Skip to main content

The Hemoglobin-Based Oxygen Carrier, HBOC-201, as a Resuscitation Fluid for Traumatic Hemorrhagic Shock: The Naval Medical Research Center Experience

  • Chapter
  • First Online:
Hemoglobin-Based Oxygen Carriers as Red Cell Substitutes and Oxygen Therapeutics

Abstract

In response to the terrorist attacks in the United States on September 11, 2001 and the subsequent advent of conflicts in Afghanistan and Iraq, the Naval Medical Research Center (NMRC, Silver Spring, MD) initiated a search for an oxygen-carrying resuscitation fluid that could be used for combat trauma and in situations with wide-spread civilian casualties. The ability to supply blood to mass casualties or far-forward combat trauma victims in austere environments with long evacuation times is wrought with logistical complications.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Arnaud F, Hammett M, Asher L, Philbin N, Rice J, Dong F, Pearce B, Flournoy WS, Nicholson C, McCarron R, Freilich D (2005) Effects of bovine polymerized hemoglobin on coagulation in controlled hemorrhagic shock in swine. Shock 24(2):145–152

    Article  Google Scholar 

  • Arnaud F, Handrigan M, Hammett M, Philbin N, Rice J, Dong F, Pearce LB, McCarron R, Freilich D (2006) Coagulation patterns following haemoglobin-based oxygen carrier resuscitation in severe uncontrolled haemorrhagic shock in swine. Transfus Med 16(4):290–302

    Article  Google Scholar 

  • Arnaud F, Fasipe D, Philbin N, Rice J, Flournoy WS, Ahlers S, McCarron R, Freilich D (2007) Hematology patterns after hemoglobin-based oxygen carrier resuscitation from severe controlled hemorrhage with prolonged delayed definitive care. Transfusion 47(11):2098–2109

    Article  Google Scholar 

  • Arnaud F, Hammett M, Philbin N, Scultetus A, McCarron R, Freilich D (2008) Hematologic effects of recombinant factor VIIa combined with hemoglobin-based oxygen carrier-201 for prehospital resuscitation of swine with severe uncontrolled hemorrhage due to liver injury. Blood Coagul Fibrinolysis 19(7):669–677

    Article  Google Scholar 

  • Arnaud F, McCarron R, Freilich D (2011) Amylase and lipase detection in hemorrhaged animals treated with HBOC-201. Artif Cells Blood Substit Immobil Biotechnol 39(3):155–161. Epub 2010 Dec 21

    Google Scholar 

  • Arnaud F, Scultetus AH, Kim B, Haque A, Saha B, Nigam S, Moon-Massat P, Auker C, McCarron R, Freilich D (2011) Dose response of sodium nitrite on vasoactivity associated with HBOC-201 in a swine model of controlled hemorrhage. Artif Cells Blood Substit Immobil Biotechnol 39(4):195–205. Epub 2010 Dec 6

    Google Scholar 

  • Arnaud F, Scultetus AH, Haque A, Saha B, Kim B, Auker C, Moon-Massat P, McCarron R, Freilich D (2012) Sodium nitroprusside ameliorates systemic but not pulmonary HBOC-201-induced vasoconstriction: an exploratory study in a swine controlled haemorrhage model. Resuscitation 83(8):1038–1045. Epub 2012 Jan 28

    Google Scholar 

  • Bessa KL, Belletati JF, Santos L, Rossoni LV, Ortiz JP (2011) Drag reduction by polyethylene glycol in the tail arterial bed of normotensive and hypertensive rats. Braz J Med Biol Res 44(8):767–777. Epub 2011 Jun 10

    Google Scholar 

  • Bilello K, Schultz S, Powell C, Jaffin J, Cole F, Malcolm D (1994) Diaspirin crosslinked hemoglobin (DCLHb): control of pressor effect with anti-hypertensive agents. Art Cells, Blood Subs Immob Biotech 22:819–825

    Article  Google Scholar 

  • Bowyer M (2005) USUHS/NMRC Study Report: “resuscitative strategies for delayed evacuation: comparison of bovine polymerized hemoglobin, artificial starch colloid, and normal saline for hypotensive and normotensive resuscitation in a swine model of uncontrolled hemorrhagic shock with delayed evacuation to definitive care”

    Google Scholar 

  • Butler FK, Holcomb JB, Giebner SD, McSwain NE, Bagian J (2007) Tactical combat casualty care 2007: evolving concepts and battlefield experience. Mil Med 172S:1–19

    Google Scholar 

  • Dong F, Hall CH, Golech SA, Philbin NB, Rice JP, Gurney J, Arnaud FG, Hammett M, Ma X, Flournoy WS, Hong J, Kaplan LJ, Pearce LB, McGwin G, Ahlers S, McCarron R, Freilich D (2006) Immune effects of resuscitation with HBOC-201, a hemoglobin-based oxygen carrier, in swine with moderately severe hemorrhagic shock from controlled hemorrhage. Shock 25(1):50–55

    Article  Google Scholar 

  • Dudkiewicz M, Harpaul TA, Proctor KG (2008) Hemoglobin-based oxygen carrying compound-201 as salvage therapy for severe neuro- and polytrauma (injury severity score = 27–41). Crit Care Med 36(10):2838–2848

    Article  Google Scholar 

  • Duncker D (2009a) Systemic hemodynamic effects of HBOC-201 and new HBOC compounds in anesthetized normovolemic mice. Erasmus Medical Center, University Medical Center, Rotterdam (2009-Erasmus-001 Study Report, PI)

    Google Scholar 

  • Duncker D (2009b) Hemodynamic effects of HBOC-201, with and without concurrent vasodilators, in awake pigs. Erasmus Medical Center, University Medical Center, Rotterdam (2009-Erasmus-02 Study Report, PI)

    Google Scholar 

  • Erhart SM, Cole DJ, Patel MP, Drummond JC, Burhop KE (2000) Effect of a–a diaspirin crosslinked hemoglobin (DCLHb) on the potency of sodium nitroprusside and nitroglycerine to decrease blood pressure in rats: a dose-response study. Art Cells Blood Subs Immob Biotech 28:385–396

    Article  Google Scholar 

  • Feinstein AJ, Cohn SM, King DR, Sanui M, Proctor KG (2005a) Early vasopressin improves short-term survival after pulmonary contusion. J Trauma 59:876–882

    Article  Google Scholar 

  • Feinstein AJ, Patel MB, Sanui M, Cohn SM, Majetschak M, Proctor KG (2005b) Resuscitation with pressors after traumatic brain injury. J Am Coll Surg 201:536–545

    Article  Google Scholar 

  • Fitzpatrick CM, Savage SA, Kerby JD, Clouse WD, Kashyap VS (2004) Resuscitation with a blood substitute causes vasoconstriction without nitric oxide scavenging in a model of arterial hemorrhage. J Am Coll Surg 199(5):693–701

    Article  Google Scholar 

  • Fonseca V, Avizinis J, Moon-Massat P, Freilich D, Kim HW, Hai CM (2010) Differential sensitivities of pulmonary and coronary arteries to hemoglobin-based oxygen carriers and nitrovasodilators: study in a bovine ex vivo model of vascular strips. Vascul Pharmacol 52(5–6):215–223. Epub 2009 Dec 22

    Google Scholar 

  • Gladwin M (2009) A multifunctional blood substitute for field resuscitation of polytrauma combat casualties with brain injury and concomitant hemorrhagic shock. NIH, Bethesda and University of Pittsburg, PA (2009-UPITT-01 Study Report, PI)

    Google Scholar 

  • Gladwin M (2011) A multifunctional blood substitute for field resuscitation of polytrauma combat casualties with brain injury and concomitant hemorrhagic shock, National Institutes of Health, Bethesda and the University of Pittsburg, PA (UPITT-CDMRP-2011-24092011-HR Study Report, PI)

    Google Scholar 

  • Gurney J, Philbin N, Rice J, Arnaud F, Dong F, Wulster-Radcliffe M, Pearce LB, Kaplan L, McCarron R, Freilich D (2004) A hemoglobin based oxygen carrier, bovine polymerized hemoglobin (HBOC-201) versus Hetastarch (HEX) in an uncontrolled liver injury hemorrhagic shock swine model with delayed evacuation. J Trauma 57(4):726–738

    Article  Google Scholar 

  • Hai CM (2009) HBOC-mediated vascular smooth muscle reactivity and inflammation. Brown University, Providence (2009-Brown-01 Study Report, PI)

    Google Scholar 

  • Hall C, Malkevich N, Handrigan M, Vandermolen C, Aranaud F, Hong J, Dong F, Rice J, Philbin N, Ahlers S, McCarron R, Freilich D, McGwin G, Flournoy WS, Pearce LB (2007) Innate immune responses in Swine resuscitated from severe traumatic hemorrhagic shock with hemoglobin-based oxygen carrier-201. Artif Cells Blood Substit Immobil Biotechnol 35(3):259–274

    Article  Google Scholar 

  • Haque A, Arnaud F, Teranishi K, Okada T, Kim B, Moon-Massat PF, Auker C, McCarron R, Freilich D, Scultetus AH (2012) Pre-hospital resuscitation with HBOC-201 and rFVIIa compared to HBOC-201 alone in uncontrolled hemorrhagic shock in swine. Artif Cells Blood Substit Immobil Biotechnol 40(1–2):44–55. Epub 2011 Aug 2

    Google Scholar 

  • Hu F, Zha D, Du R, Chen X, Zhou B, Xiu J, Bin J, Liu Y (2011) Improvement of the microcirculation in the acute ischemic rat limb during intravenous infusion of drag-reducing polymers. Biorheology 48(3–4):149–159

    Google Scholar 

  • Johnson T, Arnaud F, Dong F, Philbin N, Rice J, Asher L, Arrisueno M, Warndorf M, Gurney J, McGwin G, Kaplan L, Flournoy WS, Apple FS, Pearce LB, Ahlers S, McCarron R, Freilich D (2006) Bovine polymerized hemoglobin (hemoglobin-based oxygen carrier-201) resuscitation in three swine models of hemorrhagic shock with militarily relevant delayed evacuation–effects on histopathology and organ function. Crit Care Med 34(5):1464–1474

    Article  Google Scholar 

  • Katz LM, Manning JE, McCurdy S, Pearce LB, Gawryl MS, Wang Y, Brown C (2002) Carolina Resuscitation Research Group. HBOC-201 improves survival in a swine model of hemorrhagic shock and liver injury. Resuscitation 54(1):77–87

    Article  Google Scholar 

  • Katz LM, Manning JE, McCurdy S, Sproule C, McGwin G Jr, Moon-Massat P, Cairns CB, Freilich D (2010) Nitroglycerin attenuates vasoconstriction of HBOC-201 during hemorrhagic shock resuscitation. Resuscitation 81(4):481–487. Epub 2010 Jan 18

    Google Scholar 

  • Kelly JF, Ritenour AE, McLaughlin DF et al (2008) Injury severity and causes of death from Operation Iraqi Freedom and Operation Enduring Freedom: 2003–2004 versus 2006. J Trauma 64:S21–S27

    Article  Google Scholar 

  • Kerby J (2009) Evaluation of the effects of nitric oxide donor solutions with HBOC-201 resuscitation after hemorrhage and shock in a small animal model. University of Alabama, Birmingham (2009-UAB-01 Study Report, PI)

    Google Scholar 

  • Knudson MM, Lee S, Erickson V, Morabito D, Derugin N, Manley GT (2003) Tissue oxygen monitoring during hemorrhagic shock and resuscitation: a comparison of lactated Ringer’s solution, hypertonic saline dextran, and HBOC-201. J Trauma 54(2):242–252

    Article  Google Scholar 

  • Malkevich NV, Dong F, Vandermolen CA, Philbin NB, Rice JP, Scultetus A, Hong J, Arnaud F, Hall CH, McGwin G Jr, Pearce LB, Handrigan M, Ahlers S, McCarron RM, Freilich D (2008) Innate immune response after resuscitation with hemoglobin-based oxygen carrier and recombinant factor VIIA in uncontrolled hemorrhagic shock in a swine model. J Trauma 64(6):1498–1510

    Article  Google Scholar 

  • Manning J (2009) Concurrent administration of HBOC-201 and nitroglycerin in an equivolume injury and resuscitation model of hemorrhagic shock in swine: eight group comparison, draft final report. University of North Carolina, Chapel Hill (2009-UNC-01 Study Report, PI)

    Google Scholar 

  • Manning JE, Katz LM, Brownstein MR, Pearce LB, Gawryl MS, Baker CC (2000) Bovine hemoglobin-based oxygen carrier (HBOC-201) for resuscitation of uncontrolled, exsanguinating liver injury in swine. Carolina Resuscitation Research Group. Shock 13(2):152–159

    Article  Google Scholar 

  • Manning JE, Katz LM, Pearce LB, Batson DN, McCurdy SL, Gawryl MS, Baker CC (2001) Selective aortic arch perfusion with hemoglobin-based oxygen carrier-201 for resuscitation from exsanguinating cardiac arrest in swine. Crit Care Med 29(11):2067–2074

    Article  Google Scholar 

  • Marhefka JN, Zhao R, Wu ZJ, Velankar SS, Antaki JF, Kameneva MV (2009) Drag reducing polymers improve tissue perfusion via modification of the RBC traffic in microvessels. Biorheology 46(4):281–292

    Google Scholar 

  • McCarron R (2012) Evaluation of the vasoactive effects of co-administration nitroglycerin (NTG) and a hemoglobin based oxygen carrier (HBOC-201) for resuscitation from uncontrolled hemorrhage in a swine (Sus scrofa domestica) model with 72 h survival. NMRC, Silver Spring (KO02-08 Uncontrolled HS HBOC-201 NTG Study Report, PI)

    Google Scholar 

  • McNeil CJ, Smith LD, Jenkins LD, York MG, Josephs MJ (2001) Hypotensive resuscitation using a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201) leads to reversal of anaerobic metabolism. J Trauma 50(6):1063–1075

    Article  Google Scholar 

  • Moon-Massat P, Pittman R, Duncker D, Light WR, Hai CM, Freilich D, McCarron R (2010) Point of diminishing returns: contribution of tetramer content and molecular weight on vasoactivity of HBOC-201. Presented as a poster at the 2011 International Society for Blood Substitutes (ISBS), Boston

    Google Scholar 

  • Moon-Massat P, Scultetus A, Arnaud F, Brown A, Haque A, Saha B, Kim B, Sagini E, McGwin G Jr, Auker C, McCarron R, Freilich D (2012) The effect HBOC-201 and sodium nitrite resuscitation after uncontrolled haemorrhagic shock in swine. Injury 43(5):638–647. Epub 2010 Nov 20

    Google Scholar 

  • Natanson C, Kern SJ, Lurie P, Banks SM, Wolfe SM (2008) Cell-free hemoglobin-based blood substitutes and risk of myocardial infarction and death: a meta-analysis. JAMA 299(19):2304–2312. Epub 2008

    Google Scholar 

  • Philbin N, Rice J, Gurney J, McGwin G, Arnaud F, Dong F, Johnson T, Flournoy WS, Ahlers S, Pearce LB, McCarron R, Freilich D (2005) A hemoglobin-based oxygen carrier, bovine polymerized hemoglobin (HBOC-201) versus hetastarch (HEX) in a moderate severity hemorrhagic shock swine model with delayed evacuation. Resuscitation 66(3):367–378

    Google Scholar 

  • Philbin N, Handrigan M, Rice J, McNickle K, McGwin G, Williams R, Warndorf M, Arnaud F, Malkevich N, McCarron R, Freilich D (2007) Resuscitation following severe, controlled hemorrhage associated with a 24 h delay to surgical intervention in swine using a hemoglobin based oxygen carrier as an oxygen bridge to definitive care. Resuscitation 74(2):332–343. Epub 2007 Mar 23

    Google Scholar 

  • Rice J, Philbin N, Handrigan M, Hall C, McGwin G, Ahlers S, Pearce LB, Arnaud F, McCarron R, Freilich D (2006a) Vasoactivity of bovine polymerized hemoglobin (HBOC-201) in swine with traumatic hemorrhagic shock with and without brain injury. J Trauma 61(5):1085–1099

    Article  Google Scholar 

  • Rice J, Philbin N, McGwin G, Arnaud F, Johnson T, Flournoy WS, Pearce LB, McCarron R, Kaplan L, Handrigan M, Freilich D (2006b) Bovine polymerized hemoglobin versus hextend resuscitation in a swine model of severe controlled hemorrhagic shock with delay to definitive care. Shock 26(3):302–310

    Article  Google Scholar 

  • Rice J, Philbin N, Light R, Arnaud F, Steinbach T, McGwin G, Collier S, Malkevich N, Moon-Massatt P, Rentko V, Pearce LB, Ahlers S, McCarron R, Handrigan M, Freilich D (2008) The effects of decreasing low-molecular weight hemoglobin components of hemoglobin-based oxygen carriers in swine with hemorrhagic shock. J Trauma 64(5):1240–1257

    Article  Google Scholar 

  • Rioux F, Drapeau G, Marceau F (1995) Recombinant human hemoglobin (rHb1.1) selectively inhibits vasorelaxation elicited by nitric oxide donors in rabbit isolated aortic rings. J Cardiovasc Pharmacol 25:587–594

    Article  Google Scholar 

  • Rodriguez C, Vitturi DA, He J, Vandromme M, Brandon A, Hutching A, Rue LW, Kerby JD, Patel RP (2009) Sodium nitrite therapy attenuates hypertensive effects of HBOC-201 via nitrite reduction. Biochem J 422(3):423–432

    Article  Google Scholar 

  • Sampson JB, Davis MR, Mueller DL, Kashyap VS, Jenkins DH, Kerby JD (2003) A comparison of the hemoglobin-based oxygen carrier HBOC-201 to other low-volume resuscitation fluids in a model of controlled hemorrhagic shock. J Trauma 55(4):747–754

    Article  Google Scholar 

  • Sanui M, King DR, Feinstein AJ et al (2006) Effects of arginine vasopressin during resuscitation from hemorrhagic hypotension after traumatic brain injury. Crit Care Med 34:433–438

    Article  Google Scholar 

  • Scultetus A, Arnaud F, Haque A, Kim B, Okada T, Saha B, Sagini E, Solomon D, Moon-Massat P, Auker C, McCarron R, Freilich D (2010) Attenuation of vasoactivity associated with hemoglobin-based oxygen carrier HBOC-201 compromises survival in TBI and hemorrhagic shock in swine. Presented as a poster at the 2011 International Society for Blood Substitutes (ISBS), Boston, the 2010 Annual Meeting of the National Neurotrauma Society, Las Vegas

    Google Scholar 

  • Scultetus A, Arnaud F, Kaplan L, Shander A, Philbin N, Rice J, McCarron R, Freilich D (2011) Hemoglobin-based oxygen carrier (HBOC-201) and escalating doses of recombinant factor VIIa (rFVIIa) as a novel pre-hospital resuscitation fluid in a swine model of severe uncontrolled hemorrhage. Artif Cells Blood Substit Immobil Biotechnol 39(2):59–68. Epub 2010 Jul 20

    Google Scholar 

  • Sefton W, Pudmat P, Bina S, Lojeski E, Mongan P, Muldoon S (1999) Inhaled nitric oxide attenuates increased pulmonary artery pressure following diaspirin crosslinked hemoglobin (DCLHB) administration. Art Cells Blood Subs Immob Biotech 27:203–213

    Article  Google Scholar 

  • Stern S (2010a) Evaluation of the efficacy of resuscitation of a model of major arterial injury in swine with a next generation hemoglobin-based oxygen carrier (HBOC-201) with and without L-arginine infusion. University of Michigan, Ann Arbor (2010-UMich-01 Study Report, PI)

    Google Scholar 

  • Stern S (2010b) Evaluation of the efficacy of resuscitation of a model of combined traumatic brain injury and major arterial injury in swine with a vasoactivity attenuated hemoglobin-based oxygen carrier (VA-HBOC-201) with and without nitroglycerine infusion as a nitric oxide donor. University of Washington, Seattle (2010-UWash-01 Study Report, PI)

    Google Scholar 

  • Stern S, Rice J, Philbin N, McGwin G, Arnaud F, Johnson T, Flournoy WS, Ahlers S, Pearce LB, McCarron R, Freilich D (2009) Resuscitation with the hemoglobin-based oxygen carrier, HBOC-201, in a swine model of severe uncontrolled hemorrhage and traumatic brain injury. Shock 31(1):64–79

    Article  Google Scholar 

  • Teranishi K, Scultetus A, Haque A, Stern S, Philbin N, Rice J, Johnson T, Auker C, McCarron R, Freilich D, Arnaud F (2012) Traumatic brain injury and severe uncontrolled haemorrhage with short delay pre-hospital resuscitation in a swine model. Injury 43(5):585–593. Epub 2010 Oct 30

    Google Scholar 

  • VanderMolen C, Malkevich N, Philbin N, Rice J, Collier S, Hall C, Ahlers S, McCarron R, Freilich D, McGwin G, Pearce LB (2007) Immune effects of decreasing low-molecular weight hemoglobin components of hemoglobin-based oxygen carriers (HBOC) in a swine model of severe controlled hemorrhagic shock. Artif Cells Blood Substit Immobil Biotechnol 35(5):507–517

    Article  Google Scholar 

  • White NJ, Wang X, Bradbury N, Stern SA, Moon-Massat PF, Freilich D, Auker C, McCarron R, Scultetus A (2012) Fluid resuscitation of uncontrolled hemorrhage using a hemoglobin-based oxygen carrier: effect of traumatic brain injury (Submitted to Shock)

    Google Scholar 

  • York GB, Eggers JS, Smith DL, Jenkins DH, McNeil JD, Mueller D, Josephs JD, Kerby JD (2003) Low-volume resuscitation with a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201) provides adequate tissue oxygenation for survival in a porcine model of controlled hemorrhage. J Trauma 55(5):873–885

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Charles Auker .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Auker, C., Moon-Massat, P., Scultetus, A., McCarron, R., Freilich, D. (2013). The Hemoglobin-Based Oxygen Carrier, HBOC-201, as a Resuscitation Fluid for Traumatic Hemorrhagic Shock: The Naval Medical Research Center Experience. In: Kim, H., Greenburg, A. (eds) Hemoglobin-Based Oxygen Carriers as Red Cell Substitutes and Oxygen Therapeutics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40717-8_27

Download citation

Publish with us

Policies and ethics