title: Resuscitation with the hemoglobin-based oxygen carrier, HBOC-201, in a swine model of severe uncontrolled hemorrhage and traumatic brain injury.
abstract: The purpose of this investigation was to compare the effects of initial resuscitation with HBOC-201 to that of lactated Ringer (LR) solution in the setting of uncontrolled hemorrhage and traumatic brain injury (TBI). Anesthetized immature swine underwent fluid-percussion TBI and liver laceration. During a 75-min "prehospital phase," the animals were resuscitated with HBOC-201, LR solution, or nothing (NON). Upon "hospital arrival," the animals were provided blood and 0.9% NaCl as needed, and the liver injury was repaired. Surviving animals were killed 6 h after injury. Brain tissue was processed for blood flow, and gross, light microscopic, and immunohistochemical analyses. Mean TBI force (2.6 +/- 0.6 atm) and blood loss (64.4 +/- 3.4 mL/kg) were similar between groups. Six-hour survival was significantly greater in HBOC-201 (8 of 13 [62%]) versus LR solution (1 of 11 [9%]) and NON (1 of 8 [3%]) animals (P < 0.02). Mean arterial pressures, cardiac indices, cerebral perfusion pressures, and brain tissue oxygen tension were significantly greater, and lactate and base deficit were lower in HBOC-201 as compared with LR solution animals. Blood transfusion requirements were reduced in HBOC-201 (3.6 +/- 0.6 mL/kg per survival hour) as compared to 7.1 +/- 1.2 mL/kg per survival hour. Severity of subarachnoid and intraparenchymal hemorrhages was statistically greater in LR solution-treated animals, but these differences were not likely to be clinically significant. There were no differences in glial fibrillary acidic protein and microtubule-associated protein 2. In this model of combined uncontrolled hemorrhage and TBI, initial resuscitation with HBOC-201 resulted in significant improvements in survival and systemic and cerebrovascular physiological parameters, as well as a reduction in transfusion requirements.
authors.affiliation: Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan 48109-0303, USA. suestern@umich.edu
authors.forename: Susan
authors.initials: S
authors.lastname: Stern
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rice
authors.forename: Nora
authors.initials: N
authors.lastname: Philbin
authors.forename: Gerald
authors.initials: G
authors.lastname: McGwin
authors.forename: Françoise
authors.initials: F
authors.lastname: Arnaud
authors.forename: Todd
authors.initials: T
authors.lastname: Johnson
authors.forename: W Shannon
authors.initials: WS
authors.lastname: Flournoy
authors.forename: Stephen
authors.initials: S
authors.lastname: Ahlers
authors.forename: L Bruce
authors.initials: LB
authors.lastname: Pearce
authors.forename: Richard
authors.initials: R
authors.lastname: McCarron
authors.forename: Daniel
authors.initials: D
authors.lastname: Freilich
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D006454:Hemoglobins / Q000494:pharmacology*; D006470:Hemorrhage / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D007552:Isotonic Solutions / Q000494:pharmacology; D008099:Liver / Q000098:blood supply / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D008107:Liver Diseases / Q000473:pathology / Q000503:physiopathology; D012151:Resuscitation; D000077325:Ringer's Lactate; D013552:Swine
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D007552:Isotonic Solutions; D000077325:Ringer's Lactate; C096798:HBOC 201