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Blood management strategies in lower limb arthroplasty
BASIC SCIENCE
Blood management strategies in lower limb arthroplasty
departmental practices for identifying and addressing all possible variables to optimise a patient’s pre-operative haemoglobin, minimising peri- and post-operative bleeding and having clear guidelines for transfusion so that patients are not transfused unnecessarily by overzealous staff. The various methods of blood management in lower limb arthroplasty are discussed below.
Lorcan McGonagle John J Murnaghan
Pre-operative autologous donation Pre-operative autologous blood donation (PABD) aims to provide a supply of safe blood for patients undergoing surgery who might need a blood transfusion. It increases the patient’s total red blood cell (RBC) mass due to the PABD induced stimulation of erythropoiesis before elective surgery.4 It avoids the risk of an immunogenic reaction, and possible transmission of blood borne viruses associated with an allogenic blood transfusion. It may also be more acceptable to patients who are reluctant to receive an allogenic transfusion for religious or personal reasons. Blood is collected pre-operatively. The sudden drop in haemoglobin that is caused stimulates erythropoiesis as the body tries to raise the blood haemoglobin concentration back to a normal level. It is expected that the patient’s haemoglobin will have normalized by the day of surgery, and therefore any blood lost at the time of surgery can be replaced with the blood that was pre-donated. Pre-operative autologous blood donation typically reduces pre-operative haemoglobin levels by 1.23 g/dl, and has been shown to decrease the rate of allogenic transfusion by 43%.5 The timing of donation varies slightly between practices; however, it has been shown that it takes an average of 36 days for haemoglobin levels to recover to pre-donation levels,6 suggesting that the time interval from donation to surgery should be no shorter than this. Withdrawing two units at a single sitting, rather than one unit at two separate sittings, results in a larger increase in RBC mass.7 This single large donation seems to stimulate erythropoiesis more aggressively and should be the preferable practice, provided the patient can cope with it physiologically. Pre-operative autologous donation of blood being made available for post-operative transfusion is very safe. However, it has high non-usage rates (45%),8 indicating that its routine use is unnecessary and that is should be reserved for selected cases. Therefore, it is rarely used in the arthroplasty setting nowadays.
Abstract Rates of post-operative allogenic blood transfusion in primary hip and knee arthroplasty can be as high as 50%. Risks of allogenic blood transfusion include increased risk of orthopaedic and non-orthopaedic infection in addition to the general risks of transfusion. Measures have been developed to minimise the requirements for post-operative allogenic blood transfusion in lower limb arthroplasty. These include preoperative screening of patients, risk stratification, raising pre-operative haemoglobin pharmacologically, pre-operative autologous donation, minimising intra- and post-operative blood loss and suitable post-operative transfusion practices. Pharmacological, haematological and surgical methods of blood management in lower limb arthroplasty are discussed.
Keywords arthroplasty; blood; hip; knee; management
Introduction The UK blood transfusion service collects about 1,900,000 blood donations per year. According to the United Kingdom National Joint Registry (UK NJR) there were 82,267 primary total knee replacements and 76,274 primary total hip replacements in 2013. Rates of allogenic blood transfusion (ABT) have been reported to be as high as 50% in elective primary total knee replacement1 and 56% in primary total hip replacement.2 Transfusion rates in revision hip and knee arthroplasty surgery are higher still. Direct comparison of transfusion rates between different studies can be difficult, as different institutes often have different transfusion triggers/protocols, and the details may not be specified in the paper. High transfusion rates put a considerable strain of the availability of donated blood. Allogenic blood transfusion has been shown to be associated with an increased risk of orthopaedic and non-orthopaedic infections in elective hip and knee arthroplasty.3 With an aging population, it is expected that the number of arthroplasties performed per year will continue to increase. There is a limited availability of allogenic blood, and transfusion of allogenic blood carries risks to the recipient. In view of these issues there is a strong emphasis on setting up routine
Erythropoietin Erythropoietin (EPO) is an erythropoiesis-stimulating glycoprotein that is 90% made by the kidneys. EPO allows erythroid precursor cells in the bone marrow to mature and eventually become erythrocytes. This process takes over 1 week, and erythrocytes have a normal survival time of 120 days. Pharmaceutical EPO is human erythropoietin produced in cell culture using recombinant DNA technology. It is administered prior to surgery and often for a few days after surgery to patients deemed at high risk of post-operative transfusion (haemoglobin <13 g/ dl) in order to boost pre-operative haemoglobin. It can be administered intravenously or subcutaneously. There is evidence that pre-operative administration of EPO to patients deemed to be at high risk of transfusion results in higher
Lorcan McGonagle (FRCS Tr & Orth) Clinical Arthroplasty Fellow, Holland Orthopaedic and Arthritic Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Conflict of interest: None declared. John J Murnaghan (FRCSC) Orthopaedic Surgeon, Associate Professor Surgery, Holland Orthopaedic and Arthritic Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Conflict of interest: None declared.
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Please cite this article in press as: McGonagle L, Murnaghan JJ, Blood management strategies in lower limb arthroplasty, Orthopaedics and Trauma (2014), http://dx.doi.org/10.1016/j.mporth.2014.11.004
BASIC SCIENCE
oozing.13 Application of a tourniquet may also tether the quadriceps muscle intra-operatively, affecting patellar tracking.
immediate post-operative haemoglobin levels and lower rates of allogenic transfusion compared with controls. However, in view of the large cost associated with this drug, it was deemed not to be cost effective when compared to allogenic blood transfusion administrated as and when necessary.9 Potential side effects of EPO use include: headache joint or muscle aches, pain, or soreness nausea/vomiting/indigestion weight loss sores in the mouth
Tranexamic acid In the final common pathway of the coagulation cascade, thrombin acts upon fibrinogen, converting it to fibrin, leading to fibrin deposition and the activation of platelets to form blood clots. Plasmin is a proteolytic enzyme derived from plasminogen that hydrolyses fibrin into soluble products. Tranexamic acid is an antifibrinolytic that competitively inhibits the activation of plasminogen to plasmin. At high concentrations it is a noncompetitive inhibitor of plasmin. It works by blocking the lysine-binding sites of the plasminogen molecule, which prevents it from binding to fibrin, as outlined in Figure 1. Its half life is approximately 2 h and it is excreted by the kidneys.14 A large multicentre review of hip and knee replacements has shown that intravenous tranexamic acid significantly decreases rates of allogenic of autologous blood transfusion and early postoperative complications, including thromboembolism and renal failure. It is suggested that a dose of 2000 mg has the best effectiveness and safety profile.15 Tranexamic acid has traditionally been given via the intravenous route; however, proponents for topical administration state that topical (intra-articular) administration will provide a maximum concentration of tranexamic acid at the bleeding site whilst being associated with 70% lower systemic absorption, theoretically reducing any side effects. Topical tranexamic acid has been shown to be effective (1 g/50 ml saline) in decreasing the absolute risk of transfusion by almost 20%, as well as pre-topost haemoglobin drop by 0.84 g/dL in total hip replacements.16 Topical tranexamic acid reduced the absolute risk of blood transfusion by 15.4% and reduced blood loss by 168 ml in total knee replacements.17 In both of these studies the control drug was normal saline. Tranexamic acid is also available for oral administration. This is infrequently used in the orthopaedic surgery setting, although there is some evidence for its use. It has been shown to result in a lower rate of transfusion, with a similar complication rate to intravenous tranexamic acid. The oral dose used was slightly higher than the intravenous dose, but it is slightly cheaper, which is pertinent in view of the constraints on healthcare budgets.18 The safest and most effective route of administration and dose of tranexamic acid is yet to be ascertained. Although it has been shown to decrease blood loss and transfusion requirements in general, it is unclear how beneficial it is to patients who are at a low risk of transfusion, and whether it should be prescribed to all patients or just high risk patients.
Iron supplement pre- and post-operatively Iron is a transition metal that forms the core of the haemoglobin molecule to which the alpha and beta proteins are attached. Daily requirements of iron for erythropoiesis are approximately 20e30 mg, and it is absorbed in the duodenum. Pre-operative oral iron supplementation is cheap and aims to maximize iron stores and subsequently haemoglobin prior to surgery. It is usually administered for 3e4 weeks pre-operatively. It can increase pre-operative haemoglobin and decrease the postoperative drop. This beneficial effect is most pronounced in patients with pre-operative anaemia due to iron deficiency, whilst those with normal haemoglobin levels generally do not benefit from pre-operative iron supplements.10 Gastric side effects such as dyspepsia, nausea, diarrhoea and black stool may limit patient compliance with drug therapy. Post-operatively, routine administration of oral iron supplements to anaemic patients does not significantly increase iron levels, although there is some evidence that administration of intravenous iron in the first 1e3 days post-operatively can result in a significantly higher haemoglobin levels at 72 h post-op, resulting in lower rates of post-op allogenic blood transfusion.11,12
Tourniquets A tourniquet is a device used to limit bleeding or blood flow. In the lower limb setting it is typically elevated to 100e150 mmHg above systolic blood pressure. The limb is usually drained of venous blood by elevation or exsanguination before inflation. Although not practical for a hip replacement, tourniquets are frequently used in knee replacement surgery. Their primary purpose is to limit intra-operative blood loss and improve visibility at the time of surgery. However, they are associated with a slight increase in post-operative blood loss compared with no tourniquet use, and there is no convincing evidence that they limit blood loss overall. This is because once the tourniquet is deflated, the vessels that were incised intra-operatively will start to bleed, resulting in hidden blood loss and bruising; conversely, when a tourniquet is not used these bleeding vessels are likely to be identified and cauterised intra-operatively. Clinical thromboembolic events have been shown to be higher amongst patients who had a tourniquet applied compared to those who did not. This is probably influenced by the stasis that occurs due to the temporary cessation of venous return in the limb. Tourniquet use has also been shown to result in a higher incidence of skin problems, including blistering, haematoma and
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Controlled anaesthetic hypotension Deliberate controlled lowering of mean arterial blood pressure by the anaesthetist intra-operatively has been shown to significantly decrease intra-operative bleeding.19 Lower blood pressure decreases the risk of dislodging a recently formed clot at the operative site. This can be performed safely with general, spinal and epidural anaesthetics in appropriately trained hands. Spinal anaesthetic has been shown to be more effective than general anaesthetic in decreasing transfusion rates in hip and knee
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BASIC SCIENCE
Figure 1 Diagram of the mechanism of action of tranexamic acid (reproduced with permission from CJ Dunn, KL Goa. Tranexamic acid. Drugs 1999:57(6);1005e1032 via Springer Rightslink).
arthroplasty.20 Spinal anaesthesia is thought to reduce bleeding in arthroplasty surgery by lowering arterial and venous blood pressure. This reduced bleeding effect may be less prevalent in knee replacement surgery if a tourniquet is used, as the effect of the anaesthetic will be decreasing by the time the tourniquet is deflated.
effective than lavage alone in minimising blood loss as it will have more time to exert its vasoconstrictive effects on the local tissues, thereby decreasing blood loss.
Intra-operative cell salvage Cell salvage is another form of autotransfusion. It is typically used in cases with medium-to-high volumes of blood loss. This process allows almost immediate reinfusion of blood that is lost intra-operatively. A normal suction device would simply remove blood from the surgical site and deposit it as waste. With cell salvage, the sucker tip is focused on the area of bleeding, and blood is salvaged through a double lumen catheter, where dilute heparinised saline is also administered. The aspirate is passed through a gross filter to remove debris before entering the reservoir. The filtered aspirate is deposited in the reservoir and processed by differential centrifugation to separate the red blood cells from the other blood components. As the red cells are deposited by centrifugation, the supernatant is fractionated off, removing remaining debris, platelets, free haemoglobin, irrigation fluid, activated clotting factors, myoglobin, heparin and damaged red cell stroma. Once the haematocrit of the deposited RBCs reaches approximately 50%, the cells are washed with saline. Remaining erythrocytes are resuspended to a final volume of 225 ml (haematocrit 50e55%) and readministered to the patient through a filter (Figure 2). The recovery rate of RBCs is between 83 and 90%. It produces an almost pure erythrocyte suspension devoid of clotting factors or platelets.24 It has been shown to decrease requirements for allogenic blood transfusion, with the effect being more consistent and greater for THR.25
Local injection of adrenaline Adrenaline is a naturally occurring catecholamine that is produced in the medulla of the adrenal glands, which acts as a hormone and neurotransmitter. When injected locally, it acts as a vasoconstrictor. This effect means that when it is added to local anaesthetics it prolongs their duration of action. In the arthroplasty setting the use of adrenaline with local anaesthetic injected around the incision and capsule has been proposed to decrease bleeding and improve immediate postoperative pain relief. There is some evidence that administration of such a local injection will decrease bleeding rates when compared with a control; however, there is a lack of evidence comparing injection of local anaesthetic alone versus injection of local anaesthetic with adrenaline.21 Other methods of adrenaline use in joint replacement include intra-operative lavage of the exposed bleeding surgical site. However, this has been shown in a non-randomised retrospective study to have no difference on blood loss.22 Whilst application of an adrenaline/saline mix into the knee via a drain that is then clamped for 30 min has been shown to result in less blood loss, the associated rate of post-operative ABT was not significantly different from a reinfusion drain group.23 Application of topical adrenaline via a clamped drain is likely to be more
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BASIC SCIENCE
Figure 2 Intra-operative cell salvage (reproduced with permission from UK Cell Salvage Action Group. Department of Medical Illustration at University Hospital of South Manchester NHS Foundation Trust).
Reinfusion drains
volunteers. The minimum age is 17 years old, with no upper limit for regular donors, although they are subject to annual health review after their 66th birthday. The upper age limit for first-time donors is 65 years. The minimum body weight for blood donation is 50 kg. Donors answer a series of questions before each donation, relating to their health, lifestyle, travel history, medical history and medication. The normal interval between whole blood donations is 16 weeks (minimum 12 weeks), but no more than three donations a year are collected from female donors because of their more precarious iron status. Donors undergo a screening test for anaemia, from a finger prick sample. The minimum pre-donation haemoglobin concentration is 125 g/L for female donors and 135 g/L for males. At each donation, the following mandatory tests are performed: Hepatitis B e HBsAg Human immunodeficiency virus e anti-HIV 1 and 2 and HIV NAT (nucleic acid testing) Hepatitis C e anti-HCV and HCV NAT Human T-cell lymphotropic virus e anti-HTLV I and II Syphilis e syphilis antibodies. Precautions are taken to try and reduce the potential transfusion transmission of prion-associated diseases such as CreutzfeldteJakob. The following are permanently deferred from blood donation:
Reinfusion drains are another mode of autologous transfusion. The drains are inserted at the end of a procedure, at the time of wound of closure. Drained blood >150 ml is reinfused within the first 6 post-operative hours. These closed systems with an internal vacuum filter the drained blood and contain a fat retention valve to prevent any potential embolisation, and they provide volumetric measurement of the blood to be reinfused (Figure 3). Drainage blood appears to be defibrinated; however, analysis has shown that reinfusion of drainage blood does not change the coagulative capacity of patients.26 Most research around reinfusion drains has been based on primary knee replacements. In these studies the use of a reinfusion drain has been shown to result in higher post-operative haemoglobin levels and lower allogenic transfusion rates when compared with non-reinfusion drains. Although the cost of reinfusion drains is greater than routine suction drains, this increased initial cost is offset by the savings associated with lower rates of allogenic transfusion.27 With concerns about potential increased infection risks with any type of drain, and with the effectiveness of other methods of blood conservation, it is questionable whether such drains are necessary for routine cases.
Allogenic blood transfusion Allogenic blood transfusion is usually carried out postoperatively on a case-by-case basis. Many centres have a transfusion trigger when the haemoglobin concentration drops below 8 g/dL, although this level may be higher if the patient is symptomatic or has cardiac disease. The process for collecting blood for allogenic transfusion in the United Kingdom involves venesection from unpaid
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Persons who have received a blood transfusion or tissue/ organ transplant from a donor since 1980. Anyone who has received human pituitary-derived hormones, grafts of human dura mater or cornea, sclera or other ocular tissue.
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BASIC SCIENCE
its own due to the lack of control groups in many of the published studies. It has been shown that a co-ordinated approach for identifying high risk cases and minimising risk factors for transfusion are the most effective ways of minimising blood loss and requirements for post-operative allogenic blood transfusion.
Conclusion Allogenic blood transfusion after lower limb arthroplasty is a common occurrence. In view of the limited availability of allogenic blood and its associated risks, a multidisciplinary team approach should be adopted to optimise pre-operative haemoglobin levels, minimise peri-operative blood loss and provide clear guidelines for post-operative blood transfusion. A REFERENCES 1 Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008 Jun 26; 358: 2776e86. 2 Eriksson BI, Borris LC, Friedman RJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008 Jun 26; 358: 2765e75. 3 Friedman R, Homering M, Holberg G, Berkowitz SD. Allogeneic blood transfusions and postoperative infections after total hip or knee arthroplasty. J Bone Joint Surg 2014 Feb 19; 96: 272e8. 4 Singbartl G. Pre-operative autologous blood donation: clinical parameters and efficacy. Blood Transfus 2011 Jan; 9: 10e8. 5 Henry DA, Carless PA, Moxey AJ, et al. Pre-operative autologous donation for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2002. Issue 2. Art. No.:CD003602. 6 Pottgiesser T, Specker W, Umhau M, Dickhuth H-H, Roecker K, Schumacher YO. Recovery of hemoglobin mass after blood donation. Transfusion 2008 Jul; 48: 1390e7. 7 Singbartl G, Malgorzata S, Quoss A. Preoperative autologous blood donation e part II. Adapting the predeposit concept to the physiological basics of erythropoiesis improves its efficacy. Minerva Anestesiol 2007 Mar; 73: 153e60. 8 Bierbaum BE, Callaghan JJ, Galante JO, Rubash HE, Tooms RE, Welch RB. An analysis of blood management in patients having a total hip or knee arthroplasty. J Bone Joint Surg Am 1999 Jan; 81: 2e10. 9 Bedair H, Yang J, Dwyer MK, McCarthy JC. Preoperative erythropoietin alpha reduces postoperative transfusions in THA and TKA but may not be cost-effective. Clin Orthop 2014 Aug 9 [Epub ahead of print]. 10 Andrews CM, Lane DW, Bradley JG. Iron pre-load for major joint replacement. Transfus Med 1997 Dec; 7: 281e6. 11 Munoz M, Gomez-Ramirez S, Martin-Montanez E, Naveira E, Seara J, Pavia J. Cost of post-operative intravenous iron therapy in total lower limb arthroplasty: a retrospective, matched cohort study. Blood Transfus 2014 Jan; 12: 40e9. 12 Sutton PM, Cresswell T, Livesey JP, Speed K, Bagga T. Treatment of anaemia after joint replacement. A double-blind, randomised, controlled trial of ferrous sulphate versus placebo. J Bone Joint Surg Br 2004 Jan; 86: 31e3. 13 Tai T-W, Lin C-J, Jou I-M, Chang C-W, Lai K-A, Yang C-Y. Tourniquet use in total knee arthroplasty: a meta-analysis. Knee Surg Sports Traumatol Arthrosc 2011 Jul; 19: 1121e30.
Figure 3 Reinfusion drain (reproduced with permission from Stryker).
Members of a family at risk of inherited prion diseases. Persons notified that they may be at increased risk of vCJD due to possible exposure to an infected individual by surgical instruments, blood product transfusion or transplant of tissues or organs. Persons notified that they may be at increased risk because a recipient of their blood or tissues has developed a prionrelated disorder. Every donation is tested to determine the ABO and RhD group of the red cells and the plasma is screened to detect the most common blood group antibodies that might cause problems in a recipient (http://www.transfusionguidelines.org.uk).
Blood management programmes Blood management programmes (BMP) involve a multidisciplinary team approach to minimise the need for post-operative allogenic blood transfusions. There are variations between published programmes, but the common facets include: preoperative identification and treatment of patients with low preoperative haemoglobin levels, minimising modifiable risk factors for transfusion, limiting intra- and post-operative blood loss, and having pragmatic guidelines for treating post-operative anaemia. Such structured programmes have been shown to significantly lower peri-operative blood loss and allogenic transfusion rates compared to pre-BMP rates.28
Discussion Many different modes of blood management are available, and these are often used in combination with each other. It is difficult to quantify how much of an effect each strategy has on
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Please cite this article in press as: McGonagle L, Murnaghan JJ, Blood management strategies in lower limb arthroplasty, Orthopaedics and Trauma (2014), http://dx.doi.org/10.1016/j.mporth.2014.11.004
BASIC SCIENCE
14 Eriksson O, Kjellman H, Pilbrant A, Schannong M. Pharmacokinetics of tranexamic acid after intravenous administration to normal volunteers. Eur J Clin Pharmacol 1974; 7: 375e80. 15 Poeran J, Rasul R, Suzuki S, et al. Tranexamic acid use and postoperative outcomes in patients undergoing total hip or knee arthroplasty in the United States: retrospective analysis of effectiveness and safety. BMJ 2014; 349. g4829. 16 Alshryda S, Mason J, Sarda P, et al. Topical (intra-articular) tranexamic acid reduces blood loss and transfusion rates following total hip replacement: a randomized controlled trial (TRANX-H). J Bone Joint Surg Am 2013 Nov 6; 95: 1969e74. 17 Alshryda S, Mason J, Vaghela M, et al. Topical (intra-articular) tranexamic acid reduces blood loss and transfusion rates following total knee replacement: a randomized controlled trial (TRANX-K). J Bone Joint Surg Am 2013 Nov 6; 95: 1961e8. 18 Irwin A, Khan SK, Jameson SS, Tate RC, Copeland C, Reed MR. Oral versus intravenous tranexamic acid in enhanced-recovery primary total hip and knee replacement: results of 3000 procedures. Bone Joint J 2013 Nov; 95-B: 1556e61. €hm G, Desmonts JM, Couderc E, Moulin D, Prokocimer P, 19 Barbier-Bo Oliver H. Comparative effects of induced hypotension and normovolaemic haemodilution on blood loss in total hip arthroplasty. Br J Anaesth 1980 Oct; 52: 1039e43. 20 Rashiq S, Finegan BA. The effect of spinal anesthesia on blood transfusion rate in total joint arthroplasty. Can J Surg 2006 Dec; 49: 391e6. 21 Lombardi AV, Berend KR, Mallory TH, Dodds KL, Adams JB. Soft tissue and intra-articular injection of bupivacaine, epinephrine, and morphine has a beneficial effect after total knee arthroplasty. Clin Orthop 2004 Nov; 428: 125e30.
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22 Malone KJ, Matuszak S, Mayo D, Greene P. The effect of intra-articular epinephrine lavage on blood loss following total knee arthroplasty. Orthopedics 2009 Feb; 32: 100. 23 Tsumara N, Yoshiya S, Chin T, Shiba R, Kohso K, Doita M. A prospective comparison of clamping the drain or post-operative salvage of blood in reducing blood loss after total knee arthroplasty. J Bone Joint Surg Br 2006 Jan 1; 88-B: 49e53. 24 DeWald RL. Spinal deformities: the comprehensive text. Thieme, 2011; 881. 25 Dusik CJ, Hutchison C, Langelier D. The merits of cell salvage in arthroplasty surgery: an overview. Can J Surg 2014 Feb; 57: 61e6. 26 Jensen CM, Pilegaard R, Hviid K, Nielsen JD, Nielsen HJ. Quality of reinfused drainage blood after total knee arthroplasty. J Arthroplasty 1999 Apr; 14: 312e8. 27 Dramis A, Plewes J. Autologous blood transfusion after primary unilateral total knee replacement surgery. Acta Orthop Belg 2006 Jan; 72: 15e7. 28 Theusinger OM, Kind SL, Seifert B, Borgeat lain, Gerber C, Spahn DR. Patient blood management in orthopaedic surgery: a four-year follow-up of transfusion requirements and blood loss from 2008 to 2011 at the Balgrist University Hospital in Zurich, Switzerland. Blood Transfus 2014 Apr; 12: 195e203.
Practice points C C C
C
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correct anaemia pre-operatively minimize intra-operative blood loss consider tranexamic acid when blood loss is anticipated to exceed 500 ml (e.g. bilateral procedures, revisions). develop transfusion guidelines and educate team members in their use
Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: McGonagle L, Murnaghan JJ, Blood management strategies in lower limb arthroplasty, Orthopaedics and Trauma (2014), http://dx.doi.org/10.1016/j.mporth.2014.11.004
Blood management strategies in lower limb arthroplasty
departmental practices for identifying and addressing all possible variables to optimise a patient’s pre-operative haemoglobin, minimising peri- and post-operative bleeding and having clear guidelines for transfusion so that patients are not transfused unnecessarily by overzealous staff. The various methods of blood management in lower limb arthroplasty are discussed below.
Lorcan McGonagle John J Murnaghan
Pre-operative autologous donation Pre-operative autologous blood donation (PABD) aims to provide a supply of safe blood for patients undergoing surgery who might need a blood transfusion. It increases the patient’s total red blood cell (RBC) mass due to the PABD induced stimulation of erythropoiesis before elective surgery.4 It avoids the risk of an immunogenic reaction, and possible transmission of blood borne viruses associated with an allogenic blood transfusion. It may also be more acceptable to patients who are reluctant to receive an allogenic transfusion for religious or personal reasons. Blood is collected pre-operatively. The sudden drop in haemoglobin that is caused stimulates erythropoiesis as the body tries to raise the blood haemoglobin concentration back to a normal level. It is expected that the patient’s haemoglobin will have normalized by the day of surgery, and therefore any blood lost at the time of surgery can be replaced with the blood that was pre-donated. Pre-operative autologous blood donation typically reduces pre-operative haemoglobin levels by 1.23 g/dl, and has been shown to decrease the rate of allogenic transfusion by 43%.5 The timing of donation varies slightly between practices; however, it has been shown that it takes an average of 36 days for haemoglobin levels to recover to pre-donation levels,6 suggesting that the time interval from donation to surgery should be no shorter than this. Withdrawing two units at a single sitting, rather than one unit at two separate sittings, results in a larger increase in RBC mass.7 This single large donation seems to stimulate erythropoiesis more aggressively and should be the preferable practice, provided the patient can cope with it physiologically. Pre-operative autologous donation of blood being made available for post-operative transfusion is very safe. However, it has high non-usage rates (45%),8 indicating that its routine use is unnecessary and that is should be reserved for selected cases. Therefore, it is rarely used in the arthroplasty setting nowadays.
Abstract Rates of post-operative allogenic blood transfusion in primary hip and knee arthroplasty can be as high as 50%. Risks of allogenic blood transfusion include increased risk of orthopaedic and non-orthopaedic infection in addition to the general risks of transfusion. Measures have been developed to minimise the requirements for post-operative allogenic blood transfusion in lower limb arthroplasty. These include preoperative screening of patients, risk stratification, raising pre-operative haemoglobin pharmacologically, pre-operative autologous donation, minimising intra- and post-operative blood loss and suitable post-operative transfusion practices. Pharmacological, haematological and surgical methods of blood management in lower limb arthroplasty are discussed.
Keywords arthroplasty; blood; hip; knee; management
Introduction The UK blood transfusion service collects about 1,900,000 blood donations per year. According to the United Kingdom National Joint Registry (UK NJR) there were 82,267 primary total knee replacements and 76,274 primary total hip replacements in 2013. Rates of allogenic blood transfusion (ABT) have been reported to be as high as 50% in elective primary total knee replacement1 and 56% in primary total hip replacement.2 Transfusion rates in revision hip and knee arthroplasty surgery are higher still. Direct comparison of transfusion rates between different studies can be difficult, as different institutes often have different transfusion triggers/protocols, and the details may not be specified in the paper. High transfusion rates put a considerable strain of the availability of donated blood. Allogenic blood transfusion has been shown to be associated with an increased risk of orthopaedic and non-orthopaedic infections in elective hip and knee arthroplasty.3 With an aging population, it is expected that the number of arthroplasties performed per year will continue to increase. There is a limited availability of allogenic blood, and transfusion of allogenic blood carries risks to the recipient. In view of these issues there is a strong emphasis on setting up routine
Erythropoietin Erythropoietin (EPO) is an erythropoiesis-stimulating glycoprotein that is 90% made by the kidneys. EPO allows erythroid precursor cells in the bone marrow to mature and eventually become erythrocytes. This process takes over 1 week, and erythrocytes have a normal survival time of 120 days. Pharmaceutical EPO is human erythropoietin produced in cell culture using recombinant DNA technology. It is administered prior to surgery and often for a few days after surgery to patients deemed at high risk of post-operative transfusion (haemoglobin <13 g/ dl) in order to boost pre-operative haemoglobin. It can be administered intravenously or subcutaneously. There is evidence that pre-operative administration of EPO to patients deemed to be at high risk of transfusion results in higher
Lorcan McGonagle (FRCS Tr & Orth) Clinical Arthroplasty Fellow, Holland Orthopaedic and Arthritic Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Conflict of interest: None declared. John J Murnaghan (FRCSC) Orthopaedic Surgeon, Associate Professor Surgery, Holland Orthopaedic and Arthritic Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. Conflict of interest: None declared.
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Please cite this article in press as: McGonagle L, Murnaghan JJ, Blood management strategies in lower limb arthroplasty, Orthopaedics and Trauma (2014), http://dx.doi.org/10.1016/j.mporth.2014.11.004
BASIC SCIENCE
oozing.13 Application of a tourniquet may also tether the quadriceps muscle intra-operatively, affecting patellar tracking.
immediate post-operative haemoglobin levels and lower rates of allogenic transfusion compared with controls. However, in view of the large cost associated with this drug, it was deemed not to be cost effective when compared to allogenic blood transfusion administrated as and when necessary.9 Potential side effects of EPO use include: headache joint or muscle aches, pain, or soreness nausea/vomiting/indigestion weight loss sores in the mouth
Tranexamic acid In the final common pathway of the coagulation cascade, thrombin acts upon fibrinogen, converting it to fibrin, leading to fibrin deposition and the activation of platelets to form blood clots. Plasmin is a proteolytic enzyme derived from plasminogen that hydrolyses fibrin into soluble products. Tranexamic acid is an antifibrinolytic that competitively inhibits the activation of plasminogen to plasmin. At high concentrations it is a noncompetitive inhibitor of plasmin. It works by blocking the lysine-binding sites of the plasminogen molecule, which prevents it from binding to fibrin, as outlined in Figure 1. Its half life is approximately 2 h and it is excreted by the kidneys.14 A large multicentre review of hip and knee replacements has shown that intravenous tranexamic acid significantly decreases rates of allogenic of autologous blood transfusion and early postoperative complications, including thromboembolism and renal failure. It is suggested that a dose of 2000 mg has the best effectiveness and safety profile.15 Tranexamic acid has traditionally been given via the intravenous route; however, proponents for topical administration state that topical (intra-articular) administration will provide a maximum concentration of tranexamic acid at the bleeding site whilst being associated with 70% lower systemic absorption, theoretically reducing any side effects. Topical tranexamic acid has been shown to be effective (1 g/50 ml saline) in decreasing the absolute risk of transfusion by almost 20%, as well as pre-topost haemoglobin drop by 0.84 g/dL in total hip replacements.16 Topical tranexamic acid reduced the absolute risk of blood transfusion by 15.4% and reduced blood loss by 168 ml in total knee replacements.17 In both of these studies the control drug was normal saline. Tranexamic acid is also available for oral administration. This is infrequently used in the orthopaedic surgery setting, although there is some evidence for its use. It has been shown to result in a lower rate of transfusion, with a similar complication rate to intravenous tranexamic acid. The oral dose used was slightly higher than the intravenous dose, but it is slightly cheaper, which is pertinent in view of the constraints on healthcare budgets.18 The safest and most effective route of administration and dose of tranexamic acid is yet to be ascertained. Although it has been shown to decrease blood loss and transfusion requirements in general, it is unclear how beneficial it is to patients who are at a low risk of transfusion, and whether it should be prescribed to all patients or just high risk patients.
Iron supplement pre- and post-operatively Iron is a transition metal that forms the core of the haemoglobin molecule to which the alpha and beta proteins are attached. Daily requirements of iron for erythropoiesis are approximately 20e30 mg, and it is absorbed in the duodenum. Pre-operative oral iron supplementation is cheap and aims to maximize iron stores and subsequently haemoglobin prior to surgery. It is usually administered for 3e4 weeks pre-operatively. It can increase pre-operative haemoglobin and decrease the postoperative drop. This beneficial effect is most pronounced in patients with pre-operative anaemia due to iron deficiency, whilst those with normal haemoglobin levels generally do not benefit from pre-operative iron supplements.10 Gastric side effects such as dyspepsia, nausea, diarrhoea and black stool may limit patient compliance with drug therapy. Post-operatively, routine administration of oral iron supplements to anaemic patients does not significantly increase iron levels, although there is some evidence that administration of intravenous iron in the first 1e3 days post-operatively can result in a significantly higher haemoglobin levels at 72 h post-op, resulting in lower rates of post-op allogenic blood transfusion.11,12
Tourniquets A tourniquet is a device used to limit bleeding or blood flow. In the lower limb setting it is typically elevated to 100e150 mmHg above systolic blood pressure. The limb is usually drained of venous blood by elevation or exsanguination before inflation. Although not practical for a hip replacement, tourniquets are frequently used in knee replacement surgery. Their primary purpose is to limit intra-operative blood loss and improve visibility at the time of surgery. However, they are associated with a slight increase in post-operative blood loss compared with no tourniquet use, and there is no convincing evidence that they limit blood loss overall. This is because once the tourniquet is deflated, the vessels that were incised intra-operatively will start to bleed, resulting in hidden blood loss and bruising; conversely, when a tourniquet is not used these bleeding vessels are likely to be identified and cauterised intra-operatively. Clinical thromboembolic events have been shown to be higher amongst patients who had a tourniquet applied compared to those who did not. This is probably influenced by the stasis that occurs due to the temporary cessation of venous return in the limb. Tourniquet use has also been shown to result in a higher incidence of skin problems, including blistering, haematoma and
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Controlled anaesthetic hypotension Deliberate controlled lowering of mean arterial blood pressure by the anaesthetist intra-operatively has been shown to significantly decrease intra-operative bleeding.19 Lower blood pressure decreases the risk of dislodging a recently formed clot at the operative site. This can be performed safely with general, spinal and epidural anaesthetics in appropriately trained hands. Spinal anaesthetic has been shown to be more effective than general anaesthetic in decreasing transfusion rates in hip and knee
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BASIC SCIENCE
Figure 1 Diagram of the mechanism of action of tranexamic acid (reproduced with permission from CJ Dunn, KL Goa. Tranexamic acid. Drugs 1999:57(6);1005e1032 via Springer Rightslink).
arthroplasty.20 Spinal anaesthesia is thought to reduce bleeding in arthroplasty surgery by lowering arterial and venous blood pressure. This reduced bleeding effect may be less prevalent in knee replacement surgery if a tourniquet is used, as the effect of the anaesthetic will be decreasing by the time the tourniquet is deflated.
effective than lavage alone in minimising blood loss as it will have more time to exert its vasoconstrictive effects on the local tissues, thereby decreasing blood loss.
Intra-operative cell salvage Cell salvage is another form of autotransfusion. It is typically used in cases with medium-to-high volumes of blood loss. This process allows almost immediate reinfusion of blood that is lost intra-operatively. A normal suction device would simply remove blood from the surgical site and deposit it as waste. With cell salvage, the sucker tip is focused on the area of bleeding, and blood is salvaged through a double lumen catheter, where dilute heparinised saline is also administered. The aspirate is passed through a gross filter to remove debris before entering the reservoir. The filtered aspirate is deposited in the reservoir and processed by differential centrifugation to separate the red blood cells from the other blood components. As the red cells are deposited by centrifugation, the supernatant is fractionated off, removing remaining debris, platelets, free haemoglobin, irrigation fluid, activated clotting factors, myoglobin, heparin and damaged red cell stroma. Once the haematocrit of the deposited RBCs reaches approximately 50%, the cells are washed with saline. Remaining erythrocytes are resuspended to a final volume of 225 ml (haematocrit 50e55%) and readministered to the patient through a filter (Figure 2). The recovery rate of RBCs is between 83 and 90%. It produces an almost pure erythrocyte suspension devoid of clotting factors or platelets.24 It has been shown to decrease requirements for allogenic blood transfusion, with the effect being more consistent and greater for THR.25
Local injection of adrenaline Adrenaline is a naturally occurring catecholamine that is produced in the medulla of the adrenal glands, which acts as a hormone and neurotransmitter. When injected locally, it acts as a vasoconstrictor. This effect means that when it is added to local anaesthetics it prolongs their duration of action. In the arthroplasty setting the use of adrenaline with local anaesthetic injected around the incision and capsule has been proposed to decrease bleeding and improve immediate postoperative pain relief. There is some evidence that administration of such a local injection will decrease bleeding rates when compared with a control; however, there is a lack of evidence comparing injection of local anaesthetic alone versus injection of local anaesthetic with adrenaline.21 Other methods of adrenaline use in joint replacement include intra-operative lavage of the exposed bleeding surgical site. However, this has been shown in a non-randomised retrospective study to have no difference on blood loss.22 Whilst application of an adrenaline/saline mix into the knee via a drain that is then clamped for 30 min has been shown to result in less blood loss, the associated rate of post-operative ABT was not significantly different from a reinfusion drain group.23 Application of topical adrenaline via a clamped drain is likely to be more
ORTHOPAEDICS AND TRAUMA --:-
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BASIC SCIENCE
Figure 2 Intra-operative cell salvage (reproduced with permission from UK Cell Salvage Action Group. Department of Medical Illustration at University Hospital of South Manchester NHS Foundation Trust).
Reinfusion drains
volunteers. The minimum age is 17 years old, with no upper limit for regular donors, although they are subject to annual health review after their 66th birthday. The upper age limit for first-time donors is 65 years. The minimum body weight for blood donation is 50 kg. Donors answer a series of questions before each donation, relating to their health, lifestyle, travel history, medical history and medication. The normal interval between whole blood donations is 16 weeks (minimum 12 weeks), but no more than three donations a year are collected from female donors because of their more precarious iron status. Donors undergo a screening test for anaemia, from a finger prick sample. The minimum pre-donation haemoglobin concentration is 125 g/L for female donors and 135 g/L for males. At each donation, the following mandatory tests are performed: Hepatitis B e HBsAg Human immunodeficiency virus e anti-HIV 1 and 2 and HIV NAT (nucleic acid testing) Hepatitis C e anti-HCV and HCV NAT Human T-cell lymphotropic virus e anti-HTLV I and II Syphilis e syphilis antibodies. Precautions are taken to try and reduce the potential transfusion transmission of prion-associated diseases such as CreutzfeldteJakob. The following are permanently deferred from blood donation:
Reinfusion drains are another mode of autologous transfusion. The drains are inserted at the end of a procedure, at the time of wound of closure. Drained blood >150 ml is reinfused within the first 6 post-operative hours. These closed systems with an internal vacuum filter the drained blood and contain a fat retention valve to prevent any potential embolisation, and they provide volumetric measurement of the blood to be reinfused (Figure 3). Drainage blood appears to be defibrinated; however, analysis has shown that reinfusion of drainage blood does not change the coagulative capacity of patients.26 Most research around reinfusion drains has been based on primary knee replacements. In these studies the use of a reinfusion drain has been shown to result in higher post-operative haemoglobin levels and lower allogenic transfusion rates when compared with non-reinfusion drains. Although the cost of reinfusion drains is greater than routine suction drains, this increased initial cost is offset by the savings associated with lower rates of allogenic transfusion.27 With concerns about potential increased infection risks with any type of drain, and with the effectiveness of other methods of blood conservation, it is questionable whether such drains are necessary for routine cases.
Allogenic blood transfusion Allogenic blood transfusion is usually carried out postoperatively on a case-by-case basis. Many centres have a transfusion trigger when the haemoglobin concentration drops below 8 g/dL, although this level may be higher if the patient is symptomatic or has cardiac disease. The process for collecting blood for allogenic transfusion in the United Kingdom involves venesection from unpaid
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Persons who have received a blood transfusion or tissue/ organ transplant from a donor since 1980. Anyone who has received human pituitary-derived hormones, grafts of human dura mater or cornea, sclera or other ocular tissue.
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BASIC SCIENCE
its own due to the lack of control groups in many of the published studies. It has been shown that a co-ordinated approach for identifying high risk cases and minimising risk factors for transfusion are the most effective ways of minimising blood loss and requirements for post-operative allogenic blood transfusion.
Conclusion Allogenic blood transfusion after lower limb arthroplasty is a common occurrence. In view of the limited availability of allogenic blood and its associated risks, a multidisciplinary team approach should be adopted to optimise pre-operative haemoglobin levels, minimise peri-operative blood loss and provide clear guidelines for post-operative blood transfusion. A REFERENCES 1 Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008 Jun 26; 358: 2776e86. 2 Eriksson BI, Borris LC, Friedman RJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008 Jun 26; 358: 2765e75. 3 Friedman R, Homering M, Holberg G, Berkowitz SD. Allogeneic blood transfusions and postoperative infections after total hip or knee arthroplasty. J Bone Joint Surg 2014 Feb 19; 96: 272e8. 4 Singbartl G. Pre-operative autologous blood donation: clinical parameters and efficacy. Blood Transfus 2011 Jan; 9: 10e8. 5 Henry DA, Carless PA, Moxey AJ, et al. Pre-operative autologous donation for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2002. Issue 2. Art. No.:CD003602. 6 Pottgiesser T, Specker W, Umhau M, Dickhuth H-H, Roecker K, Schumacher YO. Recovery of hemoglobin mass after blood donation. Transfusion 2008 Jul; 48: 1390e7. 7 Singbartl G, Malgorzata S, Quoss A. Preoperative autologous blood donation e part II. Adapting the predeposit concept to the physiological basics of erythropoiesis improves its efficacy. Minerva Anestesiol 2007 Mar; 73: 153e60. 8 Bierbaum BE, Callaghan JJ, Galante JO, Rubash HE, Tooms RE, Welch RB. An analysis of blood management in patients having a total hip or knee arthroplasty. J Bone Joint Surg Am 1999 Jan; 81: 2e10. 9 Bedair H, Yang J, Dwyer MK, McCarthy JC. Preoperative erythropoietin alpha reduces postoperative transfusions in THA and TKA but may not be cost-effective. Clin Orthop 2014 Aug 9 [Epub ahead of print]. 10 Andrews CM, Lane DW, Bradley JG. Iron pre-load for major joint replacement. Transfus Med 1997 Dec; 7: 281e6. 11 Munoz M, Gomez-Ramirez S, Martin-Montanez E, Naveira E, Seara J, Pavia J. Cost of post-operative intravenous iron therapy in total lower limb arthroplasty: a retrospective, matched cohort study. Blood Transfus 2014 Jan; 12: 40e9. 12 Sutton PM, Cresswell T, Livesey JP, Speed K, Bagga T. Treatment of anaemia after joint replacement. A double-blind, randomised, controlled trial of ferrous sulphate versus placebo. J Bone Joint Surg Br 2004 Jan; 86: 31e3. 13 Tai T-W, Lin C-J, Jou I-M, Chang C-W, Lai K-A, Yang C-Y. Tourniquet use in total knee arthroplasty: a meta-analysis. Knee Surg Sports Traumatol Arthrosc 2011 Jul; 19: 1121e30.
Figure 3 Reinfusion drain (reproduced with permission from Stryker).
Members of a family at risk of inherited prion diseases. Persons notified that they may be at increased risk of vCJD due to possible exposure to an infected individual by surgical instruments, blood product transfusion or transplant of tissues or organs. Persons notified that they may be at increased risk because a recipient of their blood or tissues has developed a prionrelated disorder. Every donation is tested to determine the ABO and RhD group of the red cells and the plasma is screened to detect the most common blood group antibodies that might cause problems in a recipient (http://www.transfusionguidelines.org.uk).
Blood management programmes Blood management programmes (BMP) involve a multidisciplinary team approach to minimise the need for post-operative allogenic blood transfusions. There are variations between published programmes, but the common facets include: preoperative identification and treatment of patients with low preoperative haemoglobin levels, minimising modifiable risk factors for transfusion, limiting intra- and post-operative blood loss, and having pragmatic guidelines for treating post-operative anaemia. Such structured programmes have been shown to significantly lower peri-operative blood loss and allogenic transfusion rates compared to pre-BMP rates.28
Discussion Many different modes of blood management are available, and these are often used in combination with each other. It is difficult to quantify how much of an effect each strategy has on
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BASIC SCIENCE
14 Eriksson O, Kjellman H, Pilbrant A, Schannong M. Pharmacokinetics of tranexamic acid after intravenous administration to normal volunteers. Eur J Clin Pharmacol 1974; 7: 375e80. 15 Poeran J, Rasul R, Suzuki S, et al. Tranexamic acid use and postoperative outcomes in patients undergoing total hip or knee arthroplasty in the United States: retrospective analysis of effectiveness and safety. BMJ 2014; 349. g4829. 16 Alshryda S, Mason J, Sarda P, et al. Topical (intra-articular) tranexamic acid reduces blood loss and transfusion rates following total hip replacement: a randomized controlled trial (TRANX-H). J Bone Joint Surg Am 2013 Nov 6; 95: 1969e74. 17 Alshryda S, Mason J, Vaghela M, et al. Topical (intra-articular) tranexamic acid reduces blood loss and transfusion rates following total knee replacement: a randomized controlled trial (TRANX-K). J Bone Joint Surg Am 2013 Nov 6; 95: 1961e8. 18 Irwin A, Khan SK, Jameson SS, Tate RC, Copeland C, Reed MR. Oral versus intravenous tranexamic acid in enhanced-recovery primary total hip and knee replacement: results of 3000 procedures. Bone Joint J 2013 Nov; 95-B: 1556e61. €hm G, Desmonts JM, Couderc E, Moulin D, Prokocimer P, 19 Barbier-Bo Oliver H. Comparative effects of induced hypotension and normovolaemic haemodilution on blood loss in total hip arthroplasty. Br J Anaesth 1980 Oct; 52: 1039e43. 20 Rashiq S, Finegan BA. The effect of spinal anesthesia on blood transfusion rate in total joint arthroplasty. Can J Surg 2006 Dec; 49: 391e6. 21 Lombardi AV, Berend KR, Mallory TH, Dodds KL, Adams JB. Soft tissue and intra-articular injection of bupivacaine, epinephrine, and morphine has a beneficial effect after total knee arthroplasty. Clin Orthop 2004 Nov; 428: 125e30.
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22 Malone KJ, Matuszak S, Mayo D, Greene P. The effect of intra-articular epinephrine lavage on blood loss following total knee arthroplasty. Orthopedics 2009 Feb; 32: 100. 23 Tsumara N, Yoshiya S, Chin T, Shiba R, Kohso K, Doita M. A prospective comparison of clamping the drain or post-operative salvage of blood in reducing blood loss after total knee arthroplasty. J Bone Joint Surg Br 2006 Jan 1; 88-B: 49e53. 24 DeWald RL. Spinal deformities: the comprehensive text. Thieme, 2011; 881. 25 Dusik CJ, Hutchison C, Langelier D. The merits of cell salvage in arthroplasty surgery: an overview. Can J Surg 2014 Feb; 57: 61e6. 26 Jensen CM, Pilegaard R, Hviid K, Nielsen JD, Nielsen HJ. Quality of reinfused drainage blood after total knee arthroplasty. J Arthroplasty 1999 Apr; 14: 312e8. 27 Dramis A, Plewes J. Autologous blood transfusion after primary unilateral total knee replacement surgery. Acta Orthop Belg 2006 Jan; 72: 15e7. 28 Theusinger OM, Kind SL, Seifert B, Borgeat lain, Gerber C, Spahn DR. Patient blood management in orthopaedic surgery: a four-year follow-up of transfusion requirements and blood loss from 2008 to 2011 at the Balgrist University Hospital in Zurich, Switzerland. Blood Transfus 2014 Apr; 12: 195e203.
Practice points C C C
C
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correct anaemia pre-operatively minimize intra-operative blood loss consider tranexamic acid when blood loss is anticipated to exceed 500 ml (e.g. bilateral procedures, revisions). develop transfusion guidelines and educate team members in their use
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Please cite this article in press as: McGonagle L, Murnaghan JJ, Blood management strategies in lower limb arthroplasty, Orthopaedics and Trauma (2014), http://dx.doi.org/10.1016/j.mporth.2014.11.004