J. Meier

Regional blood flow during hyperoxic haemodilution

Background:u2002 Ventilation with pure oxygen (hyperoxic ventilation, HV) increases arterial oxygen content (CaO2). However HV induces arteriolar constriction and thus potentially affects O2 supply. We therefore investigated the effects of HV on regional blood flow (RBF) and O2 supply of different vital organs during moderate normovolaemic anaemia.

Künstliche Sauerstofftràger als Alternative zur Bluttransfusion

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.ZusammenfassungDie 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 zweixa0Substanzgruppen 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.AbstractThe 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.

Improved short-term survival with polyethylene glycol modified hemoglobin liposomes in critical normovolemic anemia.

ObjectiveTo investigate the efficacy of axa0polyethylene glycol (PEG) modified formulation of liposome-encapsulated hemoglobin (LEH) as an oxygen-carrying blood substitute in the treatment of critical normovolemic anemia.Design and settingProspective, controlled, randomized experimental study in axa0university research facility.Subjects14 anesthetized and mechanically ventilated beagle dogs.InterventionsAnimals were splenectomized and hemodiluted by exchange of whole blood for iso-oncotic hetastarch (HES). Target parameter of the hemodilution protocol was the individual critical hemoglobin concentration (Hbcrit) corresponding with the onset of O2 supply dependency of total body O2 consumption. At Hbcrit animals were randomized to receive axa0bolus infusion (20u202fml/kg) of either LEH (nu202f=u202f7) or normal saline (NS; nu202f=u202f7). Subsequently animals were observed without further intervention.Measurements and resultsThe primary endpoint was survival time after the completion of treatment; secondary endpoints were parameters of central hemodynamics, O2 transport and tissue oxygenation. Animals in the LEH group survived significantly longer after completion of treatment (149u202f±u202f109 vs. 43u202f±u202f56u202fmin). Immediately after treatment LEH-treated animals presented with axa0more stable cardiovascular condition. After 30u202fmin tissue O2 tension on the surface of axa0skeletal muscle was significantly higher in the LEH group (23u202f±u202f8 vs. 9u202f±u202f2u202fmmHg). Nevertheless, treatment with LEH did not decrease mortality within the observation period.ConclusionsIn this present experimental study the infusion of axa0PEG-modified LEH provided adequate tissue oxygenation, hemodynamic stability, and axa0prolongation of survival time after critical anemia. However, these effects were sustained for only axa0short period of time.

New mathematical model for the correct prediction of the exchangeable blood volume during acute normovolemic hemodilution.

Background: The blood volume that has to be exchanged for crystalloids and/or colloids during acute normovolemic hemodilution (ANH) in order to reach a preset target hemoglobin concentration (hb) is usually predicted by the Bourke and Smith formula developed in 1974. This formula systematically overestimates the ‘true’ exchangeable blood volume (EBV), a fact that may potentially endanger patients because the target hb will be missed and the normovolemic anemia might turn out to be more severe than a priori intended. Our objective was to develop a more accurate mathematical model of hemodilution kinetics and to validate this new model in animals and in patients undergoing ANH.

[Tolerance to perioperative anemia. Mechanisms, influencing factors and limits].

ZusammenfassungDie zu erwartende Kostensteigerung im Transfusionswesen (steigender Fremdblutbedarf bei gleichzeitig rückläufiger Spendebereitschaft, Behandlungspflicht transfusionsassoziierter Folgeerkrankungen) erhöht den sozioökonomischen Stellenwert der Entwicklung institutionsspezifischer Transfusionsprogramme. Ein wesentlicher Bestandteil hierbei ist – neben einer schonenden Operationstechnik und der konsequenten perioperativen Anwendung fremdblutsparender Maßnahmen – die Ausschöpfung der natürlicherweise vorhandenen „Anämietoleranz“ des menschlichen Organismus (Toleranz größerer Blutverluste durch Verlust von „verdünntem“ Blut, Hinauszögern des Transfusionsbeginns bis nach chirurgischer Blutstillung, Gewinnung von autologem Blut). In der vorliegenden Übersicht werden die Mechanismen, Einflussgrößen und Grenzen dieser natürlichen Anämietoleranz für den Gesamtorganismus und für einzelne Organsysteme zusammengefasst und die sich daraus ergebende Indikation zur Erythrozytentransfusion abgeleitet. Unter kontrollierten Bedingungen (Narkose, strikte Aufrechterhaltung von Normovolämie, komplette Muskelrelaxierung, Hyperoxämie, Hypothermie) werden von kardiopulmonal gesunden Individuen kurzzeitig auch extreme Grade der Verdünnungsanämie [Hämoglobin- (Hb-)Wert <3xa0g/dl (<1,86xa0mmol/l)] ohne Transfusion toleriert. In der klinischen Routine bleibt diese Situation – nicht zuletzt in Ermangelung eines adäquaten Monitorings – jedoch auf spezielle Sonderfälle beschränkt (z.xa0B. unerwartete große Blutverluste bei Zeugen Jehovahs, unerwarteter Engpass bei der Bereitstellung von Fremdblut). Die derzeit geltenden Empfehlungen verschiedener Expertenkommissionen decken sich dahingehend, dass perioperativ (1) bis zu einer Hb-Konzentration von 10xa0g/dl (6,21xa0mmol/l) auch bei alten Patienten und Patienten mit kardiopulmonalen Begleiterkrankungen eine Transfusion von Erythrozyten in der Regel nicht notwendig ist und (2) eine Transfusion bei jungen, gesunden Patienten ohne kardiopulmonale Vorerkrankungen (einschließlich Schwangeren und Kindern) erst ab einer Hb-Konzentration von <6xa0g/dl (<3,72xa0mmol/l) notwendig wird. Auch beatmete Intensivpatienten mit Polytrauma und Sepsis scheinen nicht von einer Transfusion auf Hb-Konzentration >9xa0g/dl (>5,59xa0mmol/l) zu profitieren. Bei massiven Blutverlusten und diffuser Blutungsneigung scheint ein Hb von 10xa0g/dl (6,21xa0mmol/l) zur Stabilisierung der Blutgerinnung beizutragen.AbstractThe expected cost explosion in transfusion medicine (increasing imbalance between donors and potential recipients, treatment of transfusion-associated complications) increases the socio-economic significance of specific institutional transfusion programs. In this context the estimated use of the patient’s physiologic tolerance to anemia enables 1) the tolerance of larger blood losses (loss of “diluted blood”), 2) the onset of transfusion to the time after surgical control of bleeding to be delayed and 3) the perioperative collection of autologous red blood cells. The present review article summarizes the mechanisms, influencing factors and limits of this natural tolerance to anemia and deduces the indication for perioperative red blood cell transfusion. Under strictly controlled conditions (anesthesia, normovolemia, complete muscular relaxation, hyperoxemia, mild hypothermia) extremely low hemoglobin concentrations [Hb <3xa0g/dl (<1.86xa0mmol/l)] are tolerated without transfusion by individuals with no cardiopulmonary disease. In the clinical routine these situations are limited to borderline situations e.g. unexpected massive blood losses in Jehovah’s Witnesses or unexpected shortcomings in blood supply. The current recommendations coincide to the effect that perioperative red blood cell transfusion 1) is unnecessary up to a Hb concentration of 10xa0g/dl (6.21xa0mmol/l) even in older patients with cardiopulmonary comorbidity and 2) is only recommended in cases of Hb <6xa0g/dl (<3.72xa0mmol/l) in otherwise healthy subjects including pregnant women and children. Critically ill patients with multiple trauma and sepsis do not seem to benefit from transfusions up to Hb concentrations >9xa0g/dl (>5.59xa0mmol/l). In cases of massive hemorrhaging and diffuse bleeding disorders the maintenance of a Hb concentration of 10xa0g/dl (6.21xa0mmol/l) seems to contribute to stabilization of coagulation.

Artificial oxygen carriers as an alternative to red blood cell transfusion

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.ZusammenfassungDie 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 zweixa0Substanzgruppen 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.AbstractThe 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.

Fluid resuscitation from severe hemorrhagic shock using diaspirin cross-linked hemoglobin fails to improve pancreatic and renal perfusion

Background:u2002 Fluid resuscitation from hemorrhagic shock is intended to abolish microcirculatory disorders and to restore adequate tissue oxygenation. Diaspirin cross‐linked hemoglobin (DCLHb) is a hemoglobin‐based oxygen carrier (HBOC) with vasoconstrictive properties. Therefore, fluid resuscitation from severe hemorrhagic shock using DCLHb was expected to improve perfusion pressure and tissue perfusion of kidneys and pancreas.

Indikation zur Bluttransfusion bei orthopädischen Eingriffen

ZusammenfassungMit zunehmender Alterung der Bevölkerung steigt die Zahl großer orthopädischer Operationen bei alten Menschen. Hohe Blutverluste und eine reduzierte Anämietoleranz erhöhen die Wahrscheinlichkeit perioperativer Bluttransfusionen in dieser Patientengruppe. Die zu erwartende Kostensteigerung im Transfusionswesen (kostenintensives Qualitätsmanagement, Anstieg der Zahl potenzieller Empfänger bei gleichzeitig rückläufiger Spendebereitschaft) sowie das nach wie vor für den Empfänger bestehende Restrisiko von Hämolyse, Infektion und Immunsuppression verdeutlichen den sozioökoniomischen Stellenwert der prospektiven Entwicklung institutionsspezifischer Transfusionsprogramme. Der vorliegende Artikel gibt einen Überblick über (1) die (patho)physiologischen Zusammenhänge bei der Kompensation von akuter Anämie, (2) die Indikation zur Transfusion bei Patienten mit und ohne kardiovaskuläre Begleiterkrankungen sowie (3) die derzeit zur Verfügung stehenden prä- und intraoperativen Verfahren zur Reduktion von Fremdbluttransfusionen bei operativen orthopädischen Eingriffen.AbstractAgeing of the population increases the number of large orthopedic surgical interventions in elder people. High perioperative blood loss together with a reduced tolerance to anemia increase the transfusion probability in this patient subgroup. The expected cost explosion in the transfusion system (cost intensive quality management, imbalance between the number of donors and recipients) as well as the remaining transfusion related risk of hemolysis, infection and immunosuppression reflect the high socio-economic significance of the development of institutional transfusion programs. The present article summarizes: (1) the (patho-) physiology of anemia compensation, (2) the decision making for transfusion in healthy patients and patients with cardiovascular disease, and (3) the currently applied pre- and intraoperative techniques to reduce allogeneic transfusion in orthopedic patients.

Indications for blood transfusion during orthopedic surgery

ZusammenfassungMit zunehmender Alterung der Bevölkerung steigt die Zahl großer orthopädischer Operationen bei alten Menschen. Hohe Blutverluste und eine reduzierte Anämietoleranz erhöhen die Wahrscheinlichkeit perioperativer Bluttransfusionen in dieser Patientengruppe. Die zu erwartende Kostensteigerung im Transfusionswesen (kostenintensives Qualitätsmanagement, Anstieg der Zahl potenzieller Empfänger bei gleichzeitig rückläufiger Spendebereitschaft) sowie das nach wie vor für den Empfänger bestehende Restrisiko von Hämolyse, Infektion und Immunsuppression verdeutlichen den sozioökoniomischen Stellenwert der prospektiven Entwicklung institutionsspezifischer Transfusionsprogramme. Der vorliegende Artikel gibt einen Überblick über (1) die (patho)physiologischen Zusammenhänge bei der Kompensation von akuter Anämie, (2) die Indikation zur Transfusion bei Patienten mit und ohne kardiovaskuläre Begleiterkrankungen sowie (3) die derzeit zur Verfügung stehenden prä- und intraoperativen Verfahren zur Reduktion von Fremdbluttransfusionen bei operativen orthopädischen Eingriffen.AbstractAgeing of the population increases the number of large orthopedic surgical interventions in elder people. High perioperative blood loss together with a reduced tolerance to anemia increase the transfusion probability in this patient subgroup. The expected cost explosion in the transfusion system (cost intensive quality management, imbalance between the number of donors and recipients) as well as the remaining transfusion related risk of hemolysis, infection and immunosuppression reflect the high socio-economic significance of the development of institutional transfusion programs. The present article summarizes: (1) the (patho-) physiology of anemia compensation, (2) the decision making for transfusion in healthy patients and patients with cardiovascular disease, and (3) the currently applied pre- and intraoperative techniques to reduce allogeneic transfusion in orthopedic patients.

Effects of alterations of inspiratory oxygen fractions on heart rate variability

BACKGROUNDnChanges in heart rate variability (HRV) during anaesthesia depend on multiple influences such as hypnosis, analgesia, surgical stress, and interacting drugs. Several recent studies have aimed to establish HRV-based monitoring tools to measure perioperative stress or anaesthetic depth. Although hyperoxic ventilation (HV) is known to alter autonomic cardiovascular regulation, there have been no studies investigating its influence on time- and frequency-domain analysis during general anaesthesia. Therefore, we have examined the effects of HV on cardiovascular neuroregulation of anaesthetized patients and conscious volunteers by analysis of relevant HRV parameters.nnnMETHODSnFourteen healthy volunteers and 14 anaesthetized, ventilated ASA I patients sequentially breathed room air ( 0.21), pure oxygen ( 1.0), and then room air. During each episode, standardized HRV parameters were calculated from 5 min ECG recordings.nnnRESULTSnHV significantly reduced HR and increased the standard deviation of RR interval values, the root mean square of successive RR interval differences, and the high-frequency (HF) power of the spectral components, whereas the low-frequency (LF) power and the LF/HF ratio of HRV were reduced in both groups. All changes were reversible after was reduced to normoxia.nnnCONCLUSIONSnIn both healthy volunteers and anaesthetized patients, HV resulted in comparable and reversible changes of established HRV parameters. These changes might be relevant enough to bias HRV-based analgesia and anaesthesia monitoring and could result in a clinically relevant misinterpretation of HRV parameters as indicators of anaesthetic depth during HV.