Effectiveness of the induced membrane technique in aseptic and infected long-bone defect management: Are there any differences?

Table 1 Main differences in induced membrane technique application in aseptic and infected bone nonunion and defects

	Debridement	Fixation options	Spacer characteristics	Antibiotics administration at stage 1	Interval between stage 1 and stage 2	Consolidation rates	Infection
Aseptic defects	Thorough debridement and removal of nonunion end-plates and dead tissue in open fractures is obligatory to avoid infection. A special feature of atrophic nonunion debridement is equalization of the limb length, which is an important aspect of further rehabilitation[4,12]. It is also worth noting that extensive resection of end-plates and periosteal dissection disrupt the nutrition of the fragment ends and should be avoided	The variability of fixation methods is extremely wide depending on the segment and location. Only internal fixation has been recommended recently for nonunion. A combination of intramedullary nailing and plating is widely used[12-14]. Internal fixation at IMT stage 1 not only prevents the development of infection in pin-tracts as happens in external fixation in the postoperative period, but also reduces the invasiveness of stage 2 as an IMN remains in situ. IMN is seen as the preferred method of fixation for tibial and femoral defects whenever possible[35]	Installation of a cement spacer impregnated with antibacterial drugs is not mandatory if culture tests do not detect resistant strains of bacteria. Despite the available experimental data that antibiotics reduce the membrane potential[39], antibacterial drugs were used in most clinical trials, as orthopedic surgeons regard their use to be safe as they fear low toxic infection	Empirical antibiotic therapy or antibiotic impregnated spacer may be used after debridement in acute cases[18]	Definitive control of infection is a prerequisite for continuing with graft reconstruction. Stage 2 starts after 4-8 weeks[4,10]. Confirmation of infection control is laboratory markers of inflammation, microbiological tests to detect the pathogen (tissue samples at the site of the segmental defect). Most authors are inclined to the minimum period of spacer placement (4-6 weeks) for aseptic pseudoarthrosis. Longer intervals may be determined exclusively by problems in the administration of treatment stages and infection[15]	Despite the relatively small number of patients in the reported series, high union rates from 88.2% to 92.7% were achieved. In the comparative series, there was no reliable difference with the series of one-stage bone grafting repair[14]. In acute defects, the success rate was 89 %[15]	Superficial infection was reported[12]. There were no reports of deep infection developed in aseptic nonunion. It indicates the high safety of the technique if it is performed correctly. Deep infection developed in acute cases[16]
Septic defects	Radical debridement involves removing all infected and non-viable bone and soft tissues, revising leaks and phlegmons, and removing foreign bodies involved in the process. The boundaries of viable and non-viable tissues are determined intraoperatively with the "paprika sign" or "bloody dew". To obtain more reliable results for determining the pathogen and sensitivity to antibiotics, a minimum of 3-5 deep tissue biopsies are performed[3,20]. Repeated debridement may be performed several times at stage 1 until infection suppression in the cases of resistant bacteria. In infected CBDs, repeated debridement and cement spacer replacement may be conducted weekly until infection resolution[37]. Recurrence of infection after IMT step 1 is always due to insufficient resection[9]	Regarding primary stabilization, a large majority of patients wore an external fixator until end of treatment in the IMT series of mostly infected cases presented by its author who considered that immediate nailing incurs a risk of recurrence of sepsis[9]. Temporary external fixators are recommended in the case of chronic infection[9]. Internal fixation is more preferred nowadays, and may be immediate, especially in the femur[35]. Plating may be combined with intramedullary nailing[21]. LCP was used as an external fixator with subsequent conversion to LCP and IMN at stage 2[22]	Installation of a cement spacer impregnated with antibacterial drugs is an overall practice. The preferred ratio is 4 g of vancomycin per 40 g of cement during spacer preparation[27]. Bone cement containing gentamicin can be used with the addition of 5 g vancomycin per 40 g gentamicin-impregnated PMMA bone cement[24-26]	Initially, empirical antibiotic therapy is initiated. It largely depends on national or local protocols, local antibiograms, patient’s history, and severity of local and systemic manifestations. Once the results of intraoperative bacterial cultures are available, the principle of systemic antibiotic therapy for osteomyelitis includes pathogen-directed therapy based on susceptibility, using drugs that achieve the required concentration in bone tissue. Antibiotic therapy should be continued for at least 4-6 weeks; shorter periods may be acceptable only in children. Immunosuppression, including that caused by diabetes and human immunodeficiency virus infection, may require longer treatment for 6-12 weeks. Long-term (more than 3 months) oral antibiotic therapy at the outpatient stage may improve outcomes[42]. A severe infection variant is the aforementioned hospital-acquired infection. MRSA is associated with higher rates of recurrence[20]	Complete suppression of infection is a prerequisite for bone defect grafting in osteomyelitis. Sending tissue samples for examination is extremely important due to possible false-negative results of bacteriological culture. Stage 2 starts after 8 to 12 weeks[3,21,24,32] or longer up to 28-32 weeks due to local status[27,29,31]. In most severe cases, removal of infected tissues frequently results in extensive bone loss in the diaphysis. The resistant strains recur frequently and thus stage 1 may be longer than in aseptic cases[37] due to redebridement	Radiographic signs of consolidation were achieved on average within 5 to 9 months, with a range of 4 to 16 months; consolidation was achieved in 69%-100% of cases[20-29,47]	Although several clinical studies have yielded favorable results, high rates of infection and mixed results were reported[20,46-48]. There are few large homogenous series using a standardized IMT protocol for the treatment of infected nonunion and posttraumatic osteomyelitis. The evidence in treating challenging infections shows the rates of reinfection within 40% after bone grafting[20]. Reinfection of 68.5% was reported isolating Staphylococcus (26%) and more than one pathogen (22%)[46]

IMT: Induced membrane technique; IMN: Intramedullary nailing; CBD: Critical-size bone defect; LCP: Compression plate; PMMA: Polymethyl metacrylate; MRSA: Methicillin-resistant Staphylococcus aureus.