Frankfurt am Main, Germany
Frankfurt am Main, Germany

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PubMed | University of Tübingen, University of Mannheim, University Hospital Frankfurt and Clinic of Anesthesiology
Type: | Journal: Transfusion | Year: 2016

Restrictive intraoperative fluid management has been demonstrated to improve outcome of visceral and lung surgery in several studies. However, subsequent hypovolemia (HOV) may be accompanied by a decrease of anemia tolerance, resulting in increased transfusion needs. We therefore investigated the effect of volume status on anemia tolerance.Eighteen domestic pigs of either sex (mean weight, 23.54.8 kg) were anesthetized, ventilated, and randomized into three experimental groups: normovolemia (no intervention), HOV (blood loss of 40% of blood volume), and hypervolemia (HEV; volume infusion of 40% of blood volume). The animals were then hemodiluted until their individual critical hemoglobin concentrations (HbDespite significant differences in exchangeable blood volume, HbThe combination of hemorrhagic HOV with subsequent anemia leads to accentuated tissue hypoxia, revealed by a significant increase in pimonidazole binding at Hb


Pape A.,University Hospital Frankfurt | Steche M.,University Hospital Frankfurt | Laout M.,University Hospital Frankfurt | Wedel M.,University Hospital Frankfurt | And 4 more authors.
European Surgical Research | Year: 2014

Background: During acellular replacement of an acute blood loss, hyperoxic ventilation (HV) increases the amount of O2 physically dissolved in the plasma and thereby improves O2 supply to the tissues. While this effect could be demonstrated for HV with inspiratory O2 fraction (FiO2) 0.6, it was unclear whether HV with pure oxygen (FiO 2 1.0) would have an additional effect on the physiological limit of acute normovolemic anemia. Methods: Seven anesthetized domestic pigs were ventilated with FiO2 1.0 and subjected to an isovolemic hemodilution protocol. Blood was drawn and replaced by a 6% hydroxyethyl starch (HES) solution (130/0.4) until a sudden decrease of total body O2 consumption (VO2) indicated the onset of O2 supply dependency (primary endpoint). The corresponding hemoglobin (Hb) concentration was defined as 'critical Hb' (Hbcrit). Secondary endpoints were parameters of myocardial function, central hemodynamics, O2 transport and tissue oxygenation. Results: HV with FiO2 1.0 enabled a large blood-for-HES exchange (156 ± 28% of the circulating blood volume) until Hbcrit was met at 1.3 ± 0.3 g/dl. After termination of the hemodilution protocol, the contribution of O2 physically dissolved in the plasma to O2 delivery and VO2 had significantly increased from 11.7 ± 2 to 44.2 ± 9.7% and from 29.1 ± 4.2 to 66.2 ± 11.7%, respectively. However, at Hbcrit, cardiovascular performance was found to have severely deteriorated. Conclusion: HV with FiO2 1.0 maintains O2 supply to tissues during extensive blood-for-HES exchange. In acute situations, where profound anemia must be tolerated (e.g. bridging an acute blood loss until red blood cells become available for transfusion), O2 physically dissolved in the plasma becomes an essential source of oxygen. However, compromised cardiovascular performance might require additional treatment. © 2013 S. Karger AG, Basel.


Pape A.,University Hospital Frankfurt | Weber C.F.,University Hospital Frankfurt | Laout M.,University Hospital Frankfurt | Steche M.,University Hospital Frankfurt | And 4 more authors.
Anesthesiology | Year: 2014

Background: The initial treatment of an acute blood loss with acellular fluids leads to the dilution of the red cell mass remaining in the vasculature, that is, to acute normovolemic anemia. Whether the compensation and, thus, the tolerance of acute anemia, are affected by sympathetic block induced by thoracic epidural anesthesia has not yet been investigated.Methods: Eighteen anesthetized and mechanically ventilated pigs were instrumented with thoracic epidural catheters and randomly assigned to receive an epidural injection of either 5-ml ropivacaine 0.2% (n = 9) aiming for a Th5-Th10 block or saline (n = 9) followed by continuous epidural infusion of 5 ml/h of either fluid. Subsequently, acute normovolemic anemia was induced by replacement of whole blood with 6% hydroxyethyl starch solution until a "critical" limitation of oxygen transport capacity was reached as indicated by a sudden decrease in oxygen consumption. The critical hemoglobin concentration quantified at this time point was the primary endpoint; secondary endpoints were hemodynamic and oxygen transport parameters.Results:Thoracic epidural anesthesia elicited only a moderate decrease in mean arterial pressure and cardiac index and a transient decrease in oxygen extraction ratio. During progressive anemia, the compensatory increases in cardiac index and oxygen extraction ratio were not compromised by thoracic epidural anesthesia. Critical hemoglobin concentration was reached at identical levels in both groups (ropivacaine group: 2.5 ± 0.6 g/dl, saline group: 2.5 ± 0.6 g/dl).Conclusion: Thoracic epidural anesthesia with ropivacaine 0.2% does not decrease the tolerance to acute normovolemic anemia in healthy pigs. The hemodynamic compensation of acute anemia is fully preserved despite sympathetic block, and the critical hemoglobin concentration remains unaffected. Copyright © 2014, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.


Pape A.,Goethe University Frankfurt | Kutschker S.,Goethe University Frankfurt | Kertscho H.,Goethe University Frankfurt | Stein P.,Goethe University Frankfurt | And 4 more authors.
Critical Care | Year: 2012

Introduction: The 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 (O 2) supply during acute normovolemic anemia has not been investigated so far.Methods: Thirty-six anesthetized and mechanically ventilated pigs were hemodiluted to their physiological limit of anemia tolerance, reflected by the individual critical hemoglobin concentration (Hb crit). Hb critwas defined as the Hb-concentration corresponding with the onset of supply-dependency of total body O 2-consumption (VO 2). 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 Ringer's solution (RS-group, n = 9). The primary endpoint was the dimension of Hb crit, secondary endpoints were parameters of central hemodynamics, O 2transport and tissue oxygenation.Results: In each animal, normovolemia was maintained throughout the protocol. Hb critwas 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 (paO 2), and O 2extraction ratio was increased, when animals of the TS-, GEL- and HS-groups met their individual Hb crit.Conclusions: The 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. © 2012 Pape et al.; licensee BioMed Central Ltd.


Lauscher P.,Goethe University Frankfurt | Kertscho H.,Goethe University Frankfurt | Raab L.,Clinic of Anesthesiology | Habler O.,Clinic of Anesthesiology | Meier J.,Goethe University Frankfurt
Minerva Anestesiologica | Year: 2011

Background. We investigated changes in heart rate variability (HRV) across different degrees of acute dilutional anemia (hemoglobin [Hb]=9, 7, 5, 4, and 3 g/dL) in a pig model. Methods. Twelve anesthetized mechanically ventilated pigs of either gender (mean body weight 27.5±5.5 kg) were hemodiluted by exchange of blood for hydroxyethyl starch (6%; 200000/0.5) from baseline values to each animal's individual critical hemoglobin concentration (Hb crit 3.3 [2.3/3.6] g/dL). Differences in time- and frequency-domain calculations of HRV were analyzed throughout the hemodilution procedure by using short-term electrocardiogram recordings (analysis of variance+Dunn's post-hoc test). Results. During the hemodilution procedure, the standard deviation of normal R-R intervals and the coefficient of variation changed at Hb 5.3 (4.2/5.7) g/dL. Thereafter, the high-frequency power (HF), total power of the variance, and root mean square of successive N-N interval differences changed at Hb 3.9 (3.1/4.3) g/dL. The low-frequency power (LF) and the LF/HF ratio remained unaffected by hemodilution to Hb crit. Conclusion. Acute dilutional anemia resulted in significant changes in different time- and frequency-domain variables in HRV analysis. These changes occurred considerably earlier than did commonly recognized transfusion triggers or signs of general tissue hypoxia. Further investigation is warranted to elucidate whether these changes can be considered as indicators of imminent tissue hypoxia.


Lauscher P.,University Hospital | Kertscho H.,University Hospital | Meissner A.,University Hospital | Zacharowski K.,University Hospital | And 2 more authors.
Resuscitation | Year: 2011

Aim of the study: Recently it has been demonstrated that short term hyperoxic ventilation (HV) can improve glucose metabolism, reduce pulmonary and hepatic apoptosis, and improve gastrointestinal perfusion during acute sepsis. However, it is unknown whether additional O2 improves survival. Therefore we investigated the effects of increased plasma O2 on survival during extreme anaemia and concomitant endotoxaemia in order to quantify the efficacy of HV. Methods: Endotoxaemia (Salmonella abortus equi-LPS) was induced in 14 anesthetized pigs ventilated with room air (FiO2=0.21). Simultaneously, animals were haemodiluted by exchange of whole blood for 6% hydroxyethyl starch (200,000:0.5) until the individual critical hemoglobin concentration (Hbcrit) was achieved (outermost limit of tissue oxygenation). Subsequently, animals were either ventilated with an FiO2 of 0.21 (NOX, n=7) or an FiO2 of 1.0 (HOX, n=7), and observed thereafter for 6h without further intervention. Results: HV significantly prolonged survival time at Hbcrit (NOX, 30 [27/35] min; HOX, 172 [111/235] min, p<0.05). In contrast to the NOX group, HV maintained MAP, and improved DO2 and tissue oxygenation in the HOX group. Conclusion: The improvement of survival, oxygen transport and tissue oxygenation seems to underline the efficacy of HV during endotoxaemia and concomitant acute anaemia. Further studies are needed to transfer these results into daily clinical practice. © 2010 Elsevier Ireland Ltd.


Kanczkowski W.,TU Dresden | Tymoszuk P.,TU Dresden | Ehrhart-Bornstein M.,TU Dresden | Wirth M.P.,TU Dresden | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Context: Adrenocortical carcinoma (ACC) is a rare tumor with poor prognosis. The expression of innate immunity receptor Toll-like receptor 4 (TLR4) was recently reported in various human tumors, and TLR4 was shown to regulate tumor immune escape processes, proliferation, and resistance to chemotherapeutical agents. Objective: The aim of this study was to investigate TLR4 expression, signaling, and function in the process of tumorigenesis in the human adrenal cortex. Measurements and Main Results: Real-time PCR analysis of human ACC (n = 8), adenoma (n = 8), and ACC cell lines (SW13, NCI-H295R, and HAC15) revealed a significant down-regulation of TLR4, MD2 (myeloid differentiation protein-2), and cluster of differentiation 14 (CD14) mRNA compared with normal human adrenal cortex and adrenocortical cells in primary culture. Furthermore, immunohistochemistry revealed an abrogation of TLR4 and CD14 expression in ACC but notadenoma tissues. Western blot analysis of MAPK, AKT, activator protein-1, and nuclear factor-κB signaling revealed that the ACC cell lines are unresponsive to lipopolysaccharide action. Restoration of TLR4 signaling by stable transfection of TLR4-CD14 plasmid into NCI-H295R cells sensitized them to lipopolysaccharide incubation as shown by nuclear factor-κB activation and decreased cell viability and induced apoptosis in these cells. Conclusion: Our results demonstrate a significant reduction in the expression of TLR4 and CD14 and an inactivation of TLR4 signaling in ACCs. Furthermore, our data show that reintroduction of TLR4 expression in ACCs may provide a novel therapeutic strategy for adrenal cancer. Copyright © 2010 by The Endocrine Society.


Lauscher P.,Goethe University Frankfurt | Kertscho H.,Goethe University Frankfurt | Enselmann P.,Clinic of Anesthesiology | Lauscher S.,Clinic of Anesthesiology | And 2 more authors.
British Journal of Anaesthesia | Year: 2012

Background. Changes 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. Methods. Fourteen 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. Results. HV 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. Conclusions. In 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. © The Author [2011].


Kanczkowski W.,TU Dresden | Chatzigeorgiou A.,TU Dresden | Samus M.,TU Dresden | Tran N.,Clinic of Anesthesiology | And 3 more authors.
Molecular and Cellular Endocrinology | Year: 2013

Systemic administration of endotoxin, which closely mimics the bacteria-induced systemic inflammatory response syndrome (SIRS) can ultimately lead to organ failure. Adrenal gland insufficiency is frequently diagnosed in critically ill patients; however, the underlying mechanisms are still unclear. In the present study, we studied comprehensively the characteristics of adrenal gland dysregulation, including inflammation, leukocyte infiltration and cell death in the adrenal glands in the course of LPS-induced systemic inflammation in mice. LPS enhanced expression of many proinflammatory cytokines, chemokines and adhesion molecules, which resulted in rapid recruitment of leukocytes into the adrenal gland. Furthermore, LPS-mediated inflammation was associated with increased apoptosis of adrenocortical and chromaffin cells. Our results performed in mice, suggest that LPS-induced adrenal gland inflammation and cell death might be mechanisms potentially involved in the adrenal gland dysfunction in patients with sepsis. © 2012 Elsevier Ireland Ltd.


Kertscho H.,Goethe University Frankfurt | Lauscher P.,Goethe University Frankfurt | Raab L.,Clinic of Anesthesiology | Zacharowski K.,Goethe University Frankfurt | Meier J.,Goethe University Frankfurt
Acta Physiologica | Year: 2012

Aim: Administration of 100% oxygen [hyperoxic ventilation (HV)] has been proven to ameliorate oxygen transport, tissue oxygenation and survival in different models of extreme normovolemic and hypovolemic anaemia. However, up to date, it is unknown whether HV is also able to improve outcome of extreme anaemia if myocardial oxygen consumption is contemporaneously increased by tachycardia. Therefore, we investigated the influence of HV on the 6-h survival rate during extreme anaemia and aggravated by experimentally induced tachycardia in a prospective, randomized study in a pig model of critical anaemia. Methods: After government approval, 14 anesthetized pigs mechanically ventilated on room air were haemodiluted by replacing a certain amount of whole blood with hydroxethyl starch 6% (200.000/0.5) until their individual critical haemoglobin concentration (Hb crit) was achieved. At Hb crit, tachycardia (180bpm) was induced in all animals by atrial pacing. Thereafter, animals were observed for the next 6h either at room air (FiO 2 0.21; group NOX) or during HV (FiO 2 1.0; group HOX) without further intervention. As primary outcome parameter of this study, the 6-h survival rate was selected. Results: Hyperoxic ventilation increased the 6-h survival rate from 14 to 100%. In contrast to the NOX group, macrohaemodynamics and oxygen transport improved in the HOX group during the observation period without apparent adverse effects of HV. Conclusions: Hyperoxic ventilation can be considered a safe and effective measure for the optimization of oxygen supply during extreme anaemia and despite concomitant tachycardia within 6h. Whether HV can also be recommended beyond this period warrants further studies. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

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