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Byline: G. I. Kemming (1), M. J. Merkel (1), A. Schallerer (1), O. P. Habler (1), M. S. Kleen (1), M. Haller (1), J. Briegel (1), C. Vogelmeier (3), H. Furst (4), B. Reichart (5), B. Zwissler (1) Keywords: Key words Lung transplantation; Inhaled vasodilators; Nitric oxide; Pulmonary hypertension; Selective pulmonary vasodilation; Reperfusion injury Abstract: Objective: Inhalation of high concentrations of nitric oxide (NO) has been shown to improve gas exchange and to reduce pulmonary vascular resistance in individuals with ischemia-reperfusion injury following orthotopic lung transplantation. We assessed the cardiopulmonary effects of low doses of NO in early allograft dysfunction following lung transplantion. Design: Prospective clinical dose- response study. Setting: Anesthesiological intensive care unit of a university hospital. Patients and participants: 8 patients following a single or double lung transplantation who had a mean pulmonary arterial pressure (PAP) in excess of 4.7 kPa (35 mmHg) or an arterial oxygen tension/fractional inspired oxygen ratio (PaO.sub.2/FIO.sub.2) of less than 13.3 kPa (100 mmHg). Interventions: Gaseous NO was inhaled in increasing concentrations (1, 4 and 8 parts per million, each for 15 min) via a Siemens Servo 300 ventilator. Measurements and results: Cardiorespiratory parameters were assessed at baseline, after each concentration of NO, and 15 min after withdrawal of the agent [statistics: median (25th/75th percentiles: Q1/Q3), rANOVA, Dunnett's test, p &lt 0.05]. Inhaled NO resulted in a significant, reversible, dose-dependent, selective reduction in PAP from 5.5(5.2/6.0) kPa at control to 5.1(4.7/5.6) kPa at 1 ppm, 4.9(4.3/5.3) kPa at 4 ppm, and to 4.7(4.1/5.1) kPa at 8 ppm. PaO.sub.2 increased from 12.7(10.4/17.1) to 19.2(12.4/26.0) kPa at 1 ppm NO, to 23.9(4.67/26.7) kPa at 4 ppm NO and to 24.5(11.9/28.7) kPa at 8 ppm NO. All patients responded to NO inhalation (either with PAP or PaO.sub.2), all were subject to long-term inhalation (1--19 days). All were successfully weaned from NO and were discharged from the intensive care unit. Conclusion: The present study demonstrates that low-dose inhaled NO may be an effective drug for symptomatic treatment of hypoxemia and/or pulmonary hypertension due to allograft dysfunction subsequent to lung transplantation. Author Affiliation: (1) Department of Anesthesiology, Ludwig-Maximilians-Universitat Munchen, Klinikum Grosshadern, Marchioninistrasse 15, D-81 377 Munchen, Germany e-mail: bernhard.zwissler@ana.med.uni-muenchen.de Tel. + 49 (89) 7095-3417 Fax + 49 (89) 7095--8886, DE (2) Department of Surgical Research, Ludwig-Maximilians-Universitat Munchen, Munchen, Germany, DE (3) Department of Internal Medicine, Ludwig-Maximilians-Universitat Munchen, Munchen, Germany, DE (4) Department of Surgery, Ludwig-Maximilians-Universitat Munchen, Munchen, Germany, DE (5) Department of Cardiac Surgery, Ludwig-Maximilians-Universitat Munchen, Munchen, Germany, DE Article note: Received: 23 February 1998 Accepted: 20 August 1998

Despite current recommendations on the management of pre-operative anaemia, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in surgical patients. A number of experienced researchers and clinicians took part in an expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the peri-operative period. These statements include: a diagnostic approach for anaemia and iron deficiency in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up. We urge anaesthetists and peri-operative physicians to embrace these recommendations, and hospital administrators to enable implementation of these concepts by allocating adequate resources. [ABSTRACT FROM AUTHOR]

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 (FiO2 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 [ABSTRACT FROM AUTHOR]

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). Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Copyright of Der Urologe A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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. [ABSTRACT FROM AUTHOR]

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.Methods: Twenty-two anesthetized beagle dogs and 18 patients under balanced anesthesia underwent isovolemic hemodilution with hydroxyethyl starch (HAES 6%, 200 000) to a target hb of 7 g dl-1 or 9 g dl-1, respectively. Exchangeable blood volume predicted by use of the different mathematical models was compared with the blood volume actually exchanged to meet the preset target hb.Results: Calculation of EBV by the Bourke and Smith formula (EBVB + S) systematically overestimated the volume actually exchanged (overestimation: dogs 15%, patients 20%), whereas our new iterative model predicted EBV (EBViterative) more reliably (overestimation: dogs 1%, patients 8%). In both cases EBVB + S differed significantly from the EBViterative.Conclusion: Exchangeable blood volume is predicted more accurately by the new iterative model than by the Bourke and Smith formula. The iterative model leads to an improvement in patient safety and provides a physiologically adequate basis for future studies investigating the efficacy of ANH in reducing allogenic blood transfusions. [ABSTRACT FROM AUTHOR]

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Fluorescent microspheres (FM) have become an attractive alternative to radioactive microspheres (RM) for the measurement of regional blood flow (RBF). The aim of the present study was to investigate the comparability of both methods by measuring RBF with FM and RM. Eight anaesthetised pigs received simultaneous, left atrial injections of FM and RM with a diameter of 15 μm at six different time points. Blood reference samples were collected from the descending aorta. RBF was determined in tissue samples of the myocardium, spleen and kidneys of all 8 animals. After radioactivity of the tissue samples was determined, the samples were processed automatically for measuring fluorescence using a recently developed filter device (SPU). RBF was calculated with both the isotope and spectrometric data of both methods for each sample resulting in a total of 10,512 blood flow values. The comparison of the RBF values yielded high linear correlation (mean r[sup 2] = 0.95 ± 0.03 to 0.97 ± 0.02) and excellent agreement (bias 5.4–6.7%, precision 9.9– 16.5%) of both methods. Our results indicate the validity of MS and of the automated tissue processing technique by means of the SPU.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Intraoperative surgical blood loss is initially replaced by infusion of red cell-free, cristalloidal or colloidal solutions. When normovolemia is maintained the ensuing dilutional anemia is compensated by an increase of cardiac output and of arterial oxygen extraction. In the ideal case, a surgical blood loss can entirely be ‘bridged’ without transfusion by intraoperative normovolemic hemodilution. However major blood loss results in extreme hemodilution and the transfusion of red blood cells may finally become necessary to increase arterial oxygen content and to preserve tissue oxygenation. When transfusion has to be started before surgical control of bleeding has been achieved, parts of the red blood cells transfused will get lost, thereby increasing intraoperative transfusion needs. Beside red blood cell transfusion, arterial oxygen content can be rapidly increased by ventilating the patient with 100% oxygen (hyperoxic ventilation), thus enhancing the amount of physically dissolved oxygen in plasma (hyperoxia). In experimental and clinical studies hyperoxic ventilation has emerged as a simple, safe and effective intervention to enlarge the margin of safety for hemodynamic compensation and tissue oxygenation in hemodiluted subjects experiencing major bleeding. The hyperoxia-associated microcirculatory dysregulation and impaired tissue oxygenation known to take place in the presence of a physiologic hemoglobin concentration are not encountered in hemodiluted subjects. Hyperoxic hemodilution i.e. the combination of intraoperative extreme hemodilution and hyperoxic ventilation may therefore be considered a cost-effective, safe and efficient supplement to reduce allogeneic transfusion during surgical interventions associated with high blood losses. The vast majority of the experimental and clinical investigations this new concept is based on was initiated and performed under the guidance of Prof. Konrad Messmer.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Today, the technique to directly administer vasodilators via the airway to treat pulmonary hypertension and to improve pulmonary gas exchange is widely accepted among clinicians. The flood of scientific work focussing on this new therapeutic concept had been initiated by a fundamental new observation by Pepke-Zaba [1]and Frostell in 1991 [2]: Both scientists reported, that inhalation of exogenous nitric oxide (NO) gas selectively dilates pulmonary vessels without a concomittant systemic vasodilation. No more than another decade ago NO was identified as an important endogenous vasodilator [3]while having merely been regarded an environmental pollutant before that time. Although inhaled NO proved to be efficacious, alternatives were sought-after due to NO’s potential side-effects. In search for the ideal inhaled vasodilator another group of endogenous mediators – the prostanoids – came into the focus of interest. The evidence for safety and efficacy of inhaled prostanoids is – among a lot of other valuable work – based on a series of experimental and clinical investigations that have been performed or designed at the Institute for Surgical Research under the guidance and mentorship of Prof. Dr. med. Dr. h.c. mult. K. Messmer [4-19]. In the following, the current and newly emerging clinical applications of inhaled prostanoids and the experimental data which they are based on, will be reviewed.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In severe hemorrhagic shock, left ventricular (LV) diastolic dysfunction is an early sign of cardiac failure due to compromised myocardial oxygenation. Immediate fluid replacement or, in particular, administration of a hemoglobin-based oxygen carrier (diaspirin cross-linked hemoglobin; DCLHb) improves myocardial oxygenation; therefore, positive effects on LV diastolic function could be expected. The effects of fluid resuscitation from severe hemorrhagic shock with DCLHb were investigated in 20 anesthetized domestic pigs. After generation of a critical left anterior descending coronary artery stenosis (narrowing of the artery until disappearance of reactive hyperemia after a 10-second complete vessel occlusion), hemorrhagic shock (mean arterial blood pressure 45 mm Hg) was induced within 15 min by controlled blood withdrawal and maintained for 60 min. Fluid resuscitation consisted of replacement of the plasma volume withdrawn during hemorrhage by infusion of either 10% DCLHb (DCLHb group, n = 10) or 8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10). After completion of resuscitation, an observation period of 60 min elapsed. Measurements of central hemodynamics, myocardial oxygenation, and LV diastolic function were performed at baseline, after induction of critical coronary artery stenosis, after 60 min of hemorrhagic shock, immediately after resuscitation, and 60 min later. While 5 out of 10 animals treated with HSA died within the first 20 min after fluid resuscitation from acute LV pump failure, all DCLHb-treated animals survived until the end of the protocol (p < 0.05). Despite superior myocardial oxygenation due to augmentation of the arterial O[sub 2] content as well as of coronary perfusion pressure, no beneficial effects on LV diastolic function were observed after infusion of DCLHb. Peak velocity of LV pressure decrease (dp/dt[sub min] ) did not reveal significant differences between the two groups. Immediately after completion of fluid resuscitation with DCLHb, the time constant of LV diastolic relaxation (τ) was prolonged when compared with HSA-treated animals (p < 0.05), indicating retardation of early LV diastolic relaxation. Our data suggest that DCLHb fails to improve LV diastolic function after fluid resuscitation from severe hemorrhagic shock. However, positive effects on myocardial perfusion and oxygenation result in a significant reduction of the mortality of severe hemorrhagic shock.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]