Resuscitation with the hemoglobin-based oxygen carrier, HBOC-201, in a swine model of severe uncontrolled hemorrhage and traumatic brain injury.
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.
Stern
Susan
S
Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan 48109-0303, USA. suestern@umich.edu
Rice
Jennifer
J
Philbin
Nora
N
McGwin
Gerald
G
Arnaud
Françoise
F
Johnson
Todd
T
Flournoy
W Shannon
WS
Ahlers
Stephen
S
Pearce
L Bruce
LB
McCarron
Richard
R
Freilich
Daniel
D
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
D001802:Blood Substitutes; D006454:Hemoglobins; D007552:Isotonic Solutions; D000077325:Ringer's Lactate; C096798:HBOC 201