Prehospital HBOC-201 after traumatic brain injury and hemorrhagic shock in swine.
BACKGROUND
Data are limited on the actions of hemoglobin based oxygen carriers (HBOCs) after traumatic brain injury (TBI). This study evaluates neurotoxicity, vasoactivity, cardiac toxicity, and inflammatory activity of HBOC-201 (Biopure, Cambridge, Mass.) resuscitation in a TBI model.


METHODS
Swine received TBI and hemorrhage. After 30 minutes, resuscitation was initiated with 10 mL/kg normal saline (NS), followed by either HBOC-201 (6 mL/kg, n = 10) or NS control (n = 10). Supplemental NS was administered to both groups to maintain mean arterial pressure (MAP) >60 mm Hg until 60 minutes, and to maintain cerebral perfusion pressure (CPP) >70 mm Hg from 60 to 300 minutes. The control group received mannitol (1 g/kg) and blood (10 mL/kg) at 90 minutes and half (n = 5) received CPP directed phenylephrine (PE) therapy after 120 minutes. Serum cytokines were measured with ELISA and coagulation was evaluated with thromboelastography. Brains were harvested for neuropathology.


RESULTS
With HBOC administration, MAP, CPP, and brain tissue PO2 were restored within 30 minutes and maintained until 300 minutes. Clot strength and fibrin formation were maintained and 9/10 successfully extubated. In contrast, with control, MAP and brain tissue PO2 did not correct until 120 minutes, after mannitol, transfusion and 40% more crystalloid. Furthermore, without PE, CPP did not reach target and 0/5 could be extubated. Lactate, heart rate, cardiac output, mixed venous oxygenation, muscle oxygenation, serum cytokines, and histology did not differ between groups.


CONCLUSIONS
After TBI, a single HBOC-201 bolus with minimal supplements provided rapid resuscitation, while maintaining CPP and improving brain oxygenation, without causing cardiac dysfunction, coagulopathy, cytokine release, or brain structural changes.
Patel
Mayur B
MB
Division of Trauma, DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Feinstein
Ara J
AJ
Saenz
Alvaro D
AD
Majetschak
Matthias
M
Proctor
Kenneth G
KG
D000704:Analysis of Variance; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001802:Blood Substitutes / Q000627:therapeutic use / Q000633:toxicity*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001930:Brain Injuries / Q000628:therapy*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005440:Fluid Therapy / Q000379:methods*; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000627:therapeutic use / Q000633:toxicity*; D008297:Male; D012771:Shock, Hemorrhagic / Q000628:therapy*; D013552:Swine
D001802:Blood Substitutes; D016207:Cytokines; D006454:Hemoglobins; C096798:HBOC 201