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The religious organization of Jehovah's Witnesses numbers more than 7 million members worldwide, including 165,000 members in Germany. Although Jehovah's Witnesses strictly refuse the transfusion of allogeneic red blood cells, platelets and plasma, Jehovah's Witness patients may nevertheless benefit from modern therapeutic concepts including major surgical procedures without facing an excessive risk of death. The present review describes the perioperative management of surgical Jehovah's Witness patients aiming to prevent fatal anemia and coagulopathy. The cornerstones of this concept are 1) education of the patient about blood conservation techniques generally accepted by Jehovah's Witnesses, 2) preoperative optimization of the cardiopulmonary status and correction of preoperative anemia and coagulopathy, 3) perioperative collection of autologous blood, 4) minimization of perioperative blood loss and 5) utilization of the organism's natural anemia tolerance and its acute accentuation in the case of life-threatening anemia.

The expected cost explosion in transfusion medicine increases the socio-economic significance of specific institutional transfusion programs. In this context the estimated use of the patient's physiologic tolerance represents an integral part of any blood conservation concept. The present article summarizes the mechanisms, influencing factors and limits of this natural tolerance to anemia and deduces the indication for perioperative red blood cell transfusion. The current recommendations coincide to the effect that perioperative transfusion is unnecessary up to a Hb concentration of 10 g/dl (6.21 mmol/l) even in older patients with cardiopulmonary comorbidity and is only recommended in cases of Hb <6 g/dl (<3.72 mmol/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 >9 g/dl (>5.59 mmol/l). In cases of massive hemorrhaging and diffuse bleeding disorders the maintenance of a Hb concentration of 10 g/dl (6.21 mmol/l) seems to contribute to stabilization of coagulation.

Inherent risks and increasing costs of allogeneic transfusions underline the socioeconomic relevance of safe and effective alternatives to banked blood. The safety limits of a restrictive transfusion policy are given by a patient's individual tolerance of acute normovolaemic anaemia. latrogenic attempts to increase tolerance of anaemia are helpful in avoiding premature blood transfusions while at the same time maintaining adequate tissue oxygenation. Autologous transfusion techniques include preoperative autologous blood donation (PAD), acute normovolaemic haemodilution (ANH), and intraoperative cell salvage (ICS). The efficacy of PAD and ANH can be augmented by supplemental iron and/or erythropoietin. PAD is only cost-effective when based on a meticulous donation/transfusion plan calculated for the individual patient, and still carries the risk of mistransfusion (clerical error). In contrast, ANH has almost no risks and is more cost-effective. A significant reduction in allogeneic blood transfusions can also be achieved by ICS. Currently, some controversy regarding contraindications of ICS needs to be resolved. Artificial oxygen carriers based on perfluorocarbon (PFC) or haemoglobin (haemoglobin-based oxygen carriers, HBOCs) are attractive alternatives to allogeneic red blood cells. Nevertheless, to date no artificial oxygen carrier is available for routine clinical use, and further studies are needed to show the safety and efficacy of these substances.

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.

Ageing 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.

The aim of the present study was to demonstrate the practicality and efficacy of acute normovolemic hemodilution (ANH) to reduce allogeneic red blood cell (RBC) transfusion in patients undergoing elective surgery with anticipated high intraoperative blood loss (BL). 124 patients (age 48 +/- 18 years, ASA classes I-III) underwent major maxillofacial surgery in a university hospital (68% tumor surgery, 32% dysgnathia correction). After induction of general anesthesia, ANH was performed by standardized withdrawal of 900 ml (2 units) of whole blood and simultaneous infusion of 500 ml of hydroxyethyl starch solution (6% HES 130,000/0.4) and 1500 ml of crystalloidal solution. Intraoperative BL was fluid-compensated until physiologic parameters indicated the need for RBC transfusion. First, autologous ANH-blood was retransfused followed by, if necessary, allogeneic RBC. Total BL was referred to the patient's calculated blood volume (BV): fractional blood volume loss, BL(fract) = BL/BV. ANH took 16 +/- 2 min and was void of any adverse event. The costs for ANH was 24 per patient. 55 patients had a mean BL(fract) of 44 +/- 28% and required an intraoperative transfusion; 49/55 patients with an average BL(fract) of 37 +/- 14% were transfused with only autologous ANH-blood; 6/55 patients with a mean BL(fract) of 100 +/- 47% underwent additional transfusion with allogeneic RBC. Standardized, 2 unit, ANH is a practicable, safe and economic blood conservation technique that allowed for the complete avoidance of allogeneic RBC transfusion in 89% of patients undergoing maxillofacial surgery that required an intraoperative RBC transfusion.

Background: In subjects who have undergone acute preoperative normovolemic hemodilution (ANH), intraoperative hemorrhage is generally treated by immediate return of autologous blood collected during ANH. Simply increasing blood oxygen content by hyperoxic ventilation (HV, inspiratory fraction [FIO2] 1.0) might compensate for the acute anemia, allow further ANH, and delay onset of autologous blood return., Study Design and Methods: This study 1) evaluated the effects of HV (FIO2 1.0) upon ANH to a hemoglobin (Hb) concentration of 7 g per dL in anesthetized dogs ventilated with room air and 2) compared the effects of subsequent profound ANH (Hb, 3 g/dL) with and without an intravenous perfluorocarbon emulsion (perflubron 60% wt/vol) versus those of autologous red cell transfusion. The results of the entire study are presented in two parts. Organ tissue oxygenation was assessed in skeletal muscle and liver, and systemic oxygenation status was evaluated. Myocardial contractility was deduced from left ventricular pressure-volume relationship. Seven of 22 dogs underwent further hemodilution while breathing 100-percent O2, for a determination of the Hb concentration at which HV-induced effects were abolished., Results: HV completely reversed the ANH-induced increase in cardiac index (4.6 +/- 0.7 vs. 3.8 +/- 0.9 L/min/m2 before and during HV; p < 0.05) and partially reversed the decrease in systemic vascular resistance (1784 +/- 329 vs. 2087 +/- 524 dyn x cm-5 x sec x m-2; p < 0.05). Despite unchanged global O2 delivery, organ tissue oxygenation improved during HV (mixed venous partial pressure of O2: 40 +/- 3 vs. 59 +/- 7 torr; coronary venous pressure of O2: 30 +/- 4 vs. 43 +/- 6 torr; p < 0.05; liver surface: 31 +/- 11 vs. 39 +/- 13 torr; skeletal muscle surface: 30 +/- 14 vs. 41 +/- 22 torr; p < 0.05). This improvement was due to an increased contribution of physically dissolved O2 in plasma to O2 delivery (3.2 +/- 0.2% before HV vs. 14.6 +/- 1% during HV; p < 0.05) and O2 consumption (whole body: 6 +/- 1% vs. 47 +/- 8%, p < 0.05; myocardium: 4.3 +/- 0.9% vs. 31 +/- 6%, p < 0.05). The beneficial effects of HV were lost after an additional volume-compensated exchange of 19 percent of blood volume (Hb, 5.6 g/dL)., Conclusion: In anesthetized dogs ventilated with room air and hemodiluted to a Hb of 7 g per dL, simple oxygen therapy by HV (FIO2 1.0) rapidly improves tissue oxygenation and permits extended hemodilution to Hb of 5.8 g per dL until the HV-induced effects are lost.

Background: Intravenously administered perfluorocarbon (PFC) emulsions increase oxygen solubility in plasma. PFC might therefore temporarily replace red cells (RBCs) lost during intraoperative hemorrhage. In patients who have undergone hemodilution, the return of autologous blood may be delayed by the administration of PFC, and autologous RBCs may be saved for transfusion after surgical bleeding is stopped and PFC is cleared by the reticuloendothelial system., Study Design and Methods: In 22 anesthetized, hemodiluted dogs (hemoglobin [Hb] 7 g/dL) breathing 100-percent O2, an intraoperative volume-compensated blood loss was simulated. The efficacy of three therapeutic regimens in maintaining tissue oxygenation was compared: 1) RBC group (n = 7): maintenance of a Hb > 7 g per dL by transfusion of autologous RBCs; 2) PFC group (n = 7): bolus application of a second-generation PFC emulsion (60% wt/vol perflubron) and further acute normovolemic hemodilution (ANH) to a Hb of 3 g per dL; and 3) control group (n = 7): further ANH alone to a Hb of 3 g per dL. Systemic and myocardial oxygenation status and tissue oxygenation were assessed., Results: Autologous RBCs transfused to maintain a Hb of 7 g per dL preserved hemodynamics and tissue oxygenation during blood loss. In the PFC and control groups, heart rate and cardiac index increased significantly in response to further ANH. Tissue oxygenation was not different in the PFC and the RBC groups. Direct comparison of the PFC and control groups revealed better tissue oxygenation in the PFC group, as reflected by significantly higher mixed venous, coronary venous, and local tissue pO2 on liver and skeletal muscle., Conclusion: Bolus intravenous administration of 60-percent (wt/vol) perflubron emulsion and further hemodilution from a Hb of 7 g per dL to one of 3 g per dL were as effective as autologous RBC transfusion in maintaining tissue oxygenation during volume-compensated blood loss designed to mimic surgical bleeding.

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]

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Previously undiagnosed anaemia is common in elective orthopaedic surgical patients and is associated with increased likelihood of blood transfusion and increased perioperative morbidity and mortality. A standardized approach for the detection, evaluation, and management of anaemia in this setting has been identified as an unmet medical need. A multidisciplinary panel of physicians was convened by the Network for Advancement of Transfusion Alternatives (NATA) with the aim of developing practice guidelines for the detection, evaluation, and management of preoperative anaemia in elective orthopaedic surgery. A systematic literature review and critical evaluation of the evidence was performed, and recommendations were formulated according to the method proposed by the Grades of Recommendation Assessment, Development and Evaluation (GRADE) Working Group. We recommend that elective orthopaedic surgical patients have a haemoglobin (Hb) level determination 28 days before the scheduled surgical procedure if possible (Grade 1C). We suggest that the patient's target Hb before elective surgery be within the normal range, according to the World Health Organization criteria (Grade 2C). We recommend further laboratory testing to evaluate anaemia for nutritional deficiencies, chronic renal insufficiency, and/or chronic inflammatory disease (Grade 1C). We recommend that nutritional deficiencies be treated (Grade 1C). We suggest that erythropoiesis-stimulating agents be used for anaemic patients in whom nutritional deficiencies have been ruled out, corrected, or both (Grade 2A). Anaemia should be viewed as a serious and treatable medical condition, rather than simply an abnormal laboratory value. Implementation of anaemia management in the elective orthopaedic surgery setting will improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background. Utilization of an individual patient's tolerance of anaemia is a cornerstone of any restrictive transfusion policy. Whether the use of neuromuscular block (NMB) has an effect on anaemia tolerance has not been investigated. Methods. Fourteen anaesthetized and mechanically ventilated pigs were randomized to receive either rocuronium bromide 1% (Roc-group, n=7, 0.378 ml kg-1 bolus injection, 0.1 ml kg-1 min-1 continuous infusion) or the same volume of normal saline (Sal-group, n=7). Acute normovolaemic anaemia was induced by exchange of whole blood for a 6% HES-solution (130/0.4) until a sudden decrease in total body O2 consumption (VO2) indicated a critical limitation of O2 delivery to the tissues. The Hb concentration quantified at this critical time point (HbCRIT) was defined as the primary endpoint of the protocol. Secondary endpoints were parameters of central haemodynamics, 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-1] reflecting increased tolerance of anaemia. NMB with rocuronium bromide reduced skeletal muscle O2 consumption (mVO2) and the total body O2 extraction ratio. As cardiac index increased, body O2 consumption (VO2) decreased marginally in the Roc-group [change of VO2 relative to baseline (ΔVO2) -1.7 (0.8)% vs 3.2 (1.9)% in the Sal-group, P<0.05]. Conclusions. NMB with rocuronium bromide increases the tolerance of acute normovolaemic anaemia. The underlying mechanism probably involves a reduction in skeletal muscle O2 consumption. During acellular treatment of acute blood loss, NMB might play an adjuvant role, particularly in situations where profound normovolaemic anaemia has to be tolerated, for example, bridging an acute blood loss until compatible blood products become available for transfusion. [ABSTRACT FROM AUTHOR]