Louis M. Kwong, Yoshi P. Djaja, Brett Levine.
Response/Recommendation: Although polymethyl methacrylate (PMMA) cement and its component parts have not been demonstrated to be thrombogenic in vitro, the use of PMMA cement does influence the risk of subsequent embolization, some of which may be labeled as venous thromboembolism (VTE).
Strength of Recommendation: Moderate.
Rationale: PMMA bone cement is widely used across a variety of clinical applications in orthopaedic surgery including for implant fixation purposes, cranial surgery, and spinal fixation1. Bone cement consists of two component parts. Typically, the powder is composed of the polymer, an initiator, and a radio-opacifier. The liquid consists of the monomer, accelerator, and the inhibitor2.
An in vitro study by Blinc et al., found that the surface of aged or fresh bone cement did not exhibit thrombogenicity, and that the liquid component of bone cement inhibited both platelet aggregation and plasma clotting, but not at concentrations that would be expected in vivo 3. Similarly, Cenni et al., evaluated the compatibility of methacrylate-based bone cement on plasma, cultured human endothelial cells, and an erythrocyte suspension. That study found no effect of cement on the plasmatic phase of coagulation, did not induce the expression of endothelial cell procoagulant activity, and had no hemolytic effect on erythrocytes4. A follow-up study by the same group involving the testing of seven different bone cements found no induction of hemolysis nor any activation of the intrinsic coagulation pathway in vitro5. Animal studies, using a dog model, supports the in vitro findings and do not implicate the monomer as playing a role in cardiopulmonary/vascular events6–8.
Clinical observations, however, have identified embolic phenomenon associated with the use of PMMA bone cement. The spinal surgery literature is rich with reported complications of non-thrombotic pulmonary cement embolism due to intra-vascular extravasation of pressurized liquid cement during percutaneous vertebroplasty (PVP) and balloon kyphoplasty (BKP) procedures9–12. Embolization of the pulmonary circulation with small amounts of cement is often asymptomatic and frequently identified incidentally on plain film radiography as well as computer tomography (CT) of the chest13–17. The incidence of pulmonary cement embolization ranges from 3.5 to 23% based on imaging and is felt to underestimate the true incidence of cement extravasation into the pulmonary circulation11. Several techniques have been introduced to successfully reduce the risk of pulmonary cement embolism either by intensive monitoring using CT fluoroscopy18–20 or by reducing the pressure in the vertebral body before/during cement injection21–24. No evidence-based guidelines exist regarding the therapeutic management of patients with pulmonary cement embolism although approaches range from observation in asymptomatic patients to anticoagulation for 3-6 months in symptomatic individuals11.
Embolic and thrombotic events in association with the use of PMMA bone cement have been observed from the earliest days of arthroplasty involving both the hip and knee, as well as in the shoulder and in oncologic procedures1. Prospective studies involving the use of transesophageal echocardiography (TEE) document fat and marrow emboli during bone preparation, cementing, and implant insertion25–27. Clinical manifestations of this embolization range from transient hypoxia, loss of consciousness, to acute respiratory distress syndrome (ARDS), and even death28,29. The development of this clinical entity has been variously described as bone cement implantation syndrome (BCIS) or fat embolism syndrome (FES) both of which are incompletely understood entities occurring as rare non-thrombogenic complications in patients following total hip arthroplasty (THA) and total knee arthroplasty (TKA). A prospective study by Morda et al., on patients with fractures of the femoral neck did not identify alterations in coagulation based on thromboelastographic studies as playing any role in the development of BCIS30. Treatment of both BCIS and FES centers on supportive care, fluid resuscitation, possible corticosteroid use, and respiratory support in the face of ARDS31.
With regard to the risk of venous thromboembolism, a meta-analysis by Li et al., compared the efficacy and safety of cemented and uncemented hemiarthroplasty in the treatment of elderly patients with fracture of the femoral neck. That meta-analysis involved eight randomized control trials (RCT) encompassing 1,577 hips. The incidence of pulmonary embolism (PE) was statistically significantly higher in the cemented group32. Conversely, however, Liu et al., found no difference in cardiovascular complications—including PE—in their meta-analysis of 15 RCT encompassing 3,790 patients comparing cemented vs. cementless hemi-arthroplasty for elderly patients with a displaced femoral neck fracture33.
In association with THA, fat and marrow emboli that have been demonstrated to occur in association with cementing were found to be reduced when using changes in surgical technique involving such methods such as bone-vacuum assistance34,35. Marrow contents are felt to be activators of the coagulation cascade when introduced into the intravascular space36. In a prospective RCT by Pitto et al., a reduction in fat and bone marrow embolization demonstrated via TEE using a bone-vacuum technique resulted in a statistically significant reduction in VTE events compared to standard cementing37. With regards to TKA, limited information is available regarding the VTE risk and fixation. In a retrospective review by Hitos et al., cemented TKA was associated with a rate of deep venous thrombosis (DVT) that was statistically significantly higher than cementless TKA38. An RCT with venographic endpoints by Clark et al., comparing cementless TKA, cemented TKA, and cemented THA found an increased length of the thrombus with cemented TKA but no difference in incidence of DVT among the three groups39. Two prospective cohort studies that were underpowered found no effect of cement vs. cementless fixation on DVT rate following TKA40,41.
Surgical technique, anatomic location, and patient selection appear to play important roles in the mitigation of VTE risk when using PMMA cement.
1. Charnley J. Acrylic Cement in Orthopaedic Surgery. E&S Livingstone; 1970.
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4. Cenni E, Ciapetti G, Granchi D, et al. No effect of methacrylate-based bone cement CMW 1 on the plasmatic phase of coagulation, red blood cells and endothelial cells in vitro. Acta Orthop Scand. 2001;72(1):86-93. doi:10.1080/000164701753606761
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14. Lee IJ, Choi AL, Yie M-Y, et al. CT evaluation of local leakage of bone cement after percutaneous kyphoplasty and vertebroplasty. Acta Radiol. 2010;51(6):649-654. doi:10.3109/02841851003620366
15. Chang C-Y, Huang S-F. Asymptomatic pulmonary cement embolism. CMAJ. 2017;189(14):E543. doi:10.1503/cmaj.160579
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20. Potet J, Weber-Donat G, Curis E, et al. Incidence of pulmonary cement embolism after real-time CT fluoroscopy-guided vertebroplasty. J Vasc Interv Radiol. 2013;24(12):1853-1860. doi:10.1016/j.jvir.2013.05.048
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22. Shengzhong M, Dongjin W, Shiqing W, et al. Modification of percutaneous vertebroplasty for painful old osteoporotic vertebral compression fracture in the elderly: preliminary report. Injury. 2012;43(4):486-489. doi:10.1016/j.injury.2011.12.021
23. Hershkovich O, Lucantoni C, Kapoor S, Boszczyk B. Bone marrow washout for multilevel vertebroplasty in multiple myeloma spinal involvement. Technical note. Eur Spine J. 2019;28(6):1455-1460. doi:10.1007/s00586-018-5804-9
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28. Parvizi J, Holiday AD, Ereth MH, Lewallen DG. The Frank Stinchfield Award. Sudden death during primary hip arthroplasty. Clin Orthop Relat Res. 1999;(369):39-48. doi:10.1097/00003086-199912000-00005
29. Patterson BM, Healey JH, Cornell CN, Sharrock NE. Cardiac arrest during hip arthroplasty with a cemented long-stem component. A report of seven cases. J Bone Joint Surg Am. 1991;73(2):271-277.
30. Mordà M, Pini S, Celli F, et al. Bone cement implantation syndrome: a thromboelastographic study of the effect of bone cement on coagulation. J Biol Regul Homeost Agents. 2017;31(4 suppl 1):121-127.
31. Kwiatt ME, Seamon MJ. Fat embolism syndrome. Int J Crit Illn Inj Sci. 2013;3(1):64-68. doi:10.4103/2229-5151.109426
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33. Liu B, Li A, Wang J, et al. Cemented versus uncemented hemiarthroplasty for elderly patients with displaced fracture of the femoral neck: A PRISMA-compliant meta-analysis of randomized controlled trial. Medicine (Baltimore). 2020;99(33):e21731. doi:10.1097/MD.0000000000021731
34. Pitto RP, Koessler M, Kuehle JW. Comparison of fixation of the femoral component without cement and fixation with use of a bone-vacuum cementing technique for the prevention of fat embolism during total hip arthroplasty. A prospective, randomized clinical trial. J Bone Joint Surg Am. 1999;81(6):831-843. doi:10.2106/00004623-199906000-00010
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38. Hitos K, Fletcher JP. Venous thromboembolism following primary total knee arthroplasty. Int Angiol. 2006;25(4):343-351.
39. Clarke MT, Green JS, Harper WM, Gregg PJ. Cement as a risk factor for deep-vein thrombosis. Comparison of cemented TKR, uncemented TKR and cemented THR. J Bone Joint Surg Br. 1998;80(4):611-613. doi:10.1302/0301-620x.80b4.8612
40. Kim YH, Kim VE. Factors leading to low incidence of deep vein thrombosis after cementless and cemented total knee arthroplasty. Clin Orthop Relat Res. 1991;(273):119-124.
41. Kim Y-H, Oh SH, Kim JS. Incidence and natural history of deep-vein thrombosis after total hip arthroplasty. A prospective and randomised clinical study. J Bone Joint Surg Br. 2003;85(5):661-665.