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

Abstract

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. Prospective, controlled, randomized experimental study in a university research facility. 14 anesthetized and mechanically ventilated beagle dogs. 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 (Hb(crit)) corresponding with the onset of O(2) supply dependency of total body O(2) consumption. At Hb(crit) animals were randomized to receive a bolus infusion (20[Symbol: see text]ml/kg) of either LEH (n = 7) or normal saline (NS; n = 7). Subsequently animals were observed without further intervention. The primary endpoint was survival time after the completion of treatment; secondary endpoints were parameters of central hemodynamics, O(2) 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 O(2) 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. 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.