive Care Med 34, 1534–1543 (2008). https://doi.org/10.1007/s00134-008-1082-z

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  • DOI: https://doi.org/10.1007/s00134-008-1082-z

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