Alteration of the Postinjury Hyperinflammatory Response by Means of Resuscitation with a Red Cell Substitute

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Abstract
Transfusion of stored packed red blood cells (PRBCs) has unintended effects beyond the desired results of increased oxygen delivery. A particular concern is the potential for lipid and cytokine mediators present in PRBCs to augment the postinjury inflammatory response that sometimes culminates in multiple organ failure. Through the use of a polymerized human hemoglobin (PolyHeme), we have been able to measure the inflammatory response in patients resuscitated with minimal exposure to banked components in the early postinjury period. Critically injured patients requiring urgent transfusion were resuscitated with either PRBCs or PolyHeme in the early postinjury period. Proinflammatory cytokines (interleukin [IL]-8 and IL-6), counterregulatory cytokines (IL-10 and IL-11), and markers of endothelial injury (soluble intercellular adhesion molecule and soluble E-selectin) were serially measured. Increases in IL-8, IL-6, and IL-10 were greater in patients resuscitated with PRBCs. IL-11 plasma levels were largely below the level of detection of the assay. There was no difference in markers of endothelial injury. Consistent with concerns about the immunoinflammatory response to transfusion of PRBCs, we observed exaggerated levels of three markers associated with adverse outcome. The clinical significance of these findings with respect to the development of multiple organ failure awaits further study.