Diabetic Ulcers

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Diabe etic U Ulcerss In ntrod duction Bac ckground Diab betic foot ulc cers occur as s a result of various facttors. Such fa actors includ de mechanical chan nges in confformation of the bony arc chitecture off the foot, pe eripheral neu uropathy, an nd athe erosclerotic peripheral arterial diseas se, all of which occur with higher fre equency and d intensity in the diabetic d pop pulation. Non n-enzymatic glycosylatio on predispos ses ligaments s to stifffness. Neuro opathy cause es loss of pro otective sens sation and lo oss of coord dination of mus scle groups in i the foot an nd leg, both of which inc crease mech hanical stress ses during amb bulation.

Patthophysio ology Diab betic persons, like peoplle who are no ot diabetic, may m develop p atherosclerrotic disease e of large-sized and medium-size ed arteries, such s as aorttoiliac and fe emoropoplite eal athe erosclerosis.. However, significant s attherosclerotiic disease off the infrapop pliteal segments is pa articularly co ommon in th he diabetic population. Underlying U diigital artery d disease, whe en com mpounded by y an infected d ulcer in close proximity y, may resultt in complete e loss of digital colla aterals and precipitate p g gangrene. Th he reason forr the prevalence of this fform of arterial dise ease in diabe etic persons is thought to result from m a number of o metabolic c abnormalities, inclu uding high lo ow-density lipoprotein (L LDL) and verry-low-densiity lipoprotein (VLDL) lev vels, elev vated plasma a von Willebrrand factor, inhibition off prostacyclin n synthesis, elevated plas sma fibrinoge en levels, an nd increased d platelet adh hesiveness. Ove erall, people with w diabete es have a hig gher incidenc ce of atheros sclerosis, thickening of capiillary basement membranes, arteriolar hyalinosis s, and endotthelial prolife eration.

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  DR.  TARIK  TORKI [email protected]   YOUR   WAY  FOR  HEALTHY  LIFE   HTTP://TARIKTORKI.JIMDO.COM Calcification and thickening of the arterial media (Mönckeberg sclerosis) are also noted with higher frequency in the diabetic population, although whether these factors have any impact on the circulatory status is unclear. The Pathophysiology of diabetic peripheral neuropathy is multifactorial and is thought to result from vascular disease occluding the vasa nervorum; endothelial dysfunction; deficiency of myoinositol-altering myelin synthesis and diminishing sodium-potassium adenine triphosphatase (ATPase) activity; chronic hyperosmolarity, causing edema of nerve trunks; and effects of increased sorbitol and fructose1 The result of loss of sensation in the foot is repetitive stress; unnoticed injuries and fractures; structural foot deformity, such as hammertoes, bunions, metatarsal deformities, or Charcot foot (see Image 3); further stress; and eventual tissue breakdown. Unnoticed excessive heat or cold, pressure from a poorly fitting shoe, or damage from a blunt or sharp object inadvertently left in the shoe may cause blistering and ulceration. These factors, combined with poor arterial inflow, confer a high risk of limb loss on the patient with diabetes.

Frequency United States

According to The National Institute of Diabetes and Digestive and Kidney Diseases, "an estimated 16 million Americans are known to have diabetes, and millions more are considered to be at risk for developing the disease." Diabetic foot lesions are responsible for more hospitalizations than any other complication of diabetes. Among patients with diabetes, 15% develop a foot ulcer, and 12-24% of individuals with a foot ulcer require amputation. Indeed, diabetes is the leading cause of nontraumatic lower extremity amputations in the United States. "In fact, every year approximately 5% of diabetics develop foot ulcers and 1% require amputation." Diabetic peripheral neuropathy, present in 60% of diabetic persons and 80% of diabetic persons with foot ulcers, confers the greatest risk of foot ulceration; microvascular disease and suboptimal glycemic control contribute. Even after successful management resulting in ulcer healing, the recurrence rate in that patient population is 66% and the amputation rate rises to 12%. Half of all nontraumatic amputations are a result of diabetic foot complications, and the 5-year risk of needing a contralateral amputation is 50%.2

Mortality/Morbidity • •

Limb loss: Unfortunately, limb loss is a significant risk in patients with diabetic foot ulcers, particularly if treatment has been delayed.3 Charcot foot: Sensory neuropathy involving the feet may lead to unrecognized episodes of trauma due to ill-fitting shoes. Motor neuropathy, causing intrinsic muscle weakness and splaying of the foot on weight bearing, compounds this trauma. The result is a convex foot with a rocker-bottom appearance. Multiple fractures are unnoticed until bone and joint deformities become marked. This is termed a Charcot foot (neuropathic osteoarthropathy) and most commonly is

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observed in diabetes mellitus, affecting about 2% of diabetic persons. If neglected, ulceration may occur at pressure points, particularly the medial aspect of the navicular bone and the inferior aspect of the cuboid bone. Sinus tracts progress from the ulcerations into the deeper planes of the foot and into the bone. Charcot change can also affect the ankle, causing displacement of the ankle mortise and ulceration, which can lead to the need for amputation. Mortality: Mortality in people with diabetes and foot ulcers is often the result of associated large vessel arteriosclerotic disease involving the coronary or renal arteries.

Race The issue of diabetic foot disease is of particular concern in the Latino communities of the Eastern United States, African Americans4 , and in Native Americans, who tend to have the highest prevalence of diabetes in the world.

Age Diabetes occurs in 3-6% of Americans. Of these, 10% have type 1 diabetes and are usually diagnosed when they are younger than 40 years. Among Medicare-aged adults, the prevalence of diabetes is about 10% (of these, 90% have type 2 diabetes). Diabetic neuropathy tends to occur about 10 years after the onset of diabetes, and, therefore, diabetic foot deformity and ulceration occur sometime thereafter.

Clinical History •

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Peripheral neuropathy: The symptoms of peripheral neuropathy include the following: o Hypoesthesia o Hyperesthesia o Paresthesia o Dysesthesia o Radicular pain o Anhydrosis Peripheral arterial insufficiency o Most people harboring atherosclerotic disease of the lower extremities are asymptomatic; others develop ischemic symptoms. Some patients attribute ambulatory difficulties to old age and are unaware of the existence of a potentially correctible problem. o Patients who are symptomatic may present with intermittent claudication, ischemic pain at rest, nonhealing ulceration of the foot, or frank ischemia of the foot. o Cramping or fatigue of major muscle groups in one or both lower extremities that is reproducible upon walking a specific distance suggests intermittent claudication. This symptom increases with ambulation until walking is no longer possible, and it is relieved by resting for several minutes. The onset of

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claudication may occur sooner with more rapid walking or walking uphill or up stairs. The claudication of infrainguinal occlusive disease typically involves the calf muscles, while symptoms that occur in the buttocks or thighs suggest aortoiliac occlusive disease. Discomfort, cramping, or weakness in the calves or feet is particularly common in the diabetic population because they tend to have tibioperoneal atherosclerotic occlusions. Calf muscle atrophy may also occur. Rest pain is less common in the diabetic population. In some cases, a fissure, ulcer, or other break in the integrity of the skin envelope is the first sign that loss of perfusion has occurred. When a diabetic patient presents with gangrene it is often the result of infection.

Physical Physical examination of the extremity having a diabetic ulcer can be divided into 3 broad categories: (1) examination of the ulcer and general condition of the extremity, (2) assessment of the possibility of vascular insufficiency5 and (3) assessment for the possibility of peripheral neuropathy. Remember that diabetes is a systemic disease. Hence, a comprehensive physical examination of the entire patient is also vital. Extremity examination

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Diabetic ulcers tend to occur in the following areas: • Areas most subjected to weight bearing, such as the heel, plantar metatarsal head areas, the tips of the most prominent toes (usually the first or second), and the tips of hammer toes (Ulcers also occur over the malleoli because these areas commonly are subjected to trauma.) • Areas most subjected to stress, such as the dorsal portion of hammer toes Other physical findings include the following: o Hypertrophic calluses o Brittle nails o Hammer toes o Fissures

Peripheral arterial insufficiency

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Physical examination discloses absent or diminished peripheral pulses below a certain level. Although diminished common femoral artery pulsation is characteristic of aortoiliac disease, infrainguinal disease alone is characterized by normal femoral pulses at the level of the inguinal ligament and diminished or absent pulses distally. Specifically, loss of the femoral pulse just below the inguinal ligament occurs with a proximal superficial femoral artery occlusion. Loss of the popliteal artery pulse suggests superficial femoral artery occlusion, typically in the adductor canal. Loss of pedal pulses is characteristic of disease of the distal popliteal artery or its trifurcation. However, be aware that absence of the dorsalis pedis pulse may be a normal anatomic variant that is noted in about 10% of the pediatric population. On the other hand, the

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posterior tibial pulse is present in 99.8% of persons aged 0-19 years. Hence, absence of both pedal pulses is a more specific indicator of peripheral arterial disease. Other findings suggestive of atherosclerotic disease include a bruit heard overlying the iliac or femoral arteries, skin atrophy, loss of pedal hair growth, cyanosis of the toes, ulceration or ischemic necrosis, and pallor of the involved foot followed by dependent rubor after 1-2 minutes of elevation above heart level. For further details, see Infrainguinal Arterial Occlusive Disease.

Peripheral neuropathy

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Signs of peripheral neuropathy include loss of vibratory and position sense, loss of deep tendon reflexes (especially loss of the ankle jerk), trophic ulceration, foot drop, muscle atrophy, and excessive callous formation, especially overlying pressure points such as the heel. The nylon monofilament test helps diagnose the presence of sensory neuropathy6 A 10-gauge monofilament nylon is pressed against each specific site of the foot just enough to bend the wire. If the patient does not feel the wire at 4 or more of these 10 sites, the test is positive for neuropathy.

Causes The etiologies of diabetic ulceration include neuropathy,7 arterial disease,8 pressure,9 and foot deformity.10

Differential Diagnoses Atherosclerosis Chronic Venous Insufficiency Diabetic Foot Infections

Other Problems to Be Considered The classic diabetic trophic ulcer must be distinguished from various other problems that tend to occur in persons with diabetes, such as diabetic dermopathy, bullosis diabeticorum, eruptive xanthoma, necrobiosis lipoidica, and granuloma annulare. The leg pain of peripheral arterial disease must be distinguished from other causes of leg pain, such as arthritis, muscle pain, radicular pain, spinal cord compression, thrombophlebitis, anemia, and myxedema. Diabetic neuropathy should be distinguished from other forms of neuropathy, including vasculitic neuropathies, metabolic neuropathies, autonomic neuropathy, radiculopathy, and many others.

Workup Laboratory Studies

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CBC count: Leukocytosis may signal plantar abscess or other associated infection. Wound healing is impaired by anemia. In the face of underlying arterial insufficiency, anemia may precipitate rest pain.11 Metabolic profile and glycohemoglobin: Assessment of serum glucose, glycohemoglobin, and creatinine levels helps to determine the adequacy of acute and chronic glycemic control and the status of renal function. Noninvasive vascular laboratory study: Pulse-volume recording (PVR), or plethysmography, uses pneumatic cuffs encircling the thighs, calves, ankles, feet, and, occasionally, toes to sense segmental volume changes with each pulse beat. The resulting tracings provide useful information about the hemodynamic effects of the arterial disease at each level. In severe disease, tracings at the transmetatarsal level may become nearly flat. In mild disease, particularly involving the aortoiliac segment, PVR tracings may appear normal at rest and become abnormal only after the patient walks until symptoms occur. PVR is noninvasive and rapid and, therefore, may be repeated frequently to help assess the overall hemodynamic response to medical or surgical treatment. Ordinarily, if pedal pulses are satisfactory, arterial evaluation PVR provides no useful information. The ankle-brachial blood pressure index is potentially unreliable because of arterial calcification.

Imaging Studies •

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Duplex scanning can provide images of arterial segments that help localize the extent of disease, and simultaneous Doppler measurement of flow velocity can help estimate the degree of stenosis. Duplex scanning is quite useful in visualizing aneurysms, particularly of the aorta or popliteal segments. Use of this technique probably is best left to the discretion of the vascular specialist. Plain radiograph studies of the diabetic foot may demonstrate demineralization and Charcot joint and occasionally may suggest the presence of osteomyelitis. Note that plain radiograph studies have no role in the evaluation of arterial disease. This is because arterial calcification observed on plain radiographs is not a specific indicator of severe atherosclerotic disease. Calcification of the arterial media is not diagnostic of atherosclerosis, and even calcification of the arterial intima, which is diagnostic of atherosclerotic disease, does not necessarily imply hemodynamically significant stenosis. CT scan and MRI: Although an experienced clinician usually can diagnose a plantar abscess by physical examination alone, CT scan or MRI is indicated if a plantar abscess is suspected but not clear on physical examination. Bone scans are of questionable use because of a sizable percentage of falsepositive and false-negative results. A recent study suggests 99mTc-labeled ciprofloxacin is a somewhat useful marker for osteomyelitis12 Conventional Angiography: If vascular or endovascular surgical treatment is contemplated, angiography is needed to delineate the extent and significance of atherosclerotic disease. Major risks associated with conventional contrast-injection angiography are related to the puncture and to the use of contrast agents. • Technique: Typically, a catheter is inserted retrograde via a femoral puncture, and contrast is power-injected into the infrarenal aorta. Films are

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taken as the contrast is followed down to both feet. In certain cases, as with aortic occlusion, a femoral approach to the aorta may not be possible. In this case, the radiologist may use an alternate entry such as via an axillary artery or even directly into the infrarenal aorta via a translumbar approach. • Puncture-related complications: The arterial catheter is usually passed through a 5F sheath that is 1.6 mm in diameter. This is a sizable hole in the femoral artery, which may be only 6-10 mm in diameter. After the catheter is removed, gentle pressure must be applied to the puncture site for approximately 30 minutes, and the radiologist must balance the need for hemostasis against the possibility of arterial occlusion. Risks include hemorrhage, pseudoaneurysm formation, and clotting or dislodgement of an intimal flap, which may acutely occlude the artery at or near the entry site. Currently, newer methods of percutaneous closure of the puncture sites have significantly reduced the site complication rates. • Contrast-related risks: Angiographic contrast material is nephrotoxic. The risk of precipitating acute renal failure is highest in patients with underlying renal insufficiency and those with diabetes. Patients with both of these risk factors have a 30% rate of acute renal failure following contrast angiography. Hence, an acceptable serum creatinine level must be confirmed prior to elective angiography. Avoid contrast angiography (if possible) for patients with any significant degree of renal impairment. If contrast angiography is absolutely required despite renal impairment, use a minimal volume of contrast material. In addition, providing adequate hydration prior to, during, and after the procedure is essential. Oral administration of the antioxidant acetylcysteine (Mucomyst) the night prior to and then just before angiography may be protective of renal function for patients at risk of contrast-induced nephropathy.13 • Metformin warning: To prevent the possibility of fatal lactic acidosis, patients with diabetes who are taking metformin (Glucophage) must not take this medication immediately following contrast angiography. Patients may resume taking the medication when normal renal function is confirmed 1-2 days after contrast exposure. Alternatives to conventional angiography • Magnetic resonance angiography: Magnetic resonance angiography (MRA) is an alternative both for patients for patients who are allergic to iodinated contrast material. MRA is not innocuous. Gadolinium chelates, the contrast agents used in MRA, have been linked recently to 3 potentially serious side effects in patients with renal insufficiency: acute renal injury, pseudohypocalcemia, and nephrogenic systemic fibrosis (see this article on Medscape). MRA is contraindicated in patients with implanted hardware such as a hip prostheses or pacemakers. The resolution may be inadequate for the vascular surgeon in planning reconstructive procedures, particularly in the smaller infrapopliteal arteries, although MRA technology and contrast agents continue to improve.14 • Multidetector computed tomographic angiography (MDCT): MDCT avoids arterial puncture. By using precisely timed intravenous contrast injection, multidetector (16 or 64 channel) CT scanners can generate angiographic

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images of excellent resolution and at a relatively high acquisition speed. MDCT carries the contrast-related risks described above.15 Carbon dioxide angiography: Carbon dioxide angiography is an alternative for patients with renal insufficiency; however, it is not widely available and requires some iodinated contrast material in addition to the carbon dioxide gas in order to provide useful images. Plain radiography: Plain radiographs are not routinely obtained in the workup of peripheral arterial occlusive disease. This is because arterial calcification seen on plain radiographs is not a specific indicator of severe atherosclerotic disease. Calcification of the arterial media is not diagnostic of atherosclerosis, and even calcification of the arterial intima, which is diagnostic of atherosclerotic disease, does not necessarily imply hemodynamically significant stenosis.

Other Tests •

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A hand-held Doppler scanner may be used to assess arterial signals, to localize arteries to facilitate palpation of pulses, or to determine the loss of Doppler signal as a proximal blood pressure cuff is inflated. The latter pressure divided by the upper extremity systolic pressure is called the ankle-brachial index (ABI) and is an indication of severity of arterial compromise. Normal ABI averages 1.0. An ABI less than 0.9 suggests atherosclerotic disease, with a sensitivity of approximately 95%. In general, an ABI below 0.3 suggests a poor chance for healing of distal ischemic ulcerations. Unfortunately, ABI often is falsely elevated if the underlying arteries are heavily calcified, a finding common in diabetic persons. Transcutaneous tissue oxygen studies are reserved for borderline situations in which the advisability of arterial bypass surgery may be unclear. Laser Doppler studies also have been used but may not be reliable.

Staging Stage diabetic foot wounds based on the depth of soft tissue and osseous involvement.16,17,18 Any ulcer that seems to track into or is deep to the subcutaneous tissues should be probed gently, and, if bone is encountered, osteomyelitis is likely.

Treatment Medical Care •

Treatment of diabetic foot ulcers requires management of to a number of systemic and local factors19,20,21,22 o Precise diabetic control is, of course, vital, not only in achieving resolution of the current wound, but also in minimizing the risk of recurrence. o Management of contributing systemic factors, such as hypertension, hyperlipidemia, atherosclerotic heart disease, obesity, or renal insufficiency, is crucial23,24

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  DR.  TARIK  TORKI [email protected]   YOUR   WAY  FOR  HEALTHY  LIFE   HTTP://TARIKTORKI.JIMDO.COM Management of arterial insufficiency, treatment of infection with appropriate antibiotics, offloading the area of the ulcer, and wound care are also essential. o In the presence of an intractable wound and associated noncorrectible ischemic arterial disease, hyperbaric oxygen therapy may be beneficial (in selected cases).9 The management of diabetic foot ulcers requires offloading the wound by using appropriate therapeutic footwear25,9 daily saline or similar dressings to provide a moist wound environment,26 debridement when necessary, antibiotic therapy if osteomyelitis or cellulitis is present13,14 optimal control of blood glucose, and evaluation and correction of peripheral arterial insufficiency. Wound coverage by cultured human cells15,27 or heterogeneic dressings/grafts, application of recombinant growth factors28,29,30,31 and hyperbaric oxygen treatments also may be beneficial at times. Intractable, infected, cavity wounds sometimes improve with hydrotherapy using saline pulse lavage under pressure (PulsEvac). Clean but nonhealing deep cavity wounds may respond to repeated treatments by application of negative pressure under an occlusive wound dressing (vacuumassisted closure [VAC])32 Hyperbaric oxygen therapy is used rarely33 Charcot foot is treated initially with immobilization using special shoes or braces but eventually may require podiatric surgery such as ostectomy and arthrodesis. If neglected, ulceration may occur at pressure points, particularly the medial aspect of the navicular bone and the inferior aspect of the cuboid bone.

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Characteristics and Uses of Wound Dressing Materials Category Alginate

Hydrofiber

Examples

Description

Applications

AlgiSite Comfeel Curasorb Kaltogel Kaltostat Sorbsan Tegagel

This seaweed extract contains guluronic and mannuronic acids that provide tensile strength and calcium and sodium alginates, which confer an absorptive capacity. Some of these can leave fibers in the wound if they are not thoroughly irrigated. These are secured with secondary coverage.

These are highly absorbent and useful for wounds having copious exudate.

Aquacel Aquacel-Ag Versiva

An absorptive textile fiber pad, also available as a ribbon for packing of deep wounds. This material is covered with a secondary dressing. The hydrofiber combines with wound exudate to produce a hydrophilic gel. Aquacel-Ag contains 1.2% ionic silver that has strong antimicrobial properties against many organisms, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus.

These are absorbent dressings used for exudative wounds.

Alginate rope is particularly useful to pack exudative wound cavities or sinus tracts.

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Hypergel Various products provide some degree of chemical or enzymatic debridement. (hypertonic saline gel) Santyl (collagenase) Accuzyme (papain urea)

These are useful for necrotic wounds as an adjunct to surgical debridement.

Foam

LYOfoam Spyrosorb Allevyn

Polyurethane foam has some absorptive capacity.

These are useful for cleaning granulating wounds having minimal exudate.

These are made of microgranular suspension of natural or synthetic polymers, such as gelatin or pectin, in an adhesive matrix. The granules change from a semihydrated state to a gel as the wound exudate is absorbed.

They are useful for dry necrotic wounds, wounds having minimal exudate, and clean granulating wounds.

Hydrocolloid Aquacel

CombiDERM Comfeel Duoderm CGF Extra Thin Granuflex Tegasorb

Hydrogel

Aquasorb Duoderm IntraSite Gel Granugel Normlgel Nu-Gel Purilon Gel (KY jelly)

These are water-based or glycerin-based semipermeable hydrophilic polymers; cooling properties may decrease wound pain. These gels can lose or absorb water depending upon the state of hydration of the wound. They are secured with secondary covering.

These are useful for dry, sloughy, necrotic wounds (eschar).

Lowadherence dressing

Mepore Skintact Release

These are various materials designed to remove easily without damaging underlying skin.

These are useful for acute minor wounds, such as skin tears, or as a final dressing for chronic wounds that have nearly healed.

These are highly conformable acrylic adhesive film having no absorptive capacity and little hydrating ability, and they may be vapor permeable or perforated.

These are useful for clean dry wounds having minimal exudate, and they also are used to secure an underlying absorptive material. They are used for protection of high-friction areas and areas that are difficult to bandage such as heels (also used to secure IV catheters).

Transparent OpSite Skintact film

Release Tegaderm Bioclusive

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Surgical Care All patients harboring diabetic foot ulcers should be evaluated by a qualified vascular surgeon and/or podiatric surgeon who will consider debridement, revisional surgery on bony architecture, vascular reconstruction, and options for soft tissue coverage. Debridement: Surgical management is indicated for debridement of nonviable and infected tissue from the ulceration, removal of excess callous, curettage of underlying osteomyelitic bone, skin grafting, and revascularization. The wound usually requires an initial surgical debridement and probing to determine the depth and involvement of bone or joint structures. Visible or palpable bone implies an 85% chance of osteomyelitis. Revisional surgery: Revisional surgery for bony architecture may be required to remove pressure points34 Such intervention includes resection of metatarsal heads or ostectomy35 Vascular surgery: In general, the indications for vascular surgery in the presence of a reconstructible arterial lesion include intractable pain at rest or at night, intractable foot ulcers, and impending or existing gangrene36,8,37 Intermittent claudication alone is only infrequently disabling and intractable enough to warrant bypass surgery. Options for soft tissue coverage of the clean but nonhealing wound: Once a wound has reached a steady clean state, a decision has to be made about allowing healing by natural processes or expediting healing by a surgical procedure. Clinical experience and observation of the healing progress in each case dictate the appropriate management. Surgical options include skin grafting, application of bioengineered skin substitutes38 The autologous skin graft is the criterion standard for viable coverage of the partial thickness wound. The graft can be harvested under local anesthesia as an outpatient procedure. Meshing the graft allows wider coverage and promotes drainage of serum and blood. A cadaveric skin allograft is a useful covering for relatively deep wounds following surgical excision when the wound bed does not appear appropriate for application of an autologous skin graft. The allograft is, of course, only a temporary solution. Tissue-cultured skin substitutes

™ Dermagraft (Smith & Nephew) is a cryopreserved human fibroblast– derived dermal substitute produced by seeding neonatal foreskin fibroblasts onto a bioabsorbable polyglactin mesh scaffold. Dermagraft is useful for managing full-thickness chronic diabetic foot ulcers. It is not appropriate for infected ulcers, those that involve bone or tendon, or those that have sinus tracts. A multicenter study of 314 patients demonstrated significantly better 12-week healing rates with Dermagraft (30%) versus controls (17%). Allergic reactions to its bovine protein component have been reported. ™ Apligraf (Organogenesis) is a living, bilayered human skin substitute39,27 It is not appropriate for infected ulcers, those that

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  DR.  TARIK  TORKI [email protected]   YOUR   WAY  FOR  HEALTHY  LIFE   HTTP://TARIKTORKI.JIMDO.COM involve tendon or bone, or those that have sinus tracts. Allergic reactions to the agarose shipping medium or its bovine collagen component have been reported. ™ The use of bioengineered skin substitutes has been questioned because the mechanism of action is not clear, the efficacy is questionable, and the cost is high.

™ Xenograft: Oasis (Healthpoint, Ltd) is a xenogeneic, acellular collagen matrix derived from porcine small intestinal submucosa in a way that allows an extracellular matrix and natural growth factors to remain intact. This provides a scaffold for inducing wound healing. Do not use this for patients with allergies to porcine materials. Surgical wound closure: Delayed primary closure of a chronic wound requires well-vascularized clean tissues and tension-free apposition; it usually requires undermining and mobilization of adjacent tissue planes by creation of skin flaps or myocutaneous flaps.40

Consultations Any of the following evaluations may prove productive:

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Endocrinologist Cardiologist Nephrologist Infectious diseases specialist Vascular surgeon Podiatrist Orthopedic specialist Plastic surgeon Wound care specialist Nutritionist

Diet The recommended diet is diabetic and low in saturated fat.

Activity Offloading of the ulcerated area is imperative. This may require bed rest acutely. Custom footwear or custom clamshell orthosis (for severe deformities) or total contact casting (a fiberglass shell with a walking bar on the bottom) are required for patients who are ambulatory.

Medication The basic principle of topical wound management is to provide a moist, but not wet, wound bed.26,41 After debridement, apply a moist sodium chloride dressing or isotonic sodium chloride gel (eg, Normlgel, IntraSite gel) or a hydroactive paste (eg, Duoderm). Optimal wound coverage requires wet-to-damp dressings, which support autolytic debridement,

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  DR.  TARIK  TORKI [email protected]   YOUR   WAY  FOR  HEALTHY  LIFE   HTTP://TARIKTORKI.JIMDO.COM absorb exudate, and protect surrounding healthy skin. A polyvinyl film dressing (eg, OpSite, Tegaderm) that is semipermeable to oxygen and moisture and impermeable to bacteria is a good choice for wounds that are neither very dry nor highly exudative. Wound coverage recommendations for some other wound conditions are as follows (see Table):

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Dry wounds: Hydrocolloid dressings, such as DuoDERM or IntraSite Hydrocolloid, are impermeable to oxygen, moisture, and bacteria; maintain a moist environment; and support autolytic debridement. They are a good choice for relatively desiccated wounds. Exudative wounds: Absorptive dressings, such as calcium alginates (eg, Kaltostat, Curasorb), are highly absorptive and are appropriate for exudative wounds. Alginates are available in a rope form, which is useful for packing deep wounds. Very exudative wounds: Impregnated gauze dressings (eg, Mesalt) or hydrofiber dressings (eg, Aquacel, Aquacel-Ag) are useful for extremely exudative wounds. In these cases, twice-daily dressing changes may be needed. Infected wounds: For infected superficial wounds, use Silvadene (silver sulfadiazine) if the patient is not allergic to sulfa drugs. If a sulfa allergy exists, either bacitracin-zinc or Neosporin ointment is a good alternative. Where heavy bacterial contamination of deeper wounds exists, irrigation using one-fourth strength Dakin solution and 0.25% acetic acid may be useful for a brief period of time. A hydrofiber-silver dressing (Aquacel-Ag) can help control wounds that are both exudative and potentially colonized. Wounds covered by dry eschar: In this case, simply protecting the wound until the eschar dries and separates may be the best management. Occasionally, painting the eschar with povidone iodine (Betadine) is beneficial to maintain sterility while eschar separation occurs. An uninfected dry heel ulcer in a well-perfused foot is perhaps best managed in this fashion. Areas that are difficult to bandage: Bandaging a challenging anatomical area, such as around a heel ulcer, requires a highly conformable dressing, such as an extra thin hydrocolloid. Securing a dressing in a highly moist challenging site, such as around a sacrococcygeal ulcer, requires a conformable and highly adherent dressing, such as a wafer hydrocolloid. Fragile periwound skin: Hydrogel sheets and nonadhesive forms are useful for securing a wound dressing when the surrounding skin is fragile.

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

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Platelet-derived growth factors (PDGF): Topically applied PDGF has a modestly beneficial effect in promoting wound healing. Becaplermin gel 0.01% (Regranex), a recombinant human PDGF that is produced through genetic engineering is approved by the Food and Drug Administration (FDA) to promote healing of diabetic foot ulcers.29 Regranex is meant for a healthy, granulating wound, not one with a necrotic wound base. Regranex contraindicated with known skin cancers at the site of application. Enzymatic debridement: Collagen comprises a significant fraction of the necrotic soft tissues in chronic wounds. The enzyme collagenase, derived from fermentation

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of Clostridium histolyticum, helps remove nonviable tissue from the surface of wounds. However, it is not a substitute for an initial surgical excision of a grossly necrotic wound. Miscellaneous topical agents: Various other topical agents that have been used for wound management include sugar, antacids, and vitamin A and D ointment.

Topical agents to avoid: Avoid cytotoxic agents, such as hydrogen peroxide, povidone iodine, acetic acid, and Dakin solution (sodium hypochlorite), except as noted above under infected wounds.

Hemorrheologic Agents Many medications may have a role in the treatment of diabetes, the complications of diabetes, and the etiologies of diabetic ulcer. For example, hemorheologic agents and antiplatelet agents are sometimes used in the management of underlying atherosclerotic disease. Pentoxifylline (Trental) improves intermittent claudication in approximately 60% of patients after 3 months. Cilostazol (Pletal) is an alternative hemorheologic agent for patients who cannot tolerate pentoxifylline42 . Cilostazol is contraindicated in patients with congestive heart failure. The product's black box warning reads as follows: Cilostazol and several of its metabolites are inhibitors of phosphodiesterase III. Several drugs with this pharmacologic effect have caused decreased survival compared to placebo in patients with class III-IV congestive heart failure. Pletal is contraindicated in patients with congestive heart failure of any severity. However, there is no conclusive evidence of any direct beneficial effect of either pentoxifylline or cilostazol on the healing of diabetic foot ulcers.

Pentoxifylline (Trental)

Indicated to treat intermittent claudication. May alter rheology of red blood cells, which in turn reduces blood viscosity. From 2-8 wk of therapy may be required before symptomatic improvement occurs, and only about 60% of patients respond to this drug.

• • • •

Dosing Interactions Contraindications Precautions

Adult

400 mg PO tid with meals; if digestive or CNS adverse effects develop, decrease dose to 400 mg PO bid or discontinue

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Not established

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DosingInteractionsContraindicationsPrecautionsDosingInteractionsContraindicationsPrecautionsDosingInteraction sContraindicationsPrecautions

Cilostazol (Pletal)

Indicated for the reduction of symptoms of intermittent claudication, as indicated by an increased walking distance. Affects vascular beds and cardiovascular function. Produces nonhomogenous dilation of vascular beds, with greater dilation in femoral beds than in vertebral, carotid, or superior mesenteric arteries. Renal arteries were not responsive to its effects. Mechanism involves inhibition of PDE, especially PDE III, and reversible inhibition of platelet aggregation. Patients may respond as early as 2-4 wk after initiation of therapy, but treatment for as many as 12 wk may be needed before a beneficial effect is experienced.

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Dosing Interactions Contraindications Precautions

Adult

100 mg PO bid taken at least 0.5 h before or 2 h after breakfast and dinner; consider 50 mg bid if coadministering with inhibitors of CYP3A4, such as ketoconazole, itraconazole, erythromycin, and diltiazem, or with inhibitors of CYP2C19 such as omeprazole Pediatric

Not established

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DosingInteractionsContraindicationsPrecautionsDosingInteractionsContraindicationsPrecautionsDosingInteraction sContraindicationsPrecautions

Antiplatelet agents Antiplatelet therapy with aspirin or clopidogrel (Plavix) may be warranted in some cases for the prevention of the complications of atherosclerosis, although neither has a direct benefit in healing diabetic foot ulcers. Antiplatelet agents inhibit platelet function by blocking cyclooxygenase and subsequent platelet aggregation.

Clopidogrel (Plavix)

Selectively inhibits ADP binding to platelet receptor and subsequent ADP-mediated activation of glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Indicated as antiplatelet therapy in some patients with atherosclerotic disease.

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Dosing Interactions Contraindications Precautions

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75 mg PO qd Pediatric

Not established

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DosingInteractionsContraindicationsPrecautionsDosingInteractionsContraindicationsPrecautionsDosingInteraction sContraindicationsPrecautions

Aspirin (Bayer, Anacin, Empirin)

Inhibits prostaglandin synthesis, preventing formation of platelet-aggregating thromboxane A2. May be used in low dose to inhibit platelet aggregation and improve complications of venous stases and thrombosis. The recommended dose varies with indication, and, often, the literature is unclear on the optimal dosing.

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Dosing Interactions Contraindications Precautions

Adult

75-325 mg PO qd Pediatric

Not established

Follow-up Further Inpatient Care Hospital admission is indicated for acutely infected ulcers, infected gangrene, penetration of digital infections into the forefoot, septic involvement deep to the plantar fascia, and uncontrolled diabetes.

Further Outpatient Care •

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For the most part, diabetic ulcers are managed in the outpatient setting, with brief hospital stays often occurring for initial evaluation and debridement, subsequent vascular procedures, and, possibly, flap or skin graft wound management. Hyperbaric oxygen therapy may be beneficial in certain cases of intractable foot ulcers accompanied by uncorrectable arterial insufficiency.43

Inpatient & Outpatient Medications • • • •

Antibiotics Hemorheologic agents Antiplatelet agents Hypoglycemic medications

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ACE inhibitors

Deterrence/Prevention •

•

The risk of ulceration and limb amputation in people with diabetes can be improved by routine preventive podiatric care, appropriate shoes, and patient education.44 Diabetic clinics should screen all patients for altered sensation and peripheral vascular disease.31 Of diabetic foot ulcers, 85% are estimated to be preventable with appropriate preventive medicine. o Daily foot inspection o Gentle soap and water cleansing o Application of skin moisturizer o Inspection of the shoes to ensure good support and fit: Medicare covers custom shoes with appropriate physician documentation confirming that the patient is at risk for ulceration. o Minor wounds require prompt medical evaluation and treatment. o Prophylactic podiatric surgery to correct high-risk foot deformities may be indicated. o Avoid hot soaks, heating pads, and irritating topical agents. Glycemic control o The Diabetes Control and Complications Trial performed by The Diabetes Control and Complications Trial Research Group studied the effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus (1993).45 This trial found that uncontrolled hyperglycemia correlates with the onset of diabetic microvascular complications and that good glycemic control can reduce or even prevent the complications of diabetes, including nephropathy, neuropathy, and retinopathy. o Cigarette smoking should be stopped, and hypertension and hyperlipidemia should be controlled.

Prognosis •

•

Among people with diabetes, 1 in 20 will develop a foot ulcer and 1 in 100 will require amputation annually. Hence, diabetes is the predominant etiology for nontraumatic lower extremity amputations in the United States, accounting for half of all nontraumatic leg amputations. Contralateral amputation will be required in 50% of these patients during the subsequent 5-year interval. Peripheral neuropathy—which occurs in 60% of people with diabetes—confers the greatest risk of foot ulceration; microvascular arterial disease and suboptimal glycemic control also contribute. In diabetic people with neuropathy,46 even if successful management results in healing of the foot ulcer, the recurrence rate is 66% and the amputation rate rises to 12%.

Patient Education

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The risk k of foot ulce eration and liimb amputattion in peoplle with diabe etes is lessen ned by patie ent education n stressing the t importan nce of routine e preventive e podiatric ca are, approprriate shoes, avoidance a off cigarette sm moking, con ntrol of hyperlipidemia, and a adequatte glycemic control. c For exce ellent patient education resources, visit v eMedicine's Diabete es Center. Also, see eMe edicine's patient educatio on article Dia abetic Foot Care. C

Mis scellaneo ous Med dicolegal Pitfalls Physicians of diiabetic patients with ulce ers must dec cide between n the sometimes conflictting options of (1) pe erforming inv vasive proce edures (eg, angiography a y, bypass surrgery) for lim mb salv vage and (2) avoiding the e risks of unn necessarily aggressive managemen m t in these patie ents, who may have sign nificant card diac risk. In general, g the greatest g lega al risks are asso ociated with delay in diagnosis of isc chemia asso ociated with diabetic ulce eration, failu ure to ag ggressively débride and d treat infectiion, and failu ure to treat th he wound ca arefully. If a patie ent presents s with a new diabetic foo ot ulcer, he or o she should d receive carre from phys sicians, surg geons, podia atrists, and pedorthotists p s who have an a active interest in this com mplex problem m.

Mu ultimedia a Media file 1: Dia abetic ulcer of the medial asp pect of left fiirst toe befo ore and after approprriate wound care.

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Media fille 2: Diabetic ulcer of le eft fourth toe e as ssociated with w mild celllulitis.

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