Small-volume Resuscitation with HBOC-201: Effects on Cardiovascular Parameters and Brain Tissue Oxygen Tension in an Out-of-hospital Model of Hemorrhage in Swine

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Abstract
Hemoglobin-based oxygen carriers, such as HBOC-201, offer several potential advantages over conventional resuscitation solutions or banked blood in the acute treatment of hemorrhagic shock. While previous studies with some hemoglobin solutions revealed vasoactive effects resulting in decreased oxygen delivery, these investigations were performed without directly measuring vital tissue oxygenation. The authors tested the hypothesis that a small-volume bolus of HBOC-201 would improve and sustain brain tissue oxygen tension (PbrO(2)) without adverse effects on cardiovascular end-points, when used in an acute out-of-hospital hemorrhage model. Male Yorkshire swine (n = 7) were hemorrhaged to a mean arterial pressure (MAP) of 40 mm Hg while monitoring standard hemodynamic parameters. In addition, Clark-type polarographic probes were directly inserted into brain tissue to measure PbrO(2). Following institution of high-flow oxygen (FiO(2) = 1.0), resuscitation was performed with a bolus infusion of HBOC-201 (6 mL/kg). Swine were observed for two hours. Cardiac output (CO), MAP, pulmonary artery diastolic pressure (PAD), and PbrO(2) all decreased significantly with hemorrhage (p < 0.05). Immediately following resuscitation with HBOC-201 (mean volume = 239 mL), MAP and CO were restored to 83% and 84% of baseline levels, respectively. PbrO(2) increased significantly after treatment with HBOC-201, surpassing baseline levels by 66%. PAD rose above baseline levels during observation, but this increase was not significantly different from baseline levels (24.0 mm +/- 4.1 vs. 22.7 mm +/- 7.4). Small-volume resuscitation with HBOC-201 rapidly restored hemodynamic parameters and PbrO(2) following severe hemorrhage without detrimental vasoactive effects and without compromise to directly monitored brain tissue oxygenation. The results of this preliminary study demonstrate that HBOC-201 could potentially improve current resuscitation measures and that further investigations with HBOC-201 are warranted.