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Künstliche Sauerstoffträger als Alternative zur Bluttransfusion

Artificial oxygen carriers as an alternative to red blood cell transfusion

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Zusammenfassung

Die zu erwartende Kostensteigerung im Transfusionswesen (steigender Fremdblutbedarf bei gleichzeitig rückläufiger Spendebereitschaft, Behandlungspflicht transfusionsassoziierter Folgeerkrankungen) erhöht den sozioökonomischen Stellenwert der Entwicklung synthetischer Sauerstoffträger als Alternative zur Transfusion allogener Erythrozyten. Derzeit werden zwei Substanzgruppen im Tierexperiment und in klinischen Studien auf ihre Sicherheit und Wirksamkeit bei schwerer, transfusionsbedürftiger Anämie untersucht. Infusionslösungen auf der Basis von isoliertem menschlichem und tierischem (bovinem) Hämoglobin weisen zusätzlich zu ihrer Fähigkeit des Sauerstofftransports eine vasokonstriktorische Potenz auf, deren Bedeutung für Organperfusion und -funktion nicht vollständig geklärt ist. Dennoch erhielt die Rinderhämoglobinlösung Hemopure® im April 2001 die Zulassung in Südafrika. Perfluorokarbon- (PFC-)Emulsionen werden rein synthetisch hergestellt und erhöhen die Löslichkeit von Sauerstoff im Plasma. Die obligate Dosislimitierung zur Vermeidung immunsuppressiver Effekte (Funktionseinschränkung von Zellen des retikuloendothelialen Systems, RES, durch Phagozytose von PFC-Emulsionströpfchen) sowie die fehlende Onkotizität verbieten den 1:1-Ersatz von Blutverlusten durch PFC. Als Bestandteil eines multimodalen fremdblutsparenden Konzeptes, insbesondere in Kombination mit normovolämischer Hämodilution und Hyperoxie, kann die niedrig-dosierte Bolusanwendung der PFC-Emulsion Oxygent® die intraoperative Anämietoleranz steigern. Obwohl mit beiden Substanzgruppen, Hämoglobinlösungen und PFC, die Reduktion perioperativer Fremdbluttransfusionen bereits in einzelnen klinischen Studien nachgewiesen werden konnte, ist ihre Einführung in die breite klinische Praxis derzeit nicht absehbar.

Abstract

The expected cost-explosion in transfusion medicine (increasing imbalance between donors and recipients, treatment of transfusion-associated complications) increases the socio-economic significance of the development of safe and effective synthetic oxygen carriers as an alternative to the transfusion of allogeneic red blood cells. Currently two types of artificial oxygen carriers have been tested for safety and efficacy in cases of severe anemia otherwise requiring transfusion. Solutions based on human or bovine hemoglobin (HBOC) possess vasoconstrictor properties in addition to their oxygen transport capacity. The impact of vasoconstriction on tissue perfusion and organ function is however not yet fully understood. Nevertheless, in 2001 the bovine HBOC Hemopure® was approved in South Africa for treatment of acutely anemic surgical patients. The purely synthetic perfluorocarbon (PFC) emulsions increase the physically dissolved portion of arterial oxygen content. Due to their particulate nature (emulsion droplets) PFCs may only be infused in low doses to avoid overload and malfunction of phagocytic cells of the reticulo-endothelial system. As part of a multimodal blood conservation program (including normovolemic hemodilution and hyperoxia) the low-dose administration of Oxygent® effectively increases intraoperative anemia tolerance. Although reduction of perioperative allogeneic blood transfusion has already been demonstrated for HBOC and PFC, the global clinical establishment of artificial oxygen carriers is not to be expected in the near future.

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Der korrespondierende Autor weist auf Verbindungen mit folgenden Firmen hin: Alliance Pharmaceutical Corp., USA; Baxter Healthcare Corp., USA und Terumo Corp., Japan. (Experimentelle Untersuchungen mit Produkten der Firmen, Einwerbung von Drittmitteln.)

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Habler, O., Pape, A., Meier, J. et al. Künstliche Sauerstoffträger als Alternative zur Bluttransfusion. Anaesthesist 54, 741–754 (2005). https://doi.org/10.1007/s00101-005-0893-3

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