• Ernest E Moore, Aaron M Cheng, Hunter B Moore, Tomohiko Masuno, and Jeffrey L Johnson.
• Department of Surgery, Denver Health Medical Center, and Department of Surgery, University of Colorado Health Sciences Center, Denver, CO 80204, USA. ernest.moore@dhha.org
• World J Surg. 2006 Jul 1;30(7):1247-57.

BackgroundThe greatest need for blood substitutes worldwide 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 advanced clinical trials are polymerized hemoglobin solutions.MethodsIn the USA, the standard approach to restoring oxygen delivery for 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 in hospital clinical trials, as well as in vitro and in vivo work, suggest that resuscitation with an HBOC--in lieu of stored RBCs--attenuates the systemic inflammatory response invoked in the pathogenesis of MOF. Specifically, an HBOC has been shown to obviate stored RBC-provoked polymorphonuclear neutrophil (PMN) priming, endothelial activation, and systemic release of interleukins (IL) 6, 8, and 10. In a 2-event rodent study of shock-induced PMN-mediated acute respiratory distress syndrome (ARDS), the simulated prehospital administration of an HBOC markedly attenuated lung injury.ResultsBased on this background and work by others, we have initiated a US multicenter prehospital trial in which severely injured patients with major blood loss [systolic blood pressure (SBP)ConclusionsTo date, >500 injured patients have been enrolled in this multicenter trial, and the final interim analyses support the original target of 720.

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