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Anästhesiol Intensivmed Notfallmed Schmerzther 2005; 40(1): 38-45
DOI: 10.1055/s-2004-825914
Mini-Symposium
© Georg Thieme Verlag KG Stuttgart · New York

3. Internationales Symposium: „Autologe Transfusion - Von der Euphorie zur Ratio: Praktisches Handeln aus wissenschaftlicher Sicht” (Teil IV)
Künstliche Sauerstoffträger: Hämoglobinlösungen - Stand 2004

Autologous Transfusion - from Euphoria to Reason: Clinical Practice Based on Scientific Knowledge (Part IV)
Artificial Oxygen Carriers: Cell-free Hemoglobin Solutions - Current Status 2004T.  Standl1
  • 1Klinik für Anästhesie und operative Intensivmedizin, Städtisches Klinikum Solingen
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Publication History

Publication Date:
11 January 2005 (online)

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Zusammenfassung

Die Erforschung und Erprobung von künstlichen Sauerstoffträgern wie den zellfreien Hämoglobinlösungen (hemoglobin-based oxygen carriers = HBOC) in den letzten 15 Jahren wurde durch eine mögliche Verknappung an homologen Blutprodukten in den nächsten Jahrzehnten gefördert. Auch bestehen weiterhin Probleme in der Anwendung von Fremdblut wie Transfusionsreaktionen, Übertragung von Bakterien, Viren und Prionen, immunsupprimierende Nebenwirkungen von homologem Blut sowie steigende Kosten für Gewinnung, Testung und Lagerung von Erythrozytenkonzentraten (EK), die zusätzlich während der Lagerung Qualitätsverlusten unterliegen. Moderne chemisch modifizierte Hämoglobinlösungen enthalten keine Reste von Erythrozytenmembranen und weisen daher keine toxischen Nebenwirkungen oder AB0-Antigenität auf. Dies erlaubt die Transfusion von HBOC ohne Kenntnis der Blutgruppe des Patienten. Bovines polymerisiertes HBOC kann drei Jahre bei Raumtemperatur gelagert werden und im Gegensatz zu Perfluorocarbonen benötigt die Therapie mit HBOC keine erhöhte inspiratorische Sauerstoffkonzentration.

In Tierexperimenten konnte gezeigt werden, dass mit HBOC ein suffizienter Volumenersatz sowie eine adäquate oder sogar verbesserte Gewebsoxygenierung nach hämorrhagischem Schock und während Blutaustausch möglich sind. Durch chemische Modifikation von HBOC kann die Intensität der vasokonstriktorischen Nebeneffekte, die durch NO-Bindung verursacht sind, reduziert werden. Die erhöhte Sauerstoffextraktion in Anwesenheit von HBOC in Kombination mit dem plasmatischen Sauerstofftransport bewirken trotz Vasokonstriktion eine gesteigerte Gewebsoxygenierung sogar im poststenotischen Gewebe. Mit HBOC wird die Perfusion auf mikrozirkulatorischer Ebene verbessert, so dass Gewebsschäden nach akuter Pankreatitis oder Ischämie/Reperfusion am Herzen und am Hirn signifikant reduziert werden konnten.

Klinische Studien haben gezeigt, dass der perioperative Einsatz von unterschiedlichen Hämoglobinlösungen (Hemopure®, PolyHeme®, Hemolink® und HemAssist®) die Anzahl der benötigten homologen EK reduzieren und die Anzahl der Patienten ohne Fremdbluttransfusion erhöhen kann. Dies wurde bei Notfallpatienten, in der Gefäß-, Herz- und Abdominalchirurgie gezeigt. Polymerisierte HBOC scheinen eine geringere Inzidenz an Nebenwirkungen zu haben als intra-molekular vernetzte Hämoglobinpräparate. Bislang ist HBOC-201 (Hemopure®) die einzige Substanz mit einer Zulassung für die Therapie perioperativer Anämie in Südafrika.

Abstract

Because of an impending shortfall of allogeneic blood products within the next decades and ongoing problems such as transfusion reactions, immunomodulating side effects and the risk of bacterial, viral and prion transmission associated with relevant costs for testing and storage of banked RBC units which, additionally, suffer from aging processes, the development of alternatives has been intensified during the last 15 years. Modern chemically modified hemoglobin-based oxygen carriers (HBOC) are free of red blood cell membrane remnants eliminating renal toxicity, and they do not possess AB0 antigens which allows transfusion without knowledge of the respective blood group of a patient. Bovine polymerized cell-free hemoglobin can be stored at room temperature for three years. In contrast to the perfluorocarbon solutions, HBOC can be applied at room air oxygen concentrations.

Animal experiments have shown that HBOC can compensate for intravascular volume deficits in hemorrhagic shock, including restoration of colloid osmotic pressure and organ perfusion, and deliver oxygen to organs and tissues during nearly complete blood exchange. Chemical modifications of HBOC are able to reduce the vasoconstrictive side-effect of HBOC which is caused by NO scavenging. In spite of vasoconstriction the increased oxygen extraction in presence of HBOC in combination with the plasmatic oxygen transport provides enhanced tissue oxygenation even in post-stenotic tissues. HBOC seem to improve the diffusive oxygen transport at the microcirculatory site thus decreasing tissue damage in acute pancreatitis and the heart and brain after ischemia/reperfusion injury.

Clinical studies have shown that the peri-operative use of different HBOC (Hemopure®, PolyHeme®, Hemolink® and HemAssist®) can reduce the number of allogeneic RBC units and increase the avoidance rate of allogeneic transfusion in emergency bleeding, vascular, cardiac and non-cardiac surgery. Polymerized HBOC appear to have a lower potential of side effects in comparison to intra-molecularly cross-linked preparations. However, HBOC-201 (Hemopure®) is the only substance which has been licensed for the treatment of patients with acute peri-operative anemia in South Africa until now.

Schlüsselwörter

Blutersatz - Gewebsoxygenierung - Hämoglobinlösung - künstliche Sauerstoffträger - Volumenersatz - zellfreies Hämoglobin

Key words

Blood substitute - cell-free hemoglobin - hemoglobin solution - artificial oxygen carriers - tissue oxygenation - volume substitute

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Prof. Dr. med. Thomas Standl

Klinik für Anästhesie und operative Intensivmedizin, Städtisches Klinikum Solingen

Gotenstraße 1 · 42653 Solingen

Email: standl@klinikumsolingen.de

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