title: Use of hemoglobin-based oxygen-carrying solution-201 to improve resuscitation parameters and prevent secondary brain injury in a swine model of traumatic brain injury and hemorrhage: laboratory investigation.
abstract: OBJECTIVE
  Traumatic brain injury (TBI) often occurs as part of a multisystem trauma that may lead to hemorrhagic shock. Effective resuscitation and restoration of oxygen delivery to the brain is important in patients with TBI because hypotension and hypoxia are associated with poor outcome in head injury. We studied the effects of hemoglobin-based oxygen-carrying (HBOC)-201 solution compared with lactated Ringer (LR) solution in a large animal model of brain injury and hemorrhage, in a blinded prospective randomized study.
  
  
  METHODS
  Swine underwent brain impact injury and hemorrhage to a mean arterial pressure (MAP) of 40 mm Hg. Twenty swine were randomized to undergo resuscitation with HBOC-201 (6 ml/kg) or LR solution (12 ml/kg) and were observed for an average of 6.5 +/- 0.5 hours following resuscitation. At the end of the observation period, magnetic resonance (MR) imaging was performed. Histological studies of swine brains were performed using Fluoro-Jade B, a marker of early neuronal degeneration.
  
  
  RESULTS
  Swine resuscitated with HBOC-201 had higher MAP, higher cerebral perfusion pressure (CPP), improved base deficit, and higher brain tissue oxygen tension (PbtO(2)) than animals resuscitated with LR solution. No significant difference in total injury volume on T2-weighted MR imaging was observed between animals resuscitated with HBOC-201 solution (1155 +/- 374 mm(3)) or LR solution (1246 +/- 279 mm(3); p = 0.55). On the side of impact injury, no significant difference in the mean number of Fluoro-Jade B-positive cells/hpf was seen between HBOC-201 solution (61.5 +/- 14.7) and LR solution (48.9 +/- 17.7; p = 0.13). Surprisingly, on the side opposite impact injury, a significant increase in Fluoro-Jade B-positive cells/hpf was seen in animals resuscitated with LR solution (42.8 +/- 28.3) compared with those resuscitated with HBOC-201 solution (5.6 +/- 8.1; p < 0.05), implying greater neuronal injury in LR-treated swine.
  
  
  CONCLUSIONS
  The improved MAP, CPP, and PbtO(2) observed with HBOC-201 solution in comparison with LR solution indicates that HBOC-201 solution may be a preferable agent for small-volume resuscitation in brain-injured patients with hemorrhage. The use of HBOC-201 solution appears to decrease cellular degeneration in the brain area not directly impacted by the primary injury. Hemoglobin-based oxygen-carrying-201 solution may act by improving cerebral blood flow or increasing the oxygen-carrying capacity of blood, mitigating a second insult to the injured brain.
authors.affiliation: Department of Neurosurgery, University of California, San Francisco, CA 94117, USA.
authors.forename: Guy
authors.initials: G
authors.lastname: Rosenthal
authors.forename: Diane
authors.initials: D
authors.lastname: Morabito
authors.forename: Mitchell
authors.initials: M
authors.lastname: Cohen
authors.forename: Annina
authors.initials: A
authors.lastname: Roeytenberg
authors.forename: Nikita
authors.initials: N
authors.lastname: Derugin
authors.forename: S Scott
authors.initials: SS
authors.lastname: Panter
authors.forename: M Margaret
authors.initials: MM
authors.lastname: Knudson
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Manley
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001802:Blood Substitutes / Q000627:therapeutic use*; D001930:Brain Injuries / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D006454:Hemoglobins / Q000627:therapeutic use*; D020300:Intracranial Hemorrhages / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D007427:Intracranial Pressure; D008297:Male; D012151:Resuscitation; D013552:Swine
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; C096798:HBOC 201