Guidelines for red blood cell and plasma transfusion for adults and children
Addendum: Alternatives to allogeneic transfusions in surgical settings
Although not part of the EWG's mandate, this topic warrants a brief review. Several strategies are employed or advocated to reduce the requirement for allogeneic blood transfusion. Most of these focus on the perioperative period, and supplement surgical hemostatic techniques promoted to minimize shed blood. They can be broadly divided into 3 categories:
- creation of sources of autologous blood to be administered in the perioperative period;
- substitution of allogeneic blood with nonblood alternatives (crystalloids, colloids, oxygen-carrying solutions);
- use of pharmacologic agents to reduce blood loss.
The value of these strategies is limited by the paucity of sufficiently large randomized, controlled trials. Furthermore, most studies of pharmacologic agents focus on cardiac surgery and have limited applicability to general surgery.
Strategies to create sources of autologous blood include autologous predeposit, which has been reviewed elsewhere in this document, normovolemic hemodilution and perioperative cell salvage. Normovolemic hemodilution (NVH) has been advocated for decades.166 The principle is simple: blood is drawn from the patient and replaced with colloid and crystalloid combinations to maintain intravascular volume. When indicated, the collected blood is transfused back to the patient. Diluting the circulating volume reduces the number of red blood cells lost per unit volume of blood shed166 thereby reducing the need for allogeneic blood.
There is little evidence that the strategy is effective in many current applications.167 Goodnough and colleagues168 used NVH in patients undergoing radical prostate surgery. One litre of blood was withdrawn before the start of surgery. The net benefit was estimated to be 95 mL (range 25204 mL) of red blood cell volume saved, that is, less than 10% of the volume lost perioperatively. Mathematical modeling of NVH suggests that the allogeneic blood-sparing benefit is more likely to be clinically relevant when more than 1 L of blood is withdrawn before surgical blood loss occurs.167 Modeling consistently finds a ratio of 45 units withdrawn for each unit of allogeneic blood saved.167,169,170 Although greater degrees of hemodilution are more sparing, the volume of blood that must be removed to achieve the necessary hemodilution is rarely achieved.168 Furthermore, the surgical subpopulations that would tolerate such aggressive hemodilution have not been well defined.45
Perioperative salvage and retransfusion of washed or unwashed shed blood is being increasingly promoted to reduce allogeneic blood requirements. The underlying principle is simple: shed blood is collected and returned to the patient, either washed or unwashed. The equipment and process are expensive and are warranted primarily when major hemorrhage is expected. With smaller shed volumes, the acquisition cost per unit is high, and there is generally no indication to return the small volumes collected to the patient. Existing programs are being reviewed and restructured to accommodate these facts.
Perioperative administration of a number of medications has been advocated to reduce allogeneic blood needs. A large proportion of the published trials are small; however, meta-analysis of these studies has allowed some conclusions to be drawn.171
Aprotinin attenuates fibrinolysis, thereby diminishing clot degradation, and helps preserve platelet function after CPB. It has been used predominantly in patients undergoing cardiac surgery with CPB and been found to decrease intraoperative and postoperative blood loss and reduce the number of transfusion events, volumes transfused and use of other blood components. Because of its prothrombotic activities, concern has been expressed about the potential for increased coronary artery graft occlusion and perioperative myocardial infarction in treated patients. No convincing evidence has been presented to justify these concerns or to allay them.
Tranexamic acid and epsilon-aminocaproic acid inhibit fibrinolysis. Again, their use has been predominantly assessed in cardiac surgery populations. Both effectively decrease blood loss and volumes of blood transfused.171
Desmopressin (DDAVP) stimulates the release of von Willebrand factor and factor VIII:C from vascular endothelium, enhancing plateletsubendothelial interaction. However, meta-analysis of available evidence has failed to demonstrate a benefit with respect to reducing surgical blood losses.171
Recombinant human erythropoietin has recently been approved for perioperative use. It enhances erythropoiesis in both anemic and nonanemic patients, facilitates autologous predeposit and increases and maintains [Hb] perioperatively. However, allogeneic blood exposure is reduced only in selected patients.172174 Hypertension and thrombotic events have been reported during perioperative erthropoietin therapy. Thrombotic events occur overall at rates similar to those in patients not treated with erythropoietin.175
The use of nonblood alternatives to replace shed blood is a useful, although limited, strategy. With the acceptance of low and sometimes, very low hematocrits, it has become accepted clinical practice to replace very large volumes of shed blood with crystalloid and colloid solutions. The risk of avoidance of blood transfusion in these situations is not known and may, in some instances, be higher than the risk of transfusion. Research into oxygen-carrying solutions containing either fluorocarbons or hemoglobin compounds continues. As yet, no oxygen carriers with proven utility and safety comparable to those of blood are commercially available.176
Many alternative strategies may reduce allogeneic blood requirements. Two elements are common to all. First, the additional costs are not well defined, but are partly offset by the reduced need for allogeneic blood; typically, the party carrying the cost of the new strategies is not the same as the one benefitting from the reduction in allogeneic blood costs. Second, the risks of implementing alternative strategies measured against the benefits of avoiding allogeneic transfusion have not been adequately assessed. For example, with respect to the drug therapy, 1 drug-related death in 200 000500 000 would be sufficient to negate the risk reduction achieved with their allogeneic blood-sparing action (Andreas Laupacis, MD: unpublished data). The value of autologous predonation in reducing allogeneic exposure for patients undergoing coronary artery bypass grafting is negated if 1 patient in 101 000 has a stroke, infarction or dies as a result of the donation process.177 Reactions to autologous donations occur in about 4% of patients who would not normally meet donation criteria for medical reasons, and in about 1% of these patients the reactions are severe.178,179 In one study,67 about 1 in 17 000 autologous blood donors developed a sufficiently severe reaction to require hospitalization.
Clearly, when recommending alternatives to allogeneic transfusion to patients, physicians must consider the overall risk of the alternative. In many instances, it is not evident that alternative strategies pose fewer potential risks to the patient than allogeneic transfusion.
