A. Pape

Regional blood flow during hyperoxic haemodilution

Background:  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.

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.

Neuromuscular Blockade with Rocuronium Bromide Increases the Tolerance of Acute Normovolemic Anemia in Anesthetized Pigs

Background: The patient’s individual anemia tolerance is pivotal when blood transfusions become necessary, but are not feasible for some reason. To date, the effects of neuromuscular blockade (NMB) on anemia tolerance have not been investigated. Methods: 14 anesthetized and mechanically ventilated pigs were randomly assigned to the Roc group (3.78 mg/kg rocuronium bromide followed by continuous infusion of 1 mg/kg/min, n = 7) or to the Sal group (administration of the corresponding volume of normal saline, n = 7). Subsequently, acute normovolemic anemia was induced by simultaneous exchange of whole blood for a 6% hydroxyethyl starch solution (130/0.4) until a sudden decrease of total body O2 consumption (VO2) indicated a critical limitation of O2 transport capacity. The Hb concentration quantified at this time point (Hbcrit) was the primary endpoint of the protocol. Secondary endpoints were parameters of hemodynamics, O2 transport and tissue oxygenation. Results: Hbcrit was significantly lower in the Roc group (2.4 ± 0.5 vs. 3.2 ± 0.7 g/dl) reflecting increased anemia tolerance. NMB with rocuronium bromide reduced skeletal muscular VO2 and total body O2 extraction rate. As the cardiac index increased simultaneously, total body VO2 only decreased marginally in the Roc group (change of VO2 relative to baseline –1.7 ± 0.8 vs. 3.2 ± 1.9% in the Sal group, p < 0.05). Conclusion: Deep NMB with rocuronium bromide increases the tolerance of acute normovolemic anemia. The underlying mechanism most likely involves a reduction of skeletal muscular VO2. During acellular treatment of an acute blood loss, NMB might play an adjuvant role in situations where profound stages of normovolemic anemia have to be tolerated (e.g. bridging an unexpected blood loss until blood products become available for transfusion).

The choice of the intravenous fluid influences the tolerance of acute normovolemic anemia in anesthetized domestic pigs.

IntroductionThe correction of hypovolemia with acellular fluids results in acute normovolemic anemia. Whether the choice of the infusion fluid has an impact on the maintenance of oxygen (O2) supply during acute normovolemic anemia has not been investigated so far.MethodsThirty-six anesthetized and mechanically ventilated pigs were hemodiluted to their physiological limit of anemia tolerance, reflected by the individual critical hemoglobin concentration (Hbcrit). Hbcrit was defined as the Hb-concentration corresponding with the onset of supply-dependency of total body O2-consumption (VO2). The hemodilution protocol was randomly performed with either tetrastarch (6% HES 130/0.4, TS-group, n = 9), gelatin (3.5% urea-crosslinked polygeline, GEL-group, n = 9), hetastarch (6% HES 450/0.7, HS-group, n = 9) or Ringers solution (RS-group, n = 9). The primary endpoint was the dimension of Hbcrit, secondary endpoints were parameters of central hemodynamics, O2 transport and tissue oxygenation.ResultsIn each animal, normovolemia was maintained throughout the protocol. Hbcrit was met at 3.7 ± 0.6 g/dl (RS), 3.0 ± 0.6 g/dl (HS P < 0.05 vs. RS), 2.7 ± 0.6 g/dl (GEL, P < 0.05 vs. RS) and 2.1 ± 0.4 g/dl (TS, P < 0.05 vs. GEL, HS and RS). Hemodilution with RS resulted in a significant increase of extravascular lung water index (EVLWI) and a decrease of arterial oxygen partial pressure (paO2), and O2 extraction ratio was increased, when animals of the TS-, GEL- and HS-groups met their individual Hbcrit.ConclusionsThe choice of the intravenous fluid has an impact on the tolerance of acute normovolemic anemia induced by acellular volume replacement. Third-generation tetrastarch preparations (e.g., HES 130/0.4) appear most advantageous regarding maintenance of tissue oxygenation during progressive anemia. The underlying mechanism includes a lower degree of extravasation and favourable effects on microcirculatory function.

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

Background:  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.

ROTEM and multiplate – a suitable tool for POC?

The early recognition of perioperative coagulation disorders is essential to identify non-surgical reasons of bleeding, to initiate appropriate haemostatic treatment and finally to reduce perioperative blood loss. Conventional laboratory coagulation tests include prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen levels and platelet counts. Although these parameters are frequently assessed, their value has been challenged at least in the setting of acute perioperative bleeding [1]. PT and aPTT are performed in an artificial ‘in vitro’ system, i.e. in plasma separated from whole blood, which is then warmed to 37 C and buffered to a pH of 7AE4. These standardized conditions often do not reflect the patient’s situation [2]. Plasmatic ‘in vitro’ tests merely reflect the time elapsing until the activation of thrombin, but provide only marginal information about the functional state of the coagulation system (e.g. platelet function, interaction of plasmatic coagulation factors with platelets and red blood cells, clot firmness, fibrinolysis). Routine coagulation tests are mostly performed in the central laboratory, i.e. remote from the operating theatre. As a consequence, test results are often not available in time or with a considerable delay [3]. Current devices designed for point-of-care (POC) monitoring of coagulation have been designed for the assessment of coagulation directly at the bedside, so that results could be available earlier. Moreover, POC tests are usually performed in whole blood, thereby comprising interactions between cellular components (i.e. platelets and red blood cells) and plasmatic coagulation factors. Commonly used POC devices for assessment of plasmatic coagulation and platelet function are listed in Table 1. This review focuses on rotation thrombelastography (ROTEM ) as a global coagulation test and multiple electrode aggregometry (MEA, Multiplate ) for assessment of platelet function. Rotation thrombelastometry (ROTEM )

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.

Overview of artificial O2 carriers

Artificial O 2 carriers aim at increasing arterial O 2 content and O 2 delivery to the tissues, thereby offering a promising alternative to the transfusion of allogeneic red blood cells (RBC). Despite continuous advancement of quality assurance regarding the production and transfusion of allogeneic blood products, the transfusion of banked blood is still associated with relevant risks, the most serious of which being allergic reactions, transfusion-related lung injury (TRALI), the accidental transfusion of incompatible blood (‘clerical error’ related to the mix-up of cross-matching specimen or blood product) and the transmission of viral and bacterial infections (Hepatitis, HIV, CMV, EBV). Moreover, a deliberate transfusion regimen (i.e. indication for transfusion at Hb > 10 g/dl) seems to be associated with elevated perioperative morbidity and mortality [1]. Transfusion-related morbidity as well as continuously rising costs of blood products impose significant costs on the public health systems: although the willingness to donate blood had temporarily increased after 11 September 2001 in the USA, the Food and Drug Administration (FDA) realises a constantly decreasing rate of blood donation and therefore prognoses a shortage of 4 million units of banked blood by 2030. According to public health statistics, 43% of all donated blood products are transfused to patients aged 65 or older. Because this patient population is growing consistently with the common demographic development, the demand for banked blood will increase significantly within the next years. Due to the growing imbalance between decreasing availability and increasing demand, the costs of blood products are supposed to double until 2030 [2,3]. The expected cost explosion in transfusion medicine underlines the socio-economic significance of safely and effectively applicable alternatives to the transfusion of allogeneic RBC. The large-scale production and application of synthetic O 2 carriers, however, requires the proof of efficacy in situations normally requiring the transfusion of RBC (i.e. extreme anaemia with critical limitation of O 2 transport capacity). Moreover, the risk profile of artificial O 2 carriers should at least bear the comparison with the excellent quality standard of banked blood. Presently, two types of artificial O 2 carrieres are under experimental and clinical research: 1 Haemoglobin-based oxygen carriers (HBOC), i.e. solutions based on isolated human or bovine haemoglobin (Hb). 2 Synthetically processed perfluorocarbons (PFC).