Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1590/S0034-70942003000400014
Brazilian Journal of Anesthesiology
Review Article

Substâncias carreadoras de oxigênio à base de hemoglobina: situação atual e perspectivas

Hemoglobin-based blood substitutes: current status and perspectives

Pedro Paulo Tanaka; Maria Aparecida Almeida Tanaka

Downloads: 0
Views: 1199

Resumo

JUSTIFICATIVA E OBJETIVOS: Soluções alternativas à transfusão de sangue têm sido estudadas desde a década de 50. O objetivo deste estudo é apresentar a situação atual e as perspectivas futuras das substâncias carreadoras de oxigênio à base de hemoglobina. CONTEÚDO: São apresentadas as potenciais áreas de aplicação, bem como estudos clínicos envolvendo as principais moléculas de hemoglobina desenvolvidas, suas vantagens e limitações. CONCLUSÕES: Vários estudos aleatórios demonstraram eficácia com o propósito de evitar ou reduzir a transfusão sangüínea; entretanto, algumas limitações existem, sendo que o futuro substituto sangüíneo deverá, no mínimo, retratar a segurança e a eficácia do sangue em si.

Palavras-chave

SANGUE

Abstract

BACKGROUND AND OBJECTIVES: Alternatives to red blood cells transfusion have been studied since the fifties. This study aimed at presenting current status and perspectives of hemoglobin-based blood substitutes. CONTENTS: Potential application areas are presented, in addition to clinical studies involving major hemoglobin molecules developed, their advantages and limitations. CONCLUSIONS: Several randomized trials have shown efficacy in avoiding or decreasing red blood cells transfusions, however there are some limitations and the future blood substitute shall at least have the same safety and efficacy of blood itself.

Keywords

BLOOD

References

Goodnough LT, Brecher ME, Kanter MH. Transfusion Medicine: first of two parts - blood transfusion. N Engl J Med. 1999;340:438-447.

Goodnough LT, Brecher ME, Kanter MH. Transfusion Medicine: second of two parts - blood conservation. N Engl J Med. 1999;340:525-533.

Schreiber GB, Busch MP, Korelitz JT. The risk of transfusion transmitted viral infections. N Engl J Med. 1996;334:1685-1690.

Klein HG. Immunomodulatory aspects of transfusion. Anesthesiol. 1999;91:861-865.

Innerhofer P, Walleczek C, Luz G. Transfusion of buffy coat-depleted blood component and risk of postoperative infection in orthopedic patients. Transfusion. 1999;39:625-632.

Houbiers JG, van de Velde CJ, Hermans J. Transfusion of red cells is associated with increased incidence of bacterial infection after colorectal surgery: A prospective study. Transfusion. 1997;37:126-134.

Amato AC, Pescatori M. Effect of perioperative blood transfusions on recurrence of colorectal cancer: meta-analysis stratified on risk factors. Dis Colon Rectum. 1998;41:570-585.

Vamvakas EC. Transfusion-associated cancer recurrence and postoperative infection: Meta-analysis of randomized, controlled trials. Transfusion. 1996;36:175-186.

Vamvakas EC, Taswell HF. Epidemiology of blood transfusion. Transfusion. 1994;34:464-470.

Vuylsteke A. Artificial blood substitutes - benefits and risks. :144-147.

Remy B, Deby-Dupont G, Lamy ML. Red blood cell substitutes: fluorocarbon emulsions and hemoglobin solutions. Br Med Bull. 1999;55:277-298.

Lamy ML, Daily EK, Larbuisson RP. Randomized trial of diaspirin cross-linked hemoglobin solution as an alternative to blood transfusion after cardiac surgery. Anesthesiol. 2000;92:646-656.

Mazer CD, Cheng DCH, Belo SE. Oxygen supply and demand in patients undergoing CBAG surgery using intraoperative autologous donation with Hemolink® and Pentaspan. Anesthesiol. 2000;93:A195.

Levy JR, Goodnough LT, Greilich P. A room-temperature stable hemoglobin (HBOC-201) eliminates allogenic red blood cell transfusion in post-operative cardiac surgery patients. Circulation. 1998;98:I-132.

Vlahakes GJ. Haemoglobin solutions in surgery. Br J Surg. 2001;88:1553-1555.

Goodnough LT, Scott MG, Monk TG. Oxygen carriers as blood substitutes - past, present and future. Clin Orth Rel Research. 1998;398:89-100.

Chang TMS. Why do We Need Blood Substitutes?. Blood Substitutes: Principles, Methods, Products and Clinical Trials. 1997;1:3-8.

Shoemaker SA, Gerber MJ, Evans GL. Initial clinical experience with a rationale designed genetically engineered recombinant human Hb. Artif Cells Blood Substit Immobil Biotechnol. 1994;22:457-465.

Chang TMS. What are Modified Hemoglobin Blood Substitutes?. Blood Substitutes, Principles, Methods, Products and Clinical Trials. 1997;1:9-31.

Savitsky JP, Doozi J, Black J. A clinical safety trial of strome free hemoglobin. Clin Pharm Ther. 1978;23:73.

Dietz NM, Joyner MJ, Warner MA. Blood substitutes: fluids, drugs, or miracle solutions?. Anesth Analg. 1996;82:390-405.

Chapman KW, Snell SM, Jesse RG. Pilot scale production of pyrogen-free human hemoglobin for research. Biomater Artif Cells Immobil Biotechnol. 1992;20:415-421.

Lamy ML, Daily EK, Brichant JF. Randomized trial of diaspirin cross-linked hemoglobin solution as an alternative to blood transfusion after cardiac surgery. The DCLHb cardiac surgery trial collaborative. Anesthesiol. 2000;92:646-656.

Sloan EP, Koenigsberg M, Gens D. Diaspirin cross-linked hemoglobin (DCLHb) in the treatment of severe traumatic hemorrhagic shock. JAMA. 1999;282:1857-1864.

Dietz NM, Martin CM, Joyner MJ. The effects of cross-linked hemoglobin on regional vascular conductance in dogs. Anesth Analg. 1997;85:265-273.

Figueiredo LFP, Mathru M, Solanki D et al. Pulmonary hypertension and systemic vasoconstriction may offset the benefits of a cellular hemoglobin substitutes. J Trauma. 1997;42:847-853.

DeAngeles DA, Scott AM, McGrath AM. Resuscitation from hemorrhagic shock with diaspirin cross-linked hemoglobin, blood, or hetastarch. J Trauma. 1997;42:406-414.

Lewis RJ, Berry DA, Fost N. Monitoring a clinical trial conducted under Food and Drug Administration regulations allowing a waiver of prospective informed consent: the diaspirin cross-linked hemoglobin traumatic hemorrhagic shock efficacy trial. Ann Emerg Med. 2001;38:397-404.

Serna DL, Powell LL, Kahwaji C. Cardiac function after eight hour storage by using polyethylene glycol hemoglobin versus crystalloid perfusion. ASAIO J. 2000;34:547-552.

Glasgow SC, Shah AS, Noone RB. Comparison of various hemoglobin polyoxyethylene conjugate solutions as resuscitative fluids after hemorrhagic shock. J Trauma. 2000;48:884-893.

Noone RB, Mythen MG, Vaslef SN. Effect of alpha-alpha cross-linked hemoglobin and pyridoxalated hemoglobinpoly-oxyethylene conjugate solutions on gastrointestinal regional perfusion in hemorrhagic shock. J Trauma. 1998;45:457-469.

Conover CD, Lejeune L, Shum K. Physiological effect of polyethylene glycol conjugation on stroma-free bovine hemoglobin in the conscious dog after partial exchange transfusion. Artif Organs. 1997;21:369-378.

Yang T, Olsen KW. Thermal stability of Hb cross-linked in the T state by bis (3,5 dibromosalicyl) fumarate. Biochem Biophys Res Comm. 1991;174:518-523.

Benesch R, Benesch RE, Yung S. Hemoglobin covalgatly bridged across the polyphosphate binding site. Biochem Biophys Res Comm. 1975;63:1123.

Johnson JL, Moore EE, Offner PJ. Resuscitation of the injured patient with polymerized stroma-free hemoglobin does not produce systemic or pulmonary hypertension. Am J Surg. 1998;176:612-617.

Gould SA, Moore EE, Hoyt DB. The first randomized trial of human polymerized hemoglobin as a blood substitute in acute trauma and emergent surgery. J Am Coll Surg. 1998;187:113-120.

Moore FA, Moore EE, Sauaia A. Blood transfusion: an independent risk factor for postinjury multiple organ failure. Arch Surg. 1996;132:620-625.

Johnson JL, Moore EE, Offner P. Resuscitation with a blood substitute abrogates pathologic postinjury neutrophil cytotoxic function. J Trauma. 2001;50:449-456.

Hughes GS, Antal EJ, Locker P. Physiology and pharmacokinetics of a novel hemoglobin-based oxygen carrier in humans. Crit Care Med. 1996;24:756-764.

Cohn SM. Is blood obsolete?. J Trauma. 1997;42:730-732.

LaMuraglia GM, O´Hara PJ, Baker WH. The reduction of the allogenic transfusion requirement in aortic surgery with a hemoglobin-based solution. J Vasc Surg. 2000;31:299-308.

Manning JE, Katz LM, Pearce B. Selective aortic arch perfusion with hemoglobin-based oxygen carrier for resuscitation from exsanguinating cardiac arrest in swine. Crit Care Med. 2001;29:2067-2074.

Cheung ATW, Jahr JS, Driessen B. The effects of hemoglobin glutamer-200 (bovine) on the microcirculation in a canine hypovolemia model: a noninvasive computer-assisted intravital microscopy study. Anesth Analg. 2001;93:832-838.

McNeil JD, Smith DL, Jenkins DH. Hypotensive resuscitation using a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC 201) leads to reversal of anaerobic metabolism. J Trauma. 2001;50:1063-1075.

Sprung J, Kindscher J, Wahr JA. The use of bovine hemoglobin glutamer-250 (Hemopure®) in surgical patients: results of a multicenter, randomized, single-blinded trial. Anesth Analg. 2002;94:799-808.

Jahr JS, Dulchavsky SA, Garino JP. Hemodynamic effects of hemoglobin glutamer-250 (Hemopure®, HBOC-201) compared to red blood cells in pivotal safety and efficacy study in orthopedic surgery patients. Anesth Analg. 2002;94:S-330.

Cheng DCH, Mazer RE, Carmichael FJL. The hemodynamic effects of the red cell substitute Hemolink® (o-raffinose cross-linked human hemoglobin) on vital signs in patients undergoing CABG surgery. Anesthesiol. 2000;93:A180.

Carmichael FJL, Biro GP, Agensky L. Use of the blood substitute Hemolink® in CABG surgery. Anesth Analg. 2000;90:SCA11.

Cheng DCH. Safety and efficacy of o-raffinose cross-linked human hemoglobin (Hemolink®) in cardiac surgery. Can J Anaesth. 2001;48:S41-S48.

Ketcham EM, Cairns CB. Hemoglobin-based oxygen carriers: development and clinical potentials. Ann Emerg Med. 1999;33:327-337.

Loscalzo J. Nitric oxide binding and the adverse effects of cell-free hemoglobin’s: what make us different from earthworms. J Lab Clin Med. 1997;129:580-583.

Stampler JS, Jia L, Eu JP. Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science. 1997;276:2034-2037.

Waschke KF, Frietsch T. Modified haemoglobins and perflurocarbons. Curr Opin Anaesthesiol. 1999;12:195-202.

Chang TMS. Future Perspectives of Blood Substitutes, em Chang TMS - Blood Substitutes, Principles, Methods, Products and Clinical Trials, Basel, S. Karger AG. 1997;1:88-110.

5ddd34b80e8825ef011da3e9 rba Articles
Links & Downloads

Braz J Anesthesiol

Share this page
Page Sections