Potential of hemoglobin-based oxygen carriers in trauma patients

Injured patients have a unique requirement for early blood transfusion. A product that can be used in the prehospital setting that adequately carries and delivers oxygen to peripheral tissues would potentially be life saving for severely injured patients. Allogeneic blood is not the ideal agent in the pre-hospital setting. Present limitations in the allogeneic blood supply include the need for cross-matching, refrigeration, marginal supply, transfusion reactions, infectious disease transmission and immunomodulation increasing the risk of organ dysfunction after transfusion.Hemoglobin-based oxygen carriers have been under present development for the last 25 years. These compounds use either human or bovine hemoglobin that is then chemically altered to improve safety. These compounds exhibit many desirable characteristics that make them potential therapeutic agents in the treatment of the injured patient. These compounds do not need to be cross-matched, have favorable oxygen dissociation characteristics, long half lives, do not transmit disease, appear to be less immunoreactive than blood and theoretically can be used in the pre-hospital setting as a low volume oxygen carrying solution without need for refrigeration.There are at least three agents presently under development that use different techniques to alter the basic hemoglobin tetramer. While there is no FDA approved hemoglobin-based oxygen carrier approved for use in injured patients at this writing, phase III studies are currently either underway or being developed. There is high likelihood that one or more of these agents will be approved for clinical use in the near future.

[1]  A. Sia,et al.  Either sufentanil or fentanyl, in addition to intrathecal bupivacaine, provide satisfactory early labour analgesia , 2001, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[2]  S. Hill,et al.  Oxygen therapeutics--current concepts. , 2001, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[3]  D. Cheng.  Safety and efficacy of o-raffinose cross-linked human hemoglobin (Hemolink) in cardiac surgery. , 2001, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[4]  E. Moore,et al.  Plasma from aged stored red blood cells delays neutrophil apoptosis and primes for cytotoxicity: abrogation by poststorage washing but not prestorage leukoreduction. , 2001, The Journal of trauma.

[5]  J. Toouli,et al.  Effects of diaspirin cross-linked hemoglobin on motor function of the duodenum and biliary system in the Australian brush-tailed possum in vivo. , 2001, The Journal of pharmacology and experimental therapeutics.

[6]  M. Goldman.  Diaspirin cross-linked hemoglobin (DCLHb) in the treatment of severe traumatic hemorrhagic shock: A randomized controlled efficacy trial , 2000 .

[7]  A. Greenburg,et al.  A phase I study of oxidized raffinose cross-linked human hemoglobin , 2000, Critical care medicine.

[8]  J. Mullon,et al.  Transfusions of polymerized bovine hemoglobin in a patient with severe autoimmune hemolytic anemia. , 2000, The New England journal of medicine.

[9]  J. Berridge,et al.  Randomized Trial of Diaspirin Cross-linked Hemoglobin Solution as an Alternative to Blood Transfusion after Cardiac Surgery , 2000, Anesthesiology.

[10]  A. Gulati,et al.  Current aspects in pharmacology of modified hemoglobins. , 2000, Advanced drug delivery reviews.

[11]  G. LaMuraglia,et al.  The reduction of the allogenic transfusion requirement in aortic surgery with a hemoglobin-based solution. , 2000, Journal of vascular surgery.

[12]  E. Moore,et al.  Age of transfused blood is an independent risk factor for postinjury multiple organ failure. , 1999, American journal of surgery.

[13]  D. Gens,et al.  Diaspirin Cross-Linked Hemoglobin (DCLHb) in the Treatment of Severe Traumatic Hemorrhagic Shock: A Randomized Controlled Efficacy Trial , 1999 .

[14]  M. Welte,et al.  Perflubron emulsion delays blood transfusions in orthopedic surgery. European Perflubron Emulsion Study Group. , 1999, Anesthesiology.

[15]  E. Moore,et al.  Resuscitation with a blood substitute abrogates pathologic postinjury neutrophil cytotoxic function. , 1999, The Journal of trauma.

[16]  E. Ketcham,et al.  Hemoglobin-based oxygen carriers: development and clinical potential. , 1999, Annals of emergency medicine.

[17]  E. Moore,et al.  The first randomized trial of human polymerized hemoglobin as a blood substitute in acute trauma and emergent surgery. , 1998, Journal of the American College of Surgeons.

[18]  H. Allgayer,et al.  Influence of Autologous Blood Transfusion on Natural Killer and Lymphokine‐Activated Killer Cell Activities in Cancer Surgery , 1997, Vox sanguinis.

[19]  E. Moore,et al.  Clinical utility of human polymerized hemoglobin as a blood substitute after acute trauma and urgent surgery. , 1997, The Journal of trauma.

[20]  C. Martin,et al.  The Effects of Cross-Linked Hemoglobin on Regional Vascular Conductance in Dogs , 1997, Anesthesia and analgesia.

[21]  E. Orringer,et al.  A phase I/II study of polymerized bovine hemoglobin in adult patients with sickle cell disease not in crisis at the time of study. , 1997, Journal of investigative medicine : the official publication of the American Federation for Clinical Research.

[22]  A. Sauaia,et al.  Blood Transfusion: An Independent Risk Factor for Postinjury Multiple Organ Failure , 1997 .

[23]  R. Weiskopf,et al.  Recombinant Human Hemoglobin Does Not Affect Renal Function in Humans: Analysis of Safety and Pharmacokinetics , 1997, Anesthesiology.

[24]  T. Wobbes,et al.  Transfusion of red cells is associated with increased incidence of bacterial infection after colorectal surgery: a prospective study , 1997, Transfusion.

[25]  G. Moss,et al.  Clinical Development of Human Polymerized Hemoglobin as a Blood Substitute , 1996, World Journal of Surgery.

[26]  W. Buzello,et al.  Effects of a Hemoglobin-Based Oxygen Carrier (HBOC-201) on Hemodynamics and Oxygen Transport in Patients Undergoing Preoperative Hemodilution for Elective Abdominal Aortic Surgery , 1996, Anesthesia and analgesia.

[27]  J. Hess,et al.  Resuscitation and the limited utility of the present generation of blood substitutes. , 1996, Transfusion medicine reviews.

[28]  S. Kleinman,et al.  The Risk of Transfusion-Transmitted Viral Infections , 1996 .

[29]  J. Stamler,et al.  S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control , 1996, Nature.

[30]  E. L. Wallace,et al.  Collection and transfusion of blood and blood components in the United States, 1992 , 1995, Transfusion.

[31]  J. Murray,et al.  The effects of recombinant human hemoglobin on esophageal motor function in humans , 1995 .

[32]  S. Rebello,et al.  Role of adrenergic mechanisms in the pressor effect of diaspirin cross-linked hemoglobin. , 1994, The Journal of laboratory and clinical medicine.

[33]  J. Reves,et al.  Cardiovascular and Coronary Physiology of Acute Isovolemic Hemodilution: A Review of Nonoxygen‐Carrying and Oxygen‐Carrying Solutions , 1994, Anesthesia and analgesia.

[34]  H. Klein.  Immunologic aspects of blood transfusion. , 1994, Seminars in oncology.

[35]  C. Marwick.  More than a trickle of interest in blood substitutes. , 1994, JAMA.

[36]  M. Cuesta,et al.  Risk factors for multiple organ system failure and death in critically injured patients. , 1993, Surgery.

[37]  S. Panter,et al.  Neurotoxicity of hemoglobin in cortical cell culture , 1993, Neuroscience Letters.

[38]  M. Verani,et al.  Demonstration of myocardial reperfusion injury in humans: results of a pilot study utilizing acute coronary angioplasty with perfluorochemical in anterior myocardial infarction. , 1991, Journal of the American College of Cardiology.

[39]  S. Moncada,et al.  Nitric oxide: physiology, pathophysiology, and pharmacology. , 1991, Pharmacological reviews.

[40]  S. Cook,et al.  Transfusion practice in central Virginia , 1991, Transfusion.

[41]  N. Blumberg,et al.  Transfusion-induced immunomodulation and its possible role in cancer recurrence and perioperative bacterial infection. , 1990, The Yale journal of biology and medicine.

[42]  R. Chapman,et al.  Collection and transfusion of blood in the United States, 1982-1988. , 1990, The New England journal of medicine.

[43]  A. D. Rosen,et al.  Focal epileptogenesis after intracortical hemoglobin injection , 1979, Experimental Neurology.

[44]  J. Arnold,et al.  A clinical safety trial of stroma‐free hemoglobin , 1978, Clinical pharmacology and therapeutics.

[45]  M. Lamy,et al.  Red blood cell substitutes: fluorocarbon emulsions and haemoglobin solutions. , 1999, British medical bulletin.

[46]  S. Flaim.  Perflubron-based Emulsion: Efficacy as Temporary Oxygen Carrier , 1997 .

[47]  Govind Singh,et al.  Role of endothelin in the cardiovascular effects of diaspirin crosslinked and stroma reduced hemoglobin. , 1996, Critical care medicine.

[48]  J. Murray,et al.  The effects of recombinant human hemoglobin on esophageal motor functions in humans. , 1995, Gastroenterology.

[49]  P. Tartter.  Transfusion-induced immunosuppression and perioperative infections. , 1993, Beitrage zur Infusionstherapie = Contributions to infusion therapy.