Risks associated with blood transfusion, of an infectious nature but also immunological, continue to question our transfusion practice. Substantial variation in transfusion practice still persists, despite opinions generated at different national consensus conferences and the publication of numerous guidelines. As demonstrated recently, the institution itself remains a significant independent predictor of transfusion risk both for allogenic red blood cell units and haemostatic components in cardiac [1,2] but also in orthopaedic and colonic surgery . The adequacy of any haemoglobin concentration in a given clinical situation depends on whether a sufficient amount of oxygen is carried to the tissues to meet their metabolic requirements. The use of the haemoglobin concentration as the only transfusion ‘trigger’ will inevitably result in the over-transfusion of some patients, but also in the under-transfusion of others . Laboratory or clerical errors, the degree of haemodilution and the presence of occult blood losses are different factors, which make the haemoglobin-based transfusion trigger inaccurate.
Allogenic blood transfusion: risks and benefits
Except for emergent cases, the decision to transfuse blood products requires taking into account the risks associated with blood transfusion and those associated with acute anaemia. On one hand, it is well known that anaemia increases the risk of postoperative cardiac complications in cardiovascular patients. On the other hand, blood transfusion carries not only delayed complications due to transmission of viruses but also immediate complications related to infections and immune reactions, which affect postoperative morbidity. The incidence of such immediate complications is better evaluated by blood safety committees. Blood transfusion is a medical treatment. It therefore requires careful assessment of its efficacy. Several studies have compared the efficacy of different transfusion strategies based on the haemoglobin concentration. Most studies have not demonstrated any reduction in postoperative morbidity and mortality with strategies aiming at the maintenance of a higher haemoglobin concentration after surgery. However, these studies did not adequately address the question. First, because they used the haemoglobin concentration as the transfusion trigger. Second, because they did not have the statistical power to demonstrate the efficacy of any transfusion strategy in very anaemic patients (patients with a haemoglobin concentration < 7 g dL−1). One prospective randomized study  compared two transfusion regimens (restrictive: haemoglobin concentration of 7–9 g dL−1 vs. liberal: haemoglobin concentration of 10–12 g dL−1) in 838 intensive care unit (ICU) patients. Thirty-day mortality was similar in both groups but immediate postoperative morbidity appeared to be somewhat higher in the liberal transfusion group. A recent pilot study compared two different transfusion strategies in patients undergoing orthopaedic surgery . In one group, patients were transfused on clinical symptoms (up to a minimal haemoglobin concentration of 8 g dL−1) and in the other, patients were transfused when the haemoglobin concentration was below 10 g dL−1. From this pilot study, the authors determined that in order to demonstrate a significant difference in postoperative morbidity and mortality between these two transfusion strategies a cohort of 12.000 patients would be required.
Another important observation is related to the limited capacity of allogenic red blood cells that are older than several days to restore compromised oxygen consumption . This phenomenon might be related to the decreased deformability of aged red blood cells and to the decreased intracellular 2,3-diphosphoglycerate concentration, resulting in an increased affinity of haemoglobin to oxygen.
Knowledge of the physiological adjustments occurring during anaemia and the clinical factors which can limit the ability of the patient to maintain adequate tissue oxygen delivery will allow the clinician to better define the transfusion trigger for each patient.
Acceptable limits of acute anaemia
Physiological adjustments to acute reduction in haemoglobin concentration
Maintenance of tissue oxygen delivery during acute ‘normovolaemic’ anaemia depends on both an increase in cardiac output and an increase in oxygen extraction ratio (Table 1). The relative contribution of these mechanisms will depend on the ability of the organism to trigger each of them . Several experimental and clinical studies have demonstrated the involvement of both mechanisms even in the early stages of normovolaemic anaemia. These mechanisms allow systemic oxygen consumption to remain constant until the haematocrit falls to about 10% at which point tissue hypoxia develops. Experimental studies in different animal species have demonstrated this ‘critical’ haemoglobin concentration to be around 4 g dL−1. Corresponding values are difficult to obtain in man. A recent study demonstrated that acute normovolaemic haemodilution to an haemoglobin concentration of 5.0 g dL−1 is well tolerated in healthy volunteers . In a Jehovah’s witness patient who died from extreme haemodilution a ‘critical’ haemoglobin concentration of 4.0 g dL−1 was observed .
Tolerance to acute anaemia not only depends on the integrity of the compensatory mechanisms described above, but also on the level of tissue oxygen demand. For a given cardiac output and oxygen extraction ratio, any decrease in tissue oxygen demand will result in an increased tolerance to acute anaemia and vice versa.
Clinical limits of acute anaemia
Any factor altering either the cardiac output response and/or the oxygen extraction ratio will reduce patient’s tolerance to acute anaemia (Table 2). The efficacy of the mechanisms preserving tissue oxygen delivery when the oxygen carrying capacity of the blood is reduced depends primarily on the maintenance of an adequate blood volume. Hypovolaemia blunts the effects of decreased blood viscosity on venous return and therefore the increase in cardiac output. Although ‘normovolaemic’ conditions are difficult to define the replacement of blood and fluid losses by at least a quantity of substitute having the same expanding effect on the intravascular volume is required.
Any increase in tissue oxygen demand will also decrease patients’ tolerances to acute anaemia. This is of particular importance during the recovery phase of anaesthesia, where oxygen consumption can be multiplied by a factor of two. In critical illness, most of the compensatory mechanisms for anaemia are reduced by the presence of hypovolaemia, hypoxaemia, depressed myocardial function and/or altered oxygen extraction capabilities. In addition, tissue oxygen demand is often increased in these situations as a result of fever, pain, stress and increased respiratory work.
All these concepts apply not only at the global, but also at the organ level. The heart is probably the organ for which the response to acute anaemia is best characterized. As myocardial oxygen extraction is already nearly maximal in resting conditions, the maintenance of myocardial oxygen consumption depends essentially on the increase of coronary blood flow. This explains why, during acute normovolaemic anaemia, coronary blood flow increases proportionally more than global cardiac output. However, the coronary reserve (the ratio between maximal coronary blood flow and resting coronary blood flow) is significantly reduced in these conditions. Tolerance of the heart to anaemia is especially reduced when myocardial work is increased and/or when maximal coronary blood flow is decreased (in the presence of coronary artery disease) . This could explain the high incidence of ischaemic episodes in the early postoperative period in anaemic patients with coronary artery disease .
The transfusion trigger
The adequacy of any haemoglobin concentration in a given clinical situation depends on whether a sufficient amount of oxygen is carried to the tissues to meet their metabolic requirements. Clinical signs of intolerance to anaemia, such as tachycardia, postural hypotension dizziness, etc., have unfortunately a very high sensitivity but a low specificity. The same is true for ST segment changes in the electrocardiogram. Moreover, all these signs are usually absent in sedated or anaesthetized patients. Several authors have proposed to use variables such as the mixed venous oxygen saturation and oxygen extraction ratio (OER) as transfusion triggers when assessing the systemic oxygen balance. Measurement of this last variable indeed allowed direct evaluation of one of the two compensatory mechanisms developed by the organism during acute anaemia. Some clinical observations tended to indicate that these variables could be reliable physiological guides to transfusion [13,14]. However, to be measured, these variables require invasive monitoring. Moreover they evaluate tissue oxygenation only at a global level. New non-invasive tools such as gastric tonometry or near infra-red spectroscopy are under evaluation.
There is certainly not a single transfusion trigger that can be applied to any patient in any situation. The decision to transfuse a patient depends primarily on clinical judgement taking into account the ability of the patient to increase cardiac output and oxygen extraction, the degree of tissue oxygen demand and the potential risk for complications. The haemoglobin concentration represents only one of the variables that has to be taken into account. With the exception of emergency situations, blood transfusion will be realized on a-unit-by-unit basis, with clinical evaluation after each transfused unit. In most of the circumstances, autologous transfusion will follow the same criteria.
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