title: Vasoactivity of bovine polymerized hemoglobin (HBOC-201) in swine with traumatic hemorrhagic shock with and without brain injury.
abstract: BACKGROUND
  We previously reported that bovine polymerized hemoglobin (HBOC- 201) improved outcome in swine with hemorrhagic shock (HS) with and without traumatic brain injury (TBI). Herein, we add analyses of blood pressure (BP) responses, associated physiologic data, and HS fluid infusion guidelines.
  
  
  METHODS
  HBOC-201 versus standard fluid resuscitation was compared in four anesthetized invasively monitored swine models: moderate controlled HS, severe controlled HS, severe uncontrolled HS (liver injury), and severe uncontrolled HS/TBI (liver/parietal brain injuries). Pigs received fluid for hypotension and tachycardia, and were followed up to 6 (HS alone) or 72 hours (HS/TBI). The change in mean arterial pressure (DeltaMAP) response severity was stratified and analyzed based on infusion number and HS severity, using Student's t and Fisher's exact tests.
  
  
  RESULTS
  HBOC-201 vasoactivity resulted in higher MAP in all studies. Among HBOC-201 pigs, DeltaMAP responses were significant for the first two infusions and inversely related to HS severity. Among controls, DeltaMAP responses remained significant through the fourth infusion in controlled HS models, and through the first in severe uncontrolled HS/TBI; none were significant in severe uncontrolled HS. DeltaMAP was higher with HBOC-201 through the first infusion in moderate controlled HS, the fifth in severe uncontrolled HS, and the second in severe uncontrolled HS/TBI; there were no group differences in severe controlled HS. No severe MAP responses occurred. Higher DeltaMAP severity did not impact outcome. Hypotension satisfied fluid reinfusion criteria less consistently than tachycardia. Overall, HBOC-201 improved physiologic parameters and survival without causing hypoperfusion; in severe HS, perfusion improved.
  
  
  CONCLUSIONS
  In swine with HS +/- TBI, HBOC-201 had mild to moderate vasoactivity, resulting in significant DeltaMAP responses mainly after initial infusions, no severe/adverse responses, and improved outcome. Our data suggest that use of physiologic parameters (e.g., tachycardia), in addition to hypotension to guide fluid reinfusion during HS resuscitation with HBOC-201, will minimize hypoperfusion risk and maximize potential benefit.
authors.affiliation: Combat Casualty Directorate, Naval Medical Research Center, Silver Spring, Maryland 20910-7500, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rice
authors.forename: Nora
authors.initials: N
authors.lastname: Philbin
authors.forename: Michael
authors.initials: M
authors.lastname: Handrigan
authors.forename: Carrie
authors.initials: C
authors.lastname: Hall
authors.forename: Gerald
authors.initials: G
authors.lastname: McGwin
authors.forename: Stephen
authors.initials: S
authors.lastname: Ahlers
authors.forename: L B
authors.initials: LB
authors.lastname: Pearce
authors.forename: Francoise
authors.initials: F
authors.lastname: Arnaud
authors.forename: Richard
authors.initials: R
authors.lastname: McCarron
authors.forename: Daniel
authors.initials: D
authors.lastname: Freilich
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001802:Blood Substitutes / Q000494:pharmacology / Q000627:therapeutic use*; D001930:Brain Injuries / Q000150:complications; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005440:Fluid Therapy; D006339:Heart Rate / Q000187:drug effects; D006454:Hemoglobins / Q000494:pharmacology / Q000627:therapeutic use*; D007022:Hypotension / Q000188:drug therapy; D007262:Infusions, Intravenous; D007552:Isotonic Solutions / Q000627:therapeutic use; D012151:Resuscitation / Q000379:methods*; D000077325:Ringer's Lactate; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000503:physiopathology; D013552:Swine; D013610:Tachycardia / Q000188:drug therapy
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D007552:Isotonic Solutions; D000077325:Ringer's Lactate; C096798:HBOC 201