Red cell salvage in orthopedic surgery - Wiley Online Library

TATM

Transfusion Alternatives in Transfusion Medicine

Red cell salvage in orthopedic surgery MANUEL MUÑOZ*, M D , P h D , ARTURO CAMPOS † , M D , ENCARNACIÓN MUÑOZ*, M D , P h D , ANTONIO CARRERO ‡ , M D , JORGE CUENCA § , M D , P h D & JOSÉ ANTONIO GARCÍA-ERCE ¶ , M D , P h D

*GIEMSA (International Multidisciplinary Autotransfusion Study Group), School of Medicine, University of Málaga, Málaga; † Department of Hematology, Virgen de la Victoria University Hospital, Málaga; ‡ Blood Transfusion Center, Jaén; § Departments of Orthopedic Surgery and ¶Hematology, Miguel Servet University Hospital, Zaragoza, Spain Correspondence to: Professor M. Muñoz, GIEMSA, Facultad de Medicina, Universidad de Málaga, Campus de Teatinos, s/n, 29071 Málaga, Spain E-mail: [email protected]

Publication data Submitted: 25 January 2005 Revision received: 12 May 2005 Accepted: 16 May 2005

Keywords Coagulation Cytokines Effectiveness Fat particles Immune system Orthopedic surgery Perioperative blood salvage

• • • • • • •

SUMMARY

The increasing number of surgical procedures has raised the demand for allogeneic blood to a level that often exceeds supply. Moreover, 10% of all transfusions are given in the orthopedic surgery setting, requiring the avoidance of liberal transfusion criteria to further reduce the risk of infection and other complications. As a result, a series of bloodconservation measures have been developed. In this article, we review the use of autologous transfusion in orthopedic surgery, with a special focus on perioperative red cell salvage. From data reviewed, it can be concluded that perioperative salvage of blood, either intraoperative cell salvage or postoperative cell salvage, seems to be an excellent source of functional and viable red cells, without many of the transfusion-related risks and with few side effects. The effectiveness of perioperative cell salvage to reduce exposure to allogeneic blood is greatly enhanced by the implementation of a restrictive transfusion protocol and the association with other blood-sparing strategies [preoperative autologous blood donation (PABD), erythropoietin, intravenous iron], especially in anemic patients. Moreover, perioperative cell salvage may reduce the number of required PABD units or render PABD unnecessary. Finally, although formal cost-effectiveness studies on perioperative cell salvage are lacking, based on current allogeneic blood transfusion costs, it is generally accepted that the equivalent of at least one unit of blood needs to be recovered for these techniques to be costeffective. Therefore, these procedures should be used on a case-by-case basis.

INTRODUCTION The development of complex surgical procedures for the treatment of a number of diseases has increased the demand for allogeneic blood. In hospitals, over 50% of transfused blood units are used in the surgical setting1 and up to 60% of all transfusions are given to patients older than 65 years – patients who are excluded from

altruistic blood donation.2 Consequently, the demand for allogeneic blood often exceeds the supply. Generally speaking, allogeneic blood transfusion is a safe treatment option, especially because increased donor selection criteria and increased screening of donated blood have led to a decrease in the rate of transfusion-transmitted infections. However, liberal transfusion protocols (pre-transfusion hemoglobin [Hb]

© 2006 The Authors Journal Compilation © 2006 LMS Group • Transfusion Alternatives in Transfusion Medicine doi: 10.1111/j.1778-428X.2006.00007.x

41

42 MUÑOZ ET AL. | RED CELL SALVAGE IN ORTHOPEDIC SURGERY

concentration > 9–10 g/dL) should be avoided to further reduce the risk of infection and other complications such as incompatibility reactions, metabolic disorders, transfusion-related acute lung injury (TRALI), and transfusion-related immunomodulation (TRIM).3 As for TRIM, the results of three extensive studies involving more than 22,000 orthopedic surgical patients strongly suggest that perioperative allogeneic blood transfusion is associated with an increase in the risk of postoperative infection.4–6 Increased awareness of the greater incidence of postoperative complications and other potential hazards of allogeneic blood transfusion has prompted a review of transfusion practices and the search for bloodconservation measures, such as the correction of perioperative anemia, the reduction of perioperative blood loss, and the use of autologous transfusion. The ultimate objective is to reduce to a minimum the exposure to allogeneic blood transfusion and to transfusionassociated risks. In this article, we review the use of autologous transfusion in orthopedic surgery, with a special focus on perioperative red cell salvage. MODALITIES OF AUTOLOGOUS TRANSFUSION IN ORTHOPEDIC SURGERY

Preoperative autologous blood donation Preoperative autologous blood donation (PABD) is reputed to be one of the safest and most effective transfusion therapies. Indeed, it is considered as the ‘gold standard’ in autotransfusion. An analysis of the results obtained from 11 studies carried out in Spain and six performed overseas, involving a total of 10,500 patients subjected to elective orthopedic surgery of the knee, hip or spine, demonstrated that the mean effectiveness of PABD as measured by the percentage of patients avoiding allogeneic transfusion is 90%, with an average yield, measured as the percentage of donated units that are transfused, of 62%.7 Nevertheless, it should be taken into account that overcollection of units is lower in Europe (10–15%)6 than in the United States (40–50%)8 and is around 20% in Spain.7 The effectiveness of PABD in orthopedic surgery was corroborated by a very recent meta-analysis indicating that PABD reduced the relative risk (RR) of allogeneic blood transfusion to 0.16 [95% confidence interval (CI), 0.07–0.36] although PABD contribution to allogeneic transfusion

reduction was further decreased if a transfusion protocol was adopted (RR: 0.49; 95% CI, 0.37–0.63).9 In addition, there may be problems of overtransfusion with PABD. PABD is associated with higher rates of clerical errors and is not without infectious risks given that allogeneic transfusion may still be required (breakthrough transfusion), as may adjuvant treatment with erythropoietin to facilitate the collection of the requested units. PABD also necessitates the implementation of a tight surgical program. (For further details, see the article by Rosencher and Shander in this issue.)

Acute normovolemic hemodilution Acute normovolemic hemodilution (ANH) is another method designed to avoid allogeneic blood transfusion. The procedure entails the withdrawal of autologous blood prior to the surgical procedure and the use of asanguinous intravenous fluids for volume replacement. The replacement of blood with colloid or crystalloid solutions maintains the normal circulating blood volume and oxygen delivery. ANH has the potential to reduce the need for allogeneic blood during surgery. Other advantages include the absence of blood contamination during storage and the availability of viable clotting factors while incurring minimal costs.10 The major disadvantage of normovolemic hemodilution is its inadequacy in preventing allogeneic red blood cell transfusion. Although a prospective, randomized study comparing ANH with PABD in orthopedic surgery, specifically patients undergoing primary total hip arthroplasty (THA), concluded that ANH is safe, equivalent to PABD in effectively reducing exposure to allogeneic red blood cells, and less costly than PABD,11 a meta-analysis of nine randomized controlled trials found no significant reduction in the requirements for transfusion between patients undergoing ANH and controls (RR, 0.77; 95% CI, 0.57–1.04).9 Hence, as a blood-conservation technique, ANH cannot stand alone and must be used in conjunction with other techniques to fully gain the benefits of allogeneic transfusion reduction or avoidance. More randomized controlled trials demonstrating efficacy and safety are needed for the establishment of better guidelines and standards in order to generate more reliable data. In the future, the adjuvant use of artificial oxygen carriers may expand the use of ANH, but safety and efficacy data are needed.12

© 2006 The Authors Journal Compilation © 2006 LMS Group • Transfusion Alternatives in Transfusion Medicine 8, 41–51

MUÑOZ ET AL. | RED CELL SALVAGE IN ORTHOPEDIC SURGERY

Intraoperative cell salvage During some orthopedic surgical procedures, intraoperative cell salvage (ICS) may be accomplished using different blood processing devices. Semi-continuous flow devices are the most common. The equipment consists of an aspiration and anticoagulation assembly, a reservoir with filter, a centrifuge bowl, a waste bag, a reinfusion bag and tubing. A double-line aspiration set includes an anticoagulation line that permits either heparin or citrate to be combined with the aspirated blood at a controlled rate. The anticoagulated blood is filtered into a disposable reservoir and is then pumped into a bowl where it is centrifuged at approximately 4000 rpm, washed with saline, and pumped into a reinfusion bag as a red cell concentrate.13 Most of the white blood cells, platelets, clotting factors, proteins, cytokines, free plasma Hb and anticoagulant are removed in the washing process and eliminated in the waste bag. The entire process takes 5–10 minutes and yields a red blood cell suspension that has a hematocrit (Hct) of approximately 45–70%. In the past, these devices tended to be bulky and complex to use. Recently, however, some smallsized, fully automated and easy-to-use devices, such as OrthoPAT (Haemonetics, Braintree, MD) or Autolog (Medtronic, Watford, UK), have been introduced. We performed an evaluation of OrthoPAT using different in vitro laboratory models and compared our results with those obtained for other blood salvage processing systems (Table 1).14 High-volume blood loss is relatively rare in orthopedics, but ICS should be considered in patients in whom

43

an intraoperative blood loss of more than 1500 mL is anticipated (e.g., major pelvic, spinal or non-infected revision surgery, particularly of the hip).15 Reported contraindications to the procedure are usually related to the contamination of salvaged blood with bacteria, hemostatic agents, wound irrigants or cancer cells. Cancer surgery constitutes a relative contraindication as cancer cells may be efficiently eliminated from salvaged blood by blood irradiation before reinfusion.16 As with other strategies of autologous blood procurement, the safety and cost-effectiveness of ICS should be carefully scrutinized. While cost-effectiveness has not been adequately addressed in any large prospective controlled trial, it is generally agreed that the equivalent of at least 1.5–2 units of blood needs to be recovered in order for the method to be cost-effective. With the rising costs of allogeneic blood transfusion, this position probably needs to be reassessed. In a prospective series of 794 patients undergoing major knee or hip surgery, it was found that the intraoperative recovery varies between 30% and 45% of the blood lost during the operation time.17 However, the amount of blood that is lost during surgery and that can be recovered depends on a number of unpredictable variables besides the type of operation. Consequently, the identification of the cases in which the procedure has to be performed may be erroneous when based only on the type of operation. Potential complications related to blood salvage include air embolism, fat embolism, hemolysis, hypocalcemia, renal dysfunction, pulmonary dysfunction, intravascular disseminated inflammatory syndrome and sepsis.10 In fact, the procedure has very few complica-

Table 1. Comparative evaluation of OrthoPAT with different blood salvage processing systems

Parameter

Sequestra (Medtronic)

BRAT 2 (Cobe)

CATS (Fresenius)

Cell saver (Haemonetics)

Autolog (Medtronic)

OrthoPAT (Haemonetics)

RBC recovery; % WBC removal; % PLT removal; % PFHB removal; % TP or ALB removal; % K+ removal; % Cytokine removal; %

65–76 31–78 87–93 89 97–98 92 95

71–93 30 68 63 91–93 90 95

51–87 45–80 92–96 65–95 93–99 90–98 95

64–94 22–55 86–87 85–93 NA 91 91–95

79 78 99 92 NA 89 NA

80 72 88 96 97 97 90

Values are mean or range; ALB, albumin; CATS, continuous autotransfusion system; PFHB, plasma free hemoglobin; PLT, platelets; RBC, red blood cells; TP, total protein; WBC, leukocytes; NA, not applicable (data taken from reference 14).



tions, the most frequent being dilution coagulopathy, occurring when a large volume of processed blood is transfused, and it is more a complication of blood loss than of blood salvage.

Postoperative cell salvage Postoperative cell salvage (PCS) entails the recovery and reinfusion of shed blood from postoperative draining. There are a number of devices for collecting postoperative shed blood, the principal differentiating characteristic being the existence or not of a washing process for the salvaged blood. When ICS is not used, PCS is normally performed using devices that recover and retransfuse shed blood to the patient as unwashed filtered whole blood. This blood-saving method became popular in cardiac surgery,18 but its use declined with the introduction of aprotinin. Nevertheless, it is increasingly used in orthopedic surgery, especially in total knee arthroplasty (TKA), where a substantial portion of blood loss occurs in the early postoperative period. This method has also been shown to be useful in hip and spine surgery.7,19 Potential side effects and contraindications are similar to those of ICS, although ICS has been used in patients with renal or hepatic dysfunction and coagulation disorders. Finally, it is generally agreed that the equivalent of at least one unit of blood needs to be recovered in order for the method to be cost-effective.

Erythrocytes (106/µL) Hematocrit (%) Hemoglobin (g/dL) Leukocytes (103/µL) Platelets (103/µL) Albumin (g/L) Pre-albumin (mg/dL) Alpha-1-antitrypsin (mg/dL) Haptoglobin (mg/dL) Complement C3 (mg/dL) C-reactive protein (mg/dL) IL-6 (pg/mL) IL-8 (pg/mL) TNF-α (pg/mL)

CONTROVERSIES AROUND UNWASHED SALVAGED BLOOD Several authors have questioned the safety of this blood-saving method because unwashed salvaged blood is diluted and may be contaminated with fat particles, bone fragments, free Hb, activated coagulation factors, fibrin degradation products or inflammatory mediators.20 Side effects have been reported to be of low incidence. Depending on the definition of side effect and monitoring practices, some side effects are serious, even lethal complications. Consequently, an upper limit on the volume of unwashed salvaged blood to be reinfused has been set. We shall briefly analyze these topics in the next section.

Hematology As shown in Table 2, unwashed salvaged blood from samples obtained in the first six postoperative hours have lower erythrocyte and platelet counts as well as lower Hb and Hct values than blood drawn from the patient in the preoperative period. Erythrocytes in unwashed salvaged blood present a normal osmotic fragility and maintain a normal energy metabolism (normal ATP and glucose uptake levels). In addition, shed blood erythrocytes have normal diphosphoglycerate levels, leading to an oxygen-delivery capacity even

Preoperative venous blood

Postoperative unwashed shed blood

4.6 ± 0.5 39.9 ± 4.1 13.7 ± 1.4 6.9 ± 1.9 213 ± 81 37.8 ± 0.7 24 ± 7 137 ± 34 136 ± 49 126 ± 35 0.5 ± 0.3 2.6 ± 1.2 7.8 ± 3.0 5.9 ± 2.4

3.7 ± 0.4** 30.2 ± 4.8** 10.6 ± 1.6** 3.2 ± 0.5** 28 ± 16** 29.7 ± 0.4* 19 ± 6 97 ± 31 75 ± 38* 98 ± 21 0.3 ± 0.2 443 ± 372** 223 ± 235** 20 ± 11*

Table 2. Hematological, biochemical and immunological characteristics of postoperative shed blood in comparison with preoperative venous blood in patients undergoing total knee arthroplasty

Data are the mean ± SD of 28 determinations. *P < 0.05, **P < 0.01.21,22 IL, interleukin; TNF, tumor necrosis factor.



superior to that of blood stored for > 15 days.21,22 Combined, these results seem to show that shed red cells are not significantly damaged, maintain their functionality, exhibit viability comparable to that seen in blood collected during the preoperative and intraoperative period, and have excellent rheological properties.23

Hemolysis Measurement of plasma free Hb has been used as an index of hemolysis and, certainly, its levels in unwashed salvaged blood were above the normal limits (Table 2). However, it has been previously reported that for a total unwashed salvaged blood volume of 1000–1500 mL there is enough circulating haptoglobin to bind the reinfused plasma free Hb, avoiding possible renal damage.19

Fat particles Return of fat probably increases the risk of fat embolism syndrome, which is mostly associated with acute lung injury. Very recently, we validated a new method, based on the use of the different hematological cytometers, that allows for the detection of fat particles in unwashed salvaged blood and verification of their elimination by means of several leukocyte filters, thereby avoiding this potential side effect.24–26 Also, there are data that support the efficacy of these filters in the elimination of tumor cells and bacteria although other authors recommend washing and irradiation of the blood.16

Hemostasis Unwashed salvaged blood contains certain activated coagulation factors as well as fibrinogen degradation products so that its reinfusion could lead to a coagulopathy. In a recent study, Biagini et al.27 found that unwashed salvaged blood reinfusion was associated with an activation of blood coagulation in patients undergoing total knee replacement. The authors concluded that the clinical relevance of this activation has to be tested in prospective studies with adequate sample size. However, in 13 studies with nearly 700 orthopedic patients, those who received an average of 560 mL of unwashed salvaged blood experienced neither clinically significant coagulopathy nor an increase in postoperative bleeding.7

45

Inflammatory mediators As for the presence of inflammatory mediators, we and other investigators have found increased serum levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α and anaphylatoxins in unwashed salvaged blood (Table 2). The use of a leukocyte filter between the wound and the drain blood container reduces IL-8 and TNF-α in unwashed salvaged blood, but at the same time triggers complement activation.23 Nevertheless, despite the high concentration of certain proinflammatory cytokines in unwashed salvaged blood that produces a temporary increase in circulatory levels after the infusion, there was no observed difference between reinfused and non-reinfused patients 12–18 hours post infusion.22,28 Moreover, it should be remembered that these cytokines are also present in stored blood, sometimes at levels even higher than those in unwashed salvaged blood.29,30

Immune response The influence of reinfused unwashed salvaged blood on cellular immune response is largely unknown. However, data from two recent reports seem to indicate a positive effect of unwashed salvaged blood on cellular immunity, namely a significant increase in the production of reactive oxygen species by the neutrophils31 and in natural killer cell precursor frequency32 in patients who received unwashed salvaged blood. These findings may support the hypothesis suggesting that reinfusion of unwashed salvaged blood may be another way of reducing postoperative infections after orthopedic surgery. They also support previous clinical studies in which infection rates after unwashed salvaged blood transfusion were lower than after conventional treatment despite one study showing an increased rate of wound infection rate in unwashed salvaged blood recipients.6

Bacterial contamination Bacterial contamination may occur during cell salvage, generally as a result of inappropriate use of the device or skin contamination. Another source of bacteria is the presence of infection at the operative site, a contraindication to blood salvage. In one study, only five of 200 unwashed salvaged blood samples from revision hip surgery showed bacterial growth (Staphylococcus epidermidis, Staphylococcus coagulase negative, Propi-



onibacterium acnes, Corynebacterium bovis, Corynebacterium minutisimun and Moraxella species). In another study of patients undergoing the same type of surgery, the analysis of 223 devices yielded similar results. Overall, the authors concluded that bacterial growth, whenever it occurs, is tolerated by the immunocompetent patient under antibiotic prophylaxis and does not lead to the development of sepsis.7 Although the problems discussed in this paper may occur infrequently, they are in themselves serious (e.g., acute cardiorespiratory dysfunction, respiratory distress and upper airway edema, coagulopathy).33–35 Beside these reported complications, there exist a large number of clinical studies that seem to support the notion that retransfusion of unwashed wound blood is safe. In an evaluation of 2190 unwashed salvaged blood reinfusions after elective lower limb arthroplasty in 35 Dutch hospitals, only 71 side effects were reported: vagal reaction (6; 0.27%), hypotension (3; 0.14%), fever > 38°C (13; 0.59%), and transient shivering (49; 2.24%) (R. Slappendel, personal communication). The incidence of real side effects is only 1%, i.e. lower than the side effects reported for allogeneic blood transfusion. Characteristically, for a risk evaluation, 10 or 100 studies showing no side effect cannot negate one reported severe complication. For this reason, several authors prefer intra- and postoperative retransfusion with washed salvaged blood.20 A large, well-conducted, carefully planned randomized trial is urgently needed to address this issue definitively. EFFECTIVENESS OF PERIOPERATIVE RED CELL SALVAGE One of the major advantages of perioperative cell salvage is that it is logistically easier to organize than other autotransfusion techniques. It is not affected by cancellation of the operation and is applicable in emergencies cases. The salvaging of blood does not involve any manipulation of the patient’s physiology and is therefore applicable in patients where other techniques are not, e.g. in anemic patients.17 As for clinical trial results, a meta-analysis of the effectiveness of cell salvage in minimizing perioperative allogeneic transfusion concluded that in orthopedic surgery devices producing either washed or unwashed cells decreased the frequency of exposures to allogeneic blood to a similar degree when compared with a control group [RR, 0.33 (95% CI, 0.30–0.51) vs. 0.35 (95% CI,

0.26–0.46) for washed and unwashed blood, respectively].36 The effectiveness of perioperative red cell salvage in orthopedic surgery was corroborated by a more recent meta-analysis indicating the same reduction of RR of allogeneic blood transfusion (0.35; 95% CI, 0.21– 0.52) although the benefit seems to be slightly higher when washed blood is used.9 However, as stated by the authors, methodological quality of the trials was poor. As the trials were not blinded and lacked adequate concealment of treatment allocation, transfusion practices may have been influenced by knowledge of the patient’s treatment status, thus biasing the results in favor of cell salvage.9 The effectiveness of cell salvage may be enhanced when applied to surgical procedures allowing both ICS and PCS, or when used in combination with PABD. Borghi et al.37 used this combination of autotransfusion methods in a prospective series of 1785 patients undergoing primary or revision arthroplasty of the knee or hip, and only 7.3% of patients received allogeneic blood transfusions. As for PABD, the contribution of cell salvage to allogeneic blood transfusion reduction decreased if a transfusion protocol was adopted (RR, 0.62; 95% CI, 0.50–0.78).9 From these data, it can be inferred that a transfusion protocol intrinsically reduces the RR of allogeneic blood transfusion by 25–30% and must therefore be the first strategy to be included in a blood-saving program. Between 1994 and 2003, Téllez et al.38 studied a prospective series of 1559 patients undergoing primary (91%) or revision (9%) surgery of the knee (without tourniquet), hip or spine. In addition to a restrictive and uniform transfusion protocol (transfusion trigger: Hb < 7.5 g/dL and/or signs and symptoms of acute anemia), they used the Compact Advance and Recovery 797 apparatus (Dideco Sorin, Quedgeley, UK) to perform ICS and PCS in all procedures. The anesthesiologist was responsible for assessing indications for allogeneic blood transfusion during the entire hospitalization period, and no patient was a participant in a PABD program. Almost 99% of the patients received salvaged red cells, but only 2.1% (32 patients) required allogeneic blood transfusion. Mean Hb at discharge was 10.8 g/dL. These excellent results seem to further support the effectiveness of perioperative cell salvage in combination with a transfusion protocol and raise the question about the need for PABD in these patients when cell salvage is available. Usually a tourniquet is used during knee surgery and, under these conditions, ICS is not possible. However, the



tourniquet is deflated shortly before wound closure and substantial blood loss occurs in the early postoperative period. During the first 6 hours, this blood may be collected and reinfused, either washed or unwashed. Thomas et al.39 randomized 231 patients either to receive their postoperative wound drainage after processing in a Cell Saver 5 (Haemonetics) or to have this wound drainage discarded. Allogeneic blood transfusion was given if Hb concentration fell below 9 g/dL. Only 7% of the patients in the autotransfusion group required allogeneic blood transfusion compared with 28% in the control group (P < 0.001). In addition, there was a higher incidence of infection requiring intervention in the allogeneic blood transfusion group. The authors concluded that in this type of surgery PCS is a safe and effective method for reducing the use of allogeneic blood transfusion. Recently, a new cell-processing device (OrthoPAT, Haemonetics), specifically designed for orthopedic surgery, has been introduced. The system seems to be useful in orthopedic and trauma patients with preoperative Hb no lower than 13 g/dL, especially those undergoing knee and hip arthroplasty or spinal surgery.40 Uninterrupted intra- and postoperative cell salvage using OrthoPAT reduced the percentage of patients receiving allogeneic blood transfusion from 71% to 33% in primary THA and from 95% to 73% in revision THA.41 As this machine is small, simple to operate and does not require devoted personnel, we deem it suitable for PCS in the post-anesthesia recovery unit. Between November 2003 and June 2004, perioperative data were prospectively collected from 100 consecutive knee arthroplasty patients (28 men/72 women; 69 ± 8 years) undergoing PCS with OrthoPAT. The salvage procedure was performed until the postoperative blood loss rate was < 60 mL/hour, for a maximum of 6 hours (2.9 ± 0.7 hours), and 608 ± 342 mL of shed blood were processed to yield 280 ± 104 mL of packed red cells (Hct 65–70%). The transfusion trigger both for allogeneic and autologous blood was Hb < 8 g/dL. Reinfusion was performed in 77% of patients, with 25% of patients receiving allogeneic blood transfusions. We believe that this allogeneic transfusion rate, although lower than that of a retrospective control group (54%), might be further reduced by extending the collection-processing time up to the sixth postoperative hour, regardless of the blood loss rate, and by giving back all the salvaged autologous blood, regardless of Hb level (five of 22 non-reinfused patients received allogeneic blood transfusions later on).

47

Reinfusion of unwashed salvaged blood is the most commonly used blood-saving method for knee arthroplasty. As stated above, the meta-analysis by Huet et al.36 showed that washed and unwashed blood were equally effective in reducing the need for allogeneic blood transfusion. However, this meta-analysis has been the subject of criticism because the number of patients in the included studies was small and also because there were some studies failing to show a blood-saving effect.42,43 The problem for some authors is the low volume and the low Hct of the drained blood (i.e., low amount of recovered red blood cells and low percentage with regard to total blood volume), rendering so many efficacy studies unexplainable. In addition, they feel that regular retransfusion of drained blood poses a problem of legitimacy (transfusion of hemolyzed and activated blood without indication for transfusion) and of cost-efficacy (systems being paid for unnecessary retransfusions).20 We therefore compiled data from randomized and observational studies on the effectiveness of unwashed blood salvage for reducing allogeneic blood transfusion requirements in knee replacement surgery performed between 1999 and 2005. Included in the study were at least 100 patients and a control group. As shown in Table 3, the allogeneic blood transfusion rate in the unwashed salvaged blood group (20%; 213/1085) was significantly lower than that of the control group (58%; 575/983) (RR, 0.34; P < 0.01).44 In one of the studies included in this analysis,44 we compared the requirements for allogeneic blood transfusion in 200 patients undergoing TKA with unwashed salvaged blood return (group 2) with those of 100 control patients (group 1). The percentage of patients with allogeneic blood transfusion (48 vs. 11%, for groups 1 and 2, respectively; P < 0.01) (RR, 0.23) and number of packed red cells/patient index were lower in the unwashed blood salvage group (1.31 ± 1.27 vs. 0.29 ± 0.87 units/patient, respectively; P < 0.01). The differences in transfusion requirements persisted even after patient stratification according to preoperative Hb: 42.6 vs. 3.2% for Hb > 13 g/dL (P < 0.01) (RR, 0.08) and 59.4 vs. 23% for Hb ≤ 13 g/dL (P < 0.01) (RR, 0.39). In addition, the amount of unwashed salvaged blood returned to patients in this particular study (the equivalent of 0.98 ± 0.4 units/patient, calculated according to preoperative Hct and postoperative unwashed salvaged blood Hct22) seems to be as effective as one unit



Table 3. Summary of the relative risk of allogeneic blood transfusion associated with postoperative unwashed shed blood return in primary total knee arthroplasty (data taken from reference 44) Unwashed salvaged blood

Control

Study

Year

Allogeneic transfusion/Total (%)

Allogeneic transfusion/Total (%)

Relative risk

Henderson et al. Díaz & Moral Peter et al. Sinha et al. Fernández et al. Sanz et al. Steinberg et al. Muñoz et al. All studies

1999 1999 2001 2001 2002 2004 2004 2005

35/159 13/91 30/160 8/50 26/81 43/250 36/194 22/200 213/1085

134/180 25/57 67/93 44/50 56/82 112/250 89/171 48/100 575/983

0.30 0.33 0.26 0.25 0.47 0.38 0.36 0.23 0.34

22 14 19 22 32 17 19 11 20

74 44 72 88 68 45 52 48 58

Values are mean or range; ALB, albumin; CATS, continuous autotransfusion system; PFHB, plasma free hemoglobin; PLT, platelets; RBC, red blood cells; TP, total protein; WBC, leukocytes; NA, not applicable (data taken from reference 14).

of PABD for avoiding allogeneic blood transfusion.45 As 20–25% of the anemic patients with unwashed blood salvage return both in this study and in the one conducted by Friederichs et al.46 needed allogeneic blood transfusion, we combined the administration of intravenous iron sucrose (200 mg, day 0 and postoperative day 2) and recombinant human erythropoietin (40,000 IU, day 0). Preliminary data indicate that this combination of blood-saving methods virtually abrogates the need for allogeneic blood transfusion. It is, however, quite probable that a substantial proportion of patients with preoperative Hb > 13 g/dL would not benefit from PCS, either with washed or unwashed blood, given the low transfusion risk.5,6 Compared with controls, in a series of 365 patients who underwent surgery for total knee replacement, Steinberg et al.47 reported that postoperative salvage and reinfusion of unwashed salvaged blood decreased the requirement for allogeneic blood transfusion by 65% and also reduced the packed red cell/patient index. In addition, they reported that the preoperative Hb cut-off point for receiving a blood transfusion was 13.25 g/dL in both groups. These data clearly indicate that better patient selection is needed. However, as postoperative blood loss is unpredictable, we believe that the use of an autotransfusion system would benefit patients with preoperative Hb ≤ 14 g/dL to provide a wider safety margin.

In spine surgery, the effectiveness of ICS is controversial and its use is recommended only for selected operations with high intraoperative blood loss.48–50 As for PCS, we initiated a blood-saving program in spine surgery introducing the use of unwashed salvaged blood recovered postoperatively with the ConstaVac CBCII (Stryker, Kalamazoo, MI). The initial study group was comprised of 28 consecutive patients who had undergone lumbar spinal fusion and from whom postoperative shed blood was collected and reinfused (group B). In comparison with a previous series of 31 patients (group A), the procedure reduced allogeneic blood requirements by almost 30% (P < 0.05) without any increase in postoperative complications (Figure 1).22 Despite these good results, it became evident that the exclusive use of postoperative unwashed salvaged blood was not enough to avoid allogeneic blood transfusion and we decided to complement it with a short-time PABD protocol. Eligible patients (Hb > 12 g/dL) were asked to donate two units of autologous blood, the first one being donated 7–10 days before surgery (real PABD). The second unit was drawn the day before surgery and the donated blood volume was replaced with saline (delayed isovolemic hemodilution). Between 1999 and 2000, 64 patients undergoing instrumented lumbar spinal fusion were included in this new protocol (group C). On the one hand, despite a higher perioperative blood loss, due to an increased proportion of revision surgery, 80% of



Transfusions (unit/pt)

4 **

3 2 1 * 0 Group A

Group B

* ** Group C #

Figure 1. Blood transfusion in patients undergoing instrumented lumbar spinal surgery. Group A: control; group B: postoperative unwashed salvaged blood; group C: preoperative autologous blood donation plus unwashed salvaged blood. All data are expressed as the mean ± SE (n). *P < 0.05, **P < 0.01. #Seven patients donated three units (data taken from references 19, 22). , total transfusions; , allogeneic intraoperative; , allogeneic postoperative; , autologous intraoperative; , autologous postoperative

patients avoided exposure to allogeneic blood transfusion with this blood-saving strategy (Figure 1) and postoperative complications were reduced by 50%. On the other hand, 96% of PABD units were transfused and the overall transfusion rate was higher than in group A, suggesting a tendency to more liberal transfusion criteria when autologous blood is available.15 Hence, the addition of PCS might be of use to complement ICS51 and to reduce PABD requirements, as well as in patients undergoing extensive instrumented spine fusion where postoperative blood loss is substantial. Finally, ICS should be considered for all acute emergency procedures. In severely traumatized patients with intense hemorrhage, the use of ICS may literally be lifesaving, possibly because of the limited supply of allogeneic blood transfusion to compensate for extreme blood loss. For these reasons, it is recommended that at least one ICS device always be available in emergency rooms and operating units and that the attending staff be well-trained in its proper use. Unfortunately, there are a number of factors that limit the use of ICS in the acute trauma setting. A pragmatic analysis of use of the

49

cell-saver device found that only 25% of the patients actually had reinfusion of autologous blood.52 The reasons were threefold: (i) it was difficult to predict who would require the blood; (ii) there was inadequate collection of blood in most patients; and (iii) abdominal trauma was associated with contamination of blood in many cases. In a retrospective series of 238 spine fractures, Cavallieri et al.53 reported a reduction in the use of allogeneic blood transfusion when ICS was used, but still found it difficult to predict which patients would benefit. Similar results were published by Goulet et al.54 for patients with pelvic, open acetabular or spine fractures. In summary, while ICS offers many potential advantages as an alternative to allogeneic blood transfusion in elective orthopedic surgery, its role in the polytraumatized patient has yet to be defined. CONCLUSIONS • From data reviewed in this paper, it can be concluded that perioperative salvage of blood, either intraoperative or postoperative, seems to be an excellent source of functional and viable red cells, without many of the transfusion-related risks and with few side effects. • The effectiveness of perioperative cell salvage to reduce exposure to allogeneic blood transfusion is greatly enhanced by the implementation of a restrictive transfusion protocol. • For certain types of surgery (e.g., scoliosis or revision hip), the effectiveness increases when combined with other blood-sparing strategies (PABD, erythropoietin, intravenous iron), especially in anemic patients. • Perioperative cell salvage may reduce the number of required PABD units or render PABD unnecessary. • Based on current allogeneic blood transfusion costs, the equivalent of at least one unit of blood needs to be recovered for these techniques to be cost-effective. Therefore, these procedures should be used on a caseby-case basis. ACKNOWLEDGEMENT GIEMSA studies are supported by grant FIS PI02/1826 from Instituto de Salud Carlos III (Spain), and the European Union.



REFERENCES 1 Stanworth SJ, Cockburn HA, Boralessa H, Contreras M. Which groups of patients are transfused? A study of red cell usage in London and southeast England. Vox Sang 2002; 83: 352–7. 2 Kleinman S, Marshall D, AuBuchon J, Patton M. Survival after transfusion as assessed in a large multistate US cohort. Transfusion 2004; 44: 386–90. 3 Shandler A. Emerging risks and outcomes of blood transfusion in surgery. Semin Hematol 2004; 41(Suppl. 1): 117–24. 4 Carson JL, Altman DG, Duff A, et al. Risk of bacterial infection associated with allogenic blood transfusion among patients undergoing hip fracture repair. Transfusion 1999; 39: 694–700. 5 Bierbaum BE, Callaghan JJ, Galante JO, et al. An analysis of blood management in patients having a total hip or knee arthroplasty. J Bone Joint Surg Am 1999; 81: 2–10. 6 Rosencher N, Kerkkamp HE, Macheras G, et al. Orthopedic Surgery Transfusion Hemoglobin European Overview (OSTHEO) study: blood management in elective knee and hip arthroplasty in Europe. Transfusion 2003; 43: 459–69. 7 Muñoz M, García-Vallejo JJ, Lópezandrade A, et al. Autotransfusión postoperatoria en cirugía ortopédica. Un análisis de la calidad, seguridad y eficacia de la sangre recuperada de los drenajes postoperatorios. Rev Esp Anestesiol Reanim 2001; 48: 131–40. 8 Brecher ME, Goodnough LT. The rise and fall of preoperative autologous blood donation. Transfusion 2001; 41: 1459–62. 9 Carless P, Moxey A, O’Connell D, Henry D. Autologous transfusion techniques: a systematic review of their efficacy. Transfus Med 2004; 14: 123–44. 10 Waters JH. Overview of blood conservation. Transfusion 2004; 44(Suppl. 1): 1S– 3S. 11 Goodnough LT, Despotis GJ, Merkel K, Monk TG. A randomized trial comparing acute normovolemic hemodilution and preoperative autologous blood donation in total hip arthroplasty. Transfusion 2000; 40: 1054–7. 12 Shander A, Rijhwani TS. Acute normovolemic hemodilution. Transfusion 2004; 44(Suppl.): 26S–34S. 13 Tobias JD. Strategies for minimizing blood loss in orthopedic surgery. Semin Hematol 2004; 41(Suppl. 1): 145–56.

14 Muñoz M, Ariza D, Romero A, et al. Evaluación del sistema de autotransfusión OrthoPAT®, utilizando modelos experimentales de simulación de recuperación de sangre intra y postoperatoria. Rev Esp Anestesiol Reanim 2005; 52: 235–41. 15 Scottish Intercollegiate Guidelines Network. Perioperative Blood Transfusion for Elective Surgery. A National Clinical Guideline, 2001 (Update in 2004). Accessed at http://www.sign.uk. 16 Hansen E, Knuechel R, Altmeppen J, Taeger K. Blood irradiation for intraoperative autotransfusion in cancer surgery: demonstration of efficient elimination of contaminating tumor cells. Transfusion 1999; 39: 608–15. 17 Mercuriali F. Future Role of Autologous Blood Transfusion. ‘My own blood’ Symposium, Göteborg, 2002. 18 Salas J, Muñoz M, Perán S, Negri S, de Vega NG. Autotransfusion of shed mediastinal blood after cardiac operations. Ann Thorac Surg 1995; 59: 257–8. 19 Muñoz M, García-Vallejo JJ, Ruiz MD, et al. Transfusion of postoperative shed blood: laboratory characteristics and clinical utility. Eur Spine J 2004; 13(Suppl. 1): S107–13. 20 Hansen E, Pawlik M. Reasons against the retransfusion of unwashed wound blood. Transfusion 2004; 44(Suppl. 1): 45S–53S. 21 Muñoz M, Sánchez-Arrieta Y, GarcíaVallejo JJ, et al. Autotransfusión pre y postoperatoria. Estudio comparativo de la hematología, bioquímica y metabolismo eritrocitario en sangre predonada y sangre de drenaje postoperatorio. Sangre (Barc) 1999; 44: 433–50. 22 Sebastián C, Romero R, Olalla E, et al. Postoperative blood salvage and reinfusion in spinal surgery. Blood quality, effectiveness and impact on patient blood parameters. Eur Spine J 2000; 9: 458–65. 23 Dalen T, Bengtsson A, Brorsson B, Engstrom KG. Inflammatory mediators in autotransfusion drain blood after knee arthroplasty, with and without leucocyte reduction. Vox Sang 2003; 85: 31–9. 24 Ramírez G, Romero A, García-Vallejo JJ, Muñoz M. Detection and removal of fat particles from postoperative salvaged shed blood in orthopedic surgery. Transfusion 2002; 42: 66–75. 25 Muñoz M, Romero A, Campos A, Ramírez G. Detection of fat particles in postoperative shed blood from orthopaedic surgery using haematologic cell counter. Transfusion 2004; 44: 620–2.

26 Muñoz M, Romero A, Ariza D, et al. Capacidad de los filtros leucoreductores en la eliminación de partículas de grasa en sangre recuperada. Un estudio in vitro. Rev Esp Anestesiol Reanim 2005; 52: 81– 7. 27 Biagini D, Filippucci E, Agnelli G, Pagliaricci S. Activation of blood coagulation in patients undergoing postoperative blood salvage and re-infusion of unwashed whole blood after total knee arthroplasty. Thromb Res 2004; 113: 211–15. 28 Muñoz M, Cobos A, Campos A, et al. Impact of postoperative shed blood transfusion, with or without leukocyte reduction, on acute phase response to surgery for total knee replacement. Acta Anaesthesiol Scand 2005; 49: 1182–90. 29 Jacobi KE, Wanke C, Jacobi A, Weisbach V, Hemmerling TM. Determination of eicosanoid and cytokine production in salvaged blood, stored blood cell concentrates, and whole blood. J Clin Anesth 2000; 12: 94–9. 30 Kristiansson M, Soop M, Saraste L, Sundqvist KG. Cytokines in stored red blood cell concentrates: promoters of systemic inflammation and stimulators of acute transfusion reactions? Acta Anaesthesiol Scand 1996; 40: 496–501. 31 Iorwerth A, Wilson C, Topley N, Pallister I. Neutrophil activity in total knee replacement: implications in preventing post-arthroplasty infection. Knee 2003; 10: 111–13. 32 Gharehbahian A, Haque G, Truman C, et al. Effect of autologous salvaged blood on postoperative natural killer cell precursor frequency. Lancet 2004; 363: 1025– 30. 33 Murray DJ, Gress K, Weinstein SL. Coagulopathy after reinfusion of autologous scavenged red blood cells. Anesth Analg 1992; 75: 125–9. 34 Woda R, Tetzlaff JE. Upper airway oedema following autologous blood transfusion from a wound drainage system. Can J Anaesth 1992; 39: 290–2. 35 Wheeler TJ, Tobias JD. Complications of autotransfusion with salvaged blood. J Post Anesth Nurs 1994; 9: 150–2. 36 Huet C, Salmi LR, Fergusson D, et al. A meta-analysis of the effectiveness of cell salvage to minimize perioperative allogeneic blood transfusion in cardiac and orthopaedic surgery. International Study of Perioperative Transfusion (ISPOT) Investigators. Anesth Analg 1999; 89: 861–9.



37 Borghi B, Pignotti E, Montebugnoli M, et al. Autotransfusion in major orthopaedic surgery: experience with 1785 patients. Br J Anaesth 1997; 79: 662–4. 38 Téllez J, Velázquez J, Castillo A, Ortells PM, Ruiz JL. Cirugía mayor ortopédica: 10 años de experiencia en autotransfusión intraoperatoria. In: Muñoz M (ed.), Actualización en Medicina Transfusional Perioperatoria. SPICUM: Málaga, 2004, pp. 135–46. 39 Thomas D, Wareham K, Cohen D, Hutching H. Autologous blood transfusion in total knee replacement surgery. Br J Anaesth 2001; 86: 669–73. 40 Gramolini R. The impact of the perioperative autotransfusion system OrthoPAT Haemonetics in orthopedic surgery. TATM 2002; 4(Suppl. 1): 27–9 (abstract). 41 Khiroya R, Boralessa H, Cockburn H. Intra- and postoperative uninterrupted cell salvage in hip replacement surgery. TATM 2003; 5(Suppl 1): 57 (abstract). 42 Niskanen RO, Korkala OL, Haapala J, et al. Drainage is of no use in primary uncomplicated cemented hip and knee arthroplasty for osteoarthritis: a prospective randomized study. J Arthroplasty 2000; 15: 567–9.

43 Umlas J, Foster RR, Dalal SA, et al. Red cell loss following orthopedic surgery: the case against postoperative blood salvage. Transfusion 1994; 34: 402–6. 44 Muñoz M, Ariza D, Garcerán MJ, Gómez A, Campos A. Benefits of postoperative shed blood reinfusion in patients undergoing unilateral total knee replacement. Arch Orthop Trauma Surg 2005; 125: 385–9. 45 Woolson ST, Wall WW. Autologous blood transfusion after total knee arthroplasty. A randomized, prospective study comparing predonated and postoperative salvage blood. J Arthroplasty 2003; 18: 243–9. 46 Friederichs MG, Mariani EM, Bourne MH. Perioperative blood salvage as an alternative to predonating blood for primary total knee and hip arthroplasty. J Arthroplasty 2002; 17: 298–303. 47 Steinberg EL, Ben-Galim P, Yaniv Y, Dekel S, Menahem A. Comparative analysis of the benefits of autotransfusion of blood by a shed blood collector after total knee replacement. Arch Orthop Trauma Surg 2004; 124: 114–18. 48 Abildgaard L, Aaro S, Lisander B. Limited effectiveness of intraoperative autotrans-


49

50

51

52

53

54

51

fusion in major back surgery. Eur J Anaesthesiol 2001; 18: 823–8. Cha CW, Deible C, Muzzonigro T, et al. Allogeneic transfusion requirements after autologous donations in posterior lumbar surgeries. Spine 2002; 27: 99–104. Chanda A, Smith DR, Nanda A. Autotransfusion by cell saver technique in surgery of lumbar and thoracic spinal fusion with instrumentation. J Neurosurg 2002; 96(3 Suppl.): 298–303. Behrman MJ, Keim HA. Perioperative red blood cell salvage in spine surgery. A prospective analysis. Clin Orthop 1992; 278: 51–7. Jurkovich GJ, Moore EE, Medina G. Autotransfusion in trauma. A pragmatic analysis. Am J Surg 1984; 148: 782–5. Cavallieri S, Riou B, Roche S, et al. Intraoperative autologous transfusion in emergency surgery for spine trauma. J Trauma 1994; 36: 639–43. Goulet JA, Bray TJ. Complex acetabular fractures. Clin Orthop 1989; 240: 9–20.