title: Resuscitation of severe chest trauma with four different hemoglobin-based oxygen-carrying solutions.
abstract: 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 unpolymerized (alphaalphaHb) or 70% polymerized (polyHb) in a clinically relevant model that combines pulmonary injury and reperfusion. To our knowledge, four different HBOC formulations have never been compared in the same trauma model.
  
  
  METHODS
  Anesthetized, ventilated swine (n = 45) received a unilateral lung contusion + 25% hemorrhage. After 60 minutes, 250 mL of either PNalphaalphaHb (n = 5), alphaalphaHb (n = 10), PNpolyHb (n = 6), polyHb (n = 5), or normal saline (NaCl, n = 10) was administered for 20 minutes, followed by standard crystalloid resuscitation for 30 minutes, and supplemental crystalloid as required for 6 hours to maintain heart rate <100 beats/min and mean arterial pressure >70 mm Hg.
  
  
  RESULTS
  Nine of 45 deaths occurred before resuscitation. Survival time was 395 minutes with NaCl versus 303 minutes with alphaalphaHb (p = 0.03) or 238 minutes with PNalphaalphaHb (p = 0.04). With both polymerized HBOCs, survival was 480 minutes (polyHb vs. alphaalphaHb, p = 0.005; PNpolyHb vs. PNalphaalphaHb, p = 0.006). All HBOCs were pressors (all p < 0.05) and all reduced the supplemental fluid required to maintain systemic hemodynamics 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 alphaalphaHb (p = not significant), 63% with PNalphaalphaHb (p < 0.01), 79% with PNpolyHb (p < 0.01), and 67% with polyHb p < 0.02). Relative to NaCI, no HBOC altered trauma-induced neutrophilia, thrombocytopenia, or the trauma-induced increases in bronchoalveolar lavage protein or bronchoalveolar lavage neutrophils.
  
  
  CONCLUSIONS
  After resuscitation from chest trauma, we observed the following: (1) all HBOCs reduced fluid requirements and increased right and left ventricular afterload versus NaCl, which further compromised an already marginal cardiac performance; (2) mortality was less with polyHbs relative to alphaalphaHb, but the pressor action was unchanged; (3) the pressor action was less with polynitroxylated compounds relative to the unmodified HBOC, but this chemical modification had no effect on mortality; and (4) the pressor action of HBOCs must be attenuated by strategies other than polymerization or polynitroxylation for these compounds to be safe, effective resuscitants in humans.
authors.affiliation: Department of Surgery, University of Tennessee Health Science Center, Memphis, 38163, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Maxwell
authors.forename: J B
authors.initials: JB
authors.lastname: Gibson
authors.forename: T C
authors.initials: TC
authors.lastname: Fabian
authors.forename: K G
authors.initials: KG
authors.lastname: Proctor
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004195:Disease Models, Animal; D005260:Female; D005440:Fluid Therapy; D006439:Hemodynamics; D006454:Hemoglobins / Q000627:therapeutic use*; D015601:Injury Severity Score; D008297:Male; D011108:Polymers; D015532:Rehydration Solutions / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D013552:Swine; D013898:Thoracic Injuries / Q000401:mortality / Q000628:therapy*; D013997:Time Factors
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D011108:Polymers; D015532:Rehydration Solutions