**3. Management of diabetic foot ulceration**

The over-arching goal of healthcare professionals engaged in the management of persons with DM is to successfully intervene in the causal pathway leading to diabetic foot ulcers and ultimately amputation. Management of the diabetic foot can be viewed in 4 phases: prevention, accommodation or adaptation, healing and rehabilitation which unfortunately often circles around to become prevention again in an effort to prevent re-ulceration. The scope of this chapter limits discussion primarily to the healing phase of this process.

Clinical trial data suggest better glycemic control mitigates the microvascular complications of the disease including peripheral neuropathy (DCCT, 1993; UKPDS, 1998). Preventing or delaying onset of peripheral neuropathy and its attendant sensory, motor, and autonomic sequelae is paramount to prevention of diabetic foot ulcers. Peripheral polyneuropathy and the tissue changes it induces: loss of protective sensation; inability to perceive trauma; structural changes leading to deformity and areas prone to excessive pressure; impaired sweat gland function producing dry, atrophic skin, all lead to a foot susceptible to injury.

Once peripheral neuropathy is present, focus of care shifts to managing and successfully adapting to the attendant tissue changes. Patient education on foot care becomes even more critical including routine foot inspection, lubrication of dry skin, avoidance of soaking feet, and appropriate callus and nail management. Adaptive footwear must be provided at frequent intervals to accommodate structural changes and relieve pressure.

## **3.1 Treatment of diabetic foot ulcers**

Healing of DFUs is related to how well the underlying etiologies of neuropathy and ischemia and their consequences are addressed. Traditionally, five elements are considered critical to adequate treatment of diabetic foot disease: off-loading or pressure relief, revascularization when appropriate, debridement, management of infection, and wound care. As the magnitude of diabetic foot disease has continued to grow along with our understanding of wound healing in general and the pathophysiology of DM in particular, wound care strategies have progressed as well and there are an ever growing number of advanced wound care products and therapies available. Some of the more widely available include preventive surgery, negative pressure wound therapy (NPWT), hyperbaric oxygen therapy (HBO), and advanced wound care products such as growth factors and living skin equivalents.

## **3.2 Off-loading**

Diabetic foot ulcers on weight or pressure bearing areas in feet lacking protective sensation must be unloaded or relieved of pressure to facilitate healing. A recent review of off-loading techniques for the diabetic foot by Cavenagh and Bus (2011) notes total contact casting

prognosis following LEA amputation reported 1, 3, and 5 year mortality rates of 15%, 38%, and 68%, respectively for both minor and major amputations combined (Larsson et al., 1997). Almost 10 years later, researchers were still reporting people with DM who underwent LEA had a 55% greater risk of dying than those without DM (Schofield et al.,

The over-arching goal of healthcare professionals engaged in the management of persons with DM is to successfully intervene in the causal pathway leading to diabetic foot ulcers and ultimately amputation. Management of the diabetic foot can be viewed in 4 phases: prevention, accommodation or adaptation, healing and rehabilitation which unfortunately often circles around to become prevention again in an effort to prevent re-ulceration. The

Clinical trial data suggest better glycemic control mitigates the microvascular complications of the disease including peripheral neuropathy (DCCT, 1993; UKPDS, 1998). Preventing or delaying onset of peripheral neuropathy and its attendant sensory, motor, and autonomic sequelae is paramount to prevention of diabetic foot ulcers. Peripheral polyneuropathy and the tissue changes it induces: loss of protective sensation; inability to perceive trauma; structural changes leading to deformity and areas prone to excessive pressure; impaired sweat gland function producing dry, atrophic skin, all lead to a foot susceptible to injury.

Once peripheral neuropathy is present, focus of care shifts to managing and successfully adapting to the attendant tissue changes. Patient education on foot care becomes even more critical including routine foot inspection, lubrication of dry skin, avoidance of soaking feet, and appropriate callus and nail management. Adaptive footwear must be provided at

Healing of DFUs is related to how well the underlying etiologies of neuropathy and ischemia and their consequences are addressed. Traditionally, five elements are considered critical to adequate treatment of diabetic foot disease: off-loading or pressure relief, revascularization when appropriate, debridement, management of infection, and wound care. As the magnitude of diabetic foot disease has continued to grow along with our understanding of wound healing in general and the pathophysiology of DM in particular, wound care strategies have progressed as well and there are an ever growing number of advanced wound care products and therapies available. Some of the more widely available include preventive surgery, negative pressure wound therapy (NPWT), hyperbaric oxygen therapy (HBO), and advanced wound care products such as growth factors and living skin

Diabetic foot ulcers on weight or pressure bearing areas in feet lacking protective sensation must be unloaded or relieved of pressure to facilitate healing. A recent review of off-loading techniques for the diabetic foot by Cavenagh and Bus (2011) notes total contact casting

frequent intervals to accommodate structural changes and relieve pressure.

scope of this chapter limits discussion primarily to the healing phase of this process.

2006).

**3. Management of diabetic foot ulceration** 

**3.1 Treatment of diabetic foot ulcers** 

equivalents.

**3.2 Off-loading**

(TCC) remains the gold standard for off-loading although removable walkers have also been shown to provide a similar degree of pressure relief. Peak pressure reduction in the forefoot is reported to be up to 87% with TCC but only 44% to 64% with cast shoes and forefoot offloading shoes (Cavanagh and Bus, 2011). Rocker bottom outsoles, custom insoles, metatarsal pads and arch supports may reduce forefoot peak pressure 16% to 52% compared to controls (Cavanagh and Bus, 2011).

Effectiveness of an off-loading device must be gauged by both its ability to relieve pressure and patients' adherence to the treatment. TCCs are considered to be effective in part because they essentially coerce patient adherence to treatment. Some of the unloading is achieved by restricting ankle motion and redistributing load to the device itself which may explain why devices that extend only to the ankle are less effective in off-loading the foot than those that reach above the ankle (Cavanagh and Bus, 2011). The majority of evidence for off-loading comes from studies examining uncomplicated neuropathic plantar ulcers. TCC has been shown to be more effective in time to healing than removable devices in some randomized clinical trials while a recent RCT showed similar healing rates between a TCC and an ankle high removable walker (Faglia et al., 2010). Off-loading has been used to treat neuroischemic or infected wounds but success rates are much lower than for purely neuropathic ulcers (Nabuurs-Franssen et al., 2005). TCCs are not in wider use because of potential adverse reactions which include diminished activity level, problems sleeping or driving a car and iatrogenic ulcers from poorly applied casts.

Cavanagh and Bus (2011) summarized the recommendations of the International Working Group on the Diabetic Foot for use of off-loading in management of non-complicated foot ulcers in their review: 1) pressure relief should be part of every treatment plan; 2) TCC and non-removable walkers are preferred but clinicians should be aware of potential adverse effects; 3) forefoot off-loading shoes or cast shoes may be used when the above devices are contraindicated or not tolerated; and 4) conventional or standard footwear should not be used as other devices are more effective.

#### **3.3 Revascularization**

Peripheral vascular disease is common in persons with DM and is characterized by impairment at both macro- and microvascular levels. Re-establishing arterial supply is the key to healing ischemic and neuroischemic ulcers. Treatment of peripheral arterial disease involves management of risk factors, medical therapy, and endovascular or open surgery. Smoking cessation, weight loss, and adherence to a low fat diet are all areas in which eliciting patient cooperation is critical for successful management. Antiplatelet therapy, anticoagulation, and LDL lowering drugs may also play a role in treatment. However, many diabetic patients will need re-vascularization to achieve healing. Macrovascular disease is morphologically the same in diabetics and non-diabetics differing only in location with the anterior and posterior tibial and peroneal arteries of the calf being most affected in persons with DM. Surgical options are dependent on whether the vascular disease is supra-inguinal (aorto-iliac) or infra-inguinal (femoro-popliteal-crural) or both ((Ruef et al., 2004). Angioplasty, endoarterectomy, grafting, and by-pass are some available surgical interventions. Vascular surgery may be able to aid in revascularization of an area via restoring flow through larger vessels but will not completely restore the microvascular flow disrupted by structural changes in the basement membranes or functional impairment in microcirculation caused by the disease.

Diabetic Foot Ulceration and Amputation 11

Surgery may be necessary to correct biomechanical faults and/or distribute pressure in order to promote healing of a diabetic foot ulcer or prevent re-ulceration. Prophylactic surgery to correct deformities prior to ulceration has been advocated as a preventive strategy (Mueller et al., 2003). Ulcer healing can be accelerated and recurrence prevented in feet with toe deformities by utilization of extensor tenotomy (Margolis et al., 2005). Achilles tendon lengthening reduces pressure under the metatarsal heads and promotes ulcer healing but the concomitant gait alteration increases the risk of heel ulcers prompting these authors to recommend avoiding this procedure in individuals with complete sensory loss of the heel pad (Holstein et al., 2004). Metatarsal osteotomy and metatarsal head resection have been advocated by some but these procedures pose the risk of secondary ulceration or Charcot foot formation (Petrov et al., 1996; Fleischli et al., 1999). RCTs comparing surgical and non-surgical management of DFUs are scarce. Finally, any surgery is producing a

Negative pressure wound therapy utilizes a vacuum pump to create a subatmospheric wound environment. A wound dressing, typically an open cell foam or saline moistened gauze is placed in the wound cavity to distribute the pressure. A tube connects the cavity to the vacuum pump and the area is sealed with an adhesive film. The portable vacuum pump exerts and maintains a negative pressure in the range of about 50 to 125 mmHg. The mechanical force exerted by the vacuum on the wound surface creates microstrain induced microdeformations of the wound tissue which in turn promotes cellular stretch and proliferation. Micromechanical forces resulting from the negative pressure encourage cell proliferation and migration, extracellular matrix deposition and gene expression. The subatmospheric pressure also prompts angiogenesis and reduction in local edema, excess interstitial fluid, increased lymphatic flow, and removal of waste by-products (Krasner Diane L; Rodeheaver, 2007). Authors of an RCT examining the effectiveness of NPWT in DFUs reported the incidence of secondary amputation was significantly lower when using NPWT (4.1%) compared to moist wound care (10.2%) (Blume et al., 2008). Increased granulation tissue formation and decreased healing times were seen in a RCT of 162 diabetic

Recognizing that a fundamental problem in non-healing wounds was hypoxia; researchers sought ways to raise tissue oxygen levels. Hyperbaric oxygen therapy entails breathing 100% oxygen pressurized typically between 2.0 and 2.5 absolute atmospheres or ATAs (1 ATA = atmospheric pressure at sea level) with the goal of raising the oxygen partial pressure to about 1500 mmHg. Oxygen delivery to the wound is subsequently improved by the HBO-provided increase in blood oxygen concentration. In addition, HBO has been shown stimulate angiogenesis, enhance neutrophil killing ability, and stimulate fibroblast activity and collagen synthesis (Hunt and Pai, 1972; Knighton et al., 1986). A number of RCTs supporting the efficacy of HBO in the treatment of DFUs have been published but there are still questions about its therapeutic benefits (Tecilazich et al., 2011) and its non-

**3.7 Preventive surgery** 

wound that carries a risk of non-healing and infection.

subjects with partial foot amputations (Armstrong et al., 2005).

selective use among persons with diabetic foot ulcers (Londahl et al., 2011).

**3.8 Negative pressure wound therapy**

**3.9 Hyperbaric oxygen therapy**

## **3.4 Debridement**

Debridement is necessary for removal of devitalized tissue in order to create a healthier wound bed. Removal of nonviable tissue permits better visualization of the wound base, removes a growth medium for bacteria and stimulates release of growth factors. Sharp debridement is the gold standard for diabetic foot ulcers and is the most efficient method for removing large amounts of tissue quickly. Other types of debridement include autolytic, enzymatic, and biologic.
