Strategies utilized in PBM generally revolve around the 3 pillars discussed previously (Figure 1). The rapidly evolving nature of medicine and development of various medications and devices mean that any review of PBM strategies is bound to be outdated soon. However, certain general strategies and approaches of PBM can be considered universal and unlikely to undergo any major changes.17 Examples of the suggested perioperative PBM strategies are depicted in Figure 2. It should be emphasized that many of these strategies are not limited to surgical cases and can be used in all patients who are at risk of being transfused.
Indication of Transfusion
Judicious use of allogeneic blood products, in accordance with current guidelines, has been included as part of early definitions of PBM. Unlike most modern medical treatments, the safety and efficacy of allogeneic blood transfusions have never been established through randomized controlled trials; and hence, formulation of evidence-based indications for blood transfusion has remained a challenge.19 Transfusion guidelines for various patient populations are available, and they all emphasize that blood products should be transfused when clear physiologic need exists, rather than blindly based on arbitrary hemoglobin or hematocrit triggers. The goal should be treating the patient, rather than attaining a certain hemoglobin level.17,20–23 Nonetheless, it can be concluded from the current guidelines that blood transfusions are generally not indicated in management of patients with hemoglobin levels >10 g/dL, and they are often needed in patients with hemoglobin levels <6 g/dL, and although not substantiated, possibly <8 g/dL in patients with ischemic heart disease. In light of available evidence, a consensus multidisciplinary panel has concluded that allogeneic red blood cell transfusions are unlikely (or uncertain) to improve patients' outcomes in the vast majority of clinical scenarios in which transfusions are commonly used, when patients' hemoglobin level is ≥8 g/dL.24
Whenever possible, physiologic indicators of tissue oxygen delivery and ischemia should be used in guiding transfusion decisions.17,25 This is a field of ongoing research, and new devices for (preferably noninvasive) continuous monitoring of hemoglobin levels, oxygen delivery, oxygen consumption, and ischemia are being developed for routine clinical use. Similarly, guidelines for transfusion of other blood products are available and should be considered in making objective transfusion decisions.
Whenever possible, physiologic indicators of tissue oxygen delivery and ischemia should be used in guiding transfusion decisions.
Surgical planning and rehearsal in complicated procedures can be effective in improving the pace and efficiency of the procedure, minimizing length of surgery and blood loss. Patient blood management strategies during surgery generally focus on minimizing blood loss, collecting and reinfusing shed blood, and improving tolerance of anemia. Vital signs should be closely monitored, and unnecessary hypovolemia and tachycardia should be avoided.17,26
Various options are available to limit the blood flow to the site of surgery, thereby limiting the blood loss. Examples include patient positioning to elevate the site of blood loss, use of tourniquet, and infusion of local vasoconstrictive agents. Hypotensive anesthesia is the other approach to limit blood loss, although hypotension must be closely monitored and controlled to ensure adequate perfusion of vital organs.44 Other approaches revolve around improving hemostasis at the site of bleeding. Electrocautery and argon-beam coagulation provide cleaner cuts and more effective hemostasis at the site of incisions.26,31 Topical hemostatic agents contain active ingredients such as thrombin, fibrinogen, collagen, gelatin, and cellulose and act by promoting coagulation at the site of application and/or physical blockade and tamponade of bleeding vessels.45 Alternatively, systemic agents to promote hemostasis are available. Lysine analogues (tranexamic acid and epsilon aminocaproic acid) are the most commonly used antifibrinolytic agents, which act by inhibiting plasmin and preserving blood clots formed at sites of bleeding. Several studies and meta-analyses have indicated that these agents are safe and effective in reducing bleeding, transfusions, and mortality in various patient populations.46–48 Systemic infusion of certain coagulation factors (eg, activated factor VII, prothrombin complex, factor XIII, and fibrinogen) has also been investigated as means to reduce blood loss (occasionally used in conjunction with point-of-care coagulation tests), and the verdict on the safety and efficacy of these agents for this indication is still unclear.46 Particularly, recent meta-analyses of clinical trials have questioned the efficacy of off-label recombinant activated factor VII in reducing bleeding49 and concluded that the off-label use at high doses increases the risk of thromboembolic events.50 Another systemic approach to minimize blood loss is avoiding hypothermia (if not otherwise indicated), as hypothermia can adversely affect platelet function and result in increased blood loss.17 Even mild perioperative hypothermia has been reported to be associated with increased blood loss and risk of transfusion.51
Certain perfusion strategies are available to reduce surgical blood loss. One option is to collect (or salvage) the blood lost during the surgery, wash and/or filter it, and reinfuse it into the patient when transfusion is needed. This technique is known as autologous blood cell salvage and it has been shown to be effective in reducing allogeneic transfusion.52,53 The technique is generally safe, although concerns have been raised regarding the possibility of reintroducing unwanted cells or materials (eg, tumor cells, fat droplets, amniotic fluid, bacteria, or pharmaceutical agents present in the surgical field) into the blood circulation during the procedure.54,55 However, published case reports and studies have not indicated a significant risk with the use of currently available cell salvage systems.41,56–60 Notably, several studies have indicated that leukocyte depletion filters are able to substantially reduce and remove unwanted cells and particulate materials from the salvaged blood.61,62 Overall, intraoperative cell salvage remains a safe and effective technique in reducing allogeneic transfusions and improving patient outcomes.17,53
On the other hand, acute normovolemic hemodilution relies on removing a part of the blood volume from the circulation and replacing it with other fluids (crystalloids or colloids) before bleeding takes place. Therefore, the blood lost during the surgery is diluted, and the total amount of blood loss from the surgical wound is reduced. The collected blood is kept in the operating room and is reinfused back to the patient at wound closure or whenever transfusion is needed. Despite a reasonable theoretical basis, the safety and efficacy of acute normovolemic hemodilution in clinical practice is still debated. Although some studies show its efficacy in reducing allogeneic blood transfusions and complications,63,64 other studies fail to demonstrate significant benefits.65,66 Acute normovolemic hemodilution is more likely to be beneficial in patients undergoing high-blood-loss procedures, in whom most of the collected blood is expected to be reinfused and waste will be minimal.8,63,67,68 Depending on the specific type of procedure performed, other PBM strategies such as the use of smaller prime volume and smaller circuits in patients undergoing cardiopulmonary bypass can be considered.31
Patient blood management strategies continue after the surgery into the postoperative care unit and beyond. Red-cell salvage can be performed postoperatively and any blood lost in the drains can be washed, filtered, and reinfused if needed. During the first few hours following the surgery, close attention must be given to continued blood loss. If the bleeding persists, the patient should be returned to the operating room for re-exploration without further delay. Vital signs should be closely monitored, and hypothermia (unless otherwise indicated) should be avoided, as previously explained. Cardiac output and ventilation/oxygenation should be optimized. Close attention should be paid to medications and drug interactions that could result in or exacerbate anemia. Prophylaxis of upper gastrointestinal bleeding is recommended in specific cases. Any blood draws for laboratory investigations should be limited to the lowest blood volume needed to successfully carry out the required tests. Additionally, standing laboratory orders (eg, daily complete blood counts for all postsurgical patients) should be avoided, and laboratory tests should only be ordered when a clear indication exists and the result is likely to change the management of the case.26,31
If anemia is present, treatment with hematinics should be considered and additional diagnostic work-up should be performed if other possible causes are suspected. Anemia in the postoperative period is usually due to surgical blood loss (iron-restricted hematopoiesis) and can take weeks to correct if left untreated. Treatment with iron in this period can be highly effective and hasten recovery.69 However, some levels of functional iron deficiency due to the inflammatory inhibition of hematopoiesis may also be present and treatment with ESAs may also be needed, although limited evidence is available in surgical patients.70 Throughout the care, particularly in the postoperative recovery period, allogeneic blood products should only be transfused when clear indication exists and according to the current transfusion guidelines. Transfusions for vague reasons (eg, to speed up recovery or because of fatigue) should be avoided as the associated risks are likely to outweigh any potential benefits.17