Published in:
01-08-2008 | Experimental
Improved short-term survival with polyethylene glycol modified hemoglobin liposomes in critical normovolemic anemia
Authors:
Andreas Pape, Harry Kertscho, Jens Meier, Oliver Horn, Mohamed Laout, Max Steche, Mischa Lossen, Alf Theisen, Bernhard Zwissler, Oliver Habler
Published in:
Intensive Care Medicine
|
Issue 8/2008
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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.