Management of Diabetic Foot Lesions

7/15/2014 Management of diabetic foot lesionshttp://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTer… 1/23 Official reprint from UpToDate www.uptodate.com ©2014 UpToDate Authors David K McCulloch, MD Richard J de Asla, MD Section Editors John F Eidt, MD Joseph L Mills, Sr, MD David M Nathan, MD Deputy Editor Kathryn A Collins, MD, PhD, FACS Management of diabetic foot lesions All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2014. | This topic last updated: Mar 27, 2013. INTRODUCTION — The lifetime risk of a foot ulcer for patients with diabetes (type 1 or 2) may be as high as 25 percent [1-3]. Diabetic foot ulcers are a major cause of morbidity and mortality, accounting for approximately two-thirds of all nontraumatic amputations performed in the United States [4,5]. This observation illustrates the importance of prompt treatment of foot ulcers in patients with diabetes. The management of diabetic foot lesions is provided here. Evaluation and prevention of foot ulcers and the treatment of diabetes-related foot infections (cellulitis and osteomyelitis) are discussed separately. (See "Evaluation of the diabetic foot" and "Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities".) WOUND CLASSIFICATION — The first step in managing diabetic foot ulcers is classifying the wound. Classification is based upon clinical evaluation of the extent of the lesion and, in some classification systems, an assessment of the vascular status of the foot. The intensity and duration of treatment can be determined after clinical evaluation of the ulcer. (See "Evaluation of the diabetic foot", section on 'Wound evaluation'.) A widely used classification of diabetic foot ulcers is that proposed by Wagner [6]: Grade 0 – No ulcer in a high-risk foot Grade 1 – Superficial ulcer involving the full skin thickness but not underlying tissues (picture 1) Grade 2 – Deep ulcer, penetrating down to ligaments and muscle, but no bone involvement or abscess formation (picture 2) Grade 3 – Deep ulcer with cellulitis or abscess formation, often with osteomyelitis (picture 3) Grade 4 – Localized gangrene (picture 4) Grade 5 – Extensive gangrene involving the whole foot The Wagner classification is based upon clinical evaluation (depth of ulcer and presence of necrosis) alone and does not account for the vascular status of the foot. A modified system that is frequently used by orthopedic surgeons individually scores the components of wound depth and ischemia [7]. Other ulcer classification systems have also been published [8-11]. The International Working Group on the Diabetic Foot proposed classifying all ulcers according to the following categories: perfusion, extent, depth, infection, and sensation (PEDIS) [12]. The PEDIS system is primarily used for research purposes. The usual approach to the management of lesions of each Wagner grade is given below, followed by a discussion of some newer approaches. GRADE 0 LESIONS — Counseling regarding preventive foot care should be given to any patient whose feet are at risk for ulcer development, particularly patients with existing neuropathy. There are several measures that can markedly diminish ulcer formation, such as avoiding poorly fitting shoes, walking barefoot, and smoking. This topic is reviewed separately. (See "Evaluation of the diabetic foot", section on 'Risk factors' and "Evaluation of the diabetic foot", section on 'Preventive foot care'.) [1] GRADE 1 AND 2 LESIONS — Extensive debridement, good local wound care, relief of pressure on the ulcer, and control of infection (when present) are believed to be important components of therapy for grade 1 and 2 foot ulcers [9,13,14]. There are limited data evaluating the efficacy of this standard approach, particularly the benefits of debridement and local wound care. In a meta-analysis of the control groups from 10 trials (622 patients) ® ® 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTer… 2/23 evaluating standard treatment (debridement and local wound care) versus various new therapies, 24 and 31 percent of ulcers healed after 12 and 20 weeks, respectively, of standard treatment [15]. In clinical practice, measurements of a patient's ulcer size should be taken at every office visit so that comparisons can be made and progress documented. The surface area of a healthy diabetic foot ulcer should decrease in size at a rate of approximately one percent a day. Ulcers that do not improve should be evaluated for ongoing soft tissue infection or osteomyelitis requiring antibiotics, insufficient vascular flow, or most commonly, the need for more effective off-loading. (See 'Assessment for peripheral artery disease' below and 'Assess for osteomyelitis' below.) Method of debridement — Debridement of necrotic tissue is important for ulcer healing [16], although there are few trials comparing the different methods of debridement (sharp, enzymatic, autolytic, mechanical, and biological). The types of debridement are reviewed separately. (See "Treatment of pressure ulcers", section on 'Debridement'.) Sharp debridement involves the use of a scalpel or scissors to remove necrotic tissue [17]. It is the most widely used method except in certain settings, such as highly vascular ulcers or when there is significant vascular compromise such that concerns exist as to the patient's ability to heal any new wounds created by sharp debridement. In such settings, enzymatic debridement (topical application of proteolytic enzymes such as collagenase) may be preferable [8]. Autolytic debridement, using a semiocclusive or occlusive (hydrogel) dressing to cover a wound so that necrotic tissue is digested by enzymes normally present in wound tissue, may be a good option in patients with painful ulcers. In a systematic review of six small randomized trials, hydrogels were significantly more effective than wet to moist saline or dry gauze in healing foot ulcers in diabetic patients [18]. However, a hydrogel combined with good wound care (defined as sharp debridement, saline dressings, pressure relief, and control of infection) was not significantly better than good wound care alone. Larval therapy (a form of biological debridement) showed no significant benefit in small studies. Overall, the review was limited by the small number of trials and poor methodological quality. Thus, there are few data to guide choice of debridement. When surgeons with expertise in sharp debridement are available, we prefer this method. As an alternative, we suggest application of a hydrogel since limited data support its efficacy in promoting ulcer healing. For patients with evidence of arterial insufficiency, we suggest referral to a vascular specialist. Infection control — The diagnosis of infection is clinical and is likely to be present if the ulcer contains obvious purulent material or there is redness, swelling or warmth around the ulcer [19]. Cultures of the ulcer base are taken after debridement and prior to initiation of empiric antibiotic therapy. Tissue samples taken by curettage, rather than wound swab or irrigation, are preferable because they provide more accurate results [20]. The most common infecting organisms are aerobic gram-positive cocci. Other frequent pathogens are aerobic gram- negative bacilli and anaerobes, usually as a second organism [21]. In general, the limited data on antibiotic therapy of diabetic foot infections lack standardization to allow comparison of outcomes of different regimens. On the basis of the available studies, no single drug or combination appears to be superior to others. Empiric antibiotic therapy should cover gram-positive cocci (table 1). Subsequent antibiotic therapy should be tailored to culture and susceptibility results. It is not always necessary to cover all microorganisms isolated from cultures. (See "Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities", section on 'Antimicrobial therapy'.) [22] Local wound care — After debridement, ulcers should be kept clean and moist but free of excess fluids. Moisture accelerates tissue healing. Dressings should be selected based upon wound characteristics, such as the extent of exudate, desiccation, or necrotic tissue. Some dressings simply provide protection, whereas others promote wound hydration or prevent excessive moisture. Wet-to-dry saline dressings are frequently used, but some ulcers may require a moister environment. In addition, wet-to-dry dressings will remove both nonviable and viable tissues. Thus, caution is required to avoid damaging healthy tissue. 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTer… 3/23 Some dressings are impregnated with antimicrobial agents to prevent infection and enhance ulcer healing. However, there are no clinical trial data to support their effectiveness [23]. (See "Treatment of pressure ulcers", section on 'Dressing choices'.) Mechanical off-loading — Off-loading devices, including total contact casts, cast walkers, shoe modifications and other devices to assist in ambulation are available to reduce or eliminate pressure in the region of the ulcer, which is important for healing. The evidence supports the use of total contact casts and nonremovable cast walkers for relief of pressure associated with diabetic ulcer healing [24]. A 2000 Cochrane database review updated in 2013 evaluated 14 trials comparing various forms of pressure-relieving treatments (nonremovable, removable) and dressings [25,26]. In five trials, the likelihood of wound healing was significantly better at 12 weeks for nonremovable, pressure-relieving casts compared with removable devices or dressings (relative risk [RR] 1.17, 95% CI 1.01-1.36). In one trial, no significant differences were found between different types of nonremovable pressure-relieving treatments [27]. Total contact cast — A total contact cast is a padded fiberglass shell designed to take pressure off the heel or elsewhere on the foot by averaging the pressure across the sole of the foot (ie, eliminates high and low pressure regions by providing contact at all points) or to generally un-weight the entire foot through a total contact fit at the calf. The most aggressive unloading is achieved by making the patient non-weight-bearing. Disadvantages of total contact casting include expertise needed in applying the cast, inability to inspect the wound frequently, inconvenience in activities of daily living (eg, bathing), and the risk of developing a secondary ulcer in an ill-fitting cast (particularly in patients with neuropathy) [9]. Frequent cast changes may be needed to avoid complications. Based upon randomized trials, total contact casting enhances diabetic ulcer healing and is the standard for relieving pressure from the forefoot [25-33]. As an example, in a trial of off-loading modalities in 63 diabetic patients with superficial, noninfected, nonischemic plantar ulcers, the proportion of ulcers that were healed at 12 weeks was significantly higher in those randomly assigned to a total contact cast compared with a half-shoe or removable cast walker (90 versus 58 and 65 percent, respectively) [30]. Patients with a total contact cast also had faster wound healing. Another small trial found that a casting combined with Achilles tendon lengthening resulted in significantly fewer ulcer recurrences at seven months (15 verus 59 percent) and two years (38 versus 81 percent) compared with the casting alone [34]. Total contact casts should not be used in patients with infected wounds, osteomyelitis, peripheral ischemia, bilateral ulceration, lower extremity amputation or heel ulceration [35]. Cast walkers — An alternative to total contact casting is a prefabricated brace called a cast walker that is designed to maintain a total contact fit (figure 1). Several cast walkers (non-removable, removable) are commercially available and provide capability to off-load the foot similar to contact casts. Cast walkers also appear to facilitate wound healing, but a significant disadvantage is poor patient compliance if the cast walker is removed [36]. Cast walkers appear to have a similar ability to off-load the foot compared with total contact casting. One study compared plantar foot pressure metrics in a standard shoe, total contact cast and prefabricated pneumatic walking brace [37]. Five plantar foot sensors were placed at the first, third, and fifth metatarsal heads, fifth metatarsal base, and mid-plantar heel of 10 healthy male subjects who walked at a constant speed over a distance of 280 meters. Peak pressures were significantly reduced in the pneumatic walking brace compared with the standard shoe for all sensor locations to an equal or greater degree compared with the total contact cast in all sensor locations. Another study measured foot pressures using an in-shoe pressure measurement system (Novel Pedar®) in 18 healthy subjects while wearing a cast walker or total contact cast [38]. Peak foot pressures using the cast walker were significantly reduced in the forefoot (12 versus 18 N/cm ) and foot as a whole (14 versus 19 N/cm ) compared with a fiberglass total contact cast, but no differences were found for the heel or midfoot. These studies suggest these prefabricated products are at least as good as total contact casting for off-loading 2 2 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTer… 4/23 the foot and equalizing foot pressures when the foot anatomy is normal, but data are not available demonstrating these effects for patients with diabetic foot deformities. Cast walkers have been used for the treatment of neuropathic plantar ulcers but these devices, thus far, have not been found to be superior to total contact casting in randomized trials. In one trial, the rate of ulcer healing was significantly higher in those randomly assigned to total contact casting compared with a half-shoe or removable cast walker [30]. Another trial that randomly assigned 48 patients to total contact casting or a removable cast walker (ie, Stabil-D®), found no difference in the number of days to achieve healing (35 versus 39 days) [39]. Therapeutic shoes — After healing of the ulcer is achieved, extra-depth and -width shoes with orthotic inserts are often prescribed to prevent recurrent ulceration [25]. However, in one trial, 400 diabetic patients with a history of foot ulcer were randomly assigned to wear therapeutic shoes or their usual footwear for two years [40]. The risk of re-ulceration was not found to be different between the groups. Non-prescription rocker sole shoes (figure 2) may also offload the foot [41,42]. In a non-randomized prospective study of 92 patients with healed diabetic foot ulcers, the first-year annual rate of foot ulcer relapse was significantly lower in patients who used stock diabetic shoes (rocker sole) compared with those who wore their usual footwear (15 versus 60 versus percent) [42]. In the United States, reimbursement from insurance carriers can be expected for at least one pair of shoes and/or shoe inserts, provided the design of the shoe/insert meets qualifying guidelines. Wedge shoes (eg, Darco International), also called half shoes, are available as a forefoot wedge and heel wedge shoes to off-load the forefoot and heel, respectively (figure 3). These shoes may be useful under certain circumstances. For example, plantar heel ulcers are particularly difficult to heel because of an inability to adequately off-load this region; the heel wedge shoe can be useful to achieve this goal. The disadvantage of wedge shoes is that most patients, especially elderly patients or those with proprioception abnormalities may not be able to maintain their balance, and some patients find walking in them difficult, if not impossible. Knee walkers — Knee walkers are ambulatory assist devices that may be indicated for anyone with a lower extremity issue where weight bearing needs to be avoided (figure 4). These devices are becoming more popular in the treatment of diabetic ulcer as a means to off-load the foot. There are no trials evaluating the effectiveness of these devices in healing diabetic foot ulcers. Summary — Debridement, good local wound care, and relief of pressure on the ulcer are believed to be important components of therapy for grade 1 and 2 foot ulcers [9]. This treatment program does not require hospitalization. Close monitoring is required, and hospitalization for bed rest and intravenous antibiotic therapy is advisable if the ulcer does not improve. (See "Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities".) GRADE 3 LESIONS — Before deciding upon appropriate management of deep ulcers, it is important to evaluate for substantial peripheral vascular disease or bony involvement. A brief review is found here. These topics are discussed in detail separately. (See "Evaluation of the diabetic foot", section on 'Physical signs of peripheral artery disease' and "Evaluation of the diabetic foot", section on 'Signs of infection'.) Assessment for peripheral artery disease — Assessment of the adequacy of the circulation is an important component of the evaluation of all wounds, and particularly wounds found in patients with diabetes. Symptoms of claudication or extremity pain at rest, and physical findings of diminished or absent pulses, cool temperature, pallor on elevation, or dependent rubor should raise suspicion about the presence of peripheral artery disease. Noninvasive vascular studies including ankle-brachial index, pulse volume recordings and duplex ultrasonography should be obtained to confirm the diagnosis. (See "Evaluation of the diabetic foot", section on 'Physical signs of peripheral artery disease'.) The ankle-brachial index is a measurement of the ratio of blood pressure at the ankle to that in the brachial artery that correlates with the presence and severity of arterial occlusive disease [43]. In patients with diabetes, the blood vessels may be incompressible and ankle-brachial index values misleading. Segmental volume plethysmography and toe-brachial index values are more reliable for determining the severity of disease. The noninvasive diagnosis of lower extremity peripheral artery disease is reviewed in detail elsewhere. (See 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTer… 5/23 "Noninvasive diagnosis of arterial disease".) Assess for osteomyelitis — Osteomyelitis is likely to be present if bone can be seen at the floor of a deep ulcer, or if it can be easily detected by probing the ulcer with a sterile, blunt stainless steel probe. Other signs that suggest osteomyelitis are an ulcer size larger than 2 x 2 cm and an otherwise unexplained elevation in the erythrocyte sedimentation rate. (See "Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities", section on 'Diagnosis of underlying osteomyelitis'.) Radiologic tests — Radiologic tests may be useful if the diagnosis of osteomyelitis remains uncertain. The diagnosis is clear if osteomyelitis is visible on plain radiographs. However, radiologic changes occur late in the course of osteomyelitis and negative radiographs do not exclude it. Other imaging techniques that may be useful in selective cases include radionuclide bone imaging, magnetic resonance imaging and imaging with indium-labeled leukocytes. Bone biopsy — If clinical and radiographic assessments fail to provide a diagnosis, then bone biopsy can be considered. Bone biopsy does carry the risk of inoculating an otherwise uninfected bone if the biopsy is obtained through an infected soft tissue bed. (See "Approach to imaging modalities in the setting of suspected osteomyelitis".) Treatment — The treatment of grade 3 lesions includes debridement, infection control, local wound care, and relief of pressure. The presence of osteomyelitis or peripheral artery disease warrants additional therapy [44]. Coordination of care among providers is important for keeping rates of amputation as low as possible. This was illustrated in a study of 10 Department of Veterans Affairs (VA) medical centers in which increased rates of amputation were seen in programs with the lowest scores for availability of clinical protocols, educational seminars, discharge planning and quality of care meetings [45]. Antimicrobial therapy — Whether it is important to make a definitive diagnosis of osteomyelitis and whether patients with osteomyelitis should always be treated by hospitalization, intravenous antimicrobial drug therapy, and surgical debridement of bone are debated [46]. Some authors have suggested that osteomyelitis is present in as many as two-thirds of diabetic patients who have foot ulcers [47], but this figure is much higher than is generally believed and may reflect bias in the severity of the cases studied. Surgical removal of infected bone may be necessary if the ulcer is not healing. A short period of hospitalization, with surgical debridement, including culture of material obtained from deep in the ulcer and bone biopsy, is often helpful in choosing antibiotic therapy [48]. Parenteral antibiotic therapy based upon the culture results has traditionally been given for four to six weeks in patients with osteomyelitis. The optimal regimen and when to transition to oral therapy are dependent upon the clinical features of each case. (See "Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities", section on 'Antimicrobial therapy'.) Mechanical off-loading — Mechanical off-loading relieves pressure on the ulcer and enhances healing. Total contact casting and cast walkers are alternatives to prolonged bed rest for the relief of pressure and allow for continued ambulation. (See 'Mechanical off-loading' above.) Revascularization — Revascularization plays an important role in the management of diabetic foot ulcers in patients with documented peripheral artery disease (to avoid the need for amputation) [9]. In patients with diabetes, foot ulcers, and critical limb ischemia, revascularization, when possible, is associated with a lower incidence of amputation. As an example, in a longitudinal study of 564 patients with diabetes, foot ulcers (in 85 percent of subjects), and critical limb ischemia (defined as ankle-pressure <70 mmHg), angioplasty (PTA) or bypass grafting (BPG) was performed in 74.5 and 20.6 percent, respectively [49]. Neither procedure was possible in the remaining 4.9 percent. Among patients who received PTA, BPG, or no revascularization, amputations were ultimately performed in 8.2, 21.2, and 59.2 percent, respectively. GRADE 4 AND 5 LESIONS — Patients with these more advanced lesions require urgent hospital admission and surgical consultation, and amputation may sometimes be required. (See "Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities".) ADVANCED THERAPIES — Several approaches have been reported that may improve ulcer healing, such as vacuum-assisted wound closure, the use of custom-fit semipermeable polymeric membrane dressings, cultured human dermis, and application of products such as platelet-derived growth factors and platelet releasate [50-52]. 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTer… 6/23 Negative pressure wound therapy — Negative pressure wound therapy (NPWT), also called vacuum-assisted closure (VAC), involves the application of controlled subatmospheric pressure to the surface of the wound. NPWT enhances wound healing by increasing wound perfusion, reducing edema, reducing the local bacterial burden and increasing the formation of granulation tissue. The indications, contraindications, and uses of negative pressure wound therapy systems are discussed in detail separately. (See "Negative pressure wound therapy".) Randomized trials have found that NPWT reduces time to closure of diabetic foot ulcers, and wounds following diabetic foot surgery [53-58]. In this patient population, NPWT also decreases length of hospitalization, complication rates, and cost [59-61]. One multicenter trial randomized 342 patients with diabetic foot ulcers (stage 2 or 3 Wagner ulcers, and adequate vascular perfusion) to negative pressure wound therapy or moist wound therapy (ie, hydrogel, alginate) [54]. All ulcers were debrided (as needed) within two days of randomization, and the majority of the patients also received off-loading therapy. The primary endpoint was wound closure. A significantly greater percentage of patients treated with negative pressure wound therapy achieved wound closure within the 16 week timeframe of the study compared with alternative medical therapy (43 versus 29 percent). The negative pressure wound therapy group also demonstrated significantly fewer amputations compared with the alternate medical therapy group (4 versus 10 percent). Another multicenter trial followed 162 diabetic patients for 16 weeks following partial foot amputation [53]. The percentage of patients with healed wounds (56 versus 39 percent) and time to complete closure (42 versus 84 days) were significantly improved in patients randomized to vacuum-assisted wound closure group compared with the control group. Skin substitutes — Human skin equivalents have been studied in diabetic patients with noninfected, nonischemic chronic plantar ulcers [51,62-65]. In one study of 208 patients, weekly application of the cultured skin equivalent (Graftskin) for four weeks improved the healing rate compared with usual care (complete wound healing in 56 and 38 percent of patients, respectively) [62]. Bioengineered skin substitutes (Dermagraft, Apligraf) are also available for the treatment of nonhealing diabetic foot ulcers [63,64]. Growth factors — A platelet-derived growth factor gel preparation (becaplermin) is approved by the US Food and Drug Administration as an adjuvant therapy for diabetic foot ulcers [66]. It promotes cellular proliferation and angiogenesis and thereby improves wound healing. However, its use has been limited by high cost and by post- marketing reports of an increased rate of mortality secondary to malignancy in patients treated with three or more tubes of becaplermin (3.9 versus 0.9 in controls per 1000 person years) [67]. In another trial, local application of human epidermal growth factor was shown to promote healing of diabetic foot ulcers [68]. Hyperbaric oxygen therapy — Hyperbaric oxygen therapy, as a component of diabetic ulcer management, may be associated with improved healing but the indications for hyperbaric oxygen in the treatment of nonhealing diabetic foot ulcers remain uncertain. Several metaanalyses of these trials have concluded that hyperbaric oxygen therapy in the treatment of diabetic foot ulcers may offer a benefit; however, each noted that the methodologic quality of the included studies was poor and there was a potential for bias [69-73]. The available trials are limited by small sample size and heterogeneity of the wounds being treated (eg, ulcer size, ulcer depth, microbial environment, presence of ischemia) [74-83]. No conclusions could be drawn regarding specific indications for or timing of therapy. A pooled analysis found significantly improved wound healing (OR 9.99, 95% CI 3.97-25.1), and decreased risk of amputation (OR 0.24, 95% CI 0.14-0.43) [70]. A later metaanalysis found similar results [73]. As an example of these effects, in one of the larger trials that included 70 patients with severely ischemic foot ulcers (Wagner grades 3 and 4), the amputation rate was 9 percent in the treatment group and 33 percent in the control [74]. In another trial that included 94 patients, a significantly increased incidence of complete healing (Wagner 2 though 4 ulcers) was achieved in the hyperbaric oxygen therapy group (52 versus 29 percent) compared with a placebo group [81]. Therapies that combine hyperbaric oxygen therapy with known mediators of wound healing may augment the effects of hyperbaric oxygen. Activation and mobilization of endothelial progenitor cells (EPCs) are impaired in 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTer… 7/23 patients with diabetes. These cells are known to play an important role in wound healing by participating in the formation of new blood vessels in areas of hypoxia [84-87]. Hyperoxia effectively improves EPC mobilization, but does not specifically target to a specific site which may, in part, explain the nonuniform improvement in diabetic foot wounds with hyperbaric oxygen therapy alone [88]. However, in a murine model of diabetes, coadministration of the chemokine stromal cell-derived factor-1 alpha (SDF-1 alpha) resulted in homing of activated EPCs into the wound site [89]. These data suggest that combining hyperbaric oxygen therapy with administration of SDF-1 alpha may be synergistic. Other combination therapies (eg, fibroblast growth factor) are also being studied [90,91]. Other agents — Small trials have shown some promise for other topical agents. In a randomized study, application of .05 percent tretinoin solution for 10 minutes a day followed by iodine gel for four weeks resulted in complete resolution of 46 percent of the ulcers in the treatment group (n = 13) compared with 18 percent in the control group (n = 11) [92]. In addition, electrical stimulation near the ulcer may also help slowly healing ulcers [93,94]. INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.) Beyond the Basics topics (see "Patient information: Diabetes mellitus type 1: Overview (Beyond the Basics)" and "Patient information: Diabetes mellitus type 2: Overview (Beyond the Basics)" and "Patient information: Foot care in diabetes mellitus (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS The treatment of diabetic foot ulcers begins with a comprehensive assessment of the ulcer and the patient's overall medical condition. Evidence of underlying neuropathy, bony deformity, and peripheral artery disease should be actively sought. The wound is classified upon initial presentation and with each follow-up visit using a standardized system to document the examination, plan treatment, and follow the progress of healing. (See 'Introduction' above and 'Wound classification' above.) Adequate debridement, proper local wound care, relief of pressure on the ulcer by mechanical off-loading, and control of infection (when present) are important components of therapy. Dressings are selected based upon wound characteristics. (See 'Local wound care' above.) Several methods are available to achieve mechanical off-loading and include total contact casts, cast walkers, wedge shoes, and bedrest. (See 'Mechanical off-loading' above.) Few data are available comparing methods of debridement (sharp, enzymatic, autolytic, mechanical, and biological). In the absence of such data, we suggest surgical (sharp) debridement rather than another method (Grade 2C). If a surgeon with clinical expertise in sharp debridement is not available, we suggest autolytic debridement with hydrogels (Grade 2C). (See 'Method of debridement' above.) Alternatively, the patient can be referred to a facility with appropriate surgical expertise in the management of diabetic foot problems. For managing extensive open wounds following debridement for infection or necrosis, or partial foot amputation, we suggest negative pressure wound therapy (Grade 2A). All necrotic tissue or infected bone (osteomyelitis) must be removed from the wound prior to using this device. (See 'Negative pressure wound therapy' above and "Negative pressure wound therapy", section on 'Contraindications'.) th th th th 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTer… 8/23 In patients with Wagner grade 3 and higher ulcers with critical limb ischemia, we recommend revascularization (Grade 1B). Revascularization should also be performed in patients with any degree of limb ischemia and a nonhealing ulcer. (See 'Grade 3 lesions' above.) Patients with Wagner grade 4 and 5 ulcers require immediate surgical consultation. (See 'Grade 4 and 5 lesions' above.) Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Boulton AJ, Armstrong DG, Albert SF, et al. 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Decision and cost- effectiveness analyses. JAMA 1995; 273:712. 47. Newman LG, Waller J, Palestro CJ, et al. Unsuspected osteomyelitis in diabetic foot ulcers. Diagnosis and monitoring by leukocyte scanning with indium in 111 oxyquinoline. JAMA 1991; 266:1246. 48. Mushlin AI, Littenberg B. Diagnosing pedal osteomyelitis: testing choices and their consequences. J Gen Intern Med 1994; 9:1. 49. Faglia E, Clerici G, Clerissi J, et al. Long-term prognosis of diabetic patients with critical limb ischemia: a population-based cohort study. Diabetes Care 2009; 32:822. 50. Blackman JD, Senseng D, Quinn L, Mazzone T. Clinical evaluation of a semipermeable polymeric membrane dressing for the treatment of chronic diabetic foot ulcers. Diabetes Care 1994; 17:322. 51. Marston WA, Hanft J, Norwood P, et al. The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial. Diabetes Care 2003; 26:1701. 52. Margolis DJ, Kantor J, Santanna J, et al. Effectiveness of platelet releasate for the treatment of diabetic neuropathic foot ulcers. Diabetes Care 2001; 24:483. 53. Armstrong DG, Lavery LA, Diabetic Foot Study Consortium. Negative pressure wound therapy after partial diabetic foot amputation: a multicentre, randomised controlled trial. Lancet 2005; 366:1704. 54. Blume PA, Walters J, Payne W, et al. Comparison of negative pressure wound therapy using vacuum- assisted closure with advanced moist wound therapy in the treatment of diabetic foot ulcers: a multicenter randomized controlled trial. Diabetes Care 2008; 31:631. 55. McCallon SK, Knight CA, Valiulus JP, et al. Vacuum-assisted closure versus saline-moistened gauze in the healing of postoperative diabetic foot wounds. Ostomy Wound Manage 2000; 46:28. 56. Eginton MT, Brown KR, Seabrook GR, et al. A prospective randomized evaluation of negative-pressure wound dressings for diabetic foot wounds. Ann Vasc Surg 2003; 17:645. 57. Ford CN, Reinhard ER, Yeh D, et al. Interim analysis of a prospective, randomized trial of vacuum- assisted closure versus the healthpoint system in the management of pressure ulcers. Ann Plast Surg 2002; 49:55. 58. Etoz, A, Ozgenel, Y, Ozcan, M. The use of negative pressure wound therapy on diabetic foot ulcers. Wounds 2004; 16:264. 59. Philbeck, TE, Schroeder, WJ, Whittington, KT. Vacuum-assisted closure therapy for diabetic foot ulcers: clinical and cost analysis. Home Health Consultant 2001; 8:1. 60. Armstrong DG, Lavery LA, Abu-Rumman P, et al. Outcomes of subatmospheric pressure dressing therapy on wounds of the diabetic foot. Ostomy Wound Manage 2002; 48:64. 61. Andros G, Armstrong DG, Attinger CE, et al. Consensus statement on negative pressure wound therapy (V.A.C. Therapy) for the management of diabetic foot wounds. Ostomy Wound Manage 2006; Suppl:1. 62. Veves A, Falanga V, Armstrong DG, et al. Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. Diabetes Care 2001; 24:290. 63. Edmonds M, Bates M, Doxford M, et al. New treatments in ulcer healing and wound infection. Diabetes Metab Res Rev 2000; 16 Suppl 1:S51. 64. Barber C, Watt A, Pham C, et al. Influence of bioengineered skin substitutes on diabetic foot ulcer and venous leg ulcer outcomes. J Wound Care 2008; 17:517. 65. Kirsner RS, Warriner R, Michela M, et al. Advanced biological therapies for diabetic foot ulcers. Arch Dermatol 2010; 146:857. 66. Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers. A phase III randomized placebo-controlled double-blind study. Diabetes Care 1998; 21:822. 67. http://www.regranex.com/ (Accessed on October 07, 2010). 68. Tsang MW, Wong WK, Hung CS, et al. Human epidermal growth factor enhances healing of diabetic foot ulcers. Diabetes Care 2003; 26:1856. 69. Kranke P, Bennett M, Roeckl-Wiedmann I, Debus S. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev 2004; :CD004123. 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTe… 11/23 70. Goldman RJ. Hyperbaric oxygen therapy for wound healing and limb salvage: a systematic review. PM R 2009; 1:471. 71. Roeckl-Wiedmann I, Bennett M, Kranke P. Systematic review of hyperbaric oxygen in the management of chronic wounds. Br J Surg 2005; 92:24. 72. Wang C, Schwaitzberg S, Berliner E, et al. Hyperbaric oxygen for treating wounds: a systematic review of the literature. Arch Surg 2003; 138:272. 73. Liu R, Li L, Yang M, et al. Systematic review of the effectiveness of hyperbaric oxygenation therapy in the management of chronic diabetic foot ulcers. Mayo Clin Proc 2013; 88:166. 74. Faglia E, Favales F, Aldeghi A, et al. Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer. A randomized study. Diabetes Care 1996; 19:1338. 75. Duzgun AP, Satir HZ, Ozozan O, et al. Effect of hyperbaric oxygen therapy on healing of diabetic foot ulcers. J Foot Ankle Surg 2008; 47:515. 76. Kessler L, Bilbault P, Ortéga F, et al. Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study. Diabetes Care 2003; 26:2378. 77. Abidia A, Laden G, Kuhan G, et al. The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial. Eur J Vasc Endovasc Surg 2003; 25:513. 78. Doctor N, Pandya S, Supe A. Hyperbaric oxygen therapy in diabetic foot. 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[Diabetes and peripheral arterial occlusive disease: therapeutic potential and pro- angiogenic strategies]. Ann Cardiol Angeiol (Paris) 2006; 55:100. 86. Capoccia BJ, Robson DL, Levac KD, et al. Revascularization of ischemic limbs after transplantation of human bone marrow cells with high aldehyde dehydrogenase activity. Blood 2009; 113:5340. 87. Hung SC, Pochampally RR, Chen SC, et al. Angiogenic effects of human multipotent stromal cell conditioned medium activate the PI3K-Akt pathway in hypoxic endothelial cells to inhibit apoptosis, increase survival, and stimulate angiogenesis. Stem Cells 2007; 25:2363. 88. Berendt AR. Counterpoint: hyperbaric oxygen for diabetic foot wounds is not effective. Clin Infect Dis 2006; 43:193. 89. Gallagher KA, Liu ZJ, Xiao M, et al. Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1 alpha. J Clin Invest 2007; 117:1249. 90. Efrati S, Gall N, Bergan J, et al. 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Topic 8175 Version 15.0 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTe… 12/23 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTe… 13/23 GRAPHICS Wagner grade 1 ulcer Foot from a diabetic patient showing a superficial ulcer (Wagner grade 1) that involves the full thickness of the skin but no underlying tissues. This lesion healed quickly with rest and local foot care. Courtesy of David McCulloch, MD. Graphic 70998 Version 1.0 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTe… 14/23 Wagner grade 2 ulcer Foot from a diabetic patient with a penetrating neuropathic ulcer that is not associated with abscess formation or bone involvement (Wagner grade 2). The toes have been pulled anteriorly because the anterior tibial muscles are unopposed due to motor neuropathy- induced weakness of the intrinsic foot muscles. This promotes subluxation of the proximal interphalangeal-metatarsal joints, resulting in a claw toe appearance (arrow) and in increased pressure on the metatarsal heads, predisposing to ulcer formation at this site. Courtesy of David McCulloch, MD. Graphic 51991 Version 2.0 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTe… 15/23 Wagner 3 foot ulcer The patient presented with a fluctuant eschar on the plantar surface of the foot. The abscess was unroofed and drained and, following debridement, exposed bone was apparent at the base of the wound. Courtesy of Paul Thottingal, MD. Graphic 71315 Version 1.0 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTe… 16/23 Wagner grade 4 ulcer Foot from a diabetic patient with a Wagner grade 4 ulcer that extends to the deep layers with signs of local infection, cellulitis, and necrosis. This lesion healed completely after an extensive hospital stay involving excision of necrotic tissue but no amputation. Courtesy of David McCulloch, MD. Graphic 63780 Version 3.0 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTe… 17/23 Oral agents for empiric treatment of mild to moderate diabetic foot infections SINGLE-drug regimens with activity against streptococci and staphylococci (MSSA) Cephalexin or Dicloxacillin or Amoxicillin-clavulanate or clindamycin TWO-drug regimens with activity against streptococci and MRSA Clindamycin* or Linezolid or Penicillin or cefazolin or dicloxacillin PLUS Trimethoprim-sulfamethoxazole or doxycycline TWO-drug regimens with activity against streptococci, MRSA, aerobic gram-negative bacilli and anaerobes Trimethoprim-sulfamethoxazole PLUS Amoxicillin-clavulanate -OR- Clindamycin PLUS Ciprofloxacin or levofloxacin or moxifloxacin Antibiotic dosing for adults Cephalexin 500 mg every 6 hours Dicloxacillin 500 mg every 6 hours Clindamycin 300 to 450 mg every 6 to 8 hours Linezolid 600 mg every 12 hours Penicillin V potassium 500 mg every 6 hours Trimethoprim-sulfamethoxazole (co- trimoxazole) 2 double-strength tablets (trimethoprim 160 mg and sulfamethoxazole 800 mg per tablet) every 12 hours Doxycycline 100 mg orally every 12 hours Amoxicillin-clavulanate 875/125 mg every 12 hours Ciprofloxacin 750 mg every 12 hours Levofloxacin 750 mg every 24 hours Moxifloxacin 400 mg every 24 hours • 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTe… 18/23 MSSA: methicillin-susecptible staphylococcus aureus; MRSA: methicillin-resistant staphylococcus aureus. * Check susceptibility testing. • Many of these agents require adjustment of the dose in the setting of renal dysfunction. Data courtesy of authors with additional data from: Lipsky BA, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2012; 54:e132. Graphic 69671 Version 4.0 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTe… 19/23 Removable cast walker Graphic 64409 Version 1.0 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTe… 20/23 Rocker sole shoe Graphic 86276 Version 1.0 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTe… 21/23 Wedge shoes Graphic 53678 Version 1.0 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTe… 22/23 Knee walker Graphic 73730 Version 1.0 7/15/2014 Management of diabetic foot lesions http://www.uptodate.com/contents/management-of-diabetic-foot-lesions?topicKey=SURG%2F8175&elapsedTimeMs=3&source=search_result&searchTe… 23/23 Di scl osures: David K McCulloch, MD Nothing to disclose. Richard J de Asla, MD Nothing to disclose. John F Eidt, MD Grant/Research Support: Medtronic CEC (drug eluting balloon). Joseph L Mills, Sr, MD Nothing to disclose. David M Nathan, MD Nothing to disclose. Kathryn A Collins, MD, PhD, FACS Nothing to disclose. Contributor disclosures are reviewed f or conf licts of interest by the editorial group. When f ound, these are addressed by vetting through a multi-level review process, and through requirements f or ref erences to be provided to support the content. Appropriately ref erenced content is required of all authors and must conf orm to UpToDate standards of evidence. Conflict of interest policy Disclosures