The diabetic foot

Author’s Accepted Manuscript The diabetic foot Richard F. Neville, Ahmed Kayssi, Michael S. Stempel, Teresa Buescher

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To appear in: Current Problems in Surgery Received date: 18 July 2016 Accepted date: 25 July 2016 Cite this article as: Richard F. Neville, Ahmed Kayssi, Michael S. Stempel and Teresa Buescher, The diabetic foot, Current Problems in Surgery, http://dx.doi.org/10.1067/j.cpsurg.2016.07.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

The Diabetic Foot

Richard F. Neville, MD Director of Vascular Services Vice-Chairman, Surgical Sub-specialties Associate Director, INOVA Heart and Vascular Institute INOVA Healthcare System Falls Church, Virginia

Ahmed Kayssi, MD Limb Preservation Fellow INOVA Heart and Vascular Institute Falls Church, Virginia.

Teresa Buescher, MD Assistant Professor of Plastic Surgery George Washington University Washington, DC Michael S. Stempel, DPM Assistant Professor of Medicine and Surgery Chief of Podiatry George Washington University Washington, DC

Introduction Diabetic foot lesions have a multifactorial etiology, including neuropathy, infection and arterial insufficiency, that results in foot ulceration, sepsis, pain, and eventual amputation. In fact, diabetes remains the primary cause of lower extremity amputation of non-traumatic origin in the United States, placing diabetic patients at significantly greater risk of amputation compared to the general population. Despite advancing medical technology, and efforts at education of the diabetic population and medical community at large, there continues to be more than 80,000 lower extremity amputations in the United States (U.S.) every year.1 The incidence of ulceration in the U.S. diabetic population is as high as 15%, with the individual lifetime risk of ulceration estimated to be as high as 25%.2

The socioeconomic implications of ulceration and amputation on the diabetic patient population are profound, including diminished quality of life, progressive disability, increased risk of medical complications, and limb loss. Additionally, there is a high financial cost to the medical system and society at large due to lost productivity. Foot ulceration is the leading cause of hospitalization for the diabetic patient in the U.S. and Britain, and is the most common precursor to lower extremity amputation.3 The average cost of treating a diabetic ulcer in the U.S. ranges from $8,000 to $17,000, depending on the presence of infection, with the cost over three years after a limb amputation ranging from $43,000 for a partial amputation up to $63,100 after a major amputation.4 A more recent audit of 2.5 million inpatient diabetic foot ulcer cases across the U.S. between 2001 and 2010 reported a 16.5% incidence of amputation and an average cost of treatment of more than $100,000.5 The estimates include the cost of diagnostic testing, surgical and medical treatment, as well as the ongoing costs of ulcer prevention after healing the original wound or amputation. Ulceration

reoccurrence rates range from 28% at 12 months.6 In patients who have a lower limb amputation, 42% will require an amputation of the contralateral limb within one to three years.7

Patients experience decreased quality of life that is associated with the reduced mobility, multiple and prolonged hospitalizations and nursing facility stays that are often required for the treatment of diabetic foot complications. These patients experience a generalized deconditioning, loss of social contacts, and worsening of other diabetic comorbidities. Specifically, there is increased cardiovascular stress in patients that are already predisposed to vascular disease. This leads to an increased risk of mortality, with the median time to death being 27.2 months in diabetic patients after a leg amputation as compared to 46.7 months in patients without diabetes.8

Risk factors for diabetic foot pathology Foot ulceration in diabetic patients precedes lower extremity amputation in approximately 85% of cases.9 The primary risk factor that leads to a diabetic foot ulcer is peripheral neuropathy, but there are usually multiple accompanying factors associated with the disease. These additional factors include hyperglycemia, duration of diabetes, peripheral arterial disease, visual impairment, renal disease, orthopedic deformities, and the age of the patient.

Peripheral neuropathy Loss of protective sensation in the feet of diabetic patients results in unperceived trauma to the foot, the primary factor leading to the development of foot wounds. These traumatic events may present as repetitive pathologic levels of pressure while walking and micro-trauma that results in blistering of

the skin or deep tissue breakdown. Without perception of the painful stimuli, the patient develops full thickness skin breakdown or skin ulceration.

Loss of protective sensation can also allow direct mechanical injury to the skin to occur without the patient being aware of the event. Common examples include puncture wounds to the bare foot or though the sole of a shoe, thermal or chemical burns, self-induced trauma to the skin while trimming nails or callused skin. These events then lead to chronic wound formation because the anesthetic patient is unaware to the presence or extent of the insult. Loss of protective sensation also places the patient at risk if there is improper fit or poor function of shoe-gear, with shoe rubbing or tightness resulting in skin trauma.10

The patient with an insensate foot is also unaware of the progressive signs of inflammation as infection ensues. They may be unaware of tissue necrosis or impending ischemic gangrene. Without visual inspection of the wound by the patient or another party, the opportunity to limit tissue damage or infection is lost. Sensory loss is not the only manifestation of peripheral diabetic neuropathy that plays a role in the development of ulceration. Autonomic and motor neuropathies should also be considered. Peripheral autonomic nerve damage can result in dry fragile skin, as well as failure of the sympathetic response of the vascular system in response to tissue stress. This may result in arterialvenous shunting and impaired microvascular regulation of the skin.11

The forefoot is the most common location of neurotrophic ulceration, as a result of structural and functional changes in the foot brought on by motor and orthopedic deformities.12 Motor neuropathy causes muscle atrophy and imbalance, and may result in structural deformities within the foot. Manifestations of advanced neuropathy include atrophy of the intrinsic musculature of the foot,

weakening of the anterior calf musculature, and development of equinus. These motor changes can result in structural and functional changes within the foot. The diminished strength of the intrinsic foot musculature produces extensor flexor tendon imbalance and contributes to hammering, which is characterized by dorsiflexion at the metatarsal-phalangeal joint and plantarflexion at the interphalangeal joints of the toes.13 Prominence at the interphalangeal joints increases the risk of rubbing against the toe-box of the shoe, and the contracted position of the toes creates plantar prominence of the metatarsal heads. Ulcerations at the distal tip and dorsal aspects of the toes are common wound sites. The presence of equinus, along with the dorsal contracture of the toes can also increase the loading pressure on the metatarsal heads, also common ulceration sites.14

Peripheral arterial disease Peripheral arterial disease has a direct effect on the risk for ulcerations as well as the likelihood of amputation. Neuropathic and ischemic components are present in up to 45% of lower extremity ulcerations.15 Though not as common a direct cause of ulceration as neuropathy, impaired skin perfusion results in impaired healing and ability to mount a response to and deliver antibiotics to sites of infection. Poor diabetic control, duration of diabetes, visual impairment, advanced age of the patient, and renal disease are factors that increase both the risk of ulceration and the ability to heal wounds.

Soft tissue infection Tissue cultures should be obtained when gross signs of infection, including purulence, peri-wound cellulitis, malodor and tissue necrosis are present. Generally, ulcers without accompanying signs of infections should not be cultured and swabbing of the wound bed should not be performed under any circumstances.16 Swabbing of the ulcer bed will yield multiple mixed organisms, often representing

contaminant organisms from the patient’s shoe that are not associated with an active infection. A tissue sample obtained by incision or curettage of the wound bed will yield a more accurate culture for causative organisms, thus avoiding the unnecessary or unwarranted use of broad-spectrum antibiotics.

Bone abnormalities Bony foot deformities such as bunions and hammertoes can also create points of pressure, which are potential ulceration sites. These bone and joint prominences are vulnerable to friction and injury against the toe-box of the shoe, and, with the presence of neuropathy, can lead to ulceration. Restricted motion in the hallux due to misalignment or arthritis will alter gait and biomechanics. 17 This may result in increased pressure elsewhere within the foot, such as under the second metatarsal or off of the edge of the hallux. In a sensate foot, this would result in callus formation or pain. However, ulceration may develop in the insensate foot. Overall biomechanics of gait may play a role as well, and include factors such as restricted motion within the foot due to flatfoot deformities, tendon dysfunction, and equinus, as well as knee or back issues. Several studies have supported the association of high plantar pressures and foot ulceration, orthopedic foot adaptations, and deformities that alter biomechanics.18

Wound assessment in the diabetic patient Patient history When a diabetic patient presents with a foot ulceration or wound the essential first step is to obtain a detailed history. The focus should be both on the history of the foot wound as well as the patient’s medical history. This assessment will allow the initiation of proper first-line care of the wound as

well as initiation of a multispecialty team approach that has been shown to improve outcomes.14 The initial focus is to ascertain the onset and origin of the ulceration, the duration of the wound, and whether there has been a wound at this location in the past. It is also relevant to know if the patient has any systemic signs of infection, pain, prior history of foot ulcerations, infections or amputations, or if the patient received any prior treatment of the wound. The focus should then turn to the patient’s history of diabetes management, peripheral or cardiovascular disease, renal disease and history of prior amputations, as these factors are immediately relevant to the patient’s ability to heal and combat infection.

Social circumstances, such as the patient’s overall level of activity, work place environment, shoe and weight-bearing requirements, family and home support, are important but often overlooked factors. There can be a profound effect on the patients’ ability to comply with treatment plans, especially limited weight bearing. Smoking history is critical to healing and vascular disease, and it is imperative to discuss smoking cessation early in the treatment process.19

Physical Examination Every evaluation of a diabetic patient’s foot includes a neurologic exam, peripheral vascular exam, musculoskeletal evaluation, and dermatologic exam. If there is a wound present, then there is an additional focus on signs and symptoms relevant to the wound. The goal of the exam is to determine the extent and severity of the wound, the influence of the above factors on successful wound healing, the need for investigative studies, and the possible need for surgery and hospitalization.

Clinical evaluation and screening for peripheral neuropathy focuses primarily on detection of the loss of protective sensation. Light touch testing with a 10 gram Semmes-Weinstein monofilament is the most predictive and easily reproducible test to assess the risk of plantar ulceration. Failure to perceive more than four or more of 10 test sites has been associated with a 15-fold increased risk of plantar ulceration.20 Testing perception of vibration with a 128 mHz tuning fork is also predicative of ulceration risk,21 although this test is more difficult to perform in a reproducible manner than the Semmes-Weinstein light touch test. Other tests such as pinprick, 2-point discrimination, temperature perception and deep tendon reflexes are informative but less clinically relevant to determining the risk of plantar ulceration and guiding ulcer care. Clinical changes that indicate the presence of autonomic neuropathy are dry brittle skin, anhydrosis, and diminished autonomic-mediated skin perfusion. Diminished autonomic peripheral neuropathy results in skin that is structurally vulnerable to physical stressors and microtrauma and prone to cracking and fissuring.11

Changes in the patient’s foot due to motor neuropathy are suggested by visible atrophy of the intermetatarsal musculature. There may be visible hollowing of tissue between the metatarsals and arch of the foot. This neurologically-induced muscular weakness creates functional imbalances between the tendons that dorsiflex, plantarflex and stabilize the toes. There is a progression towards hammertoe development, with the toes eventually attaining a dorsiflexion contracture at the metatarsal phalangeal joint and plantarflexion at the proximal phalangeal joint. With time this position becomes fixed and non-reducible and results in a toe that is vulnerable to shoe rubbing at the knuckles. The contracted toes also induce increased pressure at the plantar aspect of the metatarsal heads. The patient should also be questioned for subjective symptoms of diabetic neuropathy, as to whether they experience symptoms of burning, tingling, feelings of numbness or pain. While subjective neuropathic symptoms do not always correlate with a risk of ulceration, there is a relationship with the progression of their diabetes, and pain management may be indicated as well.

Vascular exam The physical vascular exam should include palpation of the lower extremity arteries, including the femoral, popliteal, dorsalis pedis and posterior tibial arteries. Palpation of the arteries within the foot has a high degree of intra-observer variability, with potential for false positives and false negatives and requires careful technique. While absence of pedal pulses has a strong predictability of peripheral arterial disease, presence of pedal pulses does not rule out vascular disease. Ankle brachial indices (ABI) can also be obtained at the time of initial evaluation. However, due to the frequent presence of medial arterial calcification of foot vessels, falsely elevated ankle pressures may result in false normal values.22 ABI’s therefore do not replace the need for a comprehensive set of non-invasive vascular tests. If the ABI is found to be less than 0.9 or above 1.2 in a diabetic patient, there should be a suspicion for peripheral arterial disease and consultation with a vascular specialist.23 Examination should also focus on the presence of edema due to venous insufficiency, dependent rubor, palor with elevation, abnormal diminishment of temperature gradient from the proximal to distal leg, absence of digital hair and trophic skin changes. The patient should also be questioned for subjective symptoms of rest pain and claudication.

Positive findings of vascular insufficiency, poorly palpable or non-palpable pedal pulses, clinical evidence of poor skin or wound perfusion, and diminished or elevated ABIs necessitate formal vascular laboratory testing. Waiting to observe poor progression of wound healing is an unnecessary delay as options for intervention and treatment of peripheral arterial disease should be considered in the earliest stages of treatment. Once peripheral arterial disease is suspected, vascular surgical consultation should be rapidly obtained to guide the need for further vascular studies and

angiography, with options for revascularization to facilitate treatment of the wound and reduce the inherent risk of amputation.

Dermatologic examination The skin of the patients’ feet should be evaluated for overall health and integrity, as well as for any evidence of ulcerative and pre-ulcerative changes. As previously mentioned, when assessing the foot for signs of neuro-vascular changes, one looks for signs of change in skin color, texture, turgor, dryness and overall skin appearance.

Areas of hyperkeratosis on the plantar aspect of the sole, on the dorsal aspect of the toes, and at the distal tips of the digits indicate pressure points within the foot and should be inspected for preulcerative or ulcerative changes. Pre-ulcerative changes may be subtle and can appear as pinpoint hemorrhages deep within the callused skin, or as a shallow hematoma within the deep layers of the dermis. One may also visualize redness just below and around the callused skin, with rapid color return when the skin is pressed to blanching then released. A waxy appearance below a callus may indicate fluid beneath the lesion, and should be palpated for fluctuance. A hyperkeratotic lesion with changes suspicious for underlying ulceration should be pared down with a scalpel blade to inspect the underlying integument for integrity.

The patient’s skin should be inspected for cracks and fissures such as those caused by anhidrotic or xerotic skin and for signs of tinea pedis, especially in the web spaces. Keratomas may be found in the intertriginous regions as well. Onychomycosis and incurvated in-growing nail borders and hypertrophic nails can also be potential sites of ulceration or cellulitic infection.

Musculoskeletal exam Evaluation of the patient’s foot structure and function should be performed with a high index of suspicion for fixed and functional orthopedic changes that create pressure points within the foot. Pressure against prominent joints in the forefoot and functional biomechanical changes within the foot structure induce skin pressures that may result in foot wounds. Proper preventative care includes offloading of pressure from a healing wound, prophylactic reconstructive procedures to reduce the bone deformity, and long-term protection to prevent reoccurrence of the wound.24

Orthopedic foot deformities, bunions, hammertoes, and pes planus are common within in the general public. However, in diabetic patients they may result in sites vulnerable to ulceration. Hammertoe formation in the lesser digits is a progressive contracture and misalignment of the lesser toes. Initially, the contractures are flexible or reducible, but with time the toes become more fixed in the contracted position and eventually may become rigid and arthritic. The contracture of the digits can result in rubbing of the prominent joints against the toe box of the shoe and against the knuckles of adjacent digits, resulting in hyperkeratosis formation, a heloma or “corn”. Also, if the toe is rigidly dorsiflexed at the metatarsal-phalangeal joint, there is retrograde pressure that will increase weight bearing plantar pressure at the ball of the foot. The hyperkeratosis, a tyloma or “callus” that results are also common sites of forefoot ulcerations.

Similarly, alterations in alignment and biomechanical function of the great toe, hallux valgus and hallux rigid us, will lead to plantar pressure points, altered gait, and are potential ulcer sites in patients with poorly fitted shoes. Other orthopedic conditions of potential concern include flat foot deformities, high arch cavus foot deformities, gastroc equinus, foot drop, and prior amputations

because they create problems with shoe fit, increase plantar pressures, and significantly alter the patient’s gait.

A potentially catastrophic orthopedic deformity that may occur in patients with advanced diabetic polyneuropathy is Charcot neuropathic osteoarthropathy, commonly referred to as “Charcot foot”. It is critical that an acute Charcot joint collapse, with or without ulceration, be accurately and rapidly diagnosed. The presenting signs of an acute Charcot foot are easily and often misdiagnosed as cellulitis, ordinary fracture, foot sprain, osteomyelitis or gout. Presence of an ulceration together with a Charcot joint collapse may further complicate the presentation as there may be overlapping symptoms of cellulitis, abscess formation, and osteomyelitis, along with the Charcot joint collapse, which makes it essential to obtain an accurate history and a methodical work-up of the patient.

The clinical presentation of a red hot swollen foot with intact skin should be evaluated radiographically, especially if there is a visible collapse of the mid-foot. The classic presentation of a “rocker bottom foot” due to the collapse and inversion of the arch, with dropping out of the cuneiform joints, creates severe plantar pressures in the midfoot. This is an area of the foot that normally does not bear weight and plantar ulceration is not expected. Thus, plantar ulceration in the middle of the foot sole is another indication to suspect Charcot.25

Wound evaluation and classification After assessment of the risk factors and comorbidities that have led to a patient developing a wound at a given location, attention is directed to the characteristics of the wound itself. These characteristics will have implications to the initial management, as well as to the need for additional

studies, hospitalization, surgical intervention, and involvement of other medical specialties. The ulcer should be visually inspected for the presence of viable tissue, size and depth, drainage, purulence, and odor.

A sterile probe should be used to explore the wound sinus tracks for any possible tracking abscesses, exposed tendons, or altered joint structures or bone. Wound margins may undermine, revealing a larger wound perimeter. When a probe encounters bone, there is high index of suspicion for osteomyelitis.26 The appearance of the intact skin adjacent to the wound should be evaluated for clinical signs of cellulitis: peri-wound erythema, edema, calor and tenderness. Sometimes, the presenting signs of cellulitis may be proximal to the wound. Erythema may be present in the arch or ankle area when the wound is in the forefoot. Areas of erythema, hyperpigmentation or discoloration proximal to the wound may indicate an abscess tracking, and should be palpated. Tenderness in the area should further raise suspicion of a deep abscess. The peri-wound tissue should be compressed and palpated and purulence should be expressed from the wound.

Ulcer classification systems have been used for describing wounds by corresponding clinicians, documentation for research, coding for billing purposes, and ideally should be used in guiding treatment. The Wagner Classification was developed for pressure wounds not diabetic neurotrophic ulcers. It has limited specificity and does not guide or predict treatment .27 Other systems, such as the University of Texas Classification System and the Perfusion, Extent, Depth, Infection and Sensation (PEDIS) Ulcer classification ,28,29 provide clinically relevant guidance as they correlate wound characteristics, infection and ischemia and outcomes. They are often cited in research studies but have not seen widespread use either clinically or for billing purposes. The Society for Vascular Surgery has recently proposed a new lower extremity threatened limb classification system, WiFi

(Wound, Ischemia, Foot infection), designed to assess the risk of limb amputation.30 As the wound progresses to the more advanced grades and stages in these systems, the likelihood of healing without revascularization diminishes and the likelihood of amputation increases.31

Radiologic and laboratory tests Radiologic studies are indicated when initial studies are inconclusive for the presence of osteomyelitis. When ulcerations fail to heal as anticipated, progress to more advanced stages, or manifest clinical signs of infection, follow-up radiographs should be obtained first, but the threshold for advanced studies should now be lower. Diagnostic imaging options include magnetic resonance imaging (MRI), labeled white blood cell scans, computed tomography (CT), single-photon emission computed tomography (SPECT), and positive emission tomography (PET) scans. When the goal is to determine the presence of osteomyelitis, MRI is generally preferred to CT scans as the imaging modality of choise. Technetium-99 bone scans are highly sensitive for bone infection. However, they lack specificity and often necessitate the use of an additional scan, such as Indium-111 or other labeled white blood cell scans. The need for additional testing and the long duration of time necessary to perform labeled white cell scans has led to the increased primary use of MRI despite its associated higher cost. The enhanced resolution and sensitivity of MRIs allows visualization of the extent of infection in tissues and bone and reveals greater anatomic detail.

Appropriate tests to assess glucose control include measuring fasting and random serum glucose levels, glycosylated hemoglobin (HgA1C), as well as panels to detect the body’s mobilization against acute or chronic infection including a complete blood count, erythrocyte sedimentation rate, C-reactive protein, alkaline phosphatase, and a urinalysis. Lipid panels should also be considered as part of the evaluation of peripheral arterial disease.

Foot Wound Management Initial approach At the time of a diabetic patient’s initial presentation with a foot wound, there may be a need to immediately admit the patient to the hospital based on the severity of the presentation. Severe infection, as indicated by a deep abscess, gas seen on radiographs, and symptoms of sepsis presents a need for hospital admission for an urgent surgical incision and drainage to limit further tissue destruction and sepsis. Advancing wet gangrenous tissue loss or a cold painful pulseless limb is an emergent surgical situation.

Once a patient has been deemed appropriate for outpatient wound care, the focus of the treatment plan should be on the initial treatment of the wound and coordinating appropriate consultations. Sharp debridement of the wound bed and margins is essential in most cases. As the majority of these patients are profoundly neuropathic, debridement can be performed in the outpatient setting. A local anesthetic block or sedation in an operating room setting may be necessary if the patient is sensate or overly anxious. Debridement allows for the complete assessment of the wound, obtaining tissue for culture if indicated, and is a necessary component of initiating wound healing.32

Sharp debridement is the most efficient and effective means of removing non-viable tissue and biofilm and decreasing the bio-burden of hyperkeratotic margins typical of plantar neurotrophic ulcers. As these wounds are most commonly the result of pressure, reduction of the hyperkeratosis will assist in the offloading of the epithelizing margin of the wound. This has been dubbed the “edge effect”, and this hyperkeratotic edge will need to be reduced throughout the healing process. The

goal of sharp debridement, besides the removal of non-viable tissue, is to convert a chronic stagnant wound into an acute healing wound. The debridement process releases growth factors from platelets, reduces presence of proteinases and bacteria found in wound biofilms, and thus potentiates the function of growth factors that promote granulation and epithelization.33 Other means of outpatient debridement include enzymatic, autolytic, mechanical, as well as intraoperative with ultrasonic and hydrosurgery devices.

Once the wound has been adequately debrided and the assessment for signs of infection is complete, the focus turns to wound management. The goal is to maintain a moist and healthy wound bed, treatment with antibiotics, offloading of the foot to gain the full benefit of the stimulating effect of debridement, keep a moist wound bed, and prevent infection. There is often overlap between these goals as the dressing may serve multiple roles: control of infection, inflammation, moisture balance, and pressure relief. Infection is best managed with broad spectrum oral antibiotics, with coverage for gram positive and negative organisms until culture sensitivities are obtained and coverage may be narrowed as appropriate. Use of topical antimicrobial medications or dressings may be of use initially to combat bacterial wound colonization. These options will be discussed in further detail in a later section.

Offloading weight-bearing pressure from plantar diabetic foot ulcerations is essential to healing. Just as many of these wounds are created by unperceived pathologic pressure on the insensate foot, so will these pressures negate granulation and epithelialization of the wound. The likelihood of healing increases with the effectiveness of the offloading modality used, and with the compliance of the patient in adhering to the offloading plan.34 Many offloading devices and techniques exist and have been used for decades. Those include postoperative shoes, wedge shoes, healing sandals, braces, and

boots. However, most have low-level evidence supporting their effectiveness. The most commonly used device, a postoperative shoe, is often chosen based on its low cost, availability, ease of dressing changes, and acceptance by the patient. However, the amount of pressure reduction and the diffusion of forefoot peak pressures by the foot-bed material is low.

The effectiveness of offloading devices increases when the ankle is fixed at 90 degrees to reduce forefoot loading, if high quality-offloading material is in contact with the foot and, most importantly, if the device cannot be removed, thus increasing compliance by the patient. Pressure on the healing wound can also be achieved with use of mobility devices such as knee rollers, crutches, wheelchairs, walkers and motorized scooters. However, as with all offloading approaches patient compliance is essential.

Patient Education After evaluation of an at-risk diabetic patient, it is valuable to explain to the patient how the clinical findings are related to their diabetes so that the patient gains an understanding of how their disease can affect their feet. Indeed, the Society for Vascular Surgery’s recently-published diabetic foot guidelines recommend the education of patients and their families about preventative foot care.35 Often, patients’ fear, poor understanding of their disease, and misinformation must be overcome. When a wound is present, it is critical that patients understand how limiting weight bearing and medical compliance is essential to wound healing, and that they must report and seek urgent medical care if they detect signs of worsening infection.

Advanced treatment modalities

When applying the principles optimal to wound healing, it has been demonstrated that a 50% reduction in wound surface area at week four of treatment is predictive of complete wound closure at week 12.36 If the wound is not healing at the expected rate, advanced therapies may be considered, and there should be an investigation into the cause of the delay in healing. Frequent sharp surgical debridement, the most effective means of promoting healing by keeping the wound in an acute inflammatory state, should be performed every seven to 14 days.36 If adequate debridement cannot be achieved in the office setting, then the patient should be brought to the operating room. The moisture balance of the wound should limit excessive maceration while not allowing the wound to dry between dressing changes. The wound should be monitored for signs of bacterial colonization, accumulation of biofilm, and onset of acute infection. Culturing or re-culturing of the wound and biofilm may be indicated. There may be a need for topical antimicrobials or oral antibiotics to reduce the bioburden or treat an active infection. Patient compliance with glycemic control and poor nutritional status may be an issue, as would poor patient compliance and suboptimal design of offloading strategies. If consultations for further vascular work-up or intervention was deferred for borderline clinical or vascular laboratory findings, consultation should at this point be reconsidered.

Advanced wound modalities include an ever-growing list of bioengineered cultured cell grafts, allografts, collagen xenografts and amniotic membranes. There is evidence to support the use of these products for wounds that have demonstrated a decreased rate of healing at four weeks with reported improved rates of healing at up to 12 weeks. However, there are minimal controlled comparison studies between products and there is no means of determining which product type is best for a given wound. Choice of product is often based on practitioner experience and clinical response.37

Negative pressure wound therapy can be utilized both for ulcerations and in surgical settings, such as post incision and drainage, open amputations, delayed primary closure of wounds and amputations, and to augment the grafting of wounds. Two recent studies of negative pressure wound therapy (NPWT) reported a reduced time to achieve 90% granulation of the wound, with reduced time to wound closure, increased incidence of healing by 16 weeks, and a reduced incidence of minor amputations.38

Soft tissue surgery for the diabetic foot Principles Ulcerations or wounds that present with tracking abscesses, wet gangrenous changes, gas in the tissue on plain film radiographs, or systemic signs of sepsis, are surgically urgent, or, in the case of a necrotizing infection, emergent. Diabetic foot infections can become rapidly severe and limbthreatening due to a lack of pain and the presence of mixed causative bacteria. Also, patients with diabetes-associated immunosuppression and peripheral arterial disease may exhibit leukocytosis and systemic signs of infection only late in the progression of the infection or after incision and drainage of the wound.39 Uncontrollable hyperglycemia in the presence of infection is often a presenting sign.

Surgical incision and drainage must be aggressively and thoroughly performed, with exploration of all fascial compartments and layers of the foot into which the abscess may have tracked. Purulence will track proximally along tendon paths of the dorsal or plantar areas, and may track between the dorsal and plantar aspects of the foot. It is not uncommon for an abscess originating from a forefoot ulcer to track up to the ankle or lower leg, and, once incised, to produce several cubic centimeters of purulence. Radiographs revealing gas in the tissue or palpable crepitus can guide surgical exploration. At the time of initial surgical incision and drainage, amputation of digits or portions of

the foot may be necessary due to tissue death, gangrene, or to limit the advancement of infection to areas of viable tissue. Non-viable infected or ischemic tissue must be resected, but if tissue is indeterminate in appearance it may be appropriate to preserve it for later closure options. Highpressure pulse irrigation after debridement will further lower the bacterial count within the wound. Margins and flaps can be resected at a later date with additional debridement if they become unviable or necrotic.

Bone samples should be obtained for culture and for pathologic evaluation. Bone pathology is more accurate for confirmation of the presence of infection as prior antibiotic management and technical issues with microbiology specimens may yield negative bone cultures. Bone pathology is also more precise when evaluating for margins that are “clean”, being free of acute or chronic osteomyelitis proximal to the margin of resection. Bone samples should be chosen based on exposure of bone and joints or suspicious radiographic changes. Return to the operating room for re-debridement or further resection is not uncommon, performed both for infection control and to promote wound granulation. There should be a low threshold for return to the operating room until the spread of infection or necrosis ceases and uniform granulation is observed. Remaining connective tissue, tendons, ligaments, and cartilage should be resected from the wound as non-vascularized tissue will not granulate and may harbor bacteria. Skin margins should be resected to bleeding edges.

A team approach is critical to improve surgical outcomes, utilizing internal medicine, endocrinology, infectious disease, and vascular specialists.40 Revascularization procedures might be considered prior to subsequent surgical revision, wound closure, or definitive amputation. Hyperbaric oxygen may have utility as well in the treatment of infection and the facilitation of granulation, especially in patients with limited options for revascularization. Initial infection management should utilize broad

coverage with antibiotics, with an appreciation that mixed organisms and methicillin-resistant Staphylococcus aureus (MRSA) is prevalent in diabetic foot infections. Repeat wound and bone cultures are indicated, and management of osteomyelitis may require further bone resection. Use of NPWT is often implemented at this time to facilitate granulation for closure or grafting and to reduce the wounds’ bacterial burden.

Once bone and tissue infection control is achieved, along with tissue perfusion and wound granulation, the focus of care can be directed on wound healing, primary wound closure, or partial foot amputation. At the time of wound closure, antibiotic impregnated bone beads can be utilized to enhance treatment of osteomyelitis when clean bone margins cannot be achieved and closure of the site is planned.41 Due to anatomic changes from tissue loss, some wounds cannot be closed primarily and the best option is wound care is to facilitate secondary intention healing. The treatment modalities previously described for the treatment of diabetic wounds, such as collagen grafts, allografts as well as autografts are often used in conjunction with NPWT, although the evidence for their use is based on small and limited studies.

Incomplete foot amputations, such as partial or complete ray (toe and associated metatarsal bone) or trans-metatarsal and mid foot amputations, are sometimes the best option for the patient. While an amputation can result in significant psychological trauma to the patient, there are cases when prolonged courses of wound care, multiple surgeries, or poor post wound anatomy may be more detrimental to the patient. In these situations, amputation can result in a more predictable outcome, with more rapid healing, shorter hospitalization, lower risk of re-infection or reoccurrence of a wound, and a better functional outcome. With advances in revascularization and advanced wound

care, a partial foot amputation may be possible when previously a below the knee amputation would have been likely.

Post-procedure management Once a patient’s ulceration, surgical wound, or amputation has healed, the focus should become function and prevention of future wounds. Appropriate footwear and accommodative orthoses are vital to the offloading of pressure in an at-risk diabetic patient. Achieving proper shoe fit may be challenging if there has been further change in anatomy after healing. Multilayer customized offloading orthoses and fillers at sites of partial foot amputation are designed stabilize the position of the foot within the shoe. It is necessary to balance and offload pressure from both prior and potential ulceration sites.42 Referral to an orthotist for prescription footwear and orthoses is recommended, as the at-risk patient will need monitoring and adjustment of the devices. The patient may also benefit from additional bracing or splinting to offload pressure and will need to have these devices replaced regularly for the rest of their lives.

Physical therapy is often beneficial as well. The patient with a chronic wound is likely minimally ambulatory in a prolonged non-weight bearing state, or has had multiple medical facility admissions, and is deconditioned from both a musculoskeletal and cardiovascular standpoint. Outpatient or acute inpatient rehabilitation and physical therapy should focus on muscle strengthening, improved gait and balance, as well as the return to an active lifestyle essential to controlling underlying medical and vascular diseases. Finally, the patient will need ongoing care by their medical, vascular, and podiatric physicians to manage the risk of future diabetic limb complications.

PAD and the diabetic foot PAD and diabetes Peripheral arterial disease (PAD) impacts diabetic foot tissue integrity, healing, and limb preservation and is a primary cause of diabetic foot pathology. Diabetes mellitus is a separately recognized risk factor for PAD, especially in the tibial artery distribution. In the past, diabetic microvascular disease in the lower extremity was thought to be occlusive, leading clinicians to discount the value of bypassing diabetic patients with limb ischemia. However, this theory has since been discredited, and lower extremity revascularization can achieve healing and limb preservation in the diabetic patient. Both endovascular techniques and surgical bypass are valid interventions in attaining this goal.

Lower extremity arterial disease in diabetics characteristically results in a preponderance of tibial artery occlusive disease and sparing of occlusions at the microvascular level.43 Therefore, the indications for revascularization are similar for diabetics and non-diabetics: incapacitating claudication, rest pain, and tissue loss, including non-healing ulceration or amputation sites and gangrenous tissue changes. It is especially important to assess the severity of arterial insufficiency in the diabetic patient by physical exam and non-invasive vascular lab testing in order to assess the need for revascularization. A detailed history remains very important in evaluation of the diabetic foot. The location, depth, and time course of any ulceration or tissue loss should be noted, as well as any history of prior debridement or attempts at revascularization. Examination of the skin envelope of the foot, including a vascular examination of arterial pulses, should be a routine and frequent component of diabetic healthcare. Any sign of infection or sepsis should be addressed immediately, as well as an assessment of the functional status of the limb. The handheld Doppler ultrasound device is widely available and an experienced examiner can easily differentiate an acoustically normal from an abnormal Doppler signal. The presence of a Doppler signal indicates that there is blood flow in the

examined artery, but it does not indicate whether this flow is adequate for tissue viability. To determine the adequacy of arterial perfusion, an ABI can be measured. The ankle pressure is divided by the brachial artery blood pressure with a normal value of 1.0. In intermittent claudication, an ABI of 0.5 to 0.8 is usually obtained. With more severe ischemia, as in rest pain or tissue loss, the ABI may drop below 0.5. An abnormal pulse exam or ABI can lead to a formal vascular laboratory study to objectively assess arterial perfusion and also establish a baseline by which to compare future vascular interventions. Additional physiologic testing is especially important in diabetics because ulcerations can heal in the presence of mild ischemia if infection is eradicated and pressure is offloaded. In fact, any diabetic with tissue loss or a non-healing ulceration who does not have palpable pedal pulses should be assumed to have arterial insufficiency and undergo vascular lab testing. This decision is often appropriate for a multidisciplinary approach and can avoid unnecessary and complex vascular reconstructions.

Non-invasive vascular testing Noninvasive vascular laboratory studies can formally evaluate the severity and anatomic level of vascular occlusive disease in a standardized manner. This information is helpful in the screening, diagnosis, and management of diabetic arterial insufficiency. Vascular studies are also important in the follow-up surveillance of revascularization procedures and therapeutic efficacy. Doppler ultrasonography is used to assess ABIs, but also segmental pressures and waveform analysis. This segmental data is effective in differentiating the degree of arterial perfusion at various levels of the lower extremity: thigh, above knee, below knee, and ankle. Diabetes is associated with increased calcification of the arterial media, making the tibial arteries incompressible, and a falsely elevated ABI or ankle pressures may mask an ischemic diabetic foot. Therefore, if supra-normal ABI values are obtained, measurement of the toe pressures and a toe-brachial index (TBI) may be useful in diabetic patients with a suspected falsely elevated ABI.44 The digital arteries are often spared of

heavy calcification and more accurately reflect foot perfusion. A TBI greater than 0.6 is predictive of tissue healing. Other tests useful in this setting include pulse volume recordings (PVR)s, photoplethysmography (PPG), and measurement of transcutaneous oxygen tension (Ptco2). PVRs reflect changes in limb volume due to arterial pulsations. The PVR waveform contour and amplitude can be measured, and an amplitude less than 15 mm is indicative of ischemia. Healing is unlikely if the amplitude is less than 5 mm. PPG employs a diode that emits infrared light and the intensity of the light reflected depends on the amount of blood in the cutaneous microcirculation. PPG can be used to measure toe blood pressure by applying a cuff at the base of the toe and placing the PPG photo cell at the tip of the toe to record skin blood flow during inflation and gradual deflation of the cuff. Using this method, the toe pressure is obtained, with the lower limit of normal being 50 mm Hg.45 PtcO2 measures the partial pressure of oxygen that diffuses through warmed skin and can also predict healing potential. Healing is likely with a PtcO2 greater than 35 to 40 mmHg and a regional index can be used to account for changes in systemic arterial oxygen tension. To obtain the regional index, the PtcO2 measured on the foot is divided by the value at a reference point located on the chest. Wounds with a PtcO2 index above 0.6 are likely to heal while a value below 0.4 indicates tissue unlikely to heal.46

If it is determined that revascularization is required for pain relief, healing, or limb preservation, then an imaging study is needed to plan the appropriate procedure. Non-invasive imaging modalities such as magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) often replace catheter-based arteriography as the initial study. These imaging modalities avoid the complications associated with an arterial puncture such as bleeding, pseudoaneurysm formation, and arteriovenous fistula, as well as the renal dysfunction associated with contrast arteriography. However, these modalities also have their limitations, especially in patients with heavily-calcified arteries, and may require the placement of in-dwelling stents or result in nephrogenic systemic

fibrosis. Therefore, catheter-directed arteriography remains an important diagnostic tool, especially in planning for complex, below-the-knee revascularization procedures where tibial artery architecture is critical. However, use of CTA or MRA makes it more likely for the initial catheterbased intervention to serve as a diagnostic and therapeutic procedure. Due to the complexity of this decision making process, a vascular surgeon should assist with choosing the appropriate imaging study and subsequent plan for revascularization.

Endovascular revascularization in the diabetic patient Endovascular therapy plays a significant role in diabetic revascularization, despite the propensity for diabetics to develop tibial occlusive disease. The tibial arteries remain especially challenging for catheter-based procedures. The advantages of endovascular revascularization include a less invasive approach with a more rapid recovery and a presumed reduction in complications and perioperative mortality. Multiple authors have demonstrated comparable limb preservation rates after endovascular revascularization in diabetics as compared to non-diabetics despite the challenging pattern of arterial disease in these patients. However, beyond a reduction in incisional morbidity, a decrease in mortality or limb loss has been difficult to document. It has been recognized that diabetic patients are more likely to suffer reduced long-term primary patency following endovascular therapy compared with non-diabetics, possibly as a result of the tendency for diabetics to present with limb-threatening symptoms.47 However, secondary patency rates and limb-salvage rates, at least in the intermediate term, appear equivalent to non-diabetics.

There is a wide-ranging choice of available devices for diabetic endovascular revascularization, including balloon angioplasty, stenting, and atherectomy devices. Balloon angioplasty has been shown to be effective in diabetic patients with reasonable long-term patency and prevention of major

limb loss. Unfortunately, data evaluating devices and endovascular modalities is often difficult to interpret due to the heterogeneity of the studied patient populations, relatively short follow-up, and a lack of standardization of protocol and endpoints. The TASC guidelines (Trans Atlantic InterSociety Consensus) attempted to standardize a classification scheme according to disease anatomy in order to compare endovascular therapies more effectively. The scheme classifies disease anatomy (A thru D), with TASC A lesions being short and focal with TASC D lesions being long occlusions.48 Infra-popliteal angioplasty stratified by TASC classification was reported in 176 patients with a 93% technical success rate, a 51% primary patency at two years, and a 84% limb preservation rate. However, freedom from restenosis, re-intervention, or amputation was only 35% with 15% of patients requiring a surgical bypass after failed endovascular therapy.49 A TASC D classification predicted diminished endovascular success, indicating that infra-popliteal angioplasty may be a reasonable primary method for patients with TASC A, B, or C lesions and those unsuitable for bypass while TASC D anatomy may be better suited for surgical bypass. However, the TASC classification scheme does not account for clinical input and remains somewhat controversial in its application to patient-specific decisions. Arterial runoff may also be an important factor in determining the efficacy of diabetic endovascular revascularization. In 420 diabetics who underwent tibial angioplasty, the lack of a patent tibial artery at the end of the study resulted in a 62% amputation rate compared with 1.7% in patients with at least one open artery to the foot.50 Aggressive attempts to revascularize this poor runoff include distal tibial angioplasty technology with dedicated wires and balloons as well as pedal arch reconstruction with a “pedal loop”. The pedal loop technique involves traversing the pedal arch to establish blood flow to the foot.51 The use of stents in diabetics would necessarily involve a consideration of tibial artery stent deployment. The majority of tibial stents are currently placed in the setting of inadequate results after balloon angioplasty. Infrapopliteal stenting can be successful with restenosis rates of 20% at one year and over 70% primary patency. However, functional limb preservation was better for those patients undergoing proximal below knee angioplasty compared with treatment of distal tibial disease (100%

vs. 81.8%; P=0.0071).52 Angioplasty and stent deployment certainly play a role in diabetic foot revascularization, but continuing work to better define a role for these techniques is an active area of research and development.

One such area includes drug elution technology. Drug elution in the form of drug-eluting stents and drug coated balloons may improve device performance, especially in diabetic long segment tibial occlusive disease. Sirolimus-eluting stents have out-performed paclitaxel eluting stents with both having a seeming advantage over bare metal stents. A prospective, randomized trial compared sirolimus eluting stents with bare metal stents in patients with intermittent claudication or critical limb ischemia demonstrated that the primary patency rate at one-year was higher in the sirolimus eluting group (81%) as compared to the bare metal group (56%, P= 0.004), with secondary patency rates of 92% and 71%, respectively (P= 0.005).53 Other initial trials demonstrate that drug-eluting stents may result in improved patency as compared with other therapies as primary treatment for focal below knee disease.54 Although initial reports are promising, the efficacy and cost effectiveness of drug elution technology for diabetic revascularization remains a work in progress.

Surgical bypass in the diabetic patient Restoration of pulsatile blood flow is the goal of revascularization for healing and limb preservation of the diabetic foot. With adequate perfusion, diabetic patients show the same ability to heal as nondiabetics. Although the femoral-popliteal segment is as commonly affected in diabetics as in nondiabetics, tibial artery occlusive disease is the classic distribution in diabetic patients leading to limb threatening ischemia.55 In our experience, approximately 25% of diabetic patients with limb threatening ischemia are best treated by surgical bypass as the initial form of revascularization. These patients often present with significant wounds and tissue loss. We believe that diabetics with a larger extent of tissue

loss (>2cm) heal faster and more completely after bypass compared to endovascular therapy. Based on these observations, diabetic patients who present to our practice with significant tissue loss and long segment tibial occlusive disease are considered for a bypass as the first choice for revascularization to achieve healing. Realizing that failed endovascular therapy may make a successful bypass more difficult and unlikely, it is important to identify those patients best treated initially with surgical bypass. Diabetics with extensive tibial occlusive disease and large volume tissue loss are best treated with surgical bypass, especially if vein is available as the conduit.

Vein bypass has a record established by multi-center trials and meta-analyses. Patency at five years is as high as 70% from retrospective series, with a correspondingly high rate of limb preservation. If vein can be used for these distal bypasses in diabetics, comparable patency and limb salvage rates can be obtained as compared to those performed in non-diabetics.56 These results are comparable despite more bypasses performed for limb preservation in the diabetic group. However, there is a certain perioperative morbidity associated with surgical bypass that approaches 20%, with a 10% incisional complication rate for vein grafts. These pulmonary, cardiac, and renal complications can extend recovery and add to hospital stay and cost. Indeed, while diabetes is not a risk factor for vein graft failure, it is associated with increased risk of long-term mortality and limb loss in patients with critical limb ischemia compared with non-diabetic patients.57

Despite these concerns, bypass is an established therapy with good long-term results in limb preservation. Pomposelli et al. reported a cohort of 1000 bypasses with 92% diabetic patients with primary patency of 57% and 38% at 5 and 10 years, respectively.58 A large prospective study of vein bypass grafts for critical limb ischemia (PREVENT III) evaluated bypasses in 1404 patients, 64% of whom were diabetic and 75% of whom presented with tissue loss.59 Primary patency was 61% at one

year, but was adversely affected by vein size with a conduit diameter of less than 3 mm or construction of a composite vein graft. PREVENT III also demonstrated a reduced amputation-free survival at one year for a high risk cohort (9%), as determined by the factors of age > 75 years, dialysis, significant coronary artery disease, anemia, and tissue loss at presentation.

Advanced surgical bypass options Up to 30% of diabetic patients do not have adequate saphenous vein for bypass to distal tibial targets. In re-operative patients, this figure increases to 50%.60 In the past, primary amputation may have been suggested in this scenario without an attempt at limb preservation. Although primary amputation can be the best course of therapy for bedridden or demented patients, if revascularization is indicated for limb preservation, then alternative conduits for bypass do exist such as the lesser saphenous vein, arm vein, composite veins, and polytetrafluoroethylene (PTFE) with a patch or cuff with or without a distal arteriovenous fistula. Although these alternative conduits are not equivalent to intact great saphenous vein for tibial bypass, they can be effective for limb preservation.61-64 Attempts to improve the results of prosthetic (ePTFE) bypasses to infra-popliteal arteries involve the interposition of venous adjunctive tissue between the graft and target artery at the distal anastomosis. Benefits of this venous segment include biologic effects due to the venous endothelium, an alteration of hemodynamic factors such as compliance and shear stress, and the ease of suturing for the surgeon. However, the main benefit may be mechanical considerations such as increased anastomotic surface area and optimization of the angle of the anastomosis altered by the venous tissue contributing to improved graft function and patency.65 We developed the distal vein patch technique (DVP) to address those patients lacking autogenous conduit in need of bypass for limb healing and preservation.66 This technique can yield primary patency for tibial bypass of 50-60% at four years with limb preservation over 70%.67,68 A further modification of the DVP was the addition of an arteriovenous fistula at the distal anastomosis when arterial outflow was severely

compromised. The AV fistula increases flow velocity and decreases outflow resistance in order to improve graft performance resulting in 62% patency and 57% limb salvage at 24 months in a patient group otherwise considering primary amputation.66

Another strategy to improve prosthetic graft performance involves heparin bonding on the inner surface to reduce graft thrombosis and myointimal hyperplasia.69 The most commonly used heparinbonded graft (Propaten, W. L. Gore & Associates, Flagstaff, AZ) uses end-point covalent bonding of heparin to the luminal surface of the graft in order to maintain the bioactivity of the heparin molecule.70 This reduces platelet adherence, thrombus formation, and anastomotic myointimal hyperplasia in both canine and primate models.71,72 Dorigo et al. compared primary patency between in-situ saphenous vein, standard PTFE, and heparin bonded PTFE for below knee bypasses. At 18 months, primary patency was 75% for vein bypasses, 40% for standard PTFE, and 53% using the heparin-bonded grafts.73 There was a 57% reduction in early graft thrombosis with the heparin bonded PTFE graft compared to standard PTFE material. Nevelsteen reported a single center, retrospective experience indicating that heparin bonded grafts were comparable to saphenous vein for tibial bypass.74 The one-year primary patency for heparin bonded ePTFE and vein grafts were 78% and 81%, respectively, with 2-year rates of 76% and 80%. We compared our own experience over a similar time period with 62 heparin bonded PTFE grafts and 50 saphenous vein grafts.75 There was a higher incidence of diabetic patients in the vein group but this did not reach statistical significance. Graft thrombosis occurred in twelve PTFE grafts and seven vein grafts for a one-year primary patency of 86.0% for vein and 75.4% for heparin bonded PTFE. This difference also did not reach statistical significance (p=0.105). Diabetes did not affect outcome, but patency was decreased in those patients on active hemodialysis. Based on this experience, we continue to believe that a quality saphenous vein is the ideal conduit for a tibial bypass; although heparin bonded ePTFE can be considered when intact ipsilateral or contralateral vein is not available. Diabetes did not impact

patency, and therefore, diabetic patients should not be denied prosthetic bypass revascularization for limb salvage.

Endovascular vs. bypass for diabetic revascularization Optimal revascularization in the diabetic patient requires the selection of the best technique for each individual patient. The Bypass Versus Angioplasty in Severe Ischemia of the Leg (BASIL) trial attempted to compare endovascular intervention with surgical bypass, although only 42% of the patients in BASIL had diabetes.76 The 452 patients with severe ischemia were randomized to bypass or endovascular intervention. Perioperative morbidity was higher with surgery but amputation-free and overall survival was similar in both groups at one year. However, at the two-year interval, surgery was associated with a reduced risk of amputation and death. BASIL also revealed that bypass after failed angioplasty resulted in decreased success compared to an initial bypass. The study concluded that angioplasty should be used first for patients with a life expectancy of two years or less and that bypass is preferred if there was an available vein conduit in a patient without significant medical comorbidities. It is difficult to directly apply this data to patients with diabetic foot problems, given that the minority of diabetics in the study and less than one third of patients had tibial disease treatment. However, the conclusions may be applicable to patient-oriented decisions regarding choice of revascularization. A review of revascularization for the treatment of diabetic foot ulceration from 1980 to 2010 was published by Hinchliffe.77 Outcomes were similar with one year limb preservation of 85% after bypass and 78% following angioplasty. Interestingly, loss of patency does not always lead to amputation. There are a certain number of patients in whom the initial revascularization supplies enough perfusion to obtain healing with enough perfusion to maintain tissue integrity despite subsequent failure of the revascularization. Therefore, although prospective, randomized data comparing surgical bypass and endovascular revascularization for the diabetic foot

is lacking, similar limb preservation rates can be achieved when the physician’s best judgment is used to choose an individualized revascularization plan for each patient.

The angiosome theory in revascularization for healing Despite advances in endovascular and bypass techniques, ischemic wounds may fail to heal because of inadequate local revascularization between the target artery and the ischemic tissue. The “angiosome” concept divides the body into three-dimensional vascular territories supplied by specific source arteries.78 The foot has six distinct angiosomes: three arising from the posterior tibial artery, one from the anterior tibial artery, and two from peroneal arteries. The posterior tibial artery gives rise to a calcaneal branch that supplies the medial ankle and plantar heel, a medial planter branch that feeds the medial plantar instep, and a lateral plantar branch that supplies the lateral forefoot, plantar midfoot and the entire plantar forefoot. The anterior tibial artery continues to the dorsum of the foot as the dorsalis pedis. The peroneal artery supplies the lateral ankle and plantar heel by the calcaneal branch and the anterior upper ankle by an anterior branch.79 Choice of the target artery for revascularization is determined by factors such as the availability of conduit and quality of the recipient artery. Consideration should also be given to the arterial anatomy in relation to the foot wound’s angiosome. Direct revascularization involves the artery supplying the angiosome in which the wound is located, while indirect revascularization involves an artery that does not directly perfuse the ischemic angiosome. In a study of patients who required revascularization for wound healing, there was a significant difference in healing when direct revascularization was performed (91%) compared to wounds that were indirectly revascularized (62%).80 There may be an advantage in providing antegrade blood flow to the area containing the wound rather than relying on indirect flow via arterial-arterial connections in the lower leg and foot. Similar conclusions were reached in a recent analysis by Iida et al. of 369 limbs in 329 patients.81 Clinical outcomes were compared after endovascular revascularization based on the angiosome concept. At 18 months, limb

salvage was 81% with a 31% re-intervention rate to obtain healing. There was a difference in limb salvage between patients with and without direct revascularization of the appropriate angiosome by endovascular therapy. Obviously, wound healing occurs without consideration of angiosome anatomy. However, when there is a choice of target artery for revascularization, preference should be given to the artery directly feeding the wound’s angiosome. This may affect the need for detailed foot arterial anatomy by arteriography and the choice of the method of revascularization.

Techniques for soft tissue reconstruction The goal of soft tissue reconstruction is a durable closed wound that withstands ambulation. Because of the complex altered physiology of these wounds, as well as additional systemic issues that these patients frequently have, wound closure is slow and frequently requires multiple interventions. However, with meticulous attention to detail, closure rates of 80% or above have been reported.82 Defining principles of successful wound closure include cleanliness, adequate perfusion, offloading of pressure, and a moist environment. Small superficial wounds then go on to heal either without additional intervention or with the application of cell based materials such as Dermagraft, Apligraft, or keratinocyte allografts.83

Role of soft tissue debridement Bedside sharp debridement may suffice for small wounds, but larger wounds often require repetitive operative debridements, with the goal of a well-perfused wound bed and quantitative cultures less than 105/gm tissue before closure. Peri-wound cutaneous oxygen measurements equal to or greater than 30 mmHg are predictive of successful wound healing. In Sinkin’s series of 193 wounds in patients with Charcot changes, the average number of debridements prior to attempted closure was four.84 Patients with ischemic extremities require vascular evaluation for revascularization once their

wounds are clean and without infection. In a series of intrinsic muscle flaps for foot wounds, 42% of the diabetic patients vs. 7% of the non-diabetic patients needed revascularization before wound closure.85 Exposed bone needs to be debrided to stippled punctate bleeding and bone cultures should be obtained. The bacteria most likely to be involved in diabetic osteomyelitis are skin organisms, frequently Staphylococcus aureus.86 Copious pulse lavage irrigation (three to nine liters) should be performed at the end of each debridement.

Between debridements, wounds may be covered with moist dressings, silver- containing dressings, or creams, or treated with negative pressure therapy. In a 2014 meta-analysis of negative pressure therapy for diabetic foot ulcers in 669 patients, Zhang and colleagues found that negative pressure therapy was more likely to shrink or heal ulcers compared to standard therapy, and did so in a shorter period of time.87 While the rate of major amputation was decreased, the rate of minor amputations was not, and there was no difference in adverse events when compared to standard therapy.

In order for wound closure to be done safely, the actual blood supply of the foot must be known. Because of the frequent coexistence of vascular disease and the multiple interconnections between the vessels of the foot, imaging studies may not provide an accurate assessment as they may not distinguish retrograde flow through connections versus antegrade flow. A careful Doppler exam with selective occlusion of known connecting vessels gives the information necessary to decide on the most appropriate operative strategy. Triphasic Doppler signals imply normal flow. Biphasic signals imply some moderate decrease in flow. Monophasic flow characterizes significant arterial compromise or loss of sympathetic vessel tone. A monophasic and high resistance, blunted signal implies compromised runoff distal to a more proximal lesion. Determining the location of interarterial communications and the direction of flow in the foot can be determined by Doppler exam

with selective compression.79 This allows the actual source vessel of the wound location to be pinpointed and ensures that incisions will not inadvertently section the actual source of blood flow. Incisions between foot angiosomes should heal because of normal blow flow from either side. These safe areas include the midline Achilles tendon, the junction of the dorsal foot skin with the skin of the plantar surface, and the midline of the plantar surface of the foot. Because atherosclerosis causes gradual occlusion, the “choke vessels” related to angiosome anatomy are often patent at the time of significant proximal occlusion. Regardless, placement of foot incisions should be always be carefully considered so as not to jeopardize an open source artery. If one pedal artery is occluded, foot incisions should not compromise the adjacent angiosome choke vessels feeding the occluded vessel's angiosome to optimize skin viability. For example, if the peroneal artery is occluded, an incision over the Achilles tendon will compromise skin lateral to the Achilles tendon because the choke vessels from the posterior tibial system may have been disrupted. If placed lateral to the Achilles tendon, the choke vessels can perfuse the skin medially from the posterior tibial artery and anteriorly from the anterior tibial artery giving the incision an increased chance to heal.

In the presence of a normal blood supply, safe Achilles tendon incisions include midline, midline with extension inferolaterally along the junction of the plantar and dorsal skin, and an "S" shaped incision from proximal medial to distal lateral to avoid the sural nerve and small saphenous vein. An "L" shaped incision to approach the lateral malleolus should descend to and run along the junction of the dorsal and plantar skin. If placed above that junction, the skin between the incision and the junction is likely to be nonviable. A coronal or midline sagittal plantar heel incision is safe as long as both the posterior tibial and peroneal arteries are patent. The sagittal incision will disrupt sensory nerves, so it is a better choice for a patient with a neuropathy. Plantar incisions can be midline or along the border between the medial and lateral plantar arteries. Medial foot incisions depend on the medial plantar artery angiosome for blood flow. An incision two to three cm above the dorsal-plantar

skin junction, located at the border between the anterior tibial system and the lateral plantar artery territory, should heal. An incision at the junction should also heal as long as both branches of the medial plantar artery are open. Lateral foot incisions should be at the dorsal-plantar skin junction. The blood supply of the dorsal foot runs transversely above tarsal-metatarsal joints and vertically below the joints. Incisions should be parallel to the direction of the vessels. In the distal foot, parallel vertical incisions can made, as long as the metatarsal arteries are not sectioned.85

Local tissue flaps As with any wound patient, the medical condition of the patient should be optimized prior to definitive wound closure. Glucose should be controlled, nutritional parameters should be improving, and the patient should be free from local or systemic infection. Local flaps for wound closure should be designed according to the foot's actual blood supply. A Doppler exam to determine areas of antegrade and retrograde flow is vital. Flaps should contain arterial perforators detected by Doppler signal, designed in the direction of antegrade flow to the local flap. Random flaps include bilobe, double “v to y”, rhomboid, double Z rhomboid, rotation flaps with back grafting, and transposition flaps with back grafting. The significant advantage of using local skin flaps is the concept of “replacing like with like”: defects in specialized skin are replaced with similarly specialized skin. The downside is the limited amount of specialized skin available to close wounds, limiting the size of wounds that can be handled in this manner. If there is a bone abnormality, causing the ulcer to form, the bone must be addressed and corrected to minimize the chance of recurrence. Blume described such an approach with 67 cases of one-stage ulcer debridement and closure together with correction of underlying bone abnormalities.79 Results with this single stage approach included 97% healing, 54% without complication, and 88% without recurrence at 2.5 years. Forefoot wounds healed more quickly than mid- or rear-foot wounds (39 vs. 60 days). Deep wounds healed more slowly than superficial wounds (59 vs. 36 days), and had a longer hospital stay (9.6 vs. 2.9 days).

This experience demonstrates that local skin flaps in a carefully selected population can be very successful. Double plantar rotation flaps can also be designed to either side of the defect for closure of small (less than two cm) central plantar forefoot ulcers.88 While one flap is based on the medial plantar artery, the other is based on the lateral artery, and flap margins respect the appropriate angiosome.

Toe amputation can have a high rate of subsequent, more proximal amputation with up to 75% of patients having a higher level of amputation in fewer than 10 months.89 Another study showed that after great toe disarticulation, more ulcers appeared in 65% of the patients and 53% eventually had amputations at higher levels.90 To avoid additional amputation, Roukis and Landsman described a one-stage technique for treatment of first metatarsal head osteomyelitis with overlying plantar skin ulceration that avoids ray resection.91 After aggressive debridement of the osteomyelitis to include the sesamoids, a flap is designed and raised based on the lateral digital vessels of the big toe and includes skin from just lateral to the lateral nail fold to the plantar midline of the toe. The flap can be raised to include all tissues down to the phalangeal periosteum. The pedicle is not skeletonized, but contains web space contents together with its encircling fatty sheath. The authors feel that by including the extra tissue, the likelihood of venous congestion decreases dramatically. The donor area can be skin-grafted or can be closed primarily if the lateral thirds of the toe phalanges are resected. Antibiotic beads can be placed in any boney defect. Hospital stay is approximately one week. Antibiotic therapy is based on bone culture results. Although the great toe is narrower, the foot aesthetics are preserved and patients can walk in an extra depth rocker soled shoe with soft insoles.

Digital coverage can also be obtained with a medialis pedis flap, a fasciocutaneous flap harvested from the medial aspect of the foot, previously described by Masquelet.92 After confirming the

anatomy in five cadavers, this flap was used to cover posterior heel, medial malleolar, and first metatarsal wounds. The flap is based on the cutaneous perforators of the medial branch of the deep branch of the medial plantar artery. The proximal aspect of the flap is at the navicular tubercle and the distal aspect is the mid-shaft of the first metatarsal. The flap’s width is approximately 2.5-3.0 cm. Once the superficial branch of the medial plantar artery is ligated, the pedicle is the medial plantar artery and is five cm long. Proximally based, it can reach the distal Achilles tendon, medial malleolus, and the posterior heel. Based retrograde, it is supplied by the superficial branch of the medial plantar artery through anastomoses with the superficial plantar arch of the lateral plantar artery. This allows coverage of the first metatarsal head.

Dorsal forefoot wounds can also be difficult to close with local flaps, especially in an ischemic foot. Distally based dorsal pedis flaps or medial plantar artery flaps have had successful outcomes in very carefully selected diabetic patients, but should be reserved for a foot with normal antegrade blood flow. Loss of the dorsalis pedis artery or medial plantar artery for purposes of a flap could cause significant foot ischemia. Another option for the distal dorsal forefoot is the saphenous neurovenofasciocutaneous flap.93 This distally-based flap uses medial proximal dorsal foot skin for wound closure as the vascular supply is from the proximal superficial branch of the first plantar metatarsal artery that consistently connects with the anterior medial malleolar artery and the medial tarsal artery. These connections allow an axial flap to be designed. If the saphenous vein and nerve are included, the nutrient networks associated with these structures add to the vascularity of the flap. This flap does not sacrifice any major arteries to the foot. For this flap to work, the posterior tibial and anterior tibial systems should be open.

Intrinsic muscle flaps for wound closure were commonly used until the use of free tissue transfers became more common. Intrinsic flaps are small and their arcs of rotation are limited compared to the coverage provided by free tissue transfer. Other advantages to free tissue transfer are that flap harvest is faster than cutaneous flaps, donors can be closed directly, and the incisions are generally safe. The abductor hallucis brevis, abductor digit minimi, flexor digit minimi, and flexor digitorum brevis harvest incisions all run between angiosomes. The abductor digiti minimi works well for lateral malleolar and calcaneal wounds. The abductor hallucis brevis can cover medial heel, ankle, and mid foot wounds. The flexor digitorum brevis provides very good heel coverage. The extensor digitorum brevis can be used for dorsal wounds at the level of the ankle. Although not large, they can cover the critical structures allowing the rest of the wound to be closed by a split-thickess skin graft. Altindas described 17 diabetic foot ulcers with exposed bone and joint in the hind-foot and the lateral plantar midfoot.94 The abductor digit minimi flap, with or without a skin graft, was successfully used in all patients. Vincenti and Belczyk proposed the use of the flexor digitorum brevis flap for calcaneal osteomyelitis.95 The blood supply comes from the medial plantar artery (mid-muscle belly) and the lateral plantar artery (most of the muscle). Flap advantages include bulk, vascular density, and the fact that toe flexion is preserved through the flexor digitorum longus. Disadvantages include limited size and reach, as it will not extend distal to the instep. Moreover, it is contraindicated if the dorsalis pedis and posterior tibial vessels are compromised, and this flap frequently requires an overlying skin graft.

An Achilles tendon wound is often a challenging situation. Traditionally, surgeons have preferred local or free flap coverage, rarely performing skin grafts because of durability and wound healing concerns. Attinger reported an experience with Achilles tendon wounds that were debrided and allowed to heal by secondary intention, by skin graft, by local flap coverage, or free flaps.96 The success rate was approximately 80% in all categories with a wound closure rate of 96% and limb

salvage of 98%. Several patients treated with a skin graft developed recurrent wounds, but most healed with local wound care. There was no difference in results between those with and without diabetes. Therefore, in appropriately selected patients, skin grafting is a viable method of closure for Achilles tendon wounds.

Microvascular transfers (free flaps) Free flaps supply a large amount of tissue and can allow aggressive debridement, as the size of the wound is less of an issue than with pedicled flaps. However, as with pedicled flaps, the flap should not disturb the vascular supply of the foot, so arterial end-to-side anastomoses are a better choice than end-to-end anastomoses to maintain prograde flow in the native circulation. Microvascular transfers frequently require secondary procedures such as debulking and tissue re-inset to improve aesthetics and function. Because of flap bulk, getting shoes to fit can be very difficult. All successful series report aggressive debridement of nonviable tissue, revascularization when necessary to provide normal oxygen tension, control of medical problems, gradual protected weight-bearing, correction of underlying boney abnormalities before or during the flap procedure, and control of infection. Bed-bound patients with multiple poorly controlled medical problems are better treated with local tissue closure options. The dialysis population may be disadvantaged for such a reconstruction and dialysis should be considered a relative contraindication to free flap reconstruction.

A comparison of intrinsic muscle flaps with free flap reconstructions evaluated 38 diabetic and 42 non-diabetic patients with flap reconstruction.97 Pedicled muscle flaps were used for smaller wounds with bone and joint exposure and free flaps were reserved for the larger, more complex wounds. The pedicled muscle flap reconstructions healed the tissue wound in 91% of cases, with a 94% rate of

limb preservation. Complications occurred in 33% of patients and included wound disruption, partial flap loss, partial skin graft loss, and neuropathy. Diabetic patients took longer to heal (125 vs. 63 days) and needed more total procedures (3.1 vs. 1.7). Free flap reconstructions included rectus abdominus, gracilis, radial forearm, serratus anterior, lateral arm, parascapular, vastus lateralis, and anterolateral thigh flaps with the rectus abdominus flap most commonly used. The free flap survival rate was 93%, with a wound closure rate of 88% when skin grafts were added as needed. Patients with failed free flaps underwent local measures for closure, with an eventual 94% healing rate and 96% limb preservation. Complications were present in 18% of patients and included total flap loss, partial flap loss, wound separation, infection, hematoma, and skin flap loss. Similar to the local muscle flaps, free flaps had prolonged healing times in diabetics (110 vs. 104 days) and required more secondary procedures (3.8 vs. 2.6), although the presence of diabetes made no difference to the free flap’s survival rate. Properly chosen free flap or intrinsic muscle flap coverage of wounds significantly enhances limb preservation in diabetics with foot wounds.

Hollenbeck also described patients who had microvascular transfers for foot and ankle wounds: 75% were due to trauma, 15% to diabetes, and 5% subsequent to cancer operations.98 Flaps performed included radial forearm, lateral arm, gracilis with skin graft, anterolateral thigh flap, scapular flap, latissimus dorsi flap, and rectus abdominus flap. Dividing the foot and ankle region into seven subunits based on aesthetic and functional requirements, certain flaps fulfilled the needs of each area better than others as no one flap was ideal for all situations. Initial flap survival rate was 92% and the complication rate was 34%, including wound separation, flap compromise, and infection. A secondary procedure was required in 49% of cases, most commonly tissue debulking of the forefoot. In follow up, recurrent wounds developed in 11%, most commonly on the plantar surface at the junction between the flap and the native foot skin. The amputation rate was 6.8% and more common in patients with diabetes and free flap failure with resultant limb preservation in 89% at 5 years.

Recommendations from this experience included liberal resection of boney prominences at the time of the flap, re-inset of the flap if it looked unstable using a curving inset of the flap with the foot skin, such that de-epithelialized flap is tucked under the native skin. Large flaps in the foot and ankle area interfere with the wearing of shoes and therefore with ambulation. Accordingly, lateral arm, radial forearm, anterolateral thigh and scapular flaps may be better choices for those areas. Digits are often not reconstructed, however, and a large toe wound can be closed with a small fasciocutanoeus flap to preserve toe viability and function.

Hong reported seventy one anterolateral thigh flap reconstructions for diabetic foot wounds.99 All patients had preoperative arteriography, and flap arterial anastomoses were end-to-side or end-to-end to a side branch of an axial artery. Flaps were defatted to 4 mm thickness except in proximity to the perforator artery. Flap survival was obtained in seventy flaps with four having partial flap loss. Sixty-eight patients had a normal gait in follow up. The authors believed that the rate of shear on the flap with ambulation was less with a thin faciocutaneous flap because the subcutaneous tissue had smaller fat lobules and a better array of fibrous septae. The process of primary defatting obviated the need for secondary flap debulking after the initial procedure. A caveat, however, was the BMI difference between Eastern and Western populations, making the thicker Western anterolateral thigh flap more difficult to thin to the standards that the authors advised.

In summary, microvascular transfers are well suited to larger wounds with critical exposures. They can be safely done in diabetics and can provide wound closure and limb salvage preservation. The choice of flap should be based on functional and aesthetic requirements of the subunit of the foot.

Prevention of recurrent soft tissue defects Prevention of wound recurrence is equally important as the initial closure of the wound. Ulceration of the plantar surface correlates with increased sole and mid-foot pressures with ambulation. Shortening of the Achilles tendon by contraction or chronic tightness can significantly contribute to increased plantar foot pressures. Diabetic Achilles tendons examined with electron microscopy demonstrate increased collagen density and structural disorganization.100 Elevated glucose levels may lead to abnormal cross-linking between collagen fibrils and increasing tendon stiffness. Colen looked at diabetic wound closure comparing those that were done in conjunction with Achilles tendon lengthening versus those that did not have the tendon lengthened.101 At nearly three years’ follow-up, 2% of the patients with Achilles tendon lengthening recurred as opposed to 25% of those without tendon lengthening. Patients who cannot dorsiflex the ankle past neutral or have forefoot pressures of over 100 lb/in2 are considered at increased risk of recurrent ulceration. Achilles tendon lengthening can often be performed percutaneously to achieve neutral or within five degrees of dorsifexion in an effort to prevent recurrent foot ulceration.

Amputation Since lower extremity amputation is associated with decreased survival in the diabetic population, aggressive measures are taken for limb salvage. However, there comes a time when amputation is indicated as a life-saving or limb-saving procedure due to uncontrolled infection, recalcitrant wounds, intractable pain, or uncorrectable ischemia. At that point, the choice of amputation level must be made, and should take into account the needs of each individual patient. Pinzur recommends the following considerations: limb function, quality of life, most realistic result, cost differential, risks to the patient with either procedure for limb preservation versus amputation.102 The patient’s

functional status must also be considered with demented or bedridden patients considered for a single-stage amputation. Rehabilitation potential should also be assessed in regards to the patient’s ability to expend the extra energy and effort required to use a prosthesis and the ability to adhere to an intense rehabilitation program. Walking with a prosthesis demands more energy than normal ambulation so the amputation should be at the lowest level possible. However, it must be remembered that amputation may mean the loss of independent daily living and increased overall mortality.

The great toe keeps the medial aspect of the foot stable during ambulation. If a portion of the toe is to be removed, the proximal proximal phalanx that contains the flexor hallucis brevis insertion should be retained. Loss of the flexor causes the medial foot to be unstable and load bearing shifts to the lateral aspect of the foot, causing difficulty with ambulation. Second toe amputation can cause the distal big toe to point laterally (hallux valgus), leading to an abnormal wear pattern and breakdown. Again, the proximal proximal phalanx should be preserved if possible. Amputation of toes three to five does not often have functional implications. Ray resection as a method of amputation is not recommended except for a single toe. Two or more ray resections can produce a narrow foot that may have difficulty wearing a shoe leading to late forefoot limitation of motion and recurrent ulceration.

Amputation through the metatarsal should be done at the proximal metaphyses rather than distally. Distal amputation is associated with plantar pressure sores because of the higher force while “pushing off” in order to ambulate. Proximal amputation decreases this force. Tarsal-metatarsal or Lisfranc amputations should preserve the insertion of the peroneal and anterior tibial tendons.103 The foot is much shorter and the ankle tends to plantar-flex, resulting in an equinus deformity, defined as

an inability or limited ability to dorsiflex. An Achilles tendon lengthening can correct this. A hind foot amputation such as midtarsal or Chopart should rarely be done because of the ankle plantar flexion that will inevitably occur, shifting the weight-bearing surface away from the heel and onto the remaining tarsal bones. A Symes amputation, in which an ankle disarticulation is performed, allows direct weight-bearing on the tibial metaphyseal shaft, which is well tolerated.

An ideal below-the-knee (BKA) amputation should preserve at least 12-15 cm of tibia inferior to the knee joint and incorporate a long skin and muscle flap from the posterior thigh for stump resurfacing and closure. However, if need be, as long as the tibial tubercle and therefore the insertion of the quadriceps are preserved, this shorter BKA should still allow ambulation. A knee disarticulation is generally done when the patient has the ability to heal a BKA wound, but is not likely to be able to ambulate with a prosthesis at the BKA level, such as the profoundly obese or the renal failure patient with severe volume shifts. The advantage of the disarticulation over an above-knee amputation (AKA) is the better balance for sitting and transfers. The disarticulation allows end weight bearing so the prosthetic socket can have the looser fit needed by these patients. An AKA is best done with a medially based skin flap to cover the stump and the adductor muscles preserved and attached to the femur. Gait is more normal than the "lurching gait" that occurs if the adductors are dis-inserted.

The amputation stump must heal for a prosthesis to be worn. Adequate perfusion for healing is often assessed by transcutaneous oxygen measurement (greater than 30 mmHG), or toe pressure (more than 30-50 mmHg). The combination of serum albumin greater than three with a toe pressure greater than 30 mmHg has been demonstrated to be a reliable predictor of amputation site healing.100 Proper fit of any prosthesis is also very important especially in order to ambulate well with a below knee prosthesis. Patient with renal insufficiency or on dialysis who experience volume changes find it

difficult to have a consistent fit. If a patient has class three or four obesity, a well-fitting prosthesis may also difficult to obtain. A proper fit also allows the amputation stump to bear weight without breaking down. The human foot is well designed to shift pressure loads that are often lost with the amputation stump. The stiffness of the metaphyseal areas of the tibia or femur helps transfer pressure force from the stump. The prosthesis transfers force from the prosthetic foot to the end of the stump with the socket of the prosthesis keeping it in place without absorbing any force. The AKA or BKA creates weight bearing with "total surface bearing". After above knee amputation, the prosthesis is fit to hold the thigh in adduction, distributing the force to more of the bone surface as opposed to primarily the end. Therefore, the prosthetic socket has to fit perfectly to hold the bone in the appropriate position to distribute force. Weight or volume fluctuations disturb this. The end of the stump is best resurfaced with muscle and full thickness skin to best withstand the force of load bearing.

Limb preservation programs A successful limb preservation program requires a coordinated effort of physicians, nurses, allied health professionals, and administrators dedicated to the preservation of functional limbs. As diabetes increases worldwide, limb preservation assumes increasing clinical importance for individual patients as well as healthcare systems. Revascularization procedures and amputation constitute a significant cost burden to our healthcare system. The addition of rehabilitation needed after an amputation doubles the original cost of the amputation itself.48 As chronic ulcers are an antecedent event in 80% of non-traumatic amputations, the importance of prevention of foot ulceration cannot be forgotten. Reduction in the occurrence of chronic foot ulceration through patient education and routine surveillance of the diabetic foot would significantly impact limb loss. If ulceration does occur, prompt management by a multidisciplinary program is critical to the successful treatment of these complex patients.

Unfortunately, there continues to be geographic and demographic variation in the care delivered to patients at risk of losing a limb from diabetes. There are reported geographic variations in the delivery of care for patients in need of limb preservation as well as variations with regards to race, socioeconomic status, and insurance status.104 There is also a variety of approaches to diabetics with limb threatening ischemia: approximately 25% undergo primary amputation, 25% receive medical therapy, and only 50% undergo any attempt at revascularization. Almost half of patients undergoing major amputation do not undergo a diagnostic arteriogram despite evidence that diagnostic arteriography is an independent predictor of limb preservation.105,106 Indeed, there is evidence that amputation can be prevented by increasing access to revascularization, endovascular or via surgical bypass, and that amputation rates are lower in centers with higher volumes of revascularization procedures.107 Hopefully, limb preservation programs could standardize care for patients with diabetes and critical limb ischemia mitigating some of the factors that lead to disparity of care.

Multidisciplinary approach A multidisciplinary approach should take advantage of protocol-driven care, involving a full complement of diagnostic and therapeutic modalities involving revascularization in addition to soft tissue reconstruction and medical support.108 Preventive care and prosthetic expertise are also critical. Additionally, educational programs for patients and other physicians can be included with a research component regarding wound healing and advanced revascularization techniques. The key to the program is cooperation and communication among the participants. As “all politics is local,” different disciplines may be best positioned to assume leadership roles in different medical communities. Leadership must be based on passion for optimal patient care and outcomes as opposed

to a specific type of medical training. It is important to draw on the expertise and passion available in the entire local medical community in constructing the limb preservation team.

The Society of Vascular Surgery and the American Podiatric Medical Association have recognized these goals and prospective benefits of this multidisciplinary approach.109 Benefits to the patient include a reduction in time for vascular assessment, wound healing, and institution of treatment for infection, and the time to final correction of podiatric and orthopedic deformities. Enhanced follow up and increased surveillance of revascularization procedures contributes patient outcomes. Advantages for the physicians include the ability to efficiently manage complex patients with help from the appropriate medical specialties, an expected increase in patient referrals, the ability to obtain leadership roles both regionally and nationally, the development of an important clinical area to enhance the identity of the institution, and the infrastructure for clinical research and trials. Evidence is available that a multidisciplinary program can bestow these advantages. Dr. Vicki Driver documented a decrease in the number of amputations performed after initiation of a multidisciplinary program.42 Not only were major amputations decreased, but 70% of the amputations that were performed were at the level of the distal ankle, forefoot, or toe with avoidance of major amputation above or below the knee. This was found to be especially important for diabetic patients. Others have demonstrated a similar reduction in amputation rates with a multidisciplinary team approach.110

Staff A dedicated staff is a critical component for a successful multidisciplinary limb preservation program. The staff includes the physician team, physician extenders, nursing, administrative support, and secretarial support. An appointed Medical Director with the authority to assemble and support other team members is important. The background of the medical director can vary, but is most often

drawn from vascular surgery, podiatry, and plastic surgery. Physician extenders such as nurse practitioners or physician assistants also serve a crucial role in the program. These practitioners initiate evaluation of the patient and coordinate the complex care often required, including wound care, preoperative preparation, and prescription of medications. Wound nurses or technicians also perform much of the wound care and dressing changes as well as doing the important education required to empower the patient to participate in their own care. A dedicated program administrator should have knowledge of both clinical and business aspects of the program, and be able to coordinate facile interaction among the hospital, physicians, staff, and the local community. Medical assistants (MAs) can assist with patient flow and completing initial demographic and historic data for the electronic medical record. MAs can also help in the removal and application of dressings under direction of the wound nurse or physician. Case managers assist in work involving rehabilitation centers and insurance issues which patients often require, while a prosthetist with familiarity with the patients and direct communication with the limb team greatly enhances the patient’s functional result.

Space Identifiable outpatient space should be accessible to the patients who often have mobility problems. The outpatient space can be in proximity or connected to the hospital, as limb patients require frequent hospital services. Sufficient exam rooms are important, as patient flow is critical to financial viability and patient satisfaction. We propose six rooms for every 30 patients per clinic session as an appropriate model for room utilization in order to allow for optimal use of the time and talents of the physician and physician extender team. An identifiable hospital ward allows the nursing staff to become familiar with the medical issues associated with limb patients. Wound dressings and other medical material can be centrally-located in proximity to the admitted patients. The identifiable limb

ward in the hospital fosters the team approach and continuity of care to and from outpatient to the inpatient setting.

As mentioned previously, the noninvasive vascular laboratory is important and requires appropriate space and equipment. Vascular laboratories are used consistently in the care of the limb patient for initial diagnosis, decisions regarding need for revascularization, and follow-up care. Therefore, the vascular lab should be situated locally in the limb center in order to allow convenient and accessible testing on a regular basis. Conference space should also be available for teaching conferences to enhance the interaction between physicians and staff in terms of case review and educational lectures. Hyperbaric oxygen therapy will serve a certain segment of the threatened limb population and space, appropriate technology, and physician expertise should be available for this treatment modality. This therapy requires a facility with dedicated staff that recognizes its associated medical risks.

Outpatient endovascular procedures and minor surgery are also becoming more common and accepted by both patients and insurance reimbursement. Consideration should be given to space for an interventional room and/or minor surgery suite to offer timely and convenient care. An endovascular suite is important to perform the state-of-the-art catheter based procedures, which have become increasingly common in their performance of revascularization for limb preservation. However, the operating room, and especially a hybrid operating room remain important to treat these patients.

Role of wound care In a limb preservation program, wound care and the soft tissue reconstruction are equal in importance to revascularization procedures. The goal of wound care should be the salvage of tissues and maximize the length of a functional limb. The majority of leg ulcers can usually be managed with nonsurgical debridement in the form of dressing changes or topical wound therapy. If required, the goal of debridement is to remove nonviable, infected tissue and reach bleeding tissue or viable fat, tendon, or fascia. Delayed wound closure and the vacuum-assisted closure device (VAC), and biologic wound care adjuncts are also important, but a detailed discussion is beyond the scope of this chapter. The VAC is a negative pressure wound therapy that enhances granulation tissue ingrowth through reduction of edema and removal of proteases.111 The VAC must be used properly with relatively clean wounds, cautiously with ischemic wounds, and should not be used with wounds with known malignancy. The VAC can convert emergency wounds for which flap coverage is required into wounds that can be treated more simply. VAC therapy can be discontinued when the wound is small enough to close with simpler, less expensive dressing changes or can be closed primarily or with a skin graft.

The limb team should have the ability to perform advanced soft tissue flaps when primary wound care is ineffective. Three types of flaps are employed in the lower extremity: local random-pattern flaps, local pedicle flaps, and free tissue transfers. Local random-pattern flaps include Z-plasties, advancement flaps (e.g., V-Y), rotation flaps, and transposition flaps. These are extremely useful for closing small defects of the foot. One limitation to their use is the tautness of the skin in this area, which limits flap mobility. Local pedicle flaps are employed for coverage in both the leg and the foot, especially for closure of larger foot wounds and deeper wounds that expose bone or hardware.

These flaps are based on axial vessels, typically branches of arteries supplying the angiosomes. The use of VAC therapy and local flaps has led to a decline in the use of microsurgical free flaps in the lower extremity. However, there are certain wounds for which free flaps may still be useful, such as large defects and wounds characterized by significant exposure of bone. Free flaps can also be used for wounds with venous insufficiency. Soft tissue expertise and flap coverage can also be helpful when there are challenging perioperative complications from the revascularization procedures themselves.

Outcomes in wound care can be optimized when performed with the guidance of wound care protocols. These protocols foster uniformity of procedures and result in a limb preservation program as carried out by the medical and ancillary staff. Protocols should emphasize the importance of debridement performed to viable tissue with any cultures of exposed bony edges for infection. Infected or wet gangrene should be aggressively debrided as soon as possible with resection of all necrotic tissue to obtain the best functional result. Care should be taken to explore all tendon sheaths and fascial compartments during debridement for infected or wet gangrene. Soft tissue reconstruction should be delayed until the inflammation is gone and granulation tissue appears. There are times when primary amputation may be the correct choice to preserve the patient's life and functional status.

Role of Amputation Primary amputation may be appropriate when there is a lack of tissue for reconstruction, the patient is non-ambulatory or demented and unable to cooperate with rehabilitation. When amputation is required, there are certain principles to apply. Proper biomechanics is key to a successful amputation. In order to optimize biomechanics and obtain an ideal result, anatomy must be

appreciated and the procedure performed with technical care. Skeletal stability is also important, and the patient should not be left with pressure points or potential areas of decubitus ulceration. There are several amputations with which one should be familiar, including ray, transmetarsal, Lisfranc, Chopart's, Symes as well as above- and- below-knee amputation. The BKA must be done especially carefully to design a well-constructed posterior flap with maximal length from the tubercle of the tibia. It is also important construct a smooth anterior surface without a rough or cornered edge. Tenodesis to the tibia does help maintain function and diminish deformity postoperatively. It is also important to consider rigid postoperative dressings with early ambulation.

Marketing, education, and community outreach Marketing and community relations are essential in order to reach patients who may benefit from the program and referring physicians who may wish to take advantage of such a program. A functional electronic medical record (EMR) is essential for data collection and tracking results. The EMR requires input of accurate information and implementation of the EMR can affect staffing requirements as well as staff satisfaction. However, the EMR is necessary to assess results, maintain governmental compliance, and guide future improvements in the program. The EMR can also greatly enhance the research arm of the program and can assist marketing by demonstrating benefits related to care delivered by the program. The limb preservation program should include patient support, as there is a significant mental component to loss of limb or living with a foot ulcer. A patient support group can be important preoperatively and postoperatively in helping patients maintain function and a positive mental outlook. Education can be incorporated into the program in the form of seminars for patients and referring physicians. Education is critical to achieve the goal of limb preservation through reduction of amputation and enhancement of the patient's quality of life.

Financial considerations Financial considerations cannot be ignored when creating a viable limb preservation program. In order for such a program to be cost effective, there must be an assessment and review of direct and indirect costs with careful analysis of collections and downstream revenue. Direct costs include salaries, supplies, and space requirements. Indirect costs include maintenance, electricity, other utilities, and any loans required to finance the program. Revenue must be considered both in terms of the reimbursement generated by the immediate activities of the program as well as the incremental downstream revenue realized by the hospital and the healthcare system. The most important sources of downstream revenue are often inpatient diagnostic and therapeutic procedures. Revenue related to the limb program itself often takes a form of debridement performed in the outpatient setting and that generated from hyperbaric oxygen therapy. If this is done carefully and with organization and thought, such a program can in fact generate significant cash flow for the hospital and health care system. Financial viability has been demonstrated both in hypothetical models and real-world experience.112,113 The institution of a limb preservation program is labor-intensive and requires communication and cooperation among the interested parties. However, such a program also has great benefits to patients including preserving limbs and improving the longevity and quality of life of our patients. Limbs can be preserved and amputations avoided in the context of a viable financial entity to the hospital and health care system.

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Dr. Teresa Buescher is an Assistant Professor of Plastic Surgery at the George Washington University MFA. She attended Johns Hopkins University for her undergraduate and medical school degrees with subsequent General Surgery and Plastic Surgery residencies in the military. Duty stations included the USAISR, Walter Reed Army Medical Center, USNS Comfort, and the National Naval Medical Center in Bethesda, MD. After completion of a breast microsurgery fellowship at Mercy Medical Center in Baltimore, Md, Dr. Buescher founded the breast microsurgery program at the University of Kansas prior to moving to Washington, DC two years ago. Her interests include microsurgical reconstruction of the breast and wound closure of the extremities Ahmed Kayssi, MD, is the Limb Preservation Fellow at the INOVA Heart and Vascular Institute in Falls Church, Virginia, under the mentorship of Dr. Richard Neville. Dr. Kayssi received his medical degree from Queen's University in Kingston, Ontario, and completed both his general and vascular surgery training at the University of Toronto. During his surgical training, he also completed a Master's of Public Health in Quantitative Methods from the Harvard School of Public Health, and is currently pursuing a Doctorate of Public Health in Health Policy and Management at The Johns Hopkins University School of Public Health. His clinical and research interests are in wound care and limb preservation.

Richard F. Neville, MD, FACS is Director of Vascular Services for the INOVA healthcare system in northern Virginia, as well as Associate Director of the INOVA Heart and Vascular Institute, and, Vice-Chairman for Surgical Sub-Specialities, Department of Surgery. Prior positions include Professor of Surgery and the Ludwig Chief of the Division of Vascular Surgery at George Washington University, and, Chief of Vascular Surgery at Georgetown University. He completed medical school at the University of Maryland and a general surgery residency at Georgetown University before moving on to a fellowship at the National Institutes of Health. Dr. Neville then completed a vascular surgery fellowship under the direction of Dr. Robert Hobson. Dr. Neville is a Distinguished Fellow of the Society for Vascular Surgery, and a Fellow of the American College of Surgeons and other societies. Dr. Neville is an international lecturer and publisher of over 100 manuscripts, 200 abstracts and 150 invited lectures around the world while remaining actively involved in research and the education of students, residents, fellows, and other physicians. Michael S. Stempel, DPM is an Assistant Professor of Medicine and Surgery at the George Washington University MFA in the District of Columbia. He received his degree in podiatric medicine at the Temple University School of Podiatric Medicine, and completed residencies at the VA Medical Center, Washington, DC and at Roseland Surgical Center. Dr. Stempel is the Chief of Podiatry at George Washington University MFA. His clinical and research interests include diabetic wound healing, limb salvage as well as the treatment of foot and ankle injuries and deformities.