Emerging Role of Hemoglobin Solutions in Trauma Care

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SUMMARYMost authorities believe that the greatest need for blood substitutes is in patients with unanticipated acute blood loss, and trauma is the most likely scenario. The blood substitutes reaching advanced clinical trials today are red blood cell (RBC) substitutes, derived from hemoglobin. The hemoglobin‐based oxygen carriers (HBOCs) tested currently in FDA Phase III clinical trials are polymerized hemoglobin solutions. In the USA, the standard approach to restoring oxygen delivery in hemorrhagic shock has been crystalloid administration to expand intravascular volume, followed by stored RBCs for critical anemia. Allogeneic RBCs, however, may have adverse immunoinflammatory effects that increase the risk of postinjury multiple organ failure (MOF). Phase II clinical trials, as well as in vitro and in vivo work, suggest that resuscitation with a HBOC – in lieu of stored RBCs – attenuates the systemic inflammatory response invoked in the pathogenesis of MOF. Specifically, a HBOC has been shown to obviate stored RBC provoked neutrophil (PMN) priming, endothelial activation, and systemic release of interleukins 6,8, and 10. Based on this background and work by others, we have initiated a multicenter prehospital trial in which severely injured patients with major blood loss (SBP < 90 mm Hg) are randomized to initial field resuscitation with crystalloid versus HBOC. During the hospital phase the control group is further resuscitated with stored RBCs, whereas the study group receives HBOC (up to 6 units) in the first 12 hours. The primary study endpoint is 30‐day mortality, and secondary endpoints include reduction in allogeneic RBCs, hemoglobin levels < 5 g/dL, uncrossmatched RBCs, and MOF. The potential efficacy of HBOCs expands beyond the temporary replacement for stored RBCs. Hemoglobin solutions might ultimately prove superior in delivering oxygen to ischemic or injured tissue. The current generation of HBOCs can be lifesaving for acute blood loss today, but the next generation might be biochemically tailored for specific clinical indications.