Clinical application of a hemoglobin-based oxygen-carrying solution

Fluid therapy for the traumatized patient

“…Serious concerns associated with transfusion of allogeneic blood or pRBCs in humans, such as transmittable diseases, immunologic incompatibility, transportation and storage difficulties, short shelf‐life, supply shortage, and costs stimulated the search for blood substitutes that would possess oxygen carrying in addition to volume expanding capacity and thus have the potential to serve as an ‘ideal’ resuscitation fluid for treatment of acute blood loss and anemia 143–146 . Over the past three or more decades numerous allogeneic and xenogeneic, stroma‐free, ultra‐purified tetrameric hemoglobin solutions, also called HBOCs, have been developed to overcome these problems, however, with mixed success as subsequent pre‐clinical and clinical investigations demonstrated 89,147–156 . Although a vast spectrum of in vitro experiments, laboratory models, and human clinical trials demonstrated the efficacy of these solutions as volume expanders and oxygen carriers, these studies also revealed significant problems associated with administration of HBOCs 89,147,149–151,153–162 .…”

“…Finally, the much shorter plasma residence time of these solutions compared with transfused red blood cells has been a concern and limiting factor for their use in trauma and persistent anemia 147,148 . It is beyond the scope of this report to provide a comprehensive review of the countless animal and human studies that have been conducted with various HBOCs over the years, thus the interested reader may consult the many recently published reviews for more details 89,147–156,163 …”

“…Clinical evidence proving the efficacy of Oxyglobin ® in canine or feline trauma patients is sparse at best and independent studies are missing 155,156 . The only prospective clinical study published so far has been conducted on behalf of the manufacturer at multiple sites before FDA approval and included 64 moderately to severely anemic dogs, with 25 of them suffering from acute blood loss 183 .…”

“…Nevertheless, the observation of circulatory overload with signs of pulmonary edema and pleural effusion in 38% of the cats treated with an initial infusion bolus of Oxyglobin ® (average 15 mL/kg at ∼5 mL/kg/hr) further emphasizes the potent oncotic effect of this solution and hence the need for close monitoring of hemodynamic variables (especially CVP) when administering this HBOC. It is for this reason also that dosing regimens have been changed since the launching of Oxyglobin ® , with recommended doses being now 5–30 mL/kg for dogs, infused at a rate of ≤10 mL/kg/hr and, although not approved for use in felines, 2.5–10 mL/kg for cats, given at a rate of ≤5 mL/kg/hr 7,8,155 . The plasma half‐life ( t 1/2 ) of Oxyglobin ® in dogs is dose‐dependent, with 30–40 hours reported at a dose of 30 mL/kg and approximately 24 hours at a dose of 15 mL/kg 156 .…”

Broadband diffuse optical spectroscopy assessment of hemorrhage- and hemoglobin-based blood substitute resuscitation

“…This is not surprising given the fact that the HBOC, Oxyglobin, has a hemoglobin concentration of 13 g/dL, an osmolality of 300, and a colloid osmotic pressure of 43 mmHg 1. Administration of replacement fluid with this combination of hyper-osmolality and a 13 g/dL hemoglobin concentration, which is only slightly above that of the animals following acute hemorrhage (intravascular post hemorrhage hemoglobin concentration, averaged 12.1±0.4 g/dL compared to prehemorrhage baseline values of 14.8±0.4 g/dL), would be expected to draw fluid into the vascular space resulting in substantial increases in intravascular volume, but should cause only slight (if any) increases in intravascular hemoglobin concentration 6–8,20…”