Prehospital HBOC-201 after traumatic brain injury and hemorrhagic shock in swine

Mayur B. Patel, Ara J. Feinstein, Alvaro D. Saenz, Matthias Majetschak, Kenneth G Proctor

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)46-56
Number of pages11
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume61
Issue number1
DOIs
StatePublished - Jul 1 2006

Fingerprint

Cerebrovascular Circulation
Hemorrhagic Shock
Swine
Resuscitation
Brain
Arterial Pressure
Mannitol
Phenylephrine
Cytokines
Traumatic Brain Hemorrhage
Hemoglobins
Oxygen
Thrombelastography
Fibrin
Serum
Cardiac Output
Lactic Acid
Histology
Heart Rate
Enzyme-Linked Immunosorbent Assay

Keywords

  • Blood substitute
  • Brain injury
  • HBOC
  • Hemoglobin based oxygen carrier
  • Swine

ASJC Scopus subject areas

  • Surgery

Cite this

Prehospital HBOC-201 after traumatic brain injury and hemorrhagic shock in swine. / Patel, Mayur B.; Feinstein, Ara J.; Saenz, Alvaro D.; Majetschak, Matthias; Proctor, Kenneth G.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 61, No. 1, 01.07.2006, p. 46-56.

Research output: Contribution to journalArticle

Patel, Mayur B. ; Feinstein, Ara J. ; Saenz, Alvaro D. ; Majetschak, Matthias ; Proctor, Kenneth G. / Prehospital HBOC-201 after traumatic brain injury and hemorrhagic shock in swine. In: Journal of Trauma - Injury, Infection and Critical Care. 2006 ; Vol. 61, No. 1. pp. 46-56.
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AU - Patel, Mayur B.

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AU - Proctor, Kenneth G

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AB - 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.

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KW - HBOC

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KW - Swine

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