Healio
Healio
June 01, 2004
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Intraoperative Blood Management in Joint Replacement Surgery

ABSTRACT

Interest is growing in blood conservation and avoidance of transfusion in patients undergoing orthopedic surgery, especially in the field of joint replacement. Several methods have proven successful in reducing intraoperative blood loss, which can translate into lessened allogeneic and autologous transfusion requirements. Available techniques include acute normovolemic hemodilution, hypotensive anesthesia, intraoperative blood salvage, specialized cautery, topical hemostatic agents, and pharmacologic agents given in the perioperative period. The greatest potential benefit arises in operations with greater expected blood loss or in special situations such as in patients with religious issues, bilateral joint replacement, coagulation disorders, or significant preoperative anemia.




Issues related to cost and safety of allogeneic blood transfusion have led to an increased interest in perioperative blood management practices in orthopedic surgery, especially in the field of joint replacement. In the past 15-20 years, the risks of allogeneic blood transfusion have become well known to surgeons and patients. This has led to scrutiny of the indications and safety of its practice and reconsideration of techniques designed to minimize transfusion requirements. Potential morbidities of allogeneic transfusions include febrile, allergic, and hemolytic transfusion reactions; immunomodulation; disease transmission; and possible increased risk of postoperative bacterial infection. The risk of hepatitis C transmission has been estimated to be approximately 1:500.1

These concerns prompted increased participation in preoperative autologous donation. The practice of preoperative autologous donation lowers preoperative hemoglobin and hematocrit levels, which are the most important factors in determining who receives an allogeneic transfusion.2-4 The benefits of autologous transfusion have been called into question at our institution. Thirty percent of our patients presenting for total knee arthroplasty (TKA) were in the high-risk group for requiring transfusion (hemoglobin 10 g/dL to 13 g/dL), and this was increased to 62% after preoperative autologous donation.

The effectiveness of preoperative autologous donation in several types of surgery was recently reviewed and was found to be of uncertain benefit in most patients.5 In the orthopedic trials meeting proper criteria, preoperative autologous donation reduced a patient’s relative risk of receiving an allogeneic blood transfusion by 84%. However, the results showed that overall transfusion rates (allogeneic or autologous) in these trials were high and were increased by recruitment into the preoperative autologous donation arms of the trials (relative risk increase of 29%). Furthermore, this review showed that, on average, the hemoglobin level in patients who participated in preoperative autologous donation was 1.23 g/dL lower at the time of surgery, suggesting lack of compensatory erythropoiesis preoperatively. Finally, adherence to any form of trigger-oriented transfusion protocol postoperatively in those studies led to a 49% relative risk increase in exposure to allogeneic blood. Transfusion of autologous blood is not without risk, including transfusion reactions, circulatory overload, bacterial contamination, and clerical errors. Overcollection and waste of unused donated units are prevalent. In addition, blood donation has risks related to anemia and ischemic events.

The use of erythropoietin (epoetin alfa) to stimulate erythropoiesis in the preoperative period has also been studied extensively and has been shown to safely reduce the need for perioperative allogeneic transfusions.1,6 Epoetin alfa works like endogenous erythropoietin to stimulate synthesis of hemoglobin and thus has value in the perioperative period to combat anemia. Subcutaneous delivery resulting in sustained plasma levels allows for weekly delivery in combination with oral iron, usually in the 3 to 5 weeks directly before surgery. The use of erythropoietin requires time and expense and can be inconvenient for the patient. Despite the limitations, erythropoietin use at our institution has been helpful in surgical patients who are anemic at the time of presentation.

Intraoperative Blood Management

The aforementioned techniques are attempts made in the preoperative period to reduce the need for allogeneic transfusion, by maximizing the ability to tolerate intraoperative blood loss. To avoid transfusion by directly addressing the amount of intraoperative blood loss, surgeons have investigated improvements in surgical technique, hypotensive anesthesia, blood salvage, hemodilution, specialized cautery units, use of topical hemostatic agents such as fibrin sprays, collagen, and thrombin, or antifibrinolytics like tranexamic acid and aprotinin.7

Acute normovolemic hemodilution

Acute normovolemic hemodilution involves simultaneous removal of whole blood from a patient immediately before surgery and replacement with acellular fluids (crystalloid or colloid) to maintain normovolemia.8 This technique is recommended when the potential for blood loss may exceed 20% in patients with a hemoglobin above 10 g/dL. It avoids the cost and preoperative time commitment of preoperative autologous donation, as well as the possibility of clerical error or bacterial contamination. However, acute normovolemic hemodilution is contraindicated in patients with coronary, renal, pulmonary, or significant liver disease, and is impractical in most total joint procedures of relatively short duration and lesser blood loss.1

Combined data from 16 randomized, controlled trials of 615 patients demonstrated that acute normovolemic hemo-dilution significantly reduced the likelihood of allogeneic transfusion in patients undergoing surgery by 31%. The likelihood of allogeneic transfusion in patients undergoing surgery was reduced in cardiac and miscellaneous procedures, but not in orthopedic surgery. Patients were required to have at least 1000 mL withdrawn, and there had to be no transfusion protocols in place.9 To the contrary, Shulman et al10 found that acute normovolemic hemodilution reduced allogeneic transfusion units from 2.4 to 0.6 (75%) in primary and revision hip replacements. Others have found acute normovolemic hemodilution to be as effective as preoperative autologous donation in both total hip11,12 and total knee replacements.13 Acute normovolemic hemodilution may not be necessary when blood loss is expected to be less than 1000 mL.12

Intraoperative blood salvage

Blood salvage returns to a patient auto-logous blood lost during surgery in various states of washing and processing, and can be performed intraoperatively or postoperatively. Blood can be salvaged with systems that either collect and reinfuse whole blood, or collect, wash, and reinfuse packed red blood cells. The latter technique includes systems such as Cell Saver (Haemonetics, Braintree, Mass) and OrthoPAT (Zimmer, Warsaw, Ind), which are useful in orthopedics because they remove cellular debris, fat, bone fragments, and methylmethacrolate monomer. OrthoPAT does not require an operator, weighs little, and can be mounted on a standard intravenous pole. Its portability makes it possible to use for both intra- and postoperative autotransfusion in a patient.

Gargaro and Walls14 found that intraoperative autotransfusion with Cell Saver was not necessary in routine primary total hip arthroplasty (THA). Perioperative transfusion units, perioperative blood loss, and hemoglobin concentrations did not differ from controls. However, others have shown that intraoperative use of Cell Saver reduced amounts of transfused banked blood and maintained higher postoperative hematocrits in total hip and spine fusion surgery, but not in total knee replacement.15 Intraoperative blood salvage and autotransfusion in a large study of major orthopedic operations saved approximately 900 cc per patient, returned an average of almost 2 units, and prevented the need for an allogeneic blood transfusion.16

These surgeries involved high volumes of blood loss. Contraindications for intraoperative blood recovery included the possibility of aspiration of malignant cells, infectious agents, or other contaminants. At least 2 units must be recovered for the method to be cost-effective.8 The efficacy of blood salvage and autotransfusion in the recovery period after arthroplasty remains controversial.7,17-19

Hypotensive anesthesia

Hypotensive anesthesia is a technique for reducing intraoperative blood loss by significantly lowering mean arterial pressure during surgery. Hypotensive anesthesia may help reduce intraoperative blood loss, but depends on the relative drop in pressure, as well as the type of anesthesia.20-22 The reduction in blood loss does not appear to be related to cardiac output.23 Hypotensive anesthesia is associated with tissue hypoperfusion and major complications including death. This is especially true in patients undergoing total joint replacement who often have underlying cardiac, cerebral, or peripheral vessel disease. There is also a theoretical concern for increased thromboembolic events.

Several studies of hypotensive anesthesia have been performed in the total joint literature. In a study of 30 THAs, spinal anesthetic with mean arterial pressure maintained at 70 mm Hg was compared to hypotensive epidural anesthetic (mean arterial pressure 50 mm Hg to 60 mm Hg). Intraoperative blood loss was decreased from 900 mL to 400 mL, and total perioperative blood loss was decreased by 45%, significantly lowering the number of transfused units in the hypotensive group.21 In a similar study in 30 TKA, patients with hypotensive epidural anesthesia without a tourniquet had higher blood loss (146 cc) compared to patients with spinal anesthetic with a tourniquet (13 cc). However total perioperative blood loss was decreased by nearly 800 cc in the hypotensive group, which translated into 38% fewer patients requiring transfusion, and 75% less blood per transfusion.24 Inhalational anesthetics and hypotension have also worked to significantly reduce intraoperative blood loss in total hip replacement.22,25 Finally, hypotensive anesthesia in THA has been compared directly to acute normovolemic hemodilution with mixed results.26,27

Tissue hemostasis

A more direct method to reduce intraoperative blood loss is to obtain improved tissue hemostasis within the operative field. Topically or locally active agents include thrombin, collagen, and fibrin glues. These agents are efficacious in reducing postoperative blood loss and perioperative exposure to allogeneic blood transfusion. In seven randomized, controlled trials, fibrin sealants reduced the rate of exposure to allogeneic red cell transfusion by approximately 54%.28 The use of fibrin tissue adhesive significantly reduced mean postoperative blood loss from 878 mL to 360 mL in a study of 58 patients undergoing total knee surgery. The fibrin tissue adhesive was sprayed on the internal aspects of the operating field before skin closure.29 In addition to the direct mechanism of action, fibrin sealants contain varying amounts of antifibrinolytics, which may increase the efficacy. Again, as with any homologous blood product, there is a minute risk of viral transmission from fibrin sealants prepared from pooled human plasma. Otherwise, fibrin sealants have not been associated with any significant adverse outcomes.28

Maintenance of operative hemostasis can also be enhanced by use of specialized cautery units. One example of such technology is the TissueLink device (TissueLink, Dover, NH), which produces hemostasis via collagen shrinking at cooler temperatures, over broader fields, and with less tissue destruction than standard electrocautery devices. No articles in the orthopedic literature are dedicated to the study of cautery and its effects on perioperative blood loss. However, a drier operative field most likely leads to decreased levels of intraoperative and postoperative blood loss and exposure to allogeneic blood during a patient’s hospital stay.

Pharmacological strategies

Pharmacological strategies to decrease transfusion requirements in patients undergoing surgery have been studied extensively; however, relatively few articles exist in the orthopedic literature.1,30 A main class of drugs used in this manner are antifibrinolytics. Fibrinolysis is stimulated by surgical trauma and further augmented by the use of a tourniquet. Antifibrinolytics act to increase hemostasis within a surgical site by enhancing the clotting mechanism.

The use of antifibrinolytics for minimizing perioperative allogeneic blood transfusion after surgery has been recently systematically reviewed.31 Despite notable heterogeneity in the various trials, aprotinin appears to reduce the need for red cell transfusion and the need for reoperation due to bleeding without serious adverse effects, including thromboembolic events and renal failure. Mostly in cardiac surgery, aprotinin was found to reduce the rate of allogeneic blood transfusion by 30%. Similar trends in efficacy were seen with tranexamic acid and epsilon aminocaproic acid, but the data were sparse. Eight trials directly compared tranexamic acid and aprotinin. There was no statistically significant difference, but tranexamic acid trended toward increased risk of transfusion over aprotinin (relative risk increase of 21%).

Tranexamic acid

Tranexamic acid inhibits fribrinolysis by blocking the lysine-binding sites of plasminogen to fibrin. Several studies have shown the efficacy of tranexamic acid in reducing perioperative blood loss and transfusion requirements in TKA32-38 and THA.39,40 Blood loss reduction is between 25% and 50%. Additionally, in direct comparision studies, tranexamic acid was proven more efficacious than desmopressin and acute normovolemic hemodilution in patients undergoing TKA.41,42 A small number of studies found no effect of tranexamic acid in total joint replacement.43

Optimum timing for administration of tranexamic acid is not well defined.34 Several clinical studies have shown the efficacy of tranexamic acid boluses when given before surgery,35,39 at deflation of the tourniquet,32,36,37 and for various times after surgery.31,41 The timing and duration of additional boluses and continuous infusions varied in these studies. Generally, dosing was 10 mm/kg to 20 mm/kg.

Aprotinin

Aprotinin is a naturally occurring proteinase inhibitor derived from bovine lung. It inhibits plasmin, trypsin, and kallikreins of different origins and therefore has antifibrinolytic properties. Aprotinin may also have effects on the intrinsic coagulation pathway, as well as platelet adhesion. It has been used with success in cardiac, vascular, and major liver surgery. Aprotinin’s mechanism in orthopedic surgery has not yet been fully elucidated.44,45

The use of aprotinin has been studied in major orthopedic surgery, including large operations for malignancy, infection, trauma, revision surgery, or bilateral joint replacement. Most of these studies found an advantage of aprotinin over placebo. However, one study did not. In a prospective, double-blind study of 69 adults with pelvic, spine, or extremity malignancies, a medium dose of aprotinin (2 million kallikrein inactivator units [KIU] bolus, followed by an infusion of 0.5 million KIU/hr) did not lower perioperative blood loss or transfusion requirements relative to placebo.46 In contrast, Jeserschek et al47 performed a smaller prospective, randomized, placebo-controlled study of 18 revision joints or sarcoma resections. Medium-dose aprotinin (1 million KIU bolus, 0.5 million KIU/hr) reduced blood loss by 1221 mL (62%) and halved the mean requirement for intraoperative homologous transfusion when compared to saline placebo. In a similar study of 23 patients with malignancy or infection, with the same dosing regimen, blood loss was reduced by 56% during and 68% after surgery. Transfusion requirements decreased from 7 to 3 units.48

Two studies have looked at higher doses of aprotinin in major orthopedic surgery. In a dose-ranging study of 58 patients, large-dose aprotinin (4 million KIU bolus, 1 million KIU/hr intraoperative infusion) significantly reduced blood loss and transfusion amount versus placebo. The smaller dose regimen (2 million KIU, 0.5 million KIU/hr) did not significantly reduce blood loss and transfusion amount.45 High-dose aprotinin (3.8 million KIU) was effective in reducing blood loss by 600 mL (30%) and transfusion units in revision and bilateral THA. However, the investigators questioned whether the slight improvement justified the routine use of this expensive drug.49

Singbartl et al50,51 have shown aprotinin to be a cost-effective way of reducing blood loss and transfusion requirements in patients undergoing one-stage revision for infected total hips and total knees.

Compared to major orthopedic surgery, the use of aprotinin in primary total joint replacement achieved mixed results. Medium doses of aprotinin had no significant effect on fibrinolysis variables, reduction in postoperative bleeding and transfusion requirements in TKA, or estimated blood loss, hemoglobin levels, and transfusion requirements after THA.52-55 Similarly, small-dose aprotinin (20,000 KIU/kg) was not effective in reducing blood loss and transfusion needs in 372 patients undergoing unilateral primary THA.52

Others have found aprotinin to be successful in reducing blood loss during THA. Janssens et al56 reduced blood loss by 26% and transfusion units from 3.4 to 1.8 with what was called high-dose aprotinin dosing. In the only true dosing study in primary total joints, patients were given one of the following regimens of aprotinin: low (0.5 million KIU bolus), medium (1 million KIU bolus, 0.25 million KIU/hr), and large dose (2 million KIU bolus, 0.5 million KIU/hr). The investigators showed reduced numbers for all three regimens with regard to transfusion amounts, intraoperative blood loss, and postoperative drainage. Higher hemoglobin levels were noted in the aprotinin groups, which may affect patient vigor and prevent medical complications. Allogeneic transfusion rates were reduced from 15% to 6%. However, no clear dose-response effect was shown among the studied variables.57

The relationship between dose of aprotinin and efficacy remains unclear, although there is a bias toward higher doses. Also, maintaining a continuous infusion may be better than a prime dose (bolus). Part of the uncertainty stems from lack of strict definitions for large versus small doses. Small doses usually are less than 1 million KIU, medium does are between 1 million KIU and 2 million KIU, and large doses are 2 million KIU to 4 million KIU. Many of the dosing regimens were extrapolated from those used in cardiac or liver transplantation surgery. The optimum dosing regimen in orthopedic surgery remains to be determined.31,45,47-49,57

Although the use of antifibrinolytics to reduce intraoperative blood loss has increased, the cost of these drugs are high and there is theoretical risk of increased thromboembolic complications. The safety of aprotinin use has been commented on previously in this journal.58 None of the trials referenced herein found any significant adverse effects such as deep venous thrombosis, pulmonary embolism, myocardial infarction, stroke, or renal dysfunction, from the either the aprotinin or tranexamic acid. This has been confirmed by a systematic review of the surgical literature.31 A small study on aprotinin in TKA was stopped early secondary to development of an acute arterial thrombosis resulting in loss of limb in one patient. This may have been caused by the patients underlying peripheral vascular disease.59 Aprotinin is expensive, but this expense can be offset by the savings in transfusion requirements and hospital costs.47,50,51 Other antifibrinolytics are less costly, but are less studied.31

Antifibrinolytic drugs are safe and appear effective in reducing blood loss and the need for transfusion.31 Aprotinin is the most studied of the antifibrinolytic medications and therefore has the best proven efficacy. As aprotinin is a naturally derived small protein and hypersensitivity reactions have been observed, especially upon repeat exposure and within 6 months of prior exposure, re-exposure should be carefully weighed with respect to its risks and benefits.60 Further, most of the data have been collected in the context of major cardiac surgery, in which blood loss is substantial, and applicability to most orthopedic surgeries needs further exploration.

Conclusion

Concern about the safety and expense of allogeneic blood has led to increased research and efforts into better intraoperative blood management during total joint replacement. Several options with proven efficacy exist, including acute hemodilution, blood salvage, hypotensive anesthesia, improvements in tissue hemostasis, and pharmacological agents. In addition to reducing the need for and exposure to allogeneic blood, the potential for less blood loss may translate into less swelling, improved range of motion, and earlier return to function. However, all methods come with varying amounts of risk and cost. The surgeon must remember the ultimate significance of a patient’s preoperative hemoglobin level and the expected blood loss during surgery, and use these strategies with educated discrimination.

The literature shows that the greater the amount of bleeding, the greater is the potential benefit from specialized intraoperative blood management techniques. Routine primary joint replacement may not be the most appropriate setting. The severity of a patient’s clinical condition and the potential for blood loss must be considered. For example, preoperative donation and intraoperative cell-saving procedures are generally not performed in patients with cancer or sepsis, although massive intraoperative bleeding frequently occurs. Special cases such as patients with low preoperative hemoglobin levels, expected difficulty with prolonged prosthesis removal, religious beliefs that prevent the use of allogeneic transfusions, or bilateral procedures may broaden the indications. More research is needed, especially in the areas of cost analysis of the various techniques and dosing studies of the antifibrinolytics.

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Authors

From the Insall Scott Kelly Institute for Orthopaedics and Sports Medicine, New York, NY.

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