Diabetic Foot Ulcers Treatment & Management

The management of diabetic foot ulcers requires offloading the wound, ^{[6, 7]} daily saline or similar dressings to provide a moist wound environment, ^[8] débridement when necessary, antibiotic therapy with or without surgical intervention if osteomyelitis or soft tissue infection is present, ^{[9, 10]} optimal control of blood glucose, and evaluation and correction of peripheral arterial insufficiency. ^[11]

To promote ulcer healing in a person with diabetes and a neuropathic plantar ulcer, consider, if nonsurgical offloading therapy is unsuccessful, Achilles tendon lengthening, metatarsal head resection(s), or joint arthroplasty.

Wound coverage by cultured human cells ^{[40, 43]} or biologic skin substitutes, application of recombinant growth factors, ^{[44, 45, 46, 47]} and hyperbaric oxygen treatments also may be beneficial at times, but only if arterial insufficiency is not present.

Physicians of diabetic patients with ulcers must decide between the sometimes conflicting options of (1) performing invasive procedures (eg, soft tissue and musculoskeletal reconstruction, angiography, bypass surgery) for limb salvage and (2) avoiding the risks of unnecessarily aggressive management in these patients, who may have significant cardiac risk. In general, the greatest legal risks are associated with delay in diagnosis of ischemia associated with diabetic ulceration, failure to aggressively debride and treat infection, and failure to treat the wound carefully.

If a patient presents with a new diabetic foot ulcer, he or she should receive care from a multidisciplinary team of physicians, surgeons, podiatrists, and pedorthotists who have an active interest in this complex problem.

IWGDF guidelines

The aforementioned IWGDF practical guidelines state the following with regard to pressure offloading in ulcer treatment ^[35] :

• For patients with a neuropathic plantar ulcer, a nonremovable knee-high offloading device—ie, either a total contact cast (TCC) or a removable walker that is rendered irremovable by the provider who fits the device—is the preferred offloading treatment
• In patients who cannot tolerate a nonremovable, knee-high offloading device, or if such a device is contraindicated, a removable version can be considered; should a removable device be contraindicated or if it cannot be tolerated, an ankle-high offloading device can be considered; patients must be educated with regard to the benefits of adherence to removable device use
• In the absence of other forms of biomechanical relief, felted foam, in combination with appropriate footwear, can be considered
• While offloading remains important in the presence of infection or ischemia, greater caution is necessary
• Nonplantar foot ulcers, depending on their type and location, should be addressed with a removable, ankle-high offloading device, footwear modifications, toe spacers, or orthoses

With regard to restoration of tissue perfusion, the practical guidelines state the following ^[35] :

• When ankle pressure is below 50 mmHg or the ankle brachial index (ABI) is less than 0.5, urgent vascular imaging and, in the presence of appropriate findings, revascularization, should be considered; revascularization should also be considered if the toe pressure is below 30 mmHg or the transcutaneous pressure of oxygen (TcpO ₂) is less than 25 mmHg; however, revascularization may be considered at higher pressures should extensive tissue loss or infection occur
• If optimal treatment does not result in ulcerative healing signs within 6 weeks, revascularization should be considered, regardless of the outcomes of the above-mentioned vascular tests
• If an above-the-ankle amputation is being contemplated, revascularization should first be considered as an option
• Revascularization should be avoided in patients with an unfavorable risk-benefit ratio
• Individual factors (eg, morphologic distribution of peripheral artery disease, autogenous vein availability, patient comorbidities) and local operator expertise should be considered when selecting a revascularization technique
• Following revascularization, perfusion should be objectively measured to assess the procedure’s effectiveness
• Pharmacologic treatments have not been proven to benefit perfusion
• Smoking cessation, hypertension and dyslipidemia control, and antiplatelet drug use, as the means to reduce cardiovascular risk, should be emphasized

With regard to treatment of infection, the practical guidelines state the following ^[35] :

• For a superficial ulcer with limited soft tissue (mild) infection - The ulcer should be cleansed and all necrotic tissue and surrounding callus should be debrided; start empiric oral antibiotic therapy directed against Staphylococcus aureus and streptococci (unless there are indications that alternative or additional likely pathogens exist)
• For deep or extensive (potentially limb-threatening) infection (moderate or severe infection) - The need for surgical intervention to remove necrotic tissue, including infected bone, should be urgently evaluated, and compartment pressure should be released or abscesses drained; assess for peripheral artery disease (with urgent treatment, including revascularization, to be considered if such disease is present); empiric, parenteral, broad-spectrum antibiotic therapy aimed at common gram-positive and gram-negative bacteria, including obligate anaerobes, should be initiated; the clinical response to empirical therapy, along with culture and sensitivity results, should be used to adjust (constrain and target, if possible) the antibiotic regimen

With regard to local ulcer care, the practical guidelines recommend the following ^[35] :

• The ulcer must be inspected regularly by a trained health-care provider, with the severity of the ulcer, the underlying pathology, the presence of infection, the amount of exudation, and wound treatment provided determining the frequency of examination
• Ulcer débridement and removal of the surrounding callus (preferably with sharp surgical instruments) should be carried out, with the procedure repeated as necessary
• Selected dressings should control excess exudation and keep the environment moist
• Foot soaking may cause skin maceration and so should not be employed in treatment
• Negative pressure should be considered as an aid to healing postoperative wounds
• If noninfected ulcers do not heal after 4-6 weeks of optimal clinical care, one of the following adjunctive treatments should be considered - If severe ischemia is not present in a neuro-ischemic ulcer, a sucrose octasulfate–impregnated dressing; if moderate ischemia is either present or absent, a multi-layered patch of autologous leucocytes, platelets, and fibrin; also in the presence of absence of moderate ischemia, placental membrane allografts; in ischemic ulcers in which revascularization has not led to healing, adjunctive treatment with systemic oxygen therapy

Treatment of diabetic foot ulcers requires management of a number of systemic and local factors. ^{[48, 49, 50, 51]}

Precise diabetic control is, of course, vital, not only in achieving resolution of the current wound, but also in minimizing the risk of recurrence. Management of contributing systemic factors, such as hypertension, hyperlipidemia, atherosclerotic heart disease, obesity, or renal insufficiency, is crucial. ^{[52, 53]} Management of arterial insufficiency, treatment of infection with appropriate antibiotics, offloading the area of the ulcer, and wound care are also essential.

For more information, see Diabetes Mellitus, Type 1 and Diabetes Mellitus, Type 2.

The basic principle of topical wound management is to provide a moist, but not wet, wound bed. ^{[8, 54]}

It is prudent to address the underlying etiologies in diabetic foot ulcers for any of the following wound care modalities to be successful. Without addressing the osseous deformities and muscular imbalances, infections, and vascular insufficiency, there will be minimal benefit in employing advanced wound care dressings.

Wound coverage

After débridement, apply a moist sodium chloride dressing or isotonic sodium chloride gel (eg, Normlgel, IntraSite gel) or a hydroactive paste (eg, Duoderm). Optimal wound coverage requires wet-to-damp dressings, which support autolytic débridement, absorb exudate, and protect surrounding healthy skin. A polyvinyl film dressing (eg, OpSite, Tegaderm) that is semipermeable to oxygen and moisture and impermeable to bacteria is a good choice for wounds that are neither very dry nor highly exudative. Wound coverage recommendations for some other wound conditions are as follows (see the Table, below) ^[55] :

• Dry wounds: Hydrocolloid dressings, such as DuoDERM or IntraSite Hydrocolloid, are impermeable to oxygen, moisture, and bacteria; maintain a moist environment; and support autolytic  débridement. They are a good choice for relatively desiccated wounds.

• Exudative wounds: Absorptive dressings, such as calcium alginates (eg, Kaltostat, Curasorb), are highly absorptive and are appropriate for exudative wounds. Alginates are available in a rope form, which is useful for packing deep wounds.

• Very exudative wounds: Impregnated gauze dressings (eg, Mesalt) or hydrofiber dressings (eg, Aquacel, Aquacel-Ag) are useful for extremely exudative wounds. In these cases, twice-daily dressing changes may be needed.

• Infected wounds: For infected superficial wounds, use Silvadene (silver sulfadiazine) if the patient is not allergic to sulfa drugs; if a sulfa allergy exists, either bacitracin-zinc or Neosporin ointment is a good alternative. Where heavy bacterial contamination of deeper wounds exists, irrigation using one-fourth strength Dakin solution and 0.25% acetic acid may be useful for a brief period of time; a hydrofiber-silver dressing (Aquacel-Ag) can help control wounds that are both exudative and potentially colonized.

• Wounds covered by dry eschar: In this case, simply protecting the wound until the eschar dries and separates may be the best management. Occasionally, painting the eschar with povidone iodine (Betadine) is beneficial to maintain sterility while eschar separation occurs; an uninfected dry heel ulcer in a well-perfused foot is perhaps best managed in this fashion.

• Areas that are difficult to bandage: Bandaging a challenging anatomical area, such as around a heel ulcer, requires a highly conformable dressing, such as an extra thin hydrocolloid; securing a dressing in a highly moist challenging site, such as around a sacrococcygeal ulcer, requires a conformable and highly adherent dressing, such as a wafer hydrocolloid.

• Fragile periwound skin: Hydrogel sheets and nonadhesive forms are useful for securing a wound dressing when the surrounding skin is fragile.

Other topical preparations that occasionally may be useful in the management of diabetic foot ulcers are as follows:

• Platelet-derived growth factors (PDGF): Topically applied PDGF has a modestly beneficial effect in promoting wound healing. Becaplermin gel 0.01% (Regranex), a recombinant human PDGF that is produced through genetic engineering is approved by the US Food and Drug Administration (FDA) to promote healing of diabetic foot ulcers. ^[45] Regranex is meant for a healthy, granulating wound, not one with a necrotic wound base, and is contraindicated with known skin cancers at the site of application.

• Enzymatic débridement: Collagen makes up a significant fraction of the necrotic soft tissues in chronic wounds; the enzyme collagenase, derived from fermentation of Clostridium histolyticum, helps remove nonviable tissue from the surface of wounds. However, it is not a substitute for an initial surgical excision of a grossly necrotic wound.

• Miscellaneous topical agents: Various other topical agents that have been used for wound management include sugar, antacids, and vitamin A and D ointment.

Cytotoxic agents, such as hydrogen peroxide, povidone iodine, acetic acid, and Dakin solution (sodium hypochlorite), should be avoided, except as noted above under infected wounds.

Table. Characteristics and Uses of Wound Dressing Materials (Open Table in a new window)

For more information, see Diabetic Foot Infections.

Vacuum-assisted closure

Clean but nonhealing deep cavity wounds may respond to repeated treatments by application of negative pressure under an occlusive wound dressing (vacuum-assisted closure [VAC]). ^[56]

Hydrotherapy

Intractable, infected, cavity wounds sometimes improve with hydrotherapy using saline pulse lavage under pressure (PulsEvac).

Extracorporeal shock-wave therapy

Two multicenter, randomized, sham-controlled, double-blinded, phase III clinical trials by Snyder et al indicated that extracorporeal shock-wave therapy (ESWT) can effectively treat neuropathic diabetic foot ulcers that fail to heal with standard therapy alone. At 24 weeks, in patients with diabetic foot ulcers that had not been reduced by 50% or greater over the course of 2 weeks’ standard treatment, complete healing occurred in 37.8% of patients treated with ESWT and standard care, compared with 26.2% of patients treated with sham therapy and standard care. ^[57]

Treatment of Charcot foot

Charcot foot is treated initially with immobilization using special shoes or braces but eventually may require podiatric surgery such as ostectomy and arthrodesis.

All patients harboring diabetic foot ulcers should be evaluated by a qualified vascular surgeon and podiatric surgeon who will consider débridement, reconstructive surgery on bony architecture, vascular reconstruction, and options for soft tissue coverage.

For more information, see Perioperative Management of the Diabetic Patient.

Débridement

 Débridement is indicated for preventing ulceration of nonviable and/or infected tissue. Hyperkeratotic tissue, fibrin, eschar, biofilm, and necrotic tissue need to be removed from the wound and periwound to facilitate wound healing. It is not uncommon for the wound to be larger in size following debridment, especially after the initial débridement. Chronic wounds such as diabetic foot ulcers are often arrested in the healing cascade, and with débridement there is the creation of a reservoir of growth factors to assist the wound in moving forward in healing. These include platelet-derived growth factor, which is excreted by small vessels in the fresh, bleeding edges of a debrided wound. ^[58]

Reconstructive foot and ankle surgery

Reconstructive surgery can be considered when nonremovable knee-high offloading devices are failing to achieve wound healing, when the patient is unable to transition from knee-high offloading devices to custom diabetic orthopedic shoes/insoles due to recurring pressure, or in the setting or pre-ulcerative lesions/calluses in the neuropathic patient. Prior to surgical intervention, a thorough musculoskeletal exam must be performed, and appropriate imaging such as plain radiographs, CT scans, and MRI scans must be reviewed to determine the surgical plan. Surgical options include arthroplasties, osteotomies, resection, arthrodesis, tenotomies, tendon transfers, and tendon lengthening. The goal is to rebalance the foot and create a plantigrade foot that distributes pressure appropriately. These procedures can be considered a type of internal, surgical offloading. ^[59]

Revisional surgery for bony architecture may be required to remove pressure points. ^[60] Such intervention includes resection of metatarsal heads or ostectomy. ^[61]

Vascular reconstruction

In general, the indications for vascular surgery in the presence of a reconstructible arterial lesion include intractable pain at rest or at night, intractable foot ulcers, and impending or existing gangrene. ^{[17, 62, 63]} Intermittent claudication alone is only infrequently disabling and intractable enough to warrant bypass surgery. Physicians must specifically ask for symptoms suggestive of intermittent claudication, such as pain in the buttocks and thighs while walking and abatement of pain when at rest.

Once a wound has reached a steady clean state, a decision has to be made about allowing healing by natural processes or expediting healing by a surgical procedure. Clinical experience and observation of the healing progress in each case dictate the appropriate management. Surgical options include skin grafting, application of bioengineered skin substitutes, and flap closures. ^[64]

Clinicians have to treat the underlying etiology of these wounds for these modalities to work appropriately. This includes addressing osseous deformities and muscular imbalances, treating infection, and addressing any vascular compromise.

Skin grafts

The autologous split-thickness skin graft is the criterion standard for viable coverage of a full-thickness granular wound. The graft can be harvested under local anesthesia as an outpatient surgery. Meshing the graft allows wider coverage and promotes drainage of serum and blood. The surgery does create a secondary partial-thickness wound, which can be a site of pain and morbidity.

A cadaveric skin allograft is a useful covering for relatively deep wounds following surgical excision when the wound bed does not appear appropriate for application of an autologous skin graft. The allograft is, of course, only a temporary solution.

Tissue-cultured skin substitutes

Dermagraft (Smith & Nephew) is a cryopreserved human fibroblast–derived dermal substitute produced by seeding neonatal foreskin fibroblasts onto a bioabsorbable polyglactin mesh scaffold. Dermagraft is useful for managing full-thickness chronic diabetic foot ulcers. It is not appropriate for infected ulcers, those that involve bone or tendon, or those that have sinus tracts.

A multicenter study of 314 patients demonstrated significantly better 12-week healing rates with Dermagraft (30%) versus controls (17%). Allergic reactions to its bovine protein component have been reported.

Apligraf (Organogenesis) is a living, bilayered human skin substitute. ^{[65, 43]} It is not appropriate for infected ulcers, those that involve tendon or bone, or those that have sinus tracts. Allergic reactions to the agarose shipping medium or its bovine collagen component have been reported.

A prospective observational study by Hwang et al indicated that treatment with allogeneic keratinocyte dressings is effective in patients with chronic, intractable diabetic foot ulcers. Of the 71 patients in the study, all of whom underwent weekly keratinocyte therapy, 56 (78.9%) experienced complete wound healing, including 46 (64.8%) in whom complete healing occurred within an average of 6.1 weeks. ^[66]

The use of bioengineered skin substitutes has been questioned because the mechanism of action is not clear, the efficacy is questionable, and the cost is high.

Xenograft

Oasis (Smith & Nephew) is a xenogeneic, acellular collagen matrix derived from porcine small intestinal submucosa that allows an extracellular matrix and natural growth factors to remain intact. 

Integra (Integra LifeSciences) is a bilayered skin substitute that is composed of bovine collagen and chondroitin 6-sulfate for dermal regeneration. The silicone top layer mimics epidermis, providing protection and preventing moisture loss. 

Primatrix (Integra LifeSciences) is a collagen-based dermal repair scaffold that is derived from fetal bovine dermis. There is an option of obtaining this graft with ionic silver impregnation, which provides antimicrobial coverage for contaminated wounds.

ACell (ACell) is an acellular wound scaffold derived from porcine urinary bladder matrix that can be obtained in either fenestrated sheet form or in a particulate form that is useful for deep and tunneling wounds.

Surgical wound closure

Delayed primary closure of a chronic wound requires well-vascularized, clean tissues and tension-free apposition; it usually requires undermining and mobilization of adjacent tissue planes by creation of skin flaps, local muscle flaps, or myocutaneous flaps. ^[67]

Hyperbaric oxygen therapy is used rarely and is certainly not a substitute for revascularization. ^[68] In the presence of an intractable wound and associated noncorrectible ischemic arterial disease, hyperbaric oxygen therapy may be beneficial (in selected cases). ^[69] Löndahl et al found that 40 hyperbaric oxygen treatments (85 min daily, 5 d/wk for 8 wk) resulted in complete healing of chronic diabetic foot ulcers in 52% of patients in the treatment group. Among patients in the placebo group, 29% had complete healing at 1-year follow-up. ^[70] Although data are equivocal on the impact of hyperbaric oxygen therapy in ischemic and pressure ulcers, positive benefits have been documented in diabetic chronic foot ulcers. ^{[71, 72]}

The recommended diet is diabetic and low in saturated fat.

Offloading of the ulcerated area is imperative. This may require non–weight-bearing or weight-bearing, as tolerated in appropriate offloading devices. Custom footwear, a custom clamshell orthosis (for severe deformities), or total contact casting (a fiberglass shell with a walking bar on the bottom) are required for patients who are ambulatory.

The risk of ulceration and limb amputation in people with diabetes can be improved by routine preventive podiatric care, appropriate shoes, and patient education. ^[21] Diabetic clinics should screen all patients for altered sensation and peripheral vascular disease. ^[47] Of diabetic foot ulcers, 85% are estimated to be preventable with appropriate preventive medicine, including the following:

• Daily foot inspection

• Gentle soap and water cleansing

• Application of skin moisturizer

• Inspection of the shoes to ensure good support and fit: Medicare covers custom shoes with appropriate physician documentation confirming that the patient is at risk for ulceration.

• Minor wounds require prompt medical evaluation and treatment.

• Prophylactic podiatric surgery to correct high-risk foot deformities may be indicated.

• Avoid hot soaks, heating pads, and irritating topical agents.

A literature review by Matos et al suggested that exercise and physical activity are effective against the complications of diabetic foot. The investigators found that patients involved in physical activity and exercise had a lower annual incidence of ulcers than other patients in the study (0.02 vs 0.12, respectively). Moreover, nerve velocity conduction, peripheral sensory function, and foot peak pressure distribution significantly improved in the physical activity/exercise group. ^[73]

Glycemic control

The Diabetes Control and Complications Trial, performed by the Diabetes Control and Complications Trial Research Group, studied the effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus (1993). ^[74] This trial found that uncontrolled hyperglycemia correlates with the onset of diabetic microvascular complications and that good glycemic control can reduce or even prevent the complications of diabetes, including nephropathy, neuropathy, and retinopathy.

Cigarette smoking should be stopped, and hypertension and hyperlipidemia should be controlled.

To see complete information on the conditions below, please go to the main article by clicking on the title:

• Diabetic Neuropathy

• Diabetic Nephropathy

• Diabetic Retinopathy

Any of the following evaluations may prove productive:

• Endocrinologist

• Podiatrist

• Orthopedist

• Vascular surgeon

• Interventional cardiologist/interventional radiologist

• Infectious disease specialist

• Plastic surgeon

• Pedorthist

• Wound care specialist

• Physical therapist

• Dietitian

For the most part, diabetic ulcers are managed in the outpatient setting, with brief hospital stays often occurring for initial evaluation and débridement; management of infection, including via intravenous antibiotics and amputations; and vascular evaluation and interventions.

Risk classification and follow-up based on the comprehensive foot examination ^[75] (Open Table in a new window)

LOPS = Loss of protective sensation

PAD = Peripheral arterial disease