Fat embolism and autologous blood transfusions in orthopaedic surgery

Fat embolism and autologous blood transfusions in orthopaedic surgery

ARTICLE IN PRESS Current Anaesthesia & Critical Care (2004) 15, 87–93 www.elsevier.com/locate/cacc FOCUS ON: POSTOPERATIVE TRANSFUSION Fat embolism...

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ARTICLE IN PRESS Current Anaesthesia & Critical Care (2004) 15, 87–93

www.elsevier.com/locate/cacc

FOCUS ON: POSTOPERATIVE TRANSFUSION

Fat embolism and autologous blood transfusions in orthopaedic surgery Magnus Jacobssona,*, Anders Bengtssonb Department of Biomaterials/Handicap Research, Institute for Surgical Sciences, Go. teborg University, P.O. Box 412, SE 405 03 Gothenburg, Sweden b Department of Anaesthesiology & Intensive Care, Sahlgrenska University Hospital/East, Gothenburg, Sweden a

KEYWORDS Arthroplasty; Blood transfusionFautologous; EmbolismFfat

Summary Fat embolism is a well-known complication associated with orthopaedic procedures like total hip or knee arthroplasty. The clinical relevance of fat embolism in association with orthopaedic procedures is, however, controversial. Although transesophageal echocardiography indicates echogenic material in the central circulation in more than 90% of patients undergoing cemented hip arthroplasty, the incidence of cardiac arrest due to pulmonary fat embolism is less than 1%. Cementation is known to increase the incidence of embolic complications. The duration of the pressure and the intensity of pressure inside the bone cavity are correlated with the incidence of fat emboli and the cardiopulmonary function. The use of modern cementing techniques and non-cemented arthroplasty reduces the incidence and the clinical risk of fat embolism. The disadvantages with allogeneic blood transfusions have encouraged the development of methods to reduce the need for such transfusions. Devices for salvage of blood during or after orthopaedic procedures have been shown to reduce the need for allogeneic transfusions. Shed blood may contain high concentrations of inflammatory mediators and may be contaminated with fat particles which may increase the risk of fat embolism. Transfusion of blood after washing and centrifugation and filtration of salvaged blood are available methods for transfusion of shed blood and that may reduce the amount of transfusion of fat. & 2004 Published by Elsevier Ltd.

Introduction Fat embolism is a well-known complication associated with major orthopaedic procedures. It is defined as fat within the circulation with or without clinical effects. Fat embolism syndrome is on the *Corresponding author. Tel.: þ 46-31-7732950. E-mail address: [email protected] (M. Jacobsson). 0953-7112/$ - see front matter & 2004 Published by Elsevier Ltd. doi:10.1016/j.cacc.2004.01.001

other hand defined as fat within the circulation with an identifiable clinical pattern of symptoms.1 Major criteria of fat embolism are respiratory symptoms (tachypnoea, dyspnoea), petechial rush and neurological signs (confusion, coma). Tachycardia (HF4120/min) and pyrexia may occur. In addition jaundice and anuria or oliguria may develop.2 Fat embolism is usually difficult to diagnose. The diagnosis has to be based on clinical features and laboratory investigations.

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Fat embolism occurs, sometimes with fatal outcome, after cemented and non-cemented total hip arthroplasty (THA) and total knee arthroplasty (TKA).3–10 Intravasation of fat and marrow during orthopaedic surgery may occur due to disruption of vessels within the marrow cavity, presence of particulate fat and marrow within the cavity and pressurization of the bone canal. The incidence has been shown to be over 90% in association with hip arthroplasty. It is possible that activation of the intravascular coagulation system is required for an increase in lung vascular permeability and pulmonary oedema. The question is whether intra-vascular fat is sufficient or even necessary, to cause coagulopathy.11 The release of fat into the general circulation from the bone marrow cavities during hip and knee arthroplasty, is a well-known phenomenon, particularly if bone cement is used. Lung emboli often occur without symptoms. The duration of the pressure and the intensity of pressure inside the bone cavity are correlated with the incidence of fat emboli and the cardiopulmonary function. Methylmethacrylate, cementation, implants, rods and nails all increase the pressure inside the cavity. In one study it was shown that deaths because of cardio-respiratory collapse during primary hip arthroplasty were intiated during the cementation. Autopsies showed bone marrow in the lungs of 11 out of 13 patients and methylmethacrylate particles were seen in the lungs of three out of 13 patients.12 The clinical relevance of fat embolism in association with orthopaedic procedures is, however, still controversial. Although, transoesophageal echocardiography (TOE) indicates echogenic material in the central circulation in more than 90% of patients undergoing cemented hip arthroplasty, the incidence of cardiac arrest due to pulmonary fat embolism is less than 1%. Echocardiography cannot distinguish between marrow debris, fat, air or other particulate matter. Cementation increases the incidence of embolic complications. The use of modern surgical and cementing techniques and non-cemented arthroplasty has, however, reduced the risks.13 The risks with allogeneic blood transfusions have encouraged the development of methods to reduce the need for such transfusions. Devices for salvage of blood during or after orthopaedic procedures have been shown to reduce the need for allogeneic transfusions. Shed blood may contain high concentrations of inflammatory mediators and may be contaminated with fat particles that may increase the risk of fat embolism.

M. Jacobsson, A. Bengtsson

Studies indicate that cemented arthroplasties cause higher incidence of embolic cascades than non-cemented arthroplasties.14,15 The aim of this review was to evaluate the current literature regarding fat embolism and orthopaedic procedures and to evaluate whether different kinds of autologous transfusions influence the risks of fat embolism in orthopaedic surgery.

Fat embolism in orthopaedic surgery Fat embolism, sometimes with fatal outcome, after as well cemented and as non-cemented THA and TKA have been described.3–5,7–9 The release of fat into the general circulation from the bone marrow cavities during hip and knee arthroplasty, is a well-known phenomenon, particularly if bone cement is used. It has been demonstrated that the incidence of embolism detected by TEE in association with conventional cementing is very high. The incidence has been shown to be over 90% in association with hip arthroplasty. A prospective study of 100 patients undergoing unilateral total knee arthroplasty and 100 patients undergoing bilateral total knee arthroplasty was performed to study fat embolism.16 Arterial and right atrial blood samples were obtained before and at short time intervals after insertion of the tibial component broach. The presence of fat was determined by staining with Oil Red O fat staining and marrow cells with Wright–Giemsa stain. It was found that 65% of the patients undergoing bilateral TKA had fat embolism compared to 46% of the unilateral cases. Bone marrow cell embolism was seen in 12% of the bilateral cases and in 4% of the unilateral cases. Six patients with positive bone marrow cells had neurologic manifestations. It has also been shown that patients with femoral neck fractures undergoing cemented THA, using transesophageal echocardiography and blood gas analysis develop severe embolic events. 85% of the patients developed such complications. Significant decreases in arterial oxygen saturation were also demonstrated.17 In another study, it was found that 95% of the patients had signs of emboli of small particles during cementation. By using transesophageal echocardiography evidence of emboli during cement injection and stem insertion was demonstrated.18 Similar results were found by Koessler and co-workers.19 They detected embolism in 93.3% of 60 patients undergoing conventional cemented THA.

ARTICLE IN PRESS Fat embolism and autologous blood transfusions in orthopaedic surgery

The operation procedure causes a high pressure within the intra-medullary cavity. Studies indicate that the higher pressure the higher risk of fat emboli. Hofmann and co-workers20 performed in vivo monitoring of intra-medullary pressure during non-cemented THA. Baseline pressure was measured to be 5–25 mmHg. During forced removal of the spongy bone in the femoral canal the average pressure for the group of eight patients rose to approximately 150 mmHg, with one patient reaching 265 mmHg and another 420 mmHg. During use of rasps the average pressure was measured at approximately 125 mmHg.20 Bone marrow fat may occur in the blood at intramedullary pressures of 184 mmHg and above.21 In experimental studies it has been shown that bone marrow release into the circulation occurs already below 150 mmHg.22 A patent foramen ovale, allowing the passage of emboli from the right heart to the left heart, and thus out into the arterial circulation, was stated to have been found in circa 25% of normal hearts in an autopsy material. Paradoxical embolization may be possible in 10% of patients.23 Several studies have been performed where the embolic material has been pathologically evaluated. Some studies have failed to demonstrate that the material originates from cement, fat or bone marrow. The material may however, consist of fine particles of bone.24,25 In the study by Kim16 it was, however, found that bone marrow cell embolism occurred in 12% of the bilateral cases and in 4% of the unilateral cases. The content of fat in blood was studied in connection with intra- and postoperatively collected blood for transfusion using a cell saver device with a 40 mm filter (Sangopur) during primary and revision hip arthroplasty.26 The amount of fat in the retrieved blood was classified into three groups: (1) No fat; (2) 1–2 ml fat; (3) 42 ml fat. It was found that the amount of fat in the retrieved blood increased with the retransfused volume and that primary THAs tended to yield more fat into the retrieved blood. The 40 mm filter did not eliminate the fat from the blood. With a 20 mm filter (Microsept), however, fat from the drained blood was eliminated. In another part of the study intraoperatively retrieved blood from abdominal aneurysm surgery was analysed, and found to contain no fat.

Cemented vs. non-cemented arthroplasty Fat embolism syndrome occurs in association with cemented and non-cemented arthroplasty.5

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Studies, however, indicate that cemented arthroplasty causes higher incidence of fat emboli than non-cemented arthroplasty.14,15 The studies demonstrate that the signs of embolization were more pronounced after insertion of the prosthesis in patients undergoing cemented than in those undergoing non-cemented arthroplasty. The influence is normally transient and the increase in ventilation– perfusion mismatch could not be detected half an hour after the insertion of the prostesis.

Transesophageal echocardiography (TOE) TOE may be used to detect emboli in association with orthopaedic surgery. It does quantify the amount of right atrial filling, duration of echogenesis and the size of particles. In a study 55 patients were studied with transesophageal echocardiography during total knee arthroplasty.25 The investigators found showers of echogenic material transversing the right atrium, the right ventricle and the pulmonary artery after the tourniquet was deflated. This occurred in various degrees in all patients. Three patients out of 55 developed signs of clinical pulmonary embolism.25 In another study it was demonstrated that echogenic material passes the right atrium and the right ventricle in almost all patients undergoing cemented hip arthroplasty.27 Like other investigators the authors failed to show any clinical impact of the TEE detected emboli during cemented hip arthroplasty. It has, however, also been shown by TEE that cementation causes a transient but significant reduction in cardiac output and stroke volume and in increased pulmonary artery pressure.15,18

Lung scintigraphy To detect pulmonary embolism lung scintigraphy may be of value. By using this method it was demonstrated that 66% of patients undergoing arthroplasty developed pulmonary thrombo-embolic signs. In this study the administration of low molecular weight heparin did not change the early onset of pulmonary thrombo-embolic signs.29

Autologous blood transfusions and fat embolism Due to the concern about risks with allogeneic transfusions the return of salvaged blood has become popular in different orthopaedic procedures. Transfusion of salvaged blood in orthopaedic surgery decreases the need for allogeneic

ARTICLE IN PRESS 90 transfusions.30–32 It is, however, still controversial as salvaged blood may contain fat particles, bone matrix, methylmethacrylate and tissue debris. Transfusion of fat probably increases the risk of fat embolism. Therefore methods to decrease the transfusion of fat has been evaluated. Transfusion of blood after washing and centrifugation and filtration of salvaged blood are available methods for transfusion of shed blood and that may reduce the amount of transfusion of fat. Several experimental studies address the issue of fat embolization and autologous transfusion. Procedures using the washing and centrifugation technique (cell-saver) are capable of reducing the amount of fat in the transfusion blood. The method using washing, centrifugation and cell separator technique (CATS, Fresenius, Bad Homnurg) seems to completely eliminate fat from the blood. Filters used for transfusion of shed blood without washing and centrifugation does not seem to effectively remove fat. With an addition of specific surface filters fat particles, WBCs and micro-aggregates can, however, effectively be removed even when postoperative filters are used for transfusion of shed blood.33 The content of fat in blood has been studied in connection with intra- and postoperatively collected blood for transfusion using a cell saver device with a 40 mm filter (Sangopur) during primary and revision hip arthroplast.26 The amount of fat in the retrieved blood was classified into three groups: (1) no fat; (2) 1–2 ml fat; (3) 42 ml fat. It was found that the amount of fat in the retrieved blood increased with the transfused volume and that primary THAs tended to yield more fat into the retrieved blood. The 40 mm filter did not eliminate the fat from the blood. With a 20 mm filter (Microsept), however, fat from the drained blood was eliminated. In another part of the study intraoperatively retrieved blood from abdominal aneurysm surgery was analysed, and found to contain no fat. A case report describes fatal pulmonary embolism in the early postoperative period following revision THA.34 Intraoperative fluid replacement consisted of five units of packed RBCs, 1400 ml of autologous salvaged blood, 6 l of crystalloid and 1 l of hetastarch solution. Autopsy revealed massive, diffuse osmium tetroxide-stained fat embolization in al pulmonary capillaries and several larger pulmonary vessels. The embolism was attributed to fat from the marrow cavity reaching the pulmonary vessels during surgery secondary to preparation and insertion of the hip prosthesis. In another study regarding fat embolism during THA lost blood was replaced with predonated

M. Jacobsson, A. Bengtsson

autologous blood and with blood salvaged intraoperatively with a cell saver device.18 During the whole operation embolism to the heart was continuously monitored with a TOE probe and videotaped. In conventionally cemented THAs embolic cascades were registered during preparation of the femoral canal, implantation of stem and relocation of hip joint. Emboli were not registered during any other period of the surgical procedure, although it is highly likely that salvaged blood was transfused also during surgery. None of the patients experienced neurological alterations nor showed signs of a respiratory distress syndrome. Faris and colleagues35 studied 99 patients who received shed blood after total joint arthroplasty. They suggest that although there was no evidence that fibrinogen–fibrin products in unwashed shed blood produced a coagulopathy, the possibility remains a cause for concern. Shed blood may contain methylmethacrylate monomer, locally administered antibiotics, fat and chips of bone. They found no adverse effects except for febrile reactions, particularly if the transfused blood was collected more than 6 h after the operation. Possible complications of transfusion of filtered shed blood after non-cemented TKA were studied in 197 patients.36 The study was not controlled or randomized. Drainage collection was less than 8 h in all patients. Transfusion of banked blood was also performed. Complications (4%) included wound haematoma in five patients, deep vein thrombosis in two patients and transient chills, fever or tachycardia at the time of transfusion in four patients. No complications could be attributed directly to the transfusion process. There were no cases of peri-operative mortality, coagulopathy, pulmonary embolism or fat embolism syndrome. It is concluded that whole-blood salvage by this method is safe. The number of fat particles was analysed after transfusion of shed blood in association with orthopaedic surgical procedures in children and adolescents.37 The number of fat particles per ml blood was counted. They found 23 643756 965 fat particles o9 mm in shed blood. In the circulating blood before transfusion the corresponding numbers were 171 and at 1–2 h after surgery the corresponding numbers were 1427405 and at 12–18 h after surgery 21759. Particles measuring 9–40 mm in diameter numbered 24736 in shed blood and could not be found in the patients’ blood following transfusion. Particles 440 mm were not detected. The authors conclude that although the presence of fat particles o9 mm in transfusion blood is of concern, the data of their study indicate that the particles were rapidly cleared from the circulation.

ARTICLE IN PRESS Fat embolism and autologous blood transfusions in orthopaedic surgery

The number of fat particles in autologous transfusion blood and in circulating was studied in a prospective, randomized study after hip or knee replacement or spinal fusion in 128 patients.31 The shed blood was filtered through either a RC-100 polyester leukocyte filter or a 40 mm filter. The number of fat particles of the two size ranges studied (diameters o10 and 10–40 mm) were substantially elevated in shed blood compared to liquid-preserved red blood cells. The RC100 filter seemed to be more effective in removing fat particles and white blood cells than the 40 mm filter. In systemic blood samples, however, the amount of fat particles of both size groups was similar in patients who had received shed blood and patients who received liquid-preserved red blood cells. Also, the patients receiving shed blood by autologous transfusion showed a similar clinical course as patients who were not transfused with autologous blood. The study indicates that transfusion of filtered blood from orthopaedic wounds is an acceptable alternative to the transfusion of liquidpreserved red blood cells. Henn-Beilharz et al.26 demonstrated that 20 mm filters remove the fat from drained blood. In an experimental study38 with infusion of large amounts of collected bone marrow fat mixed with arterial blood, it was shown that 20 mm blood filters prevented fat embolism in this extreme situation. A similar scenario is unlikely in a clinical setting with postoperative collection of shed blood from a wound where the bone marrow cavity has been closed off by the implanted orthopaedic device and the surgical wound thoroughly rinsed before closure to remove debris and fat. Two clinical reports17,34 describe cases of fat embolism in connection with THA and mention that shed blood was retrieved intraoperatively and transfused, but do not attribute the fat embolism to this fact, but rather to the surgical procedure.

Experimental studies and fat embolism Transfusion of shed blood was studied in an experimental investigation in dogs undergoing thoracotomy with the use of cardio-pulmonary bypass.39 The dogs received scavenged blood that had passed through no or different arterial filters with or without the use of an intermittent or continuous cell saver device. Brain tissue was then examined by histology for the presence of small capillary and arteriolar dilatations (SCADs), indicative of microembolization. It was found that SCAD density for the cell saver group was significantly

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less than for the arterial filtration group. There were no significant differences within each group. The authors found that the use of Pall LeukoGuard AL filter (which removes leukocytes as well as lipid, by electrostatic attraction) resulted in the highest SCAD density of any method tested. There was no statistically significant difference between the 25 mm filter and the 40 mm filter. The rather limited number of animals, of course, makes this open to discussion. The elimination of fat from shed blood was evaluated in an in vitro study.40 Packed red blood cells of a volume of 250 ml were diluted with 250 ml saline and 200 ml of soybean oil was added. Soyabean oil was chosen since gas chromatography had shown that its spectrum of fatty acids is comparable to the spectrum of fatty acids found in bone marrow and salvaged autologous blood. The blood was filtered through one of three filters: (1) LipiGuard (especially designed to remove fat), (2) Microfilter Sangopur 40 mm (blood filter) and (3) Purecell RC 400 (leukocyte removal filter). It was found that LipiGuard removed 62% of the fat vs 69% of the fat for Sangopur. Purecell RC 400, on the other hand, removed 99% of the fat. The tested filters removed some of the fat, none of them was capable of total fat elimination. LipiGuard, especially designed for fat filtration, was only as effective in fat removal as the ordinary blood filter, Sangopur, with a pore size of 40 mm. In another experimental study fat embolism was evaluated after autologous transfusion in dogs.38 Experimental soft tissue contusion and femoral fractures were produced. The fat and bone marrow thus produced was bathed in arterial blood for 60 min and the blood and fat continually aspirated by the transfusion device. The shed blood/fat/ marrow mixture was then transfused intravenously on the contra-lateral side. This procedure was followed in animal groups 2–4. Animal group 1 served as a control group in which the animals were not transfused, but with similar soft tissue and femoral lesions. Groups 2–4 had heparin added to the shed blood in doses of 100, 300 and 100 USP units of heparin, respectively, before transfusion. The shed blood for groups 2 and 3 was filtered through 125 mm filters, whereas the shed blood from group 4 was filtered through a 20 mm filter. It was found that mean pulmonary dead space increased and arterial oxygen levels decreased after transfusion in-groups 2 and 3, whereas in groups 1 and 4 the values were virtually unchanged. Arterial blood pressure remained stable in all groups but pulmonary arterial pressures rose in groups 2 and 3 compared to groups 1 and 4 which had normal values. Lung biopsies

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revealed 4–5 mm fat emboli occluding only the smaller intra-alveolar capillaries and pre-capillary arterioles 15 min after transfusion in groups 2 and 3. At 30 and 60 min the number and size of the fat emboli had increased, including also larger arterioles, and formation of amorphous thrombi around fat droplets as well as peri-vascular and interstitial oedema in groups 2 and 3. Lung biopsies from groups 1 and 4 revealed no intra-vascular thrombi, embolized fat or platelet clots. Biopsies from brain, heart and kidney demonstrated evidence of embolized fat in groups 2 and 3 whereas this was not noted in groups 1 and 4. Sufficient fat is available within the femur to produce a haemodynamic and cardiorespiratory pattern similar to that, which occurs clinically.

Conclusion In conclusion it may be stated that there are no significant reports of clinical manifestations of fat embolism being attributed to transfusion of shed autologous blood. The greatest risk of fat embolization seems to be the orthopaedic surgical procedure as such, not the postoperative collection, filtration and the transfusion of shed blood.

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[27] Lafont ND, Kalonji MK, Barre J, Guillaume C, Boogaerts JG. Clinical features and echocardiography of embolism during cemented hip arthroplasty. Can J Anaesth 1997;44(2):112–7. [29] Bruce W, Van der Wall H, Peters M, Liaw Y, Morgan L, Storey G. Occurrence of pulmonary thromboembolism immediately after arthroplasty. Nucl Med Commun 2001;22(11): 1237–42. [30] Huet C, Salmi LR, Fergusson D, Koopman-van Gemert AW, Rubens F, Laupacis A. A meta-analysis of the effectiveness of cell salvage to minimize perioperative allogeneic blood transfusion in cardiac and orthopedic surgery. International Study of Perioperative Transfusion (ISPOT) Investigators. Anesth Analg 1999;89(4):861–9. [31] Healy WL, Pfeifer BA, Kurtz SR, Johnson C, Johnson W, Johnston R, et al. Evaluation of autologous shed blood for autotransfusion after orthopaedic surgery. Clin Orthop 1994:53–9. [32] Dahmani S, Orliaguet GA, Meyer PG, Blanot S, Renier D, Carli PA. Perioperative blood salvage during surgical correction of craniosynostosis in infants. Br J Anaesth 2000; 85(4):550–5. [33] Ramirez G, Romero A, Garcia-Vallejo JJ, Munoz M. Detection and removal of fat particles from postoperative salvaged blood in orthopedic surgery. Transfusion 2002; 42(1):66–75.

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[34] Heine TA, Halambeck BL, Mark JB. Fatal pulmonary fat embolism in the early postoperative period. Anesthesiology 1998;89(6):1589–91. [35] Faris PM, Ritter MA, Keating EM, Valeri CR. Unwashed filtered shed blood collected after knee and hip arthroplasties A source of autologous red blood cells. J Bone Joint Surg Am 1991;73(8):1169–78; erratum in: J Bone Joint Surg Am 1991; 73(10): 1580. [36] Martin JW, Whiteside LA, Milliano MT, Reedy ME. Postoperative blood retrieval and transfusion in cementless total knee arthroplasty. J Arthroplasty 1992;7(2): 205–10. [37] Blevins FT, Shaw B, Valeri CR, Kasser J, Hall J. Reinfusion of shed blood after orthopaedic procedures in children and adolescents. J Bone Joint Surg Am 1993;75(3):363–71. [38] Goodman WB, Seaber AV, Silver D. Acute experimental autologous fat embolism in dogs. Surg Gynecol Obstet 1978;146(1):69–75. [39] Kincaid EH, Jones TJ, Stump DA, Brown WR, Moody DM, Deal DD, et al. Processing scavenged blood with a cell saver reduces cerebral lipid microembolization. Ann Thorac Surg 2000;70(4):1296–300. [40] Booke M, Van Aken H, Storm M, Fritzsche F, Wirtz S, Hinder F. Fat elimination from autologous blood. Anesth Analg 2001;92(2):341–3.