- Email: [email protected]
Management of infected non-union of the proximal femur: A combination of therapeutic techniques
Injury, Int. J. Care Injured 45 (2014) 2101–2105
Contents lists available at ScienceDirect
Injury journal homepage: www.elsevier.com/locate/injury
Case Report
Management of infected non-union of the proximal femur: A combination of therapeutic techniques Thomas A.J. Goff *, Nikolaos K. Kanakaris 1 Academic Department of Trauma and Orthopaedics, Leeds Teaching Hospitals, NHS Trust, UK
A R T I C L E I N F O
A B S T R A C T
Article history: Accepted 30 August 2014
A challenging case of a nonunion of the proximal femur complicated by infection attributed to microbial and fungal pathogens requiring a combination of novel surgical techniques to achieve eradication of infection, preservation of the native hip joint, and restoration of function. ß 2014 Elsevier Ltd. All rights reserved.
Keywords: Masquelet Induced-membrane Infected non-union Reamer–irrigator–aspirator Proximal femur BMP-7 Diamond concept
In all cases of fracture non-union, an analytical approach to the particular problem of each individual case according to the principles of the ‘‘diamond’’ concept is of paramount importance. The mechanical factor – adequacy of applied fixation; the local and systemic biological factors – healing potential, as well as the vascularity of the bone fragments and the local soft tissue envelope, alone or in combination could determine the prognosis of a fracture [1,2]. Moreover, the inoculation of microbial pathogens at the time of initial trauma, during the initial fixation surgery or even secondarily at the process of healing, represents and additional complicating factor, leading to the delay of fracture union, and often loosening of the fixation devices and chronic osteomyelitis [3,4]. When all of the above factors are present in a non-union case, complex management strategies need to be employed, often in a sequel of surgical stages. Usually, the first aim is to eradicate the infection by means of aggressive surgical debridement, local and systemic pathogen specific antibiotics and temporary stabilisation of the non-union area, followed by definite fixation of the non-union
* Corresponding author at: Department of Orthopaedics, Huddersfield Royal Infirmary, Acre Street, Huddersfield HD3 3EA, UK. Tel.: +44 01484 342000. E-mail addresses: [email protected] (Thomas A.J. Goff), [email protected] (N.K. Kanakaris). 1 Academic Department of Orthopaedics, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK. Fax: +44 01133923290. http://dx.doi.org/10.1016/j.injury.2014.08.046 0020–1383/ß 2014 Elsevier Ltd. All rights reserved.
site and means of reconstitution of the bone/soft tissue defect either via distraction histogenesis with external fixation frames or internal fixation and bone grafting [5,6]. Significant experience already exists for long bone reconstruction within the diaphysis, however unusual presentations such as in this case of the proximal femur metaphysis in a young patient pose additional surgical dilemmas. We report our approach combining a number of novel concepts and surgical techniques.
Case report A 31-year-old healthy, non-smoking male suffered a right sided intertrochanteric proximal femoral fracture and lung contusions and severe chest trauma following a road traffic collision in Pakistan in November 2009. Soon after his injury he underwent locally operative fixation with a 4-hole dynamic hip screw device (DHS), however the post-operative period was complicated with deterioration of his respiratory function and prolonged stay at the local ICU for 2 weeks. He received prolonged antibiotic administration (second generation cephalosporin for 4 weeks), and had a slow rehabilitation, and a delayed discharge at 5 weeks post admission. Eleven months later he presented to our institution in October 2010 following a recent simple fall, with increased right hip pain and worsening mobility. On review he was apyrexial, with a well healed surgical scar on his right proximal thigh, shortening of 2 cm on the right and marginally elevated inflammatory markers (WBC 9.21,
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CRP 12, ESR 11 mm). Radiographs appeared to show an atrophic non-union of the right hip fracture with a well-positioned DHS in situ (good neck shaft angle, lag screw position in a centre-centre position, and excellent tip apex index) (Fig. 1). CT scanning confirmed fracture non-union (Fig. 2). Despite no clear history suggestive of post-operative surgical site infection, deep infection was suspected as a complicating factor considering the verified radiological evidence of an atrophic non-union in an otherwise healthy adult with high energy trauma, given the absence of poor surgical fixation technique or obvious mechanical causation. Therefore an initial exploratory operation of open biopsy was undertaken for bone and soft tissue samples. Culture confirmed infection with Candida albicans (1 of 5 specimens) and also Coagulase negative staphylococcus (1 of 5 specimens). Extended tests included serial blood cultures which had no yield, serology for Hep B/C and HIV which were negative, and samples excluding tuberculosis. Preservation of the native hip was fundamental to the staged surgical strategy. In the first stage radical debridement, removal of all existing metalwork, bridging external fixation, and filling of the created bony void with PMMA cement (Palacos1 preloaded with Gentamicin) loaded with additional 2 g of Vancomycin and 400 mg of Amphotericin-B (Fig. 3). Fluconazole 50 mg OD and Amoxicillin 1 g TDS were orally continued for six weeks, allowing time for soft tissues to settle and the inflammatory markers to normalise
Fig. 2. CT coronal section of proximal femur fracture non-union.
Fig. 1. AP femur radiograph on presentation.
(WBC 6.85, CRP 6.1, ESR 5 mm). The patient was discharged home and was followed up until re-admission as an outpatient at weekly appointments for pin site review and laboratory testing. He remained nonweight bearing on the right, using his left leg to pivot from bed to chair/wheelchair during this period. He also received chemical thromboprophylaxis (tinzaparin 4500 units sc) during the period of restricted mobilisation as per institutional guidelines. The second stage was undertaken after two months by initially harvesting morsellised bone graft from the contralateral femur (70 ml) using the Reamer/Irrigator/Aspirator system (RIA1) (Synthes Inc., West Chester, PA). This was followed by removal of the bridging external fixation, curettage of the pin sites and repositioning of the patient at the traction table. Using careful dissection in order to avoid destruction of the induced membrane, through a single longitudinal split the cement plug was removed in pieces using an osteotome. The void and the femoral canal was irrigated with 2 l of normal saline. Then the morsellised autologous graft combined with 1 vial of BMP-7 (Osigraft1 Olympus, UK) was inserted into the defect through the window created in the bioactive membrane, which was subsequently closed with a 1 pds continuous suture. A 12 hole 958 angle blade plate (Fig. 4) was inserted and his wound closed in layers. He was allowed toe touch weight bear on the right immediately post-surgery and then
T.A.J. Goff, N.K. Kanakaris / Injury, Int. J. Care Injured 45 (2014) 2101–2105
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Fig. 3. AP radiograph after stage 1 (debridement, cement spacer, Ex-fix).
progressing to partial weight bearing at 8 weeks post definite fixation. At 6 months follow up the patient had full radiological and clinical union, no wound problems, normal inflammatory markers (WBC 7.16, CRP < 5, ESR 6 mm), no leg length discrepancy, and had returned to pre-injury activities pain free (Fig. 5). Over a period of 42 months of follow up there is no radiological, clinical or biochemical relapse of his infection, or evidence of avascular necrosis of the femoral head. Discussion Infected non-union has been well defined, although the exact language may differ between authors, there is consensus to the principles of management, aiming to alter the biological environment, eradicate the infection and achieve bony union restoring function [3,4,7]. Deep fungal infection is particularly challenging because of the formation of highly resistant biofilms, necessitating
Fig. 4. AP radiograph after stage 2 (grafting, blade plate fixation).
a staged approach with radical surgical debridement for any chance of eradication [8,9]. Resultant bony defects particularly in the metaphyseal region pose unique problems, potentially compromising joint integrity, stability and function, which may necessitate reconstruction with complex arthroplasty or arthrodesis. In the young patient preservation of the native joint and normal function remains of outmost importance. Techniques such as distraction histogenesis at the proximal femoral metaphysis have no application due to high pins site infection rates, poor patient’s tolerance, and result to joint stiffness and poor function. Vascularised bone transfer has also limited application, associated with high donor site morbidity and requires specialist equipment
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Fig. 5. AP & lateral radiographs at 10 months (graft integration, bony union).
and expertise. Little instructive experience with such cases has been previously reported, we present our strategy combining developing technologies such as the induced membrane defect reconstruction (or else ‘‘Masquelet’’ technique [10]), the use of local antifungal and antibacterial cement spacer [11,12], the RIA system [13], and the application of composite graft [14] according to the ‘‘Diamond’’ concept [1,2] (morsellised autograft and potent osteoinductive agent in the form of BMP-7) with established fixation techniques such as the classic angle stable plating system (958 condylar blade plate). The ‘‘Masquelet’’ technique is a relatively new method for reconstructing significant bone defects [15] with the majority of literature describing use in the mid-diaphysis. It requires a two stage approach, firstly radical bone and soft tissue debridement is undertaken, with external fixator stabilisation, and insertion of a polymethyl-methacrylate (PMMA) cement spacer. Two to three months later a bioactive membrane is created as a result of a foreign body reaction around the cement spacer. As proven, it represents a well vascularised and biologically active bed [16] to receive, contain and protect the bone graft [17], which is inserted at the second stage surgery of grafting and definite fixation. Over the last four years a number of case series have being published [18,19], as well as basic science studies supporting this technique of bone defect reconstruction [20,21]. Besides the effect of the PMMA cement on the creation of the induced membrane, it also releases locally high doses of antimicrobial agents, which are valuable in an infected non-union environment [22]. Similar practices of local delivery of antibiotics and antifungal agents are proven effective in osteomyelitis cases, as well as in periprosthetic infections [11,19,23,24]. The Reamer/Irrigator/Aspirator system (RIA) was initially developed to address problems related to the second hit phenomenon and heat exertion during reamed intramedullary
nailing [25–28]. Furthermore, the RIA system has gained most of its popularity as a novel technique of harvesting morsellised autologous bone graft from the intramedullary canal of mostly the femur. Favoured for providing equal or larger volumes of autologous graft (25–90 cm3) compared with the anterior (5– 72 cm3) or posterior iliac crests (25–88 cm3), RIA is also reportedly technically easier and minimally invasive reducing donor site morbidity [29]. The biological properties of the RIA graft have been proven superior to that of the iliac crest regarding cellular and osteoinductive protein content [20,30–32]. Recognition of this has led to the evolution of combined use of RIA graft at the second stage of the induced membrane technique in 27 cases of segmental diaphyseal non-union achieving 90% union at 1 year, as recently published [24]. Lastly, the role of osteoinductive agents in atrophic/oligotrophic non-unions is still debated. Many authors have provided supporting evidence in randomised studies and clinical series [33,34], whilst their high cost [35,36], especially to their recombinant form, and limitations of reimbursement have decreased their generalised adoption besides referral centres. Further research is also needed to understand the effects and potential super-concentration of these agents in the intra-membranous graft environment. To our knowledge there are scarce examples in the existing literature of these techniques in combination for the management of proximal femoral metaphyseal infected non-unions. Our experience reaffirms the need to adequately address both the biological and mechanical environment to increase the chances of union.
Conflict of interest statement None.
T.A.J. Goff, N.K. Kanakaris / Injury, Int. J. Care Injured 45 (2014) 2101–2105
Authors’ contributions NK did the preoperative planning, the surgery, the postoperative follow up, and reviewed the final draft. TG reviewed the patient’s notes, collected all relevant data and wrote the manuscript. References [1] Giannoudis PV, Einhorn TA, Schmidmaier G, Marsh D. The diamond concept – open questions. Injury 2008;39(Suppl. 2):S5–8. [2] Calori GM, Giannoudis PV. Enhancement of fracture healing with the diamond concept: the role of the biological chamber. Injury 2011;42(11):1191–3. [3] Struijs PA, Poolman RW, Bhandari M. Infected nonunion of the long bones. J Orthop Trauma 2007;21(7):507–11. [4] Patzakis MJ, Zalavras CG. Chronic posttraumatic osteomyelitis and infected nonunion of the tibia: current management concepts. J Am Acad Orthop Surg 2005;13(6):417–27. [5] Roche O, Zabe´e L, Sirveaux F, Villanueva E, Mole´ D. Treatment of septic nonunion of long bones: preliminary results of a two-stage procedure. J Bone Joint Surg Br Proc 2005;87-B:111–2. [6] Lasanianos NG, Kanakaris NK, Giannoudis PV. Current management of long bones large segmental defects. Orthop Trauma 2010;24(2):149–63. [7] Cierny 3rd G, DiPasquale D. Periprosthetic total joint infections: staging, treatment, and outcomes. Clin Orthop Relat Res 2002;403:23–8. [8] Motsitsi NS. Management of infected nonunion of long bones: the last decade (1996–2006). Injury 2008;39(2):155–60. [9] Chandra J, Kuhn DM, Mukherjee PK, Hoyer LL, McCormick T, Ghannoum MA. Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance. J Bacteriol 2001;183(18):5385–94. [10] Masquelet AC, Fitoussi F, Begue T, Muller GP. Reconstruction of the long bones by the induced membrane and spongy autograft. Ann Chir Plast Esthet 2000;45(3): 346–53. [11] Deelstra JJ, Neut D, Jutte PC. Successful treatment of Candida albicans-infected total hip prosthesis with staged procedure using an antifungal-loaded cement spacer. J Arthroplast 2013;28(2):374.e5–.e8. [12] Anagnostakos K, Kelm J, Schmitt E, Jung J. Fungal periprosthetic hip and knee joint infections clinical experience with a 2-stage treatment protocol. J Arthroplast 2012;27(2):293–8. [13] Kanakaris NK, Morell D, Gudipati S, Britten S, Giannoudis PV. Reaming irrigator aspirator system: early experience of its multipurpose use. Injury 2011;42(Suppl. 4):S28–34. [14] Giannoudis PV, Kanakaris NK, Dimitriou R, Gill I, Kolimarala V, Montgomery RJ. The synergistic effect of autograft and BMP-7 in the treatment of atrophic nonunions. Clin Orthop Relat Res 2009;467(12):3239–48. [15] Masquelet AC, Begue T. The concept of induced membrane for reconstruction of long bone defects. Orthop Clin North Am 2009;41(1):27–37. table of contents. [16] Pelissier P, Masquelet AC, Bareille R, Pelissier SM, Amedee J. Induced membranes secrete growth factors including vascular and osteoinductive factors and could stimulate bone regeneration. J Orthop Res: Off Publ Orthop Res Soc 2004;22(1):73–9. [17] Knothe UR, Springfield DS. A novel surgical procedure for bridging of massive bone defects. World J Surg Oncol 2005;3(1):7.
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[18] Giannoudis PV, Faour O, Goff T, Kanakaris N, Dimitriou R. Masquelet technique for the treatment of bone defects: tips-tricks and future directions. Injury 2011;42(6):591–8. [19] Karger C, Kishi T, Schneider L, Fitoussi F, Masquelet AC, French Society of Orthopaedic Society. et al. Treatment of posttraumatic bone defects by the induced membrane technique. Orthop Traumatol Surg Res 2012;98(1):97–102. [20] Cuthbert RJ, Churchman SM, Tan HB, McGonagle D, Jones E, Giannoudis PV. Induced periosteum a complex cellular scaffold for the treatment of large bone defects. Bone 2013;57(2):484–92. [21] Dimitriou R, Mataliotakis GI, Calori GM, Giannoudis PV. The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence. BMC Med 2012;10:81. [22] Shi M, Kretlow JD, Nguyen A, Young S, Scott Baggett L, Wong ME, et al. Antibiotic-releasing porous polymethylmethacrylate constructs for osseous space maintenance and infection control. Biomaterials 2010;31(14):4146–56. [23] Mouzopoulos G, Kanakaris NK, Kontakis G, Obakponovwe O, Townsend R, Giannoudis PV. Management of bone infections in adults: the surgeon’s and microbiologist’s perspectives. Injury 2011;42(Suppl. 5):S18–23. [24] Stafford PR, Norris BL. Reamer–irrigator–aspirator bone graft and bi Masquelet technique for segmental bone defect nonunions: a review of 25 cases. Injury 2010;41(Suppl. 2):S72–7. [25] Pape HC, Zelle BA, Hildebrand F, Giannoudis PV, Krettek C, van Griensven M. Reamed femoral nailing in sheep: does irrigation and aspiration of intramedullary contents alter the systemic response? J Bone Joint Surg Am Vol 2005;87(11):2515–22. [26] Lasanianos NG, Kanakaris NK, Dimitriou R, Pape HC, Giannoudis PV. Second hit phenomenon: existing evidence of clinical implications. Injury 2011;42(7): 617–29. [27] Cox G, Jones E, McGonagle D, Giannoudis PV. Reamer–irrigator–aspirator indications and clinical results: a systematic review. Int Orthop 2011;35(7):951–6. [28] Higgins TF, Casey V, Bachus K. Cortical heat generation using an irrigating/ aspirating single-pass reaming vs conventional stepwise reaming. J Orthop Trauma 2007;21(3):192–7. [29] Dimitriou R, Mataliotakis GI, Angoules AG, Kanakaris NK, Giannoudis PV. Complications following autologous bone graft harvesting from the iliac crest and using the RIA: a systematic review. Injury 2011;42(Suppl. 2):S3–15. [30] Schmidmaier G, Herrmann S, Green J, Weber T, Scharfenberger A, Haas NP, et al. Quantitative assessment of growth factors in reaming aspirate, iliac crest, and platelet preparation. Bone 2006;39(5):1156–63. [31] Wenisch S, Trinkaus K, Hild A, Hose D, Herde K, Heiss C, et al. Human reaming debris: a source of multipotent stem cells. Bone 2005;36(1):74–83. [32] Porter RM, Liu F, Pilapil C, Betz OB, Vrahas MS, Harris MB, et al. Osteogenic potential of reamer irrigator aspirator (RIA) aspirate collected from patients undergoing hip arthroplasty. J Orthop Res: Off Publ Orthop Res Soc 2009;27(1):42–9. [33] Friedlaender GE, Perry CR, Cole JD, Cook SD, Cierny G, Muschler GF, et al. Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am Vol 2001;83-A Suppl. 1(Pt 2):S151–8. [34] Kanakaris NK, Lasanianos N, Calori GM, Verdonk R, Blokhuis TJ, Cherubino P, et al. Application of bone morphogenetic proteins to femoral non-unions: a 4year multicentre experience. Injury 2009;40(Suppl. 3):S54–61. [35] Dahabreh Z, Calori GM, Kanakaris NK, Nikolaou VS, Giannoudis PV. A cost analysis of treatment of tibial fracture nonunion by bone grafting or bone morphogenetic protein-7. Int Orthop 2009;33(5):1407–14. [36] Kanakaris NK, Giannoudis PV. The health economics of the treatment of longbone non-unions. Injury 2007;38(Suppl. 2):S77–84.
Contents lists available at ScienceDirect
Injury journal homepage: www.elsevier.com/locate/injury
Case Report
Management of infected non-union of the proximal femur: A combination of therapeutic techniques Thomas A.J. Goff *, Nikolaos K. Kanakaris 1 Academic Department of Trauma and Orthopaedics, Leeds Teaching Hospitals, NHS Trust, UK
A R T I C L E I N F O
A B S T R A C T
Article history: Accepted 30 August 2014
A challenging case of a nonunion of the proximal femur complicated by infection attributed to microbial and fungal pathogens requiring a combination of novel surgical techniques to achieve eradication of infection, preservation of the native hip joint, and restoration of function. ß 2014 Elsevier Ltd. All rights reserved.
Keywords: Masquelet Induced-membrane Infected non-union Reamer–irrigator–aspirator Proximal femur BMP-7 Diamond concept
In all cases of fracture non-union, an analytical approach to the particular problem of each individual case according to the principles of the ‘‘diamond’’ concept is of paramount importance. The mechanical factor – adequacy of applied fixation; the local and systemic biological factors – healing potential, as well as the vascularity of the bone fragments and the local soft tissue envelope, alone or in combination could determine the prognosis of a fracture [1,2]. Moreover, the inoculation of microbial pathogens at the time of initial trauma, during the initial fixation surgery or even secondarily at the process of healing, represents and additional complicating factor, leading to the delay of fracture union, and often loosening of the fixation devices and chronic osteomyelitis [3,4]. When all of the above factors are present in a non-union case, complex management strategies need to be employed, often in a sequel of surgical stages. Usually, the first aim is to eradicate the infection by means of aggressive surgical debridement, local and systemic pathogen specific antibiotics and temporary stabilisation of the non-union area, followed by definite fixation of the non-union
* Corresponding author at: Department of Orthopaedics, Huddersfield Royal Infirmary, Acre Street, Huddersfield HD3 3EA, UK. Tel.: +44 01484 342000. E-mail addresses: [email protected] (Thomas A.J. Goff), [email protected] (N.K. Kanakaris). 1 Academic Department of Orthopaedics, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK. Fax: +44 01133923290. http://dx.doi.org/10.1016/j.injury.2014.08.046 0020–1383/ß 2014 Elsevier Ltd. All rights reserved.
site and means of reconstitution of the bone/soft tissue defect either via distraction histogenesis with external fixation frames or internal fixation and bone grafting [5,6]. Significant experience already exists for long bone reconstruction within the diaphysis, however unusual presentations such as in this case of the proximal femur metaphysis in a young patient pose additional surgical dilemmas. We report our approach combining a number of novel concepts and surgical techniques.
Case report A 31-year-old healthy, non-smoking male suffered a right sided intertrochanteric proximal femoral fracture and lung contusions and severe chest trauma following a road traffic collision in Pakistan in November 2009. Soon after his injury he underwent locally operative fixation with a 4-hole dynamic hip screw device (DHS), however the post-operative period was complicated with deterioration of his respiratory function and prolonged stay at the local ICU for 2 weeks. He received prolonged antibiotic administration (second generation cephalosporin for 4 weeks), and had a slow rehabilitation, and a delayed discharge at 5 weeks post admission. Eleven months later he presented to our institution in October 2010 following a recent simple fall, with increased right hip pain and worsening mobility. On review he was apyrexial, with a well healed surgical scar on his right proximal thigh, shortening of 2 cm on the right and marginally elevated inflammatory markers (WBC 9.21,
2102
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CRP 12, ESR 11 mm). Radiographs appeared to show an atrophic non-union of the right hip fracture with a well-positioned DHS in situ (good neck shaft angle, lag screw position in a centre-centre position, and excellent tip apex index) (Fig. 1). CT scanning confirmed fracture non-union (Fig. 2). Despite no clear history suggestive of post-operative surgical site infection, deep infection was suspected as a complicating factor considering the verified radiological evidence of an atrophic non-union in an otherwise healthy adult with high energy trauma, given the absence of poor surgical fixation technique or obvious mechanical causation. Therefore an initial exploratory operation of open biopsy was undertaken for bone and soft tissue samples. Culture confirmed infection with Candida albicans (1 of 5 specimens) and also Coagulase negative staphylococcus (1 of 5 specimens). Extended tests included serial blood cultures which had no yield, serology for Hep B/C and HIV which were negative, and samples excluding tuberculosis. Preservation of the native hip was fundamental to the staged surgical strategy. In the first stage radical debridement, removal of all existing metalwork, bridging external fixation, and filling of the created bony void with PMMA cement (Palacos1 preloaded with Gentamicin) loaded with additional 2 g of Vancomycin and 400 mg of Amphotericin-B (Fig. 3). Fluconazole 50 mg OD and Amoxicillin 1 g TDS were orally continued for six weeks, allowing time for soft tissues to settle and the inflammatory markers to normalise
Fig. 2. CT coronal section of proximal femur fracture non-union.
Fig. 1. AP femur radiograph on presentation.
(WBC 6.85, CRP 6.1, ESR 5 mm). The patient was discharged home and was followed up until re-admission as an outpatient at weekly appointments for pin site review and laboratory testing. He remained nonweight bearing on the right, using his left leg to pivot from bed to chair/wheelchair during this period. He also received chemical thromboprophylaxis (tinzaparin 4500 units sc) during the period of restricted mobilisation as per institutional guidelines. The second stage was undertaken after two months by initially harvesting morsellised bone graft from the contralateral femur (70 ml) using the Reamer/Irrigator/Aspirator system (RIA1) (Synthes Inc., West Chester, PA). This was followed by removal of the bridging external fixation, curettage of the pin sites and repositioning of the patient at the traction table. Using careful dissection in order to avoid destruction of the induced membrane, through a single longitudinal split the cement plug was removed in pieces using an osteotome. The void and the femoral canal was irrigated with 2 l of normal saline. Then the morsellised autologous graft combined with 1 vial of BMP-7 (Osigraft1 Olympus, UK) was inserted into the defect through the window created in the bioactive membrane, which was subsequently closed with a 1 pds continuous suture. A 12 hole 958 angle blade plate (Fig. 4) was inserted and his wound closed in layers. He was allowed toe touch weight bear on the right immediately post-surgery and then
T.A.J. Goff, N.K. Kanakaris / Injury, Int. J. Care Injured 45 (2014) 2101–2105
2103
Fig. 3. AP radiograph after stage 1 (debridement, cement spacer, Ex-fix).
progressing to partial weight bearing at 8 weeks post definite fixation. At 6 months follow up the patient had full radiological and clinical union, no wound problems, normal inflammatory markers (WBC 7.16, CRP < 5, ESR 6 mm), no leg length discrepancy, and had returned to pre-injury activities pain free (Fig. 5). Over a period of 42 months of follow up there is no radiological, clinical or biochemical relapse of his infection, or evidence of avascular necrosis of the femoral head. Discussion Infected non-union has been well defined, although the exact language may differ between authors, there is consensus to the principles of management, aiming to alter the biological environment, eradicate the infection and achieve bony union restoring function [3,4,7]. Deep fungal infection is particularly challenging because of the formation of highly resistant biofilms, necessitating
Fig. 4. AP radiograph after stage 2 (grafting, blade plate fixation).
a staged approach with radical surgical debridement for any chance of eradication [8,9]. Resultant bony defects particularly in the metaphyseal region pose unique problems, potentially compromising joint integrity, stability and function, which may necessitate reconstruction with complex arthroplasty or arthrodesis. In the young patient preservation of the native joint and normal function remains of outmost importance. Techniques such as distraction histogenesis at the proximal femoral metaphysis have no application due to high pins site infection rates, poor patient’s tolerance, and result to joint stiffness and poor function. Vascularised bone transfer has also limited application, associated with high donor site morbidity and requires specialist equipment
2104
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Fig. 5. AP & lateral radiographs at 10 months (graft integration, bony union).
and expertise. Little instructive experience with such cases has been previously reported, we present our strategy combining developing technologies such as the induced membrane defect reconstruction (or else ‘‘Masquelet’’ technique [10]), the use of local antifungal and antibacterial cement spacer [11,12], the RIA system [13], and the application of composite graft [14] according to the ‘‘Diamond’’ concept [1,2] (morsellised autograft and potent osteoinductive agent in the form of BMP-7) with established fixation techniques such as the classic angle stable plating system (958 condylar blade plate). The ‘‘Masquelet’’ technique is a relatively new method for reconstructing significant bone defects [15] with the majority of literature describing use in the mid-diaphysis. It requires a two stage approach, firstly radical bone and soft tissue debridement is undertaken, with external fixator stabilisation, and insertion of a polymethyl-methacrylate (PMMA) cement spacer. Two to three months later a bioactive membrane is created as a result of a foreign body reaction around the cement spacer. As proven, it represents a well vascularised and biologically active bed [16] to receive, contain and protect the bone graft [17], which is inserted at the second stage surgery of grafting and definite fixation. Over the last four years a number of case series have being published [18,19], as well as basic science studies supporting this technique of bone defect reconstruction [20,21]. Besides the effect of the PMMA cement on the creation of the induced membrane, it also releases locally high doses of antimicrobial agents, which are valuable in an infected non-union environment [22]. Similar practices of local delivery of antibiotics and antifungal agents are proven effective in osteomyelitis cases, as well as in periprosthetic infections [11,19,23,24]. The Reamer/Irrigator/Aspirator system (RIA) was initially developed to address problems related to the second hit phenomenon and heat exertion during reamed intramedullary
nailing [25–28]. Furthermore, the RIA system has gained most of its popularity as a novel technique of harvesting morsellised autologous bone graft from the intramedullary canal of mostly the femur. Favoured for providing equal or larger volumes of autologous graft (25–90 cm3) compared with the anterior (5– 72 cm3) or posterior iliac crests (25–88 cm3), RIA is also reportedly technically easier and minimally invasive reducing donor site morbidity [29]. The biological properties of the RIA graft have been proven superior to that of the iliac crest regarding cellular and osteoinductive protein content [20,30–32]. Recognition of this has led to the evolution of combined use of RIA graft at the second stage of the induced membrane technique in 27 cases of segmental diaphyseal non-union achieving 90% union at 1 year, as recently published [24]. Lastly, the role of osteoinductive agents in atrophic/oligotrophic non-unions is still debated. Many authors have provided supporting evidence in randomised studies and clinical series [33,34], whilst their high cost [35,36], especially to their recombinant form, and limitations of reimbursement have decreased their generalised adoption besides referral centres. Further research is also needed to understand the effects and potential super-concentration of these agents in the intra-membranous graft environment. To our knowledge there are scarce examples in the existing literature of these techniques in combination for the management of proximal femoral metaphyseal infected non-unions. Our experience reaffirms the need to adequately address both the biological and mechanical environment to increase the chances of union.
Conflict of interest statement None.
T.A.J. Goff, N.K. Kanakaris / Injury, Int. J. Care Injured 45 (2014) 2101–2105
Authors’ contributions NK did the preoperative planning, the surgery, the postoperative follow up, and reviewed the final draft. TG reviewed the patient’s notes, collected all relevant data and wrote the manuscript. References [1] Giannoudis PV, Einhorn TA, Schmidmaier G, Marsh D. The diamond concept – open questions. Injury 2008;39(Suppl. 2):S5–8. [2] Calori GM, Giannoudis PV. Enhancement of fracture healing with the diamond concept: the role of the biological chamber. Injury 2011;42(11):1191–3. [3] Struijs PA, Poolman RW, Bhandari M. Infected nonunion of the long bones. J Orthop Trauma 2007;21(7):507–11. [4] Patzakis MJ, Zalavras CG. Chronic posttraumatic osteomyelitis and infected nonunion of the tibia: current management concepts. J Am Acad Orthop Surg 2005;13(6):417–27. [5] Roche O, Zabe´e L, Sirveaux F, Villanueva E, Mole´ D. Treatment of septic nonunion of long bones: preliminary results of a two-stage procedure. J Bone Joint Surg Br Proc 2005;87-B:111–2. [6] Lasanianos NG, Kanakaris NK, Giannoudis PV. Current management of long bones large segmental defects. Orthop Trauma 2010;24(2):149–63. [7] Cierny 3rd G, DiPasquale D. Periprosthetic total joint infections: staging, treatment, and outcomes. Clin Orthop Relat Res 2002;403:23–8. [8] Motsitsi NS. Management of infected nonunion of long bones: the last decade (1996–2006). Injury 2008;39(2):155–60. [9] Chandra J, Kuhn DM, Mukherjee PK, Hoyer LL, McCormick T, Ghannoum MA. Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance. J Bacteriol 2001;183(18):5385–94. [10] Masquelet AC, Fitoussi F, Begue T, Muller GP. Reconstruction of the long bones by the induced membrane and spongy autograft. Ann Chir Plast Esthet 2000;45(3): 346–53. [11] Deelstra JJ, Neut D, Jutte PC. Successful treatment of Candida albicans-infected total hip prosthesis with staged procedure using an antifungal-loaded cement spacer. J Arthroplast 2013;28(2):374.e5–.e8. [12] Anagnostakos K, Kelm J, Schmitt E, Jung J. Fungal periprosthetic hip and knee joint infections clinical experience with a 2-stage treatment protocol. J Arthroplast 2012;27(2):293–8. [13] Kanakaris NK, Morell D, Gudipati S, Britten S, Giannoudis PV. Reaming irrigator aspirator system: early experience of its multipurpose use. Injury 2011;42(Suppl. 4):S28–34. [14] Giannoudis PV, Kanakaris NK, Dimitriou R, Gill I, Kolimarala V, Montgomery RJ. The synergistic effect of autograft and BMP-7 in the treatment of atrophic nonunions. Clin Orthop Relat Res 2009;467(12):3239–48. [15] Masquelet AC, Begue T. The concept of induced membrane for reconstruction of long bone defects. Orthop Clin North Am 2009;41(1):27–37. table of contents. [16] Pelissier P, Masquelet AC, Bareille R, Pelissier SM, Amedee J. Induced membranes secrete growth factors including vascular and osteoinductive factors and could stimulate bone regeneration. J Orthop Res: Off Publ Orthop Res Soc 2004;22(1):73–9. [17] Knothe UR, Springfield DS. A novel surgical procedure for bridging of massive bone defects. World J Surg Oncol 2005;3(1):7.
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