Combination of Masquelet’s technique with transfer of free fasciocutaneous flap in the treatment of complex septic tibial pseudoarthrosis: preliminary results, overview of literature

Summary

Introduction:
Infected pseudoarthrosis presents a serious complication of fracture osteosynthesis. A typical example is a septic pseudoarthrosis of the distal tibia as a complication of osteosynthesis of not only pilon fractures but also extraarticular fractures of the distal tibia. Despite the advancements in diagnostics, surgical and antibiotic therapy, the final outcome and function are difficult to predict. The used surgical techniques, timing and type of surgical strategy in patients with septic pseudoarthrosis differ among individual authors. The common and dreaded complication in the treatment of septic pseudoarthrosis is the recurrence of the infection and absence of bone healing. Other specific complications depend on the technique used.

Aim:
The aim of the work is a retrospective evaluation of outcomes of treatment of complex septic pseudoarthrosis of the tibia for five years, treated with Masquelet’s technique, with a transfer of a free fasciocutaneous flap. The presented article also includes an overview of literature and comparison of outcomes with literary sources.

Methods:
Between 2012 and 2016, the authors evaluated a total of six patients (out of seven – one patient died during follow up due to cardiovascular complications) with a complex septic pseudoarthrosis of the tibia treated with Masquelet’s technique, with a transfer of a fasciocutaneous flap. The term “complex” pseudoarthrosis defines pseudoarthrosis with a defect of the skeleton, with the presumed non-healing of the defect without any further intervention, and at the same time a defect of soft tissues requiring an intervention by plastic surgeon. The author of the article treated the skeleton of all patients according to a staged protocol. The basis of the therapy is a two-stage protocol. The period of follow-up varied between 18 and 60 months. The first stage included, apart from extraction of the osteosynthetic material and radical debridement, also the so-called Masquelet induced membrane technique using a cement spacer in combination with free fasciocutaneous flap for management of defects of soft tissues. At the same time, the cement spacer was used as antibiotic carrier. In order to stabilize the skeleton in this stage, external fixator was usually applied. In the second stage, following sanation of the original infectious complication, the cement spacer is removed, after partially lifting off the flap, followed with spongioplasty and stable osteosynthesis. The outcomes of the technique were evaluated on the basis of absence of infection, bone consolidation and weight bearing ability.

Results:
The authors managed to achieve consolidation of the skeleton and healing of soft tissues, without any signs of recurrent infection in all six patients using the induced membrane technique, which was a part of the two-stage protocol. Full consolidation of the skeleton in all patients was confirmed after 18 months, only one patient healed within six months. The period of follow-up varied between 18 and 60 months. Five patients were capable of full loading after healing, one patient achieved partial loading. The pathogen was confirmed in all patients with conventional microbiological methods, two patients presented with mixed flora.

Conclusion:
Staged protocol with Masquelet’s technique, in combination with free fasciocutaneous flap is a safe method for treatment of complex septic pseudoarthrosis of the tibia with skeletal defects not exceeding five centimetres, with a high degree of bone healing, and without recurrence of infection.

Keywords:
Distal tibia, septic pseudoarthrosis, bone defect, staged protocol, diamond concept, infection control, Masquelet’s technique, cement spacer, bone graft.

Introduction

The onset and development of infected pseudoarthrosis presents a significant functional limitation and risk for development of further local and systemic complications; it significantly influences the length of sickness leave and increases financial costs of the treatment. Risk factors for the onset of infected pseudoarthrosis include risk factors on the side of the patient, character of the injury and technical aspects of the osteosynthesis. Regardless of the classification system of pseudoarthrosis, the presence of infectious complication decides about future therapeutic strategy and subsequent interventions. Apart from known local and systemic risk factors, there exist no current complete data and studies defining any of the biomarkers as a predictor for occurrence of pseudoarthrosis [33].

There exists no exact consensus regarding the definition of pseudoarthrosis, or septic pseudoarthrosis as a sub-group [4]. One of the definitions of septic pseudoarthrosis is the absence of bone healing lasting more than six to eight months and concomitant presence of a pathogen [39]. Pragmatic definition of pseudoarthrosis is based upon the presence of symptomatic fracture, which is not healed, without any perspective of future healing without any further intervention [3]. Useful classification scheme defined by Jain in 2005 divides infectious pseudoarthroses into pseudoarthroses with active or inactive infection, with or without a bone defect of at least four centimetres in size, and with or without implant failure [18]. Complete examination of each infected pseudoarthrosis then includes general condition of the patient and his/her comorbidities, localization of the pseudoarthrosis, namely in relation to the joint, and local findings, i.e. quality of vascular supply and condition of soft tissues, especially regarding the presence of a fistula or soft tissue defect. According to our opinion, possible infectious complications must be suspected in every pseudoarthrosis (e.g. in the form of mitigated infection), namely in connection with unstable osteosynthesis.

The surgical strategy applied in patients with septic pseudoarthrosis includes single- [42] or two- [36] and more staged protocols, applying various methods and their combinations [13]. Regardless of the protocol, radical debridement is crucial, together with local administration of antibiotics, on a suitable carrier. The basic concept for therapy of impaired bone healing is a triangular concept, when the restoration of bone healing and bone regeneration includes administration of growth factors, a carrier for osteoconduction and mesenchymal blood cells (so called diamond concept according to Giannoudis, 2007) [11]. Skeletal defect is usually treated with autologous spongioplasty, possibly in combination with synthetic bone substituents (calcium sulphate, beta-tricalcium phosphate). Another possibility is to use a vascularized fibular graft. Well-established techniques of external fixation, including distraction osteogenesis and segmental transport, are used namely for management of larger defects. In the individual steps and stages, also the Reamer/Irrigator/Aspirator system (RIA) [26], induced membrane technique is used, with the administration of cement as, apart from its other functions, carrier of antibiotics [28] and microsurgical transfers of free muscle and fasciocutaneous flaps, possibly also with the use of transposition flaps.

Materials, methods

Within the five-year period, from 2012 to 2016, we had the possibility to evaluate a total of six patients with a complex septic pseudoarthrosis of the tibia. The term “complex” pseudoarthrosis defines pseudoarthrosis with a defect of the skeleton, with the presumed non-healing of the defect without any further intervention, and at the same time a defect of soft tissues requiring an intervention by plastic surgeon. Among our patient population, septic pseudoarthrosis was observed in one patient, in the area of tibial diaphysis, and in four patients in the distal metadiaphysis of the tibia, in one patient, the pseudoarthrosis was localized in the meta-epiphyseal area following an original treatment of a pilon fracture. One of the original seven patients died in the course of follow-up due to cardiovascular complications, not related to the treatment of pseudoarthrosis. The author of the article treated all patients, as far as the septic complication is concerned, using a staged protocol. The first stage of treatment included, apart from radical debridement, also administration of cement spacer with antibiotics, using the so-called induced membrane technique. This stage also includes transfer of a free fasciocutaneous flap in order to cover the defect of soft tissues, in cooperation with a plastic surgeon (Fig. 1).

In five patients, the first stage of treatment included revision of the pseudoarthrosis, together with collection of samples for culture examination, extraction of the osteosynthetic material, and radical debridement, including the use of pulse lavage. Furthermore, a cement spacer with antibiotics was applied and this situation was stabilized with an external fixator in three patients; in the two remaining patients with septic pseudoarthrosis, the skeleton was primarily stabilized with a cement nail containing antibiotics, in combination with cement spacer at the defect site (Fig. 2).

In one patient, the original intramedullary osteosynthetic material was primarily left in situ, due to the finding of a mitigated infection in the stable osteosynthesis. However, leaving the original osteosynthetic material in place cannot be generally recommended. After six weeks, during the second stage of treatment, the healed fasciocutaneous flap was partially lifted off, followed by careful extraction of the cement spacer, so as not to disrupt the present induced membrane, which resulted in a stable osteosynthesis with spongioplasty. In order to ensure sufficient stability, the “double plating” technique was used in three patients, with the use of two 3.5 locking splints for the distal tibia. Ankle arthrodesis with screws was performed in one patient due to the presence of the defect near the ankle joint and the inability to perform a stable splint osteosynthesis due to a very small peripheral fragment, with advanced post-injury arthrosis of the joint. During the second stage of the protocol, samples for culture examination were collected from all patients; the results were always negative. The staged protocol includes also a systemic antibiotic therapy, including the use of antibiotics with antibiofilm activity (Rifampicin in combination, or possibly Ciprofloxacin), in relation to the second stage of treatment to protect the definite osteosynthesis. Appropriate antibiotic therapy was always consulted with antibiotic centre. Perioperative manifestation of a pathogen was performed with conventional microbiological techniques, with collection of at least three samples for culture and sensitivity examination, possibly also for histologic examination. The explanted osteosynthetic material was sent for sonication, which increases the sensitivity of microbiological assessment.

Results

Complete bone consolidation, without any recurrence of the infection or other complications was achieved in all six patients with septic pseudoarthrosis of the tibia, treated with a staged protocol using the combination of Masquelet’s technique and free fasciocutaneous flap. Five patients achieved full weight bearing, one patient only partial. Full consolidation of the skeleton could be manifested in all patients within a longer time span, i.e. 1.5 years after spongioplasty and stable osteosynthesis, one patient healed within six months (Fig. 3).

The debridement performed in the first stage, resulted in a bone defect the size of 3.5 cm (2-4 cm). It was possible to isolate the pathogen in all patients, in two patients, the findings revealed mixed flora.

Discussion

Recurrent infection and insufficient bone healing present two main complications in the surgical therapy of septic pseudoarthrosis of the tibia [10, 41]. The main causes include namely insufficient surgical debridement, leaving the original osteosynthetic material in situ, incorrect selection and use of antibiotics, unsuitable timing and incorrect technique of skeleton reconstruction. The recommended timing and type of skeletal defect reconstruction vary among individual authors [31]. In 1999, Costerton et al. [8] attributed the persistence of a chronic defect to the presence of biofilm. The basic principle of surgical treatment in patients with septic pseudoarthrosis is eradication of the infection which is the cause of supressed bone healing. This is achieved with the use of single- or two- and more staged protocols. The metaanalysis performed by Struijs et al. [39] summarizes the results of single-stage and two-stage strategy in the treatment of infected pseudoarthroses of long bones. The methods vary among individual authors, however, similar percentage of defect healing (70-100%) and infection recurrence (0-60%) was observed in both groups. In case we evaluate only the group of studies with radical debridement, local antibiotic therapy and secondary fixation (four studies, 185 patients), the percentage of healing oscillates between 93 and 100%, with the percentage of infection reaching only between 0 and 18%. This strategy is also used at our centre.

Using the single-stage surgical strategy, Wu [42] reports 25 patients with infected pseudoarthrosis following splint osteosynthesis of fractures of the distal tibia. The protocol included also extraction of the metallic mate­rial, debridement, and spongioplasty with administration of local antibiotics and stabilization of the skeleton using Ilizarov ring-shaped external fixator. The author reports full healing in 100% of patients. Similar technique was used also by the team of Blum et al. [6]. Maini et al. [23], using a single-stage protocol, use radical debridement, followed by administration of external fixator, with the principle of distraction osteogenesis or segment transport. Other authors managed complications using a two-stage protocol.

Part of a staged protocol (single- or two-stage) is, apart from radical debridement, performed in order to remove the infected and nonvital part of the skeleton, and local administration of antibiotics, also providing sufficient and high-quality dressing of soft tissues with a flap, and fixation, in order to stabilize the skeleton and soft tissues. In order to achieve this, several basic techniques and principles are used, possibly in combinations:

1. Techniques of external fixation based purely on the principle of distraction osteogenesis with compression/distraction or segmental transport [6, 35].
2. Free transfer of tissue and internal fixation, e.g. vascularized fibula [2] or flap plasty in combination with the induced membrane technique and internal fixation [36].
3. Reconstruction in situ: combination of internal osteosynthesis – splint or nail, together with spongioplasty, usually using the concept of induced membrane [12], or with a local transfer of the fibula with microvascular technique [16], or as an avascular graft. We do not have personal experience with segmental transport or microsurgical transfer of a bone graft. Also, we have never used avascularized structural graft.

Treatment of the defect of soft tissues with a transfer of a free muscle or fasciocutaneous flap using microsurgical technique is the main advantage in the treat­ment of infected septic pseudoarthrosis with fistula and surrounding nonvital tissue. The resulting increase of local blood supply is important for improving the availability of antibiotics and for bone healing. From our patient population it is clear, that the resulting effect may be also achieved with the use of a free fasciocutaneous, not only muscle flap. Nevertheless, literature shows preferential use of muscle flaps [14, 31]. Wagelse et al. [40] did not observe any significant difference in the results associated with the use of muscle versus fasciocutaneous flaps.

In patients with septic pseudoarthrosis of the distal tibia, we prefer, identically to many other authors, a two stage protocol [29]. The first stage includes eradication of the infection, removal of the metallic material and radical debridement, together with removal of nonvital tissue up to healthy tissue, with manifestations of punctuate bleeding (“paprika sign”), and subsequent sufficient covering with soft tissues – in patients with defects of soft tissues and present fistula, transfer of a free flap with microsurgical technique is usually used. Part of this stage is further administration of a cement spacer with antibiotics, and temporary stabilization of the skeleton using external fixator [23]. It is very important to perform the fixation in this stage in correct anatomical position. In case so called composite grafts are used, the procedure may be performed as single-stage. For example Yazar et al. [43] report bone healing in up to 96.7% of patients, after 6.9 months on average, with postoperative recurrent infection reaching 7.9%. The modified Masquelet’s technique, using calcium sulphate with antibiotics and gradual reconstruction without any further intervention, also enables single-stage procedure only [19]. The technique combining induced membrane with spongious autologous graft was first described by Maquelet in 1986 [24, 27], in extensive diaphyseal defects up to 25 cm long. Even other authors confirm that also defects exceeding the critical size of max. 5 cm may be successfully treated with this technique, without the use of segmental transport or a vascularized graft [20, 37]. The applied cement spacer has double effect – mechanical and biological. Considering the mechanical effect, the spacer fills in the defect and prevents from ingrowth of fibrous tissue, and thus creates a space for future spongioplasty. In order to improve the stability in combination with external fixator it is possible, according to certain recommendations, to partially implant the cement also into the marrow cavity, and in light excess also over the cortical edges of both main fragments, in order to ensure sufficient space for future spongioplasty and osteosynthesis, among others [12]. The biological effect consists of a stimulation of the process during which biological membrane is created. The characteristics of the induced membrane are used in the second stage of the reconstruction, usually six to eight weeks after the cement spacer implantation. The membrane participates, due to its characteristics, upon the revascularization and remodelling of the graft, prevents the graft resorption. The membrane has been shown to contain numerous factors. In the induced membrane, expression of several factors occurs, for example endothelial growth factor, interleukin 6, BMP-2 and type-1 collagen (= factors stimulating angiogenesis and bone formation). The formation of some of these factors culminates approximately four weeks after implantation of the cement spacer [1]. The membrane further contains osteoclasts and their precursors, facilitating osteointegration and remodelling of autologous cortico-spongious grafts [15]. The formed membrane also prevents resorption of the implanted graft [26]. A number of smaller, retrospective studies have confirmed the effect of the Masquelet’s technique [20].

The second stage, beginning approximately six weeks after implantation of the cement spacer, includes, apart from its extraction, also a second look procedure, with removal of other nonvital tissues. The precondition of the second stage, which consists, apart from the spacer removal, also of a spongioplasty and osteosynthesis following partial lifting off of the flap, is the absence of local and overall clinical signs of infection and normalization of inflammatory parameters. In cases when persisting infectious complication is suspected, it is possible to recommend extraction of the existing spacer and repeating the whole stage with implantation of a new cement spacer containing antibiotics. The local antibiotic effect of the spacer drops practically to zero after six weeks. New samples are collected for culture. When extracting the spacer in the second stage, it is necessary to save the induced membrane as much as possible and revise the marrow cavity. In this stage, considering the presence of the induced membrane, we do not recommend, contrary to the first stage, to use a pulse lavage.

The autologous spongioplasty intended for filling a defect, harvested from iliac crest, is considered a golden standard, due to its characteristic features [22]. There has not been a sufficient number of studies performed so far comparing individual new concepts with an autologous graft. The closest relation to autologous spongiosis bears tricalcium phosphate, due to its cha­racteristics [22]. In cases when larger amount of material needs to be harvested, due to the size of the defect, or the possibilities of spongiosis harvesting from typical sites have been exhausted, it is possible to obtain the material using the Reamer/Irrigator/Aspirator^® (RIA) system. With the RIA technique, we obtain further material with a harvesting cutter from the area of the greater trochanter. The material harvested using the RIA method contains an increased number of stem cells and growth factors, and therapy of bone defects is one of the elective indications for RIA. Also the combination with induced membrane seems advantageous, as the membrane prevents the material harvested with the RIA technique to progrede into surrounding soft tissues and facilitates revascularization, prevents from graft resorption [26]. It is possible to recommend combining the material harvested with the RIA technique with a more structural graft, including artificial bone substituents. Masquelet [28] recommends mixing the autologous spongiosis with demineralized bone matrix in the ratio of 1:3 when more material is required.

One of the complications associated with filling a defect in autologous spongious bone is graft resorption. Graft resorption has been described with conventional means of using spongiosis, also in cases of good vascularization of the recipient site [17]. According to some authors, delayed spongioplasty decreases the risk of graft resorption [30]. The reasons for gradual resorption of the performed spongioplasty may include, apart from insufficient vascularization and absence of the induced membrane, also insufficient amount of spongiosis, persisting infection, and unstable osteosynthesis. Masquelet sees the causes of failure of the induced membrane technique in misunderstanding, or modifications of his original technique [25]. It is also important to exclude other comorbidities, metabolic and endocrine abnormalities, such as diseases of the thyroid gland and parathyroid glands, central hypogonadism, deficit of vitamin D, and imbalance of the calcium metabolism. Brinker [7] presents on a group of 37 patients a subgroup of 31 patients (83 %), who suffered from one or more disorders described above. Eight of these patients achieved full healing with pure correction of the metabolic disorders only, without any need of further surgical interventions.

Together with spongioplasty, stable osteosynthesis is performed. We prefer splint osteosynthesis in cases of the distal tibia. Depending on the localization of the defect and the size of the peripheral fragment, it is also possible to use a nail [21]. Olesen [32], among his small retrospective group of eight patients, used a nail for stabilization of the skeleton in cases of diaphyseal defects rather than a splint. The author reports faster consolidation and ability of earlier loading in patients treated with a nail when compared to those treated with splint osteosynthesis. Some authors report stabilization with an external fixator [9], which remains in situ, depending on the first stage of treatment. Also the team of Schottle et al. [36], in their small group of six patients with septic pseudoarthrosis of the distal tibia, leaves the external fixator applied during the first stage of treatment in place, contrary to the practice at our department.

Conclusion

The results of studying our small, however for our centre pilot, patient group show that, in accordance with literature, the use of Masquelet’s technique in combination with a transfer of a free fasciocutaneous flap using a staged protocol in the treatment of septic pseudoarthrosis of the distal tibia is effective and safe. All our patients treated with this technique achieved bone consolidation, without recurrence of infection. However, bone healing is documented later than presented in the recent literature. When compared to bone transport or the use of a vascularized fibular graft, this technique is technically less demanding. The literature shows that the induced membrane technique does not have to depend on the size of the defect only, i.e. defect with the maximum size of four to five centimetres, and that it is possible to perform sanation of larger defects. This technique may be used also in smaller hospitals, due to the less demanding technical requirements, higher patient compliance, short learning curve and the possibility to use this method even without participation of a plastic surgeon in the absence of soft tissue defects. However, it requires experience with the use of external fixators. The use of the Masquelet’s technique does not exclude treatment of the defect of soft tissues in the first stage with concomitant transfer of a free fasciocutaneous flap with microsurgical technique; it is not necessary to prefer muscle flaps. Nevertheless, other prospective, randomized clinical trials will be required in order to unify and standardize the procedure in the diagnostics and therapy of septic pseudoarthroses of the distal tibia.

Alexandr Rypl, MD

alrypl@centrum.cz