Anemia Tolerance Research Articles

Influence of central sympathicolysis with clonidine on anemia tolerance in anesthetized pigs

Influence of central sympathicolysis with clonidine on anemia tolerance in anesthetized pigs

Patient Blood Management (Teil 1) – Individuelles Behandlungskonzept zur Reduktion und Vermeidung von Anämie, Blutverlust und -transfusionen

Patient blood management (PBM) is a patient-specific multidisciplinary, multimodal, evidence-based concept to appropriately conserve and manage a patient's own blood as a vital resource. PBM is based on 3 pillars: the first is the optimization of the patient's endogenous red cell mass, the second is the minimization of bleeding and blood loss and the third involves harnessing and optimizing the patient-specific physiological tolerance of anemia, including adopting more restrictive transfusion thresholds. PBM primarily identifies patients at risk of transfusion and provides a management plan aimed at reducing or eliminating the need for allogeneic transfusion, thus reducing the inherent risks, inventory pressures and the escalating costs associated with transfusion. PBM is applicable to surgical and medical patients. The application of PBM systematically reduces the impact of 3 major contributors to negative outcome: anemia, blood loss and transfusion.

P-31 Postoperative anaemia and exercise tolerance after cardiac operations in non-transfused patients: what haemoglobin level is acceptable?

P-31 Postoperative anaemia and exercise tolerance after cardiac operations in non-transfused patients: what haemoglobin level is acceptable?

Correction of anaemia on dialysis: did we forget physiology?

A frequent complication in patients with kidney diseases,chronic anaemia is commonly treated with erythropoietin-stimulating agents (ESA). At present, the optimal target forhaemoglobin (Hb) concentration is, however, unknown.The purpose of this communication is to plead for a lessaggressive correction of nephrogenic anaemia, fully justi-fied by the adaptive mechanisms that patients on dialysisare prompt to set off in order to increase their tolerance toanaemia. First, their delivery of oxygen from Hb is oppor-tunely facilitated. Second, beyond a certain threshold, ris-ing Hb concentration with ESA does not mean increasingtissue oxygenation. Although the physiological adaptationin patients with kidney failure has been known for decades,it has been constantly and startlingly ignored in the designof studies aiming at a full correction of anaemia and an‘irrational’ normalizationofHbwiththeuseofESA.Flawed in essence, these studies also demonstrate the dan-gerousness of a generic approach.Historically, the food and drug administration (FDA) ap-proved the prescription of recombinant erythropoietin(rhuEPO) in 1989 on the basis of a signal study published2 years earlier showing that rHuEPO could eliminate theneedfortransfusionsinpatientswithend-stagerenaldisease(ESRD), and thereby protect them from immunologicsensitization, infection and iron overload [1]. Twenty yearslater, on 16 February 2010, the same FDA announced thatESA should actually be prescribed under a‘risk manage-ment programme’, known as the Risk Evaluation and Miti-gation Strategy: data collected in longitudinal clinicalstudies had indeed repeatedly shown that in patients withrenal disease or with solid tumours, complete correction ofanaemiawith ESA had increased the risk of death, nonfatalmyocardial infarction [2–4], fatal or nonfatal stroke andblood clots [4]. In retrospect, thus, excessive normalizationofHblevelswithESAmayhaveimprovedthequalityoflifeofpatientswithESRD[5,6]butattheexpenseofadecreasein their ‘quantity’ of life [3]. The reasons to avoid bloodtransfusion still prevail, though, and a low Hb will increasethe risk for cardiovascular events in these patients [7], aswell. Since experimental findings have strongly suggestedthat the side effects of ESA are essentially related to a risein haematocrit and not to some off-target properties of thedrugs [8], it is now time to revise our target downwards [9].Themajorfunctionofthecentralcirculationistotransportoxygen from the lungs to the peripheral tissues at a rate thatsatisfies overall oxygen consumption. There is no storagesystem for oxygen (O

Anémie par carence martiale et grossesse. Prévention et traitement

To assess the effectiveness and the safety of prevention and treatment of iron deficiency anemia during pregnancy. French and English publications were searched using PubMed and Cochrane library. Early screening of iron deficiency by systematic examination and blood analysis seemed essential. Maternal and perinatal complications were correlated to the severity and to the mode of appearance of anemia. Systematic intakes of iron supplements seemed not to be recommended. In case of anemia during pregnancy, iron supplementation was not associated with a significant reduction in substantive maternal and neonatal outcomes. Oral iron supplementation increased blood parameters but exposed to digestive side effects. Women who received parenteral supplementation were more likely to have better hematological response but also severe potential side effects during pregnancy and in post-partum. The maternal tolerance of anemia motivated the choice between parenteral supplementation and blood transfusion. Large and methodologically strong trials are necessary to evaluate the effects of iron supplementation on maternal health and pregnancy outcomes.

A survey of blood transfusion practice in French‐speaking pediatric anesthesiologists

There are so far no existing consensus guidelines regarding red blood cell transfusion during pediatric surgery, and there is a little information regarding red blood cell transfusion policy among pediatric anesthesiologists. To determine the transfusion threshold and the volumes of packed red blood cell (PRBC) transfusion among French-speaking pediatric anesthesiologists. A questionnaire of case scenarios was sent to active members of the French Language Society of Pediatrics Anesthesiologists (ADARPEF). Of the 324 active members of the ADARPEF, 175 (54%) completed the questionnaire. The threshold for blood transfusion varied from 6 to 12 g·dl(-1) depending on the scenario. The hemoglobin threshold for blood transfusion and the volume of blood transfused vary among ADARPEF physicians, for the same class of patients. The median [95% CI] hemoglobin threshold for starting blood transfusion was 7.9 [6.9-8.9], 7.3 [6.4-8.2], and 8.1 [7.0-9.2] g·dl(-1) in the pre-, intra-, and postoperative phase, respectively. The median [95% CI] PRBC volume transfused was 11.7 [6.6-16.8] ml·kg(-1), and the median hemoglobin target was 11.3 [9.8-12.8] g·dl(-1). Physicians ranked age (79%), clinical tolerance of anemia (99%), underlying medical conditions (95%), hemodynamic instability (89%), hemostasis disorder (86%), and sepsis (79%) as the most significant factors affecting their transfusion decisions. Most pediatric anesthesiologists (89%) measure the hemoglobin level before PRBC transfusion. This survey identifies significant differences in transfusion practice patterns among pediatric anesthesiologists with a median transfusion threshold of 7.6 [6.6-8.6] g·dl(-1) and a median PRBC volume transfusion of 11.7 [16.8-6.6] ml·kg(-1).

Transfusion in the Critically Ill

Anemia and red blood cell (RBC) transfusions are common in critically ill and injured, trauma, and surgical patients. Tolerance of anemia is highly variable, depending on the presence of cardiovascular and other comorbid diseases that may diminish the hemodynamic response to a lower hemoglobin (Hb) level. The quest to define a minimum threshold Hb concentration at which patients achieve significant benefit to improve outcome has not yet been identified. Complications related to RBC transfusion are related to RBC storage and intrinsic properties of donor allogeneic RBCs, including bacterial contamination, transfusion-related acute lung injury, and transfusion-related immunomodulation. The best evidence related to transfusion-related outcome involves titrating transfusion requirements to parameters of severity of illness rather than arbitrarily defined Hb levels.

The Impact of Blood Conservation on Outcomes in Cardiac Surgery: Is It Safe and Effective?

Increasing evidence shows that perioperative blood transfusion in cardiac surgery is associated with increased postoperative morbidity and mortality and decreased long-term survival. Tolerance of "permissive anemia" is an important element of perioperative blood conservation strategy. The safety of tolerating perioperative anemia has been a significant deterrent for widespread application of blood conservation. This study examines whether blood conservation is equally safe or superior to the common practice of transfusion in cardiac surgery. The total study population consisted of 32,449 patients who underwent isolated coronary artery bypass surgery from June 2000 until December 2004 with complete data from 17 institutions in the State of New Jersey. Englewood Hospital and Medical Center (EH) has a well-established blood conservation program. Five hundred eighty-six EH patients (blood conservation cohort) were compared with a propensity score-matched cohort of 586 patients from the other New Jersey institutions (OH-M) representing the common practice of transfusion. Outcomes were classified as very serious complications, serious complications, or neither (no very serious complication or serious complication). Analysis consisted of McNemar tests and multiple logistic regression. Fewer patients were transfused at EH compared with OH-M (10.6% versus 42.5%; p < 0.0001). Englewood Hospital had 5 (0.8%) deaths versus 15 (2.5%) in the OH-M group (p = 0.02). Of the EH patients, 11.1% experienced a very serious complication or serious complication versus 18.7% in the OH-M cohort (p = 0.0002). Transfusion was associated with an increased risk of an adverse outcome in both cohorts (EH: odds ratio, 7.3; 95% confidence interval, 3.7 to 14.4 versus OH-M: odds ratio, 4.6; 95% confidence interval, 2.8 to 7.7). Blood conservation is safe and effective in reducing transfusions. Tolerance of perioperative anemia, which is one of the main components of blood conservation, does not increase the risk of complications or death in cardiac surgery. Avoidance of transfusion reduces the risk of complications. This study further solidifies the relationship between transfusion and adverse outcome in cardiac surgery.

Enquête transversale sur la transfusion dans les services de gériatrie

Purpose In the absence of specific recommendations on blood transfusion in elderly subjects, we carried out a survey to assess transfusion practices in geriatric medicine. Methods A descriptive, national, cross-sectional survey was conducted in 14 French geriatric departments (12 teaching hospitals and two general hospitals). In each department, five patients receiving transfusions were randomly selected in order to analyze their characteristics, the indications of blood transfusion, the criteria for and the methods of transfusion compared with Afssaps recommendations on transfusion thresholds. Results Data were analyzed for 70 patients (mean age 86 ± 7 years, sex ratio female to male 1.8, with an average of five ± two pathologies and six ± three treatments). The indicators of poor tolerance included confusion (23 %), somnolence (22 %), acute heart failure (17 %) or coronary heart disease (16 %), and differed from the Afssaps criteria in the majority of cases. The transfusion threshold that were considered in the absence of poor tolerance (45 % of transfusions) differed from that recommended by Afssaps in 26 % of cases. The main adverse event in transfusion recipients was heart failure. Conclusion When criteria for poor anaemia tolerance or transfusion thresholds are considered, transfusion practices in geriatric subjects have specific features. Further studies are needed to validate the appropriateness of the practices described in this survey.

Patient blood management - a new paradigm for transfusion medicine?

The saving of many lives in history has been duly credited to blood transfusions. What is frequently overlooked is the fact that, in light of a wealth of evidence as well as other management options, a therapy deemed suitable yesterday may no longer be the first choice today. Use of blood has not been based upon scientific evaluation of benefits, but mostly on anecdotal experience and a variety of factors are challenging current practice. Blood is a precious resource with an ever limiting supply due to the aging population. Costs have also continually increased due to advances (and complexities) in collection, testing, processing and administration of transfusion, which could make up 5% of the total health service budget. Risks of transfusions remain a major concern, with advances in blood screening and processing shifting the profile from infectious to non‐infectious risks. Most worrying though, is the accumulating literature demonstrating a strong (often dose‐dependent) association between transfusion and adverse outcomes. These include increased length of stay, postoperative infection, morbidity and mortality. To this end, a recent international consensus conference on transfusion outcomes (ICCTO) concluded that there was little evidence to corroborate that blood would improve patients’ outcomes in the vast majority of clinical scenarios in which transfusions are currently routinely considered; more appropriate clinical management options should be adopted and transfusion avoided wherever possible. On the other hand, there are patients for whom the perceived benefits of transfusion are likely to outweigh the potential risks. Consensus guidelines for blood component therapy have been developed to assist clinicians in identifying these patients and most of these guidelines have long advocated more conservative ‘triggers’ for transfusion. However, significant variation in practice and inappropriate transfusions are still prevalent. The ‘blood must always be good philosophy’ continues to permeate clinical practice. An alternative approach, however, is being adopted in an increasing number of centres. Experience in managing Jehovah’s Witness patients has shown that complex care without transfusion is possible and results are comparable with, if not better than those of transfused patients. These experiences and rising awareness of downsides of transfusion helped create what has become known as ‘patient blood management’. Principles of this approach include optimizing erythropoiesis, reducing surgical blood loss and harnessing the patient’s physiological tolerance of anaemia. Treatment is tailored to the individual patient, using a multidisciplinary team approach and employing a combination of modalities. Results have demonstrated reduction of transfusion, improved patient outcomes and patient satisfaction. Significant healthcare cost savings have also followed. Despite the success of patient blood management programmes and calls for practice change, the potential and actual harm to patients caused through inappropriate transfusion is still not sufficiently tangible for the public and many clinicians. This has to change. The medical, ethical, legal and economic evidence cannot be ignored. Patient blood management needs to be implemented as the standard of care for all patients.

Clinical evidence of blood transfusion effectiveness.

The transfusion of allogeneic red blood cell (RBC) concentrates is common practice in critical care medicine: up to 45% of critically ill patients are transfused during their stay in an intensive care unit (ICU)10,53. Generally, RBC transfusions are performed with the intention to increase arterial oxygen content and thus oxygen delivery to the tissues. To this end, RBC transfusions have undoubtedly been proven effective in many medical and surgical conditions, thereby particularly improving the survival of patients with critical impairment of tissue oxygenation, i.e. those with profound anaemia or circulatory shock. Nevertheless, systematic evidence about the clinical effectiveness of blood transfusions is still difficult to obtain. The most relevant clinical studies report inconsistent effects of blood transfusion on morbidity and mortality as primary outcome parameters. Patients requiring allogeneic blood are commonly reported to have worse outcomes than those who do not10,22,53. However, patients having required blood transfusions were usually more critically ill as documented by higher illness and organ failure scores at baseline. Irrespective of the final outcome, the efficacy of blood transfusions may be higher in patients who immediately need allogeneic blood transfusions, while the benefit of a RBC transfusion may be more difficult to assess in stable patients. Whether a RBC transfusion may be effective or not remains an individual decision based on a thorough analysis of the patient’s risk/benefit ratio and the identification of an appropriate transfusion trigger. The present article reviews: (i) physiological principles of oxygen transport, including compensatory mechanisms of acute anaemia and limits of anaemia tolerance, (ii) clinical evidence regarding the effects of RBC transfusion on mortality and morbidity, and (iii) the effects of such transfusions on oxygen transport and tissue oxygenation.

Transfusion practice in neuroanesthesia

Perioperative transfusion thresholds in the neurosurgical patient are undefined. Many neurosurgical procedures are associated with significant risk of bleeding. This review will summarize the current understanding of blood transfusion in the neurosurgical patient, as well as other blood component therapies and blood conservation strategies. Transfusion of red blood cells has been demonstrated to improve cerebral oxygen delivery. Clinical studies on transfusion-related morbidity and mortality in the neurosurgical patient are limited. Recent findings in both subarachnoid hemorrhage and traumatic brain injured patients have shown worse outcomes in patients with anemia (Hb <9.0 g/dl) yet transfusion of red blood cells may not be associated with improved outcome. Perioperative transfusion management for intracranial neurosurgical procedures presents the clinician with multiple challenges. Clinical evidence is sparse with view to an optimal hemoglobin level, yet anemia is known to be a predictor of poor outcome in many neurosurgical patients. Transfusion thresholds from other patient populations may not apply to this group and further prospective investigations are desperately needed. Until then, clinicians should focus on an individualized assessment of anemia tolerance, consider blood conservation strategies and understand the potential risks and benefits of blood transfusion.

Artificial oxygen carriers as a possible alternative to red cells in clinical practice.

Fluid resuscitation is intended to eliminate microcirculatory disorders and restore adequate tissue oxygenation. The safety limits for a restrictive transfusion policy are given by patients' individual tolerance of acute normovolemic anemia. Artificial oxygen carriers based on perfluorocarbon or hemoglobin are attractive alternatives to allogenic red blood cells. There are many risks involved in allogenic blood transfusions and they include transmission of infections, delayed postoperative wound healing, transfusion reactions, immunomodulation and cancer recurrence. Regardless of whether artificial oxygen carriers are available for routine clinical use, further studies are needed in order to show the safety and efficacy of these substances for clinical practice.

The influence of baseline hemoglobin concentration on tolerance of anemia in cardiac surgery

The influence of baseline hemoglobin concentration on tolerance of anemia in cardiac surgery

Transfusion chez les patients âgés

The frequency of anemia is responsible of a frequent use of transfusion in elderly patients. However, transfusion in elderly patients requires several warnings. First, semiology of elderly patients is characterized with atypical clinical signs, and anemia tolerance is often difficult to appreciate. Second, numerous comorbidities make of elderly patients an heterogeneous population, in which guidelines are poorly applicable. Last, elderly patients are particularly sensitive to iatrogenic events, and the haemodynamic overload related to transfusion has to be carefully managed. All these difficulties raise the need of prospective studies on transfusion in elderly patients to validate clinical practice.

The influence of baseline hemoglobin concentration on tolerance of anemia in cardiac surgery

Current red blood cell (RBC) transfusion guidelines assume that most acutely anemic patients can tolerate hemoglobin (Hb) concentrations as low as 6.0 to 7.0 g per dL and recommend that range as the transfusion threshold in patients who have no overt signs of organ dysfunction. Nonetheless, "normal" Hb concentrations vary widely in the population, and this variability may influence patients' tolerance of acute anemia. This retrospective cohort study was carried out to test this hypothesis. Data were analyzed on 10,179 consecutive patients who had normal Hb concentrations (12.0-16.0 g/dL in women and 13.0-18.0 g/dL in men) and underwent on-pump cardiac surgery from 1999 to 2006 at an academic hospital. The relationships of lowest intraoperative Hb concentration and maximum decrease in Hb concentration (from baseline) with the composite outcome of in-hospital death, stroke, or kidney failure were determined in various patient subgroups. The relationship between lowest Hb concentration and adverse outcomes was not independently associated with increased risk. In contrast, the relationship between maximum decrease in Hb concentration and adverse outcomes was independently associated with increased risk, with a 50 percent decrease being the threshold beyond which risk was increased (adjusted odds ratio, 1.53; 95% confidence interval, 1.12-2.08; p = 0.007). The degree of acute anemia that patients can safely tolerate during cardiac surgery is inversely related to their baseline Hb concentration. Current transfusion guidelines do not account for this relationship.

Die Behandlung auf der Intensivstation

Patients admitted to an intensive care unit with the diagnosis "polytrauma" differ from other patients by their typical trauma-associated morbidity (diffusive bleeding, traumatic brain injury, lung contusion), and by the staged surgical treatment of multiple injuries. The complexity of the clinical picture, and the complexity of the chronological order of the operative phases require a close cooperation of the medical specialist disciplines involved. The perioperative morbidity and mortality of polytrauma victims has been reduced significantly within the last 30 years due to an adapted transfusion- and substitution regime (rational utilization of anemia tolerance, calculated substitution of coagulation factors), due to modern therapeutic regimes for the patient with traumatic brain injury (stabilization of cerebral perfusion pressure, stabilization of adequate cerebral oxygenation), and due to the modern therapeutic strategies of mechanical ventilation (lung-protective ventilation, kinetic therapy, non-invasive ventilation). The aim of this review is to describe these modern therapeutic principles of the intensive care unit treatment of the polytrauma patient.

Erythropoietic therapy: Cost efficiency and reimbursement

The practice of blood conservation is aimed at improving patient outcomes by avoiding allogeneic transfusions via a coordinated multidisciplinary, multipronged approach. The numerous blood conservation techniques and transfusion alternatives now available are described. Ongoing concerns exist regarding the availability of the nation's and the world's blood supply. In addition, the number of measures required to ensure blood safety has led to increases in the price of blood and blood products over the past 10-15 years. Moreover, blood transfusion carries inherent risks even under the most favorable circumstances. Investigations have established that injudicious transfusion is associated with development of ventilator-associated pneumonia, nosocomial infection, and organ dysfunction. Because most single blood-conservation techniques reduce blood usage by a mere 1-2 units, a series of integrated conservation approaches are required. These include preoperative autologous donation, use of erythropoietic agents, blood conservation techniques such as acute normovolemic hemodilution, individualized assessment of anemia tolerance, implementation of conservative transfusion thresholds, meticulous surgical techniques, and judicious use of phlebotomy and pharmacologic agents for limiting blood loss. Erythropoietic agents such as epoetin alfa have been used successfully to increase hemoglobin and decrease transfusion requirements, and are appropriate when used in advance of elective surgical procedures. Acquisition costs of erythropoietic stimulating agents versus costs of blood justify economic evaluation by hospitals to make the most cost-effective choice under current economic constraints. Initiating a blood management program requires planning and support from those who are concerned about blood usage reduction and outcomes improvement. Launching a vigorous and ongoing educational program to raise awareness about the risks and hazards associated with blood transfusion is an important step in helping to reshape the medical staffs' attitudes about transfusion and the most cost-effective way to achieve clinical goals.

L'anémie du sujet âgé : une étiologie peut en cacher une autre !

Anemia is common in patients older than 75 years. Patho-physiologic mechanisms of anaemia are similar to that involved in younger patients even though certain mechanisms are more common in the elderly. Practical decisional algorithms have to be used for the diagnosis of anaemia. Risk factors for anaemia have been identified in this group of age: institutionalization, bad socio-economic conditions, co-morbid conditions. Particular emphasis is given to several points: 1) the clinical tolerance of anaemia is the most important feature to take into account in older patients, rather than the decline of the haemoglobin level. Even if the haemoglobin level is only slightly decreased, an evaluation of anemia should be performed by the geriatrician, including, if needed, the achievement of a bone-marrow aspiration; 2) causes of anaemia are often multiple, due to frequent co-morbid conditions and acute illnesses, associated with nutritional deficiencies, inflammation… Chronic kidney disease and dysthyroïdia are also common; 3) nutritional deficiencies (iron, folate and/or B12 deficiency) are frequent and their cause has to be identified; 4) the prevalence of myelodysplastic syndromes, which are clonal diseases, is probably underestimated in this group of age.

Impact of Preoperative Anemia on Outcome in Patients Undergoing Coronary Artery Bypass Graft Surgery

The risk of preoperative anemia in patients undergoing heart surgery has not been described precisely. Specifically, the impact of low hemoglobin per se or combined with other risk factors on postoperative outcome is unknown. Thus, we determined the effects of low preoperative hemoglobin and comorbidities on postoperative adverse outcomes in patients with coronary artery bypass graft in a large comprehensive multicenter study. The Multicenter Study of Perioperative Ischemia investigated 5065 patients with coronary artery bypass graft at 70 institutions worldwide, collecting approximately 7500 data points per patient. In 4804 patients who received no preoperative transfusions, we determined the association between lowest preoperative hemoglobin levels and in-hospital cardiac and noncardiac morbidity and mortality and the impact of concomitant risk factors, assessed by EuroSCORE, on this effect. In patients with EuroSCORE < 4 (n=2054), only noncardiac outcomes were increased, whereas patients with EuroSCORE > or = 4 (n=2750) showed an increased incidence of all postoperative events, starting at hemoglobin < 11 g/dL. Low preoperative hemoglobin was an independent predictor for noncardiac (renal > cerebral; P<0.001) outcomes, whereas the increase in cardiac events was due to other factors associated with preoperative anemia. Anemic patients undergoing cardiac surgery have an increased risk of postoperative adverse events. Importantly, the extent of preexisting comorbidities substantially affects perioperative anemia tolerance. Therefore, preoperative risk assessment and subsequent therapeutic strategies, such as blood transfusion, should take into account both the individual level of preoperative hemoglobin and the extent of concomitant risk factors.