Resuscitation of severe chest trauma with four different hemoglobin-based oxygen-carrying solutions

Background: The purpose of this study was to test whether polynitroxylation (PN) improved the therapeutic profile of hemoglobin-based oxygen-carrying compounds (HBOCs) that were unpolymerited (alpha alpha Hb) or 70% polymeriz ed (polyHb) in a clinically relevant model that combines pulmonary injury a nd reperfusion, To our knowledge, four different HBOC formulations have nev er been compared in the same trauma model. Methods: Anesthetized, ventilated swine (n = 45) received a unilateral lung contusion + 25% hemorrhage, After 60 minutes, 250 mt of either PN alpha al pha Hb (n = 5), alpha alpha Hb (n = 10), PNpolyHb (n = 6), polyHb (n = 5), or normal saline (NaCl, n = 10) was administered for 20 minutes, followed b y standard crystalloid resuscitation for 30 minutes, and supplemental cryst alloid as required for 6 hours to maintain heart rate <100 beats/min and me an arterial pressure >70 mm Hg. Results: Nine of 45 deaths occurred before resuscitation, Survival time was 395 minutes with NaCl versus 303 minutes with alpha alpha Hb (p = 0.03) or 238 minutes with PN alpha alpha Hb (p = 0.04), With both polymerized HBOCs , survival was 480 minutes (polyHb vs. alpha alpha Hb, P = 0.005; PNpolyHb vs. PN alpha alpha Hb, p = 0.006), All HBOCs were pressors (all p < 0.05) a nd all reduced the supplemental fluid required to maintain systemic hemodyn amics during resuscitation (all p < 0.05), By 90 minutes postresuscitation, cardiac index was 112% of baseline with NaCl (p < 0.02), but was 78% with alpha alpha Hb (p = not significant), 63% with PN alpha alpha Hb (p < 0.01) , 79% with PNpolyHb (p < 0.01), and 67% with polyHb (p < 0.02), Relative to NaCl, no HBOC altered trauma-induced neutrophilia, thrombocytopenia, or th e trauma-induced increases in bronchoalveolar lavage protein or bronchoalve olar lavage neutrophils. Conclusions: After resuscitation from chest trauma, we observed the followi ng: (1) all HBOCs reduced fluid requirements and increased right and left v entricular afterload versus NaCl, which further compromised an already marg inal cardiac performance; (2) mortality was less with polyHbs relative to a lpha alpha Hb, but the presser action was unchanged; (3) the presser action was Less with polynitroxylated compounds relative to the unmodified HBOC, but this chemical modification had no effect on mortality; and (4) the pres ser action of NBOCs must be attenuated by strategies other than polymerizat ion or polynitroxylation for these compounds to be safe, effective resuscit ants in humans.