Historically, 50% of patients undergoing total joint arthroplasty receive an allogeneic blood transfusion. The risks of allogeneic transfusions are well described in the literature.^† These concerns often are focused on the transmission of viral agents, such as hepatitis and human immunodeficiency virus. Although these concerns persist, the main risks for transfusion-related morbidity and mortality include incorrect blood component transfusion (70%) and immunologic risks (28%), whereas transfusion-transmissible infection (2%) is of less significance.¹⁷ Newer concerns also have been raised; West Nile, TT, parvovirus B19, and SEN virus transmission have been discussed as potential infectious agents after allogeneic transfusions.¹⁰ Although less of a concern in Western countries, on a global scale, protozoan infections including malaria and toxoplasmosis remain some of the most common transfusion-transmitted infections. In addition, some cases of the bloodborne transmission of prions have been described.

Allogeneic transfusions often have been implicated in the increased incidence of infection after surgery. Houbiers and colleagues ⁶² have studied 697 patients undergoing abdominal surgery, and multivariate analysis identified allogeneic transfusions as a significant risk factor for postoperative infection. Tang and colleagues¹¹⁴ later confirmed this in a prospective series of 2809 consecutive colon resections. In their report, transfusion was the single most powerful risk factor for postoperative infection (odds ratio >5). Kendall and colleagues⁷⁶ have described immunosuppression secondary to allogeneic transfusions in 34 patients undergoing total hip arthroplasty. According to their study, lymphocyte function is impaired, which may increase the risk of deep prosthesis infection. The effect of allogeneic transfusion on the immune system was first described in 1973, and is now well documented in the literature.¹⁷ Studies have suggested that the immunomodulating effect of red blood cell transfusion may be responsible for the better outcome in transplant patients receiving transfusion, higher risk of recurrence following malignancy resection in patients receiving transfusion, and higher risk of postoperative infection following transfusion. The incriminated pathomechanism of these mostly adverse effects of blood transfusion is called transfusion-related immunomodulation (TRIM).

Pulido and coworkers ⁹⁸ have studied predisposing factors for developing periprosthetic infection in a series of 9245 arthroplasty patients. This series again identified allogeneic transfusion as an independent risk factor for infection, with a 2.1-fold increase in the rate of periprosthetic infection following transfusion. Similarly, Shander and colleagues¹⁰⁵ have demonstrated a 3.6-fold greater relative risk for developing postoperative infection following cardiac and orthopedic surgery if an allogeneic transfusion is administered. Murphy and associates⁸⁹ have also shown an increased rate of confirmed or suspected infections in a series of 84 patients undergoing total hip arthroplasty. They compared patients receiving autologous blood transfusion with those receiving allogeneic blood. Although the numbers were small in this series, the infection rate in the group receiving allogeneic transfusion was 32% compared with 3% in the autologous group.

Although disease transmission may be the main concern for patients, other complications associated with allogeneic transfusion are more common and of equaling concern. The increase in postoperative infection related to immunosuppression following transfusion is a major concern, especially in the arthroplasty patient. These risks of transfusion need to be understood by the clinician when determining the risk-benefit ratio of transfusion during the postoperative period.

Risk Factors for Transfusion

One of the best ways to predict which patients will require perioperative allogeneic transfusion is to evaluate preoperative blood values.^20,^35,⁴³ Checking the hemoglobin and hematocrit levels before scheduling the indicated procedure identifies those patients at risk for requiring transfusion. In one of our original papers, we described factors that influence transfusion rates following total knee arthroplasty.³⁰ In this study, we found preoperative hematocrit values were the best predictor for transfusion needs. Nuttall and colleagues⁹³ had similar findings, also noting the importance of preoperative hemoglobin levels. To minimize postoperative transfusion requirements, the patient’s hemoglobin level must be maximized during the preoperative period. Patients who began with higher preoperative hemoglobin concentrations are able to tolerate the 10% hematocrit loss that occurs routinely after joint arthroplasty surgery. Patients who are anemic in the preoperative process will be anemic during the postoperative period and may require transfusion.

Guerin and coworkers ⁵⁴ have prospectively reviewed 162 consecutive hip and knee arthroplasties. In this series, patients with preoperative hemoglobin levels lower than 13 g/dL were four times more likely to receive a transfusion than those patients with preoperative hemoglobin levels higher than 15 g/dL. Nuttall and colleagues⁹³ have evaluated 299 patients who underwent primary or revision total hip arthroplasty in an attempt to predict the risk factors for allogeneic transfusion. In this study, risk factors for transfusion included preoperative hemoglobin, weight, age, anticipated blood loss, and aspirin use. Interestingly, they noted that predonated blood was often not transfused, leading to blood wastage and an increase in cost. They concluded that by identifying patients who were unlikely to require transfusion, unnecessary autologous predonation can be avoided and costs can be saved.

The preoperative hemoglobin concentrate has been shown to be the best predictor for postoperative transfusion in several other studies as well. Cabibbo and coworkers ¹⁸ recently reviewed their autologous blood donation program in 1198 orthopedic patients over the past 10 years. In this series, a preoperative hemoglobin level higher than 14 g/dL was a strong predictor for not requiring postoperative transfusion. Sculco and Gallina¹⁰⁴ have evaluated 1405 patients who underwent total joint arthroplasty; they looked at the hemoglobin concentration measurement before surgery. Again, the preoperative hemoglobin level was inversely related to the frequency of perioperative allogeneic transfusions. In a large multicenter study, Bierbaum and coworkers⁹ evaluated 9482 patients undergoing major orthopedic surgery. This study not only showed an increased transfusion rate for patients with a preoperative hemoglobin value lower than 13 g/dL, but also demonstrated an increase in complication rates in patients requiring transfusion. In this series, transfusions were associated with an increase in infection, fluid overload, and a longer hospital stay. These studies suggest that the patient’s hemoglobin level should be checked and optimized prior to surgery to minimize postoperative transfusion and complication rates.

Preoperative Blood Management

Preoperative Autologous Donations

In the late 1980s, the standard of care for a patient undergoing TKA was the preoperative donation of autologous blood. Although commonplace in the United States, preoperative autologous donation (PAD) is uncommon in other areas of the world. PAD has several limitations. As noted, patients who are most anemic in the preoperative period are at greatest risk for postoperative transfusion. These same patients are often excluded from PAD. This alone severely inhibits the ability of a PAD program to help those patients with the greatest need. At the same time, PAD may actually increase the risk of transfusion in the remaining patients by reducing their preoperative hemoglobin level. Although it is often assumed that after donating blood, the patients return to their predonation status, this is often not the case. Several studies have shown that PAD can cause further anemia, is often wasteful, and may lower the patient’s preoperative blood levels.^12,^33,^81,¹¹² The patient donates the blood, does not return to baseline, and arrives for the surgery in an anemic state. The patient is then actually more at risk for allogeneic transfusion because of the autologous donation.

Hatzidakis and coworkers ⁵⁶ performed a retrospective analysis of 489 consecutive patients undergoing total joint arthroplasty. This study was limited because predonation blood values were available only in 149 of the 489 patients. A decrease in hemoglobin concentration from the time of the donation to the time of surgery was reported; the average decrease was 1.22 g/dL. This study questioned the benefit of PAD in patients with predonation hemoglobin concentrations higher than 15 g/dL. In younger patients, a lower threshold was accepted. The authors did not recommend PAD for patients with a predonation status higher than 13 g/dL.

In the review of 1198 patients enrolled in an autologous blood donation program, Cabibbo and coworkers ¹⁸ demonstrated a high degree of autologous blood wastage in patients with an optimized preoperative hemoglobin level. In this series, a preoperative hemoglobin level higher than 14 g/dL was a strong predictor for not requiring postoperative transfusion. In this subgroup of patients, autologous blood wastage was over 90%. Even in the subgroup of patients with preoperative hemoglobin levels between 13 and14 g/dL, autologous blood wastage was still over 50%. Even in a recent study that concluded that autologous blood donation was a cost-effective measure for reducing allogeneic transfusion rates following arthroplasty, Green and coworkers⁵¹ demonstrated overall autologous blood wastage of 38% in 356 patients. When looking at total knee arthroplasty alone, the autologous blood wastage was 51%. These findings are similar to those of Bierbaum and coworkers.⁹ In their large prospective series of 9482 patients, the autologous blood wastage was 45%.

Lotke and colleagues ⁸³ have evaluated medical complications after TKA. This study initially was done to evaluate the controversy regarding the administration of preoperative autologous blood. The question remained that if the blood is donated, whether all of it should be given back. They performed a prospective randomized study to compare immediate transfusion of the autologous blood in anticipation of blood loss versus delayed transfusion if the transfusion trigger was reached. The results showed that patients who received an immediate transfusion of their PAD had fewer medical complications compared with patients who did not receive their PAD until their hemoglobin concentration was lower than 9 g/dL (P < .002). These complications included myocardial infarction, cardiac dysrhythmia, mental confusion, lethargy, and orthostatic hypotension. An immediate transfusion of PAD was suggested to be particularly important in critically ill older patients because of their increased risk of cardiac and nonsurgical complications. This study concluded that the increase in the hemoglobin level, as a result of the immediate return of the PAD, improved the outcome in these patients.

Others have shown that a major concern regarding PAD programs is the failure of patients to recover their hemoglobin level fully following blood donation. This places the patient in a more vulnerable state of anemia.^30,^43,⁹³ A 1- to 2-U PAD program does not cause a significant erythropoietic response. Because no erythropoietic response occurs, patients do not return to their baseline level before their donations. In addition, postsurgical transfusion may not always result in the desired hemoglobin concentration because stored autologous blood may show a decrease in number of red blood cells. We have evaluated our previous PAD program with regard to preoperative hemoglobin levels. Between 1993 and 1995, 2 U of PAD were obtained on average, compared with 1 U of PAD obtained in the years between 1995 and 1997. Our studies have shown a 3% decrease in hematocrit values for every unit donated before surgery.³³ When 1 U was donated, a 3% decrease in hematocrit was noted before surgery. When 2 U were donated, a 6% decrease from baseline was noted; 2 U of PAD resulted in more anemia before the surgical procedure.

We also reviewed our results of a 1-U PAD program with automatic infusion of the donated blood. All patients were given their PAD immediately after surgery, resulting in 0% wastage. No numeric transfusion triggers were used and subsequent allogeneic transfusion was based on symptoms. Despite ordering the PAD unit 1 month before surgery, significant preoperative anemia was noted. In this retrospective review of 148 patients undergoing unilateral TKA, a 1.3-g/dL decrease was noted between predonation and presurgical testing.³¹ We refer to this occurrence by the term orthopedic-induced anemia. Whereas only 26.2% of patients were in the high-risk transfusion group (hemoglobin = 10-13 g/dL) before surgery, 55.7% of patients were in this high-risk category after preoperative autologous donation. The patients did not recover from the autologous donations that occurred 4 weeks before surgery. A mean hemoglobin level of 14.0 g/dL was seen before donation, whereas the mean preoperative hemoglobin level decreased to 12.6 g/dL. As documented by others, the use of PAD resulted in anemia and patients did not return to the predonation hemoglobin and hematocrit values. Although the allogeneic infusion rate was low in this series, we believe that this reflects the acceptance of lower hemoglobin levels in the immediate postoperative period. If historical transfusion triggers had been followed (hemoglobin concentration <10g/dL), a transfusion rate of 30% would have been found. Of our patients, 50% were discharged with hemoglobin concentrates lower than 9 g/dL. The low allogeneic transfusion rate should not be misconstrued as the efficacy of a 1-U PAD program, but rather a change in our transfusion practice.

Our institution has abandoned the aforementioned protocol based on the apparent lack of efficacy. In addition, this type of protocol places patients at an additional risk. A protocol with a 100% autologous rate exposes patients to the added risk of donation error. Goldman and associates ⁴⁷ have reviewed autologous error rates in Canada and found an error rate of 6 of 149 (4%). Most of these errors were related to labeling error (48%) or an error in component preparation (25%). One patient received the wrong unit of donated blood, which is not an uncommon occurrence. According to the College of American Pathologists,²⁷ 0.9% of the 3852 institutions studied had at least 1 U of PAD given to the wrong patient.

Cost is an issue of PAD—this is not an inexpensive procedure. The costs of a PAD program are related to procurement and to the expense connected with giving the blood. There is also the cost of the wastage to consider. Several series have shown that the autologous wastage rate is 50% to 90%. Billote and colleagues ¹³ have evaluated PAD in patients who were receiving total hip arthroplasty and found no benefit for PAD in nonanemic patients undergoing primary hip replacement. Each patient donated 2 U of autologous blood, with an additional cost of $758/patient. Etchason and coworkers³⁹ have studied the cost of the PAD program and concluded that increased protection afforded by autologous blood is limited and may not justify the increased cost. However, a more recent study comparing the cost of erythropoietin versus autologous and allogenic blood donation in total joint arthroplasty showed that autologous blood donation might be cost-effective.⁵¹ In 356 unilateral total joint replacements performed during an 11-month period, a combination of autologous blood donation and allogeneic blood was the least costly approach, $856 and $892/patient for total hip arthroplasty (THA) and total knee arthroplasty, respectively. The most costly strategy was allogeneic blood only, at $1769 and $1352 per THA and TKA patient, respectively.

Use of Erythropoietins

The importance of proper hemoglobin concentrations was discussed earlier. The surgeon is often limited in his or her ability to maximize the patient’s predonation hemoglobin values. In the past, we participated in a PAD program. Unhappy with the anemia caused by donations, we put our patients on a new protocol. We began incorporating a patient-specific protocol to use epoetin alfa (Procrit; Centocor Ortho Biotech, Horsham, Pa) into our busy knee practice.³³ First, we obtain preoperative hemoglobin and hematocrit levels prior to surgical booking. Patients with a hemoglobin ranging from 10 to 13 g/dL are indicated to receive epoetin alfa injections prior to surgery. Patients receive 40,000 U at 3, 2, and 1 week prior to surgery, with an average rise in hemoglobin level of 1.5 g/dL noted. The dose scheduled for the day of surgery is rarely required. We compared 50 patients who received epoetin alfa injections with 50 patients participating in the autologous program with automatic reinfusion.³¹ The patients receiving epoetin alfa had higher blood parameters preoperatively, postoperatively, and on discharge than patients who participated in the autologous program. Additionally, our overall cost was reduced because the autologous program was used in 25% of patients with epoetin alfa compared with 100% in previous protocols.

Because of the success of this protocol, our indications have expanded. Epoetin alfa injections have been found effective in other aspects of our joint replacement practice as well. By using epoetin alfa between stages during the two-stage treatment of an infected total joint arthroplasty, our allogeneic transfusion rates were decreased from a high of 88% to 33%.⁹⁴ Epoetin alfa is also being used in our revision patients.³⁴ On evaluation of blood loss and transfusion rates following revision total knee arthroplasty, we found that 75% of female patients scheduled for revision were in the high risk group (hemoglobin = 10 to 13 g/dL). Therefore, all revision patients are now screened and follow the same epoetin alfa protocol.

In our practice, approximately 25% to 30% of patients fall into the high-risk group and require epoetin alfa injections, which means that 75% require no preoperative intervention. This saves the time and inconvenience of routinely scheduling autologous blood donations for all patients, for which many would be unnecessary. Treating 25% of patients with epoetin alfa injections is significantly cheaper than using an autologous donation program for 100% of patients, especially in light of potential risks with an automatic reinfusion protocol.

A similar protocol was recently studied by Moonen and coworkers ⁸⁷ and compared with retransfusion of autologous shed blood. All patients in this study had a preoperative hemoglobin level between 10 and 13 g/dL. In 100 arthroplasty patients randomized to preoperative epoetin alfa injection or retransfusion of autologous shed blood, the allogeneic transfusion rate for the group receiving preoperative injections of epoetin alfa was 4% compared with 28% for the group with a reinfusion drain. A second recent study has compared the use of erythropoietin with a PAD program.⁷¹ In this series, 121 arthroplasty patients with a preoperative hemoglobin level of 11 to 14 g/dL received weekly erythropoietin injections or underwent PAD. The erythropoietin group demonstrated higher hemoglobin levels, lower transfusion rates, and a significant increase in postoperative vigor.

Insall-Scott Kelly Institute Protocol

We have abandoned the use of autologous blood for unicompartmental TKAs and use a patient-specific approach. We check hemoglobin values before surgery and identify patients at increased risk; approximately 25% of patients receive epoetin alfa injections. The other patients, with a preoperative hemoglobin level higher than 13 g/dL, are scheduled for surgery without any PAD or recombinant human erythropoietin (EPO) prescriptions. The patients receive their injections before surgery from our office or from their primary care physician. This approach maximizes the hemoglobin and hematocrit levels not only before surgery, but also during the perioperative period.

Intraoperative Blood Management

PAD and epoetin alfa injections are attempts in the preoperative period to reduce the need for allogeneic transfusions. Several options exist for intraoperative blood management of the TKA patient. The preoperative measures work by attempting to maximize the ability of patients to tolerate the intraoperative blood loss. To avoid transfusions, addressing the amount of intraoperative blood loss is also beneficial. In this section, hypotensive anesthesia, blood salvage, hemodilution, topical hemostatic agents, and specialized cautery are reviewed.

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 normal blood volume. This technique is recommended when the potential for blood loss may exceed 20% in patients with a hemoglobin level higher than 10 g/dL. It is a cost and preoperative time commitment for preoperative autologous donations, with the possibility of clerical error or bacterial contamination. Acute normovolemic hemodilution is common, however, in patients with coronary, renal, pulmonary, or significant liver disease. It is often impractical in most total joint programs because of the relatively short duration of the procedure and lesser blood loss.⁷²

The literature supporting normovolemic hemodilution is mixed. Combined data from 16 randomized control studies of 615 patients has shown that acute normovolemic hemodilution reduces the likelihood of allogeneic transfusions in patients undergoing surgery by 31%.⁹⁰ The likelihood of allogeneic transfusion in patients undergoing surgery was reduced in cardiac and miscellaneous procedures, but not in orthopedic surgery. The patients were required to have at least 1000 mL withdrawn, and there had to be no transfusion protocols in place. In contrast, Shulman and colleagues¹⁰⁹ have found that acute normovolemic hemodilution reduced allogeneic transfusions from 2.4 to 0.6 U/patient in a series of 80 patients undergoing total or revision hip arthroplasty. This is a 75% reduction in patients undergoing hip arthroplasty. Acute normovolemic hemodilution has been found to be as effective as a preoperative autologous donation by Goodnough and coworkers⁴⁸ in total hip and total knee replacements, with lower costs. However, in these series, a trend toward higher allogeneic transfusion rates was seen with normovolemic hemodilution compared with PAD in hip arthroplasty. Acute normovolemic hemodilution may not be necessary when blood loss is expected to be lower than 500 to 1000 mL intraoperatively. Therefore, we believe that it has little clinical usefulness in routine total knee arthroplasty.

Intraoperative Blood Salvage

Blood salvage requires a return of the patient’s autologous blood loss during surgery. Often, the indicated TKA is performed under tourniquet control. Blood salvage devices are therefore used during the postoperative period as a reinfusion drain, when most of the blood loss occurs. The use of reinfusion drains is discussed in depth later (see “Postoperative Management”). Intraoperative blood salvage is more useful in total and revision hip arthroplasty or in patients undergoing knee arthroplasty with a contraindication for the use of a tourniquet. In a recent case-matched study of 80 revision hip arthroplasty patients, intraoperative blood salvage demonstrated a median reduction in allogeneic transfusion of 4 U/patient (2 U compared with 6 U).¹⁵

Hypotensive Anesthesia

Hypotensive anesthesia is a technique for reducing intraoperative blood loss by significantly lowering the mean arterial pressure during surgery. Hypotensive anesthesia may reduce intraoperative blood loss, but it depends on the relative decrease in pressure and the type of anesthesia.^5,^91,¹⁰⁸ The reduction in blood loss does not seem to be related to cardiac output.¹⁰⁷ Hypotensive anesthesia is associated with tissue hypoperfusion and complications can occur, including death. Patients with underlying cardiac, renal, cerebral, or peripheral vessel disease are at increased risk. Two studies have shown hypotensive anesthesia during total joint arthroplasty to be safe in patients with aortic stenosis and chronic renal dysfunction, but these series were severely limited by the number of patients evaluated (22 and 54 patients, respectively).^60,¹⁰⁶ The possibility of increased deep vein thrombosis events also has been raised.

In the total joint arthroplasty literature, several studies evaluating hypotensive anesthesia have been described. In a study of 30 total hip arthroplasties, spinal anesthetic with mean arterial pressure maintained at 70 mm Hg was compared with hypotensive epidural anesthesia (mean arterial pressure, 50 to 60 mm Hg). Intraoperative blood loss was decreased from 900 to 400 mL and total perioperative blood loss was decreased by 45%, significantly lowering the number of transfusion units in the hypotensive group. A similar study was done with the use of a hypotensive epidural anesthesia protocol and compared with a spinal anesthetic in total joint arthroplasty patients.⁶⁹ Total perioperative blood loss was decreased by almost 800 mL in the hypotensive group, resulting in 38% fewer patients requiring transfusion and 75% less blood per transfusion. Inhalational anesthetics and hypotensive anesthesia also have worked to reduce intraoperative blood loss significantly in total hip replacements.¹¹⁶

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