Surgical site infection continues to be a major challenge in orthopaedic trauma. Despite the tremendous clinical and economic impact of infection, strategies directed at its prevention remain controversial. In addition, the long-term successful eradication of infection remains challenging with high rates of reoperations and poor functional outcomes, making the primary prevention of infection ever more important. The current state of the evidence around the prevention of the infected fracture is reviewed here with a focus on evidence for antibiotic therapy and debridement, the induced membrane technique, management of soft-tissue defects, patient optimization, and adjuncts to prevent infection.
THE OPEN FRACTURE: ARE THERE EVIDENCE-BASED STANDARDS FOR ANTIBIOTIC THERAPY?
The Eastern Association for the Surgery of Trauma (EAST) published practice management guidelines for prophylactic antibiotic use in open fractures in 2011.1 They provided 4 Level I recommendations; recommendations based on meta-analysis of randomized trials or evidence from at least 1 randomized trial.
- Systemic antibiotic coverage directed at Gram-positive organisms should be initiated as soon as possible after injury.
- Gram-negative coverage should be added for type III open fractures.
- High-dose penicillin should be added in the presence of fecal or potential clostridial contamination (farm injuries).
- Fluoroquinolones offer no advantage compared with cephalosporin or aminoglycoside regimens. The use of fluoroquinolones may have a detrimental effect on fracture healing and may result in higher infection rates in type III open fractures.
In addition, they provided 2 Level II recommendations; recommendations that are reasonably justified based on available evidence and supported by expert opinion.
- In type III open fractures, antibiotics should be continued for 72 hours after injury or not >24 hours after soft-tissue coverage has been achieved.
- Once-daily aminoglycoside dosing is safe and effective for types II and III open fractures.
Investigators reviewed the outcomes of 101 open tibia and femur fractures treated before implementation of the EAST guidelines with 73 open tibia and femur fractures after EAST guidelines protocol implementation.2 They found that implementation of the EAST guidelines resulted in a significant decrease in the use of aminogycosides and vancomycin from 54% to 16% (P = 0.0001). They found no increase in skin and soft-tissue infection rates, and no difference in the rates of resistant organisms including methicillin-resistant Staphylococcus aureus.
Patients with type I or II open fractures should receive a first generation cephalosporin beginning with a 2-g intravenous (IV) loading dose, then 1-g IV every 8 hours for 3 doses (24 hours). Patients with a penicillin allergy should receive a 900-mg loading dose of clindamycin and then 900 mg q 8 hours × 3 (24 hours). Patients with a type III open fracture should receive either a third generation cephalosporin or a first generation cephalosporin plus aminoglycoside for 3 days. Patients with possible fecal type contamination should also receive prophylaxis with penicillin to cover for clostridia.
HOW TO DEBRIDE AN OPEN TIBIA FRACTURE
Infection after open fracture of the shaft of the tibia is fairly uncommon in low-grade injuries. However, in high-grade type III fractures, infection has been reported to occur in up to 10% of patients with modern treatment.3 Prevention and reduction of the risk of deep infection is dependent on appropriate excisional debridement. Extensive debridement of all comminuted, nonviable fragments may result in a bone void or segmental defect, which will ultimately require reconstruction of bone defects at a later stage.
Regardless of the debridement philosophy, sound operative technique is imperative to reduce infection in the open tibia fracture. The following description outlines critical elements in the operative procedure. The leg is prepped and draped in a sterile fashion. A “dirty” or contaminated back table is established and the passing of instruments occurs only toward to the patient to reduce contamination of instruments and implants that will be used for definitive fixation after thorough debridement. The open fracture wounds are extended both proximally and distally. This is followed by a complete excisional debridement of all nonviable skin, subcutaneous tissue, muscle, periosteum, and bone. The goal is to achieve a healthy and clean surgical wound, and to convert the traumatic wound into a surgical wound. Surgical debridement may also proceed through the planned surgical incision to avoid additional trauma to the already injured soft tissues. While color, consistency, contractility and capacity to bleed (the 4Cs) are still frequently taught and used to assess muscle viability, recent work has shown that these may be poor indicators and result in the excision of normal tissue.4,5
The “tug test” is used to assess the viability of cortical bone fragments within the wound. Those that can be easily removed by a pair of forceps or 2 fingers are assumed to have insufficient viability and are thus discarded.6 All viable fragments and constructible osteochondral or articular fragments are preserved. Once a meticulous debridement of the wound bed has been completed, the tourniquet (if used) should be deflated to ensure that all nonviable soft tissue and bone (that without punctate bleeding) has been adequately debrided.6–8 We recommend against the use of a tourniquet if possible, due to the increased difficulty of assessing the viability of the injured soft tissues, and the additional ischemia/reperfusion damage this already compromised tissue may be subjected to by the use of a tourniquet.9
After complete and meticulous debridement, a thorough irrigation of the wound is then performed with 9 L of normal saline.10 Once this is completed, instruments are discarded, gloves are changed, and the limb is redraped to provide a clean field and instruments for stabilization. Since many Gustilo type IIIB fractures will continue to demarcate after the initial debridement, we typically will return to the operating room (OR) for repeat excisional debridement every 24–96 hours until the soft-tissue envelope is amenable to definitive reconstruction and wound management.11
In the setting of high energy trauma resulting in severe comminution, a thorough debridement may lead to the creation of a significant bone defect. The technique for managing these defects has evolved over time. Polymethylmethacrylate (PMMA) intercalary spacers impregnated with antibiotics may be used to achieve a healthy wound bed. These can be contoured to the appropriate defect and will develop a vascularized membrane that can facilitate bone grafting if necessary. For highly contaminated wounds with a significant soft-tissue defect, the “bead pouch” technique described by Henry et al12 may be used. This will maintain a wound environment with a very high concentration of local antibiotics, that in our experience, is useful for severe wounds. Although infection is impossible to eliminate in open tibia fractures, sound and methodical principles of debridement can reduce the risk and optimize patient outcomes.
THE INDUCED MEMBRANE TECHNIQUE: HOW TO OPTIMIZE OUTCOMES
The “induced membrane technique” (IM) or the “Masquelet technique” was described by Professor Alain C. Masquelet6 in the 1970s, but was only recently used more popularly.13–16 Union rates range from 82% to 100%, and infection recurrence rates range from 5% to 30%.13–15,17,18 The IM technique is a 2-stage procedure that aims to eradicate infection (stage 1), while promoting a pro-osteogenic environment for definitive grafting and fixation (stage 2).14,16,19 Despite numerous advantages (low cost, low morbidity, and ability to handle defects of any shape or size),14,19 there is large variability in the literature regarding outcomes. Nonmodifiable host factors and medical comorbidities, as well as soft-tissue characteristics, play an important role.19
Initially, an appropriate construct (external fixation, plating, or IM nailing) to provide stability, preserve length, alignment, and rotation should be applied or planned before destabilization of a diseased segment.13,15,19 Although external fixation is described in the original technique, the ideal fixation method is still debated and often must be individualized on a case to case basis.15,19 It is imperative that all nonviable bone is resected using the “paprika sign” intraoperatively to assess viability.13,15,19 Next, a PMMA cement spacer is placed into the defect.19 The spacer should be preshaped into a cylinder spacer that can provide 2–3 cm coverage on both resection margins.16,19 If uncured cement is molded in vivo, soft-tissue protection and continuous irrigation are required to prevent thermal injuries during exothermic polymerization.16
The PMMA cement spacer will promote formation of a pro-osteogenic cellular membrane.13–16,20 Technique modifications have included the use of antibiotic-loaded cement spacers with the idea of delivering higher antibiotic concentrations locally.13–15,19,20 Antibiotic type and concentration remain a topic of debate because both variables affect membrane mechanical and biologic properties.20 Optimal timing between the first and second stage is also controversial, since the membrane molecular structure and cellular environment activity are dynamic.14,20 Both animal and human research have demonstrated that the optimal cellularity period for enhanced osteogenic and angiogenic effects peaks at 2–4 weeks, while mechanical properties of the membrane are optimal at around 6 weeks. The optimal period for the second stage of the procedure lies somewhere in this range, and the decision to proceed between 4 and 8 weeks should be partially determined by patient factors as well as the specific infection being treated.14,20
A vertical incision through the induced membrane should carefully be made. Using an osteotome, the spacer is extracted without disrupting the membrane's integrity.16 The ultimate bone graft material should offer osteoconductive and osteinductive properties.13–16,20 Autologous bone grafts in the form of iliac crest bone graft remain the gold standard; however, the authors favor the use of the reamer irrigator aspirator, which allows for harvest of larger volumes with less donor site pain.13 The graft must be loosely packed to avoid compression (overpacking) and allow for angiogenesis and revascularization by the membrane.15–17,19 If allograft is needed to augment volume and strength, a 1:3 ratio (allograft–autograft) should be used.13,15,16
Management of Soft-Tissue Defects: From Minor to Extreme!
To undertake management of soft-tissue defects, it is necessary to be able to (1) assess a wound and its capacity to heal (with an appropriate and acceptable final outcome) in the absence of surgical intervention—that is, to be able to discern the natural history of the wound in question, (2) identify all options available for the coverage of a complex wound, and (3) choose the most appropriate option given the personality of the defect. This third consideration is surgeon, and surgical-philosophy, dependent.
It is helpful to ask the following 5 questions to arrive at an understanding of whether or not surgical coverage of a wound is needed, and also what would, could, and should be used either locally or from a distant autologous source, to achieve stable coverage. First, where is the defect? This sets the tone of the discussion to follow, as there will be different local soft tissues available for coverage of a wound of similar size, depth, and exposed underlying tissue type. Second, what is at the base of the defect? Although exposed cortical bone with extensive stripping of the overlying periosteum or tendon devoid of epitenon presents an obvious need for some form of flap coverage, an exposed arteriovenous (AV) bundle or major peripheral nerve must also be considered. Although these structures could potentially support nonvascularized tissue in the form of a split-thickness or a full-thickness skin graft, it could be argued that secondary procedures on extremities treated this way would be at greater risk of complication and injury to the neural or vascular structures in question. Third, does the tissue at the base of the defect need to be covered? If the patient is in generally good health, and the wound (if allowed to heal by secondary intention) would not lead to any short- or long-term complications, is there a compelling reason to incur the potential complications of surgical intervention when the natural history of the wound itself might be benign? Fourth, if flap coverage is deemed necessary, what local tissue is available? The local tissue should be outside of the zone of injury, should be soft and compliant, and should be well vascularized. In addition, its blood supply should be sufficiently well understood (in the case of both muscle flaps and fasciocutaneous flaps) that it can be transferred in a reliable way. Finally, if there is no local tissue that is available for the coverage of the wound, what available distant tissue is suitable? In the lower extremity, distant tissue usually takes the form of free tissue transfers, whereas in the upper extremity, it can take the form of either a free tissue transfer or a pedicled axial pattern or perforator dependent flap from the trunk or the abdomen.
A split-thickness skin graft (or a full-thickness skin graft, although far less frequently) can be used to cover muscle, well-vascularized fascia or tendon, as well as possibly peripheral nerve and blood vessels (although, as mentioned earlier, it might be ill-advised given the long-term considerations of the reconstruction required eventually). A negative pressure wound device can be helpful to provide suction and application of the graft to an irregular bed, but is not mandatory in all situations. The author prefers grafts of 0.015 inch thickness meshed to a 1:1.5 ratio.
A local flap consisting of skin plus fascia or of muscle should be considered when the defect cannot or should not be closed primarily, should not be allowed to heal secondarily, and cannot (or should not) support a skin graft.21–23 In the lower extremity, local muscle flaps that are used commonly include the medial gastrocnemius, lateral gastrocnemius, anterograde soleus, and retrograde peroneus brevis muscles, as well as propeller flaps based on either the posterior tibial artery or peroneal artery perforators, the reverse sural fasciocutaneous flap, and keystone flaps based on perforators of medial and lateral sural arteries as well as the major longitudinal running AV bundles.
Free tissue transfer is considered when the defect cannot be closed primarily, should not be allowed to heal secondarily, cannot support a skin graft, and when local or distant tissue of sufficient amount or suitable quality and compliance is not available. The main disadvantages of free tissue transfer are that it is time consuming and technically demanding, is of greater expense operatively, and has the potential for distant donor site complications such as seroma, hematoma, and neuroma development.
Beyond the Fracture: Can the Patient Be Optimized?
It has been well-established in the orthopaedic literature that a variety of factors including nutritional condition, metabolic issues, smoking status, and previous bariatric surgery can all have an effect on fracture healing. Before embarking on a course of treatment for any fracture, delayed or nonunion, or malunion, the prudent orthopaedic surgeon should make an effort to optimize the patient with regards to these issues to maximize the chance of a successful outcome. Technically, perfect surgery may still fail in the face of severe malnutrition, unrecognized vitamin D deficiency, or a poor local tissue environment created by heavy smoking.
Perhaps, the largest study that demonstrates the importance of metabolic factors in bone healing relative to mechanical or surgical factors is that of Niikura et al.24 They examined 102 consecutive patients who had developed a nonunion and divided the causes for nonunion into “mechanical” or “biological” reasons. They found that only 24 cases were due to purely mechanical reasons, 23 cases were due to purely biological reasons, and 55 had combined etiologies. Thus, biological factors played a role in 76% of nonunions in their series, and they emphasized the importance of correcting these factors before surgical intervention, to maximize success. In a similar large series examining risk factors for failure after the fixation of femoral neck fractures in 237 patients, Riaz et al25 identified 37 failures. Interestingly, a low serum albumen was highly predictive of fixation failure, whereas age, sex, and screw configuration were not. Although the authors recognized that the acute correction of nutritional status was not possible in this scenario, this information could be used to help the treating surgeon decide to perform an arthroplasty in a patient prone to fixation failure due to a low serum albumen.
Brinker et al examined 37 consecutive patients with “unexplained” nonunion which they defined as fractures that were adequately fixed, of low energy, or minimally displaced, that failed to heal.26 They performed a comprehensive metabolic assessment and found that 31/37 (84%) had a significant abnormality including vitamin D deficiency, hypothyroidism, and diabetes. A number of the patients with “nonunion” healed without any further surgery once their metabolic condition was corrected, illustrating the importance of proper attention to this issue. While in the acute fracture situation, it may not be possible to correct such abnormalities immediately, during the recovery phase time permits for the investigation and treatment of these various conditions. Although not truly a “metabolic condition,” the negative effects of smoking have been well defined by a variety of studies in multiple clinical situations. In a study of 84 patients with lower extremity nonunion, McKee et al described a much higher failure rate after Ilizarov reconstruction in smokers (38%) compared with nonsmokers (10%), including the fact that all 5 amputations in the series were in smokers.27 They suggested that this type of complex reconstruction be delayed in smokers until smoking cessation strategies had been instituted.
In summary, it is clear that a variety of nutritional, metabolic, and other issues such as smoking have a major effect on bone healing, in many cases equal to or greater than the quality of reduction or fixation. It is of paramount importance that the treating surgeon recognizes this and initiates appropriate investigation, consultation, and treatment. It can mean the difference between success and failure.
Adjuncts to Prevent Infection: Is Anything Ready for Prime Time?
Despite the evolution of strategies related to prophylaxis measures in the hospital and OR environment, infection continues to be the most devastating complication after fracture fixation. Administration of antibiotics, fixation of fractures in lamina flow equipped ORs, skin preparation/disinfection measures, appropriate timing of intervention in the so called “fractures at risk” (proximal tibia, distal tibia, etc.), optimization of comorbidities (ie, diabetes) in immunocompromised patients, correct debridement/irrigation, and prompt soft-tissue closure in open fractures are some of the established measures that have contributed in the advances made.
During the past decade, research is ongoing to identify other areas in the pathway of fracture fixation where potential interventions could further reduce the risk of infection. These areas include the surface topography of implants, vehicles of delivery of local antibiotics with specific elution characteristics, and wound dressings capable of managing incisional drainage.
The difference in infection susceptibility between titanium and stainless steel (SS) implants has been a topic of great interest to the scientific community.28 Data collected from animal studies found that titanium is superior to electropolished SS (EPSS) regarding infection susceptibility. This was attributed to superior biocompatibility of titanium and the fact that fibrous capsules could be developed over EPSS implants.29 Recently, to investigate further the role of implant material and surface topography, different types of implants were tested in a rabbit humeral osteotomy model. Standard EPSS, standard titanium (Ti-S), roughened SS (RSS), and surface polished titanium (Ti-P) plates were assessed. Each rabbit received 1 of 3 S. aureus inocula, intended at determining the infection rate at a low, medium, and high dose of bacteria. Quantification of bacteria on the implant and in the surrounding tissues and determination of the infectious dose 50 (ID50) were the outcome measures. No significant differences were seen in susceptibility to infection when comparing titanium and steel implants with conventional or modified topographies. However, the authors observed that the Ti-S plate had a lower bacterial load compared with both EPSS and RSS, but only when using a high bacterial inoculum. Based on this observation, they speculated that the material (or its surface) may not influence the infection risk, but rather the infection severity.30
The concept of local delivery of antibiotics using different carriers for distribution, particularly in fractures at risk (ie, open fractures), has gained great popularity lately. Impregnated collagen fleeces,31 antibiotic-loaded fast-resorbable hydrogel coatings,32 injectable gentamicin-loaded thermoresponsive hyaluronic acid derivatives,33 and mixing antibiotics into VitagelTM tissue sealant34 among others have been used with relative success in both experimental and clinical trials. However, their routine utilization in the clinical setting has not been forthcoming.
Finally, the impact of prophylactic use of a specific design of negative pressure wound therapy dressing (device) on surgical site complications has been tested in different clinical conditions by a variety of disciplines. A recent meta-analysis revealed a significant reduction in surgical site infection, wound dehiscence, and length of stay on the basis of pooled data from 16 studies showing a benefit of a single-use negative pressure wound therapy system compared with standard care in closed surgical incisions.35
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