Pain in Diabetic Foot Ulcers

Managing the Cause Local wound care for a person with a diabetic foot ulcer should occur only after assessment of the patient as a whole (see Figure 1). The patient's general health should include a review of symptoms, especially the major diabetic complications from the head down: stroke, retinopathy, heart, kidneys, hypertension, peripheral vascular disease, and neuropathy. Knowledge of co-existing conditions and medicines taken also may be important in determining the patient's ability to heal. Diabetic control has an impact on wound healing1 and can be accurately assessed with a blood test for Hgb AIC (ideal control under .084 or 8.4%) that approximates the average blood sugar over the past 90 days or the lifespan of the red blood cell containing the hemoglobin. "Pain is the gift no one wants."2 This sentiment was offered by Dr. Paul Brand, an eminent physician and former head of the National Hansen's Disease Center. To be certain, the etiology of the diabetic foot wound and the majority of foot pathology centers on the absence of pain or loss of protective sensation (LOPS). People with diabetes and neuropathy, through a combination of high plantar pressure and repetitive stress (daily activity), may wear a hole in their foot just as one would wear a hole in a stocking.3,4 Teaching patients with diabetic neuropathy and their respective healthcare providers to respond to the absence of pain is paramount to both treatment and prevention. This does not, however, discount the importance of responding to pain when it is present. In fact, the presence of pain in the neuropathic (high-risk) diabetic foot is not normal and should raise significant concerns. Ulcers related to diabetes are often caused or impacted by several health-related issues, including vascular disease, infection, Charcot arthropathy, and painful neuropathy. Critical peripheral ischemia. Peripheral ischemia, while often defined by values on various noninvasive examinations, is probably best described as the body's demand for oxygen exceeding its supply. When the body cannot meet the demand, pain associated with ischemia is frequently encountered upon exertional activities such as walking (intermittent claudication). In its most extreme cases, ischemia can cause pain at rest. A patient with this condition requires a consultation with a vascular surgeon for possible medical or surgical intervention to improve flow.5-7 An assessment of arterial circulation starts with the inspection of the extremity. An ischemic limb demonstrates dependent rubor and is blanched on elevation of the leg. An absence of hair distally should be noted, with thickened or possibly absent nails. Palpation demonstrates a cool distal extremity and absent pulse. Pulses are generally palpable in the foot at around 80 mm Hg; however, the ischemic limb pulses may not be palpable and 50 mm Hg is necessary for healing a wound in a person with diabetes. To determine if the circulation is adequate for healing despite the lack of a pulse, non-invasive vascular studies are necessary. The ankle-brachial ratio may be falsely high with calcified vessels. Toe pressures greater than 50 mm Hg or transcutaneous oxygen pressure greater than 20 to 30 mm Hg may be necessary to ensure sustained healing in the average patient. Vessel calcification disables the accurate assessment of vascular flow. Diabetic foot infection (deep compartment). Foot infections, particularly those involving deep plantar spaces, can cause foot pain even through very severe neuropathy. Unfortunately, this pain is often overlooked, as signs and symptoms of infection in the patient with diabetes are often subtle. Up to 86% of these patients are afebrile and at least half will have a normal white blood cell count despite infection.8,9 Certainly, the presence of pain in even a mildly erythematous or edematous diabetic foot with normal laboratory indices should not dissuade the clinician from taking appropriate action to assess and, if necessary, treat infection. When clinical signs of deep infection are present they may include increased warmth and swelling of greater than 2 cm in diameter (see Table 1). Caputo10 considered erythema greater than 2 cm to represent limb-threatening changes. Patients also may have new areas of breakdown and ulcer enlargement. The extension or probing of the ulcer to bone in concert with serial radiography or MRI may be an effective means of evaluating the potential extent of bony involvement and osteomyelitis.11,12 Charcot arthropathy. Charcot arthropathy is characterized by pathologic fractures, joint dislocation, and deformity in the profoundly neuropathic patient.13-16 Its incidence is approximately 8.5/1,000/year in people with diabetes.13,15,17-19 The etiology of this arthropathy is not precisely known, but may be related to multiple fractures, an inflammatory response, and decalcification (osteopenia) of the bone, causing ligamentous instability that further weightbearing will aggravate. Most patients with Charcot arthropathy will present with a red, hot, swollen foot that is frequently painful. In fact, pain is a characteristic presenting complaint of the acute form of this arthropathy in 75% of cases.15 The ligamentous instability and osteopenia combine to produce often spectacular deformities that most frequently result in classic "rocker bottom" foot types that lead to midfoot ulceration. Treating Charcot arthropathy requires pressure downloading or offloading until the skin surface temperature becomes normal20 and the Charcot changes are stabilized. Painful diabetic neuropathy. Neuropathy has three components: sensory, autonomic, and motor. Although the natural history of diabetic neuropathy often leads to sensory neuropathy with LOPS, many people with diabetes will develop a painful form of the neuropathy at some point in the course of their disease. This may temporarily overlap the development of loss of sensation, producing what Ward termed the "painful, painless foot.21 To say the etiology of diabetic neuropathy in general and painful diabetic neuropathy in particular is multifactorial is an understatement. A complex mélange of microvascular disease, oxidative stress, cytokine deficiencies, metabolic phenomena, and disturbances in inflammatory mediation combine to varying degrees to produce both the painful and painless aspects of neuropathy.22-25 In contrast to ischemic pain, diabetic neuropathic pain is not generally associated with increased activity, but instead often appears during periods of diminished external sensory stimulation (eg, at night). Because of its multifactorial nature, no single treatment has proven a panacea.26,27 Presence of painful diabetic neuropathy mandates consultation with an endocrinologist, neurologist, or pain management specialist with interest and experience in this phenomenon. Neuropathic pain often responds incompletely to traditional anti-inflammatory and opioid pain medication. Tricyclics and antidepressants often have been used successfully for treatment, especially for the burning type of sensation. Some practitioners use amitriptyline, a first generation agent, starting with a low dose of 10 to 20 mg and increasing as tolerated in 10-mg increments every 5 to 7 days until adequate pain control has been achieved. A single daily dose often is given a few hours before bedtime for its sedative side effect. Other clinicians prefer second-generation agents such as nortriptyline or desipramine that have a high noradrenalin action and fewer side effects (eg, double vision, dry mouth, and urinary retention). Tricyclics are often available in 10-, 25-, 50- and higher mg/dose tablets. For patients who do not respond adequately to tricyclics, gabapentin has been an alternative pain-relieving agent. Patients are often started on 100 mg, three times a day, and gradually increased as tolerated to as much as 3.6 g per day. Gabapentin is available in 100-, 300-, and 400-mg tablets. Patient-Centered Concerns Pain in the neuropathic foot is often what compels the patient with diabetes to seek healthcare advice. Unfortunately, such pain often reflects a deep infection or acute Charcot change and places the patient at higher risk for amputation. Detection of diabetic foot problems often occurs far too late and the human and economic cost of diabetic foot ulcers and amputation remains high.28 Effective and inexpensive techniques are available to help identify individuals at risk for diabetic foot ulcers. Awareness of these risk factors, as well as diabetic education that includes instruction on proper foot care and proper footwear, has been shown to lower amputation rates. The person with diabetes (PWD) must be made part of the decision-making process related to his/her health status, because 99% of diabetes care is self-care. Decisions that affect a person's health are made countless times each day in the context of normal life,28 but individuals with diabetes especially need information about risk, LOPS, diet, weight, alcohol, smoking, exercise, and activities of daily living, as well as problem-solving skills necessary to respond to health-related problems. Education equates to empowerment and can help people with diabetes make informed decisions concerning their health. Information about LOPS is key to reducing the rate of neuropathic foot ulcers. A 5.07/10-g monofilament applied to the foot with enough force to bend the filament and not felt by the individual with diabetes indicates a loss of protective sensation. The LEAP Program (lower extremity amputation program) is a patient-specific website that instructs individuals with diabetes on monofilament self-assessment: https://bphc.hrsa.gov/programs/LEAPprograminfo.htm. To improve the consequences of diabetes, a healthy diet needs to be designed to meet individual requirements. An Hgb AIC level below 8.4%, normal serum lipid levels, and ideal weight will help determine if the diet is balanced with appropriate caloric intake. In addition, elderly people with diabetes29 are three times as likely to have a significant alcohol abuse problem. Alcohol consumption can elevate serum lipids and have a negative effect on diabetic control. Cigarette smoking, together with impaired glucose tolerance and hypertension, are powerful predisposing factors for peripheral arterial disease. Smoking doubles the risk of arthrosclerosis in people with diabetes.30 A patient-appropriate intervention technique such as nicotine patches, hypnosis, or other behavior-modification strategies should be recommended. A careful examination and discussion of socioeconomic factors is also important to support patient adherence to a plan of care. People with diabetes are often on medication that may be expensive and they may not have a comprehensive drug plan. Dressings and pressure offloading devices often are not covered and may be neglected if they are too expensive for the patient. The healthcare provider team may need to link with a social worker to facilitate access. Interestingly, two of the top five predictors of mortality in diabetes are psychological or behavioral in nature but they receive little clinical attention compared to physiological factors.29 The quality of diabetic self-care declines in response to psychological functioning. For the patient who manages to avoid amputation, the presence of pain, disability, or reduced access to meaningful activities may significantly reduce quality of life. Local Wound Care After assessment of the cause and patient-centered concerns, attention can focus on local wound care: debridement, bacterial balance, and moisture balance. Debridement. Debridement is usually painless due to neuropathy, but if pain is present, infection, ischemia, or Charcot change should be considered. Although sharp surgical debridement is the procedure of choice,31 it should only be performed when blood supply and general patient health are adequate for healing (ascertained via a palpable pulse or vascular lab assessment). Debridement should include removal of callus and friable bright red or exuberant granulation. Calcium alginate post debridement will help control surface bleeding and prevent the formation of a hemorrhagic crust. Autolytic debridement, mechanical methods, and enzymes are less effective. Infection. Superficial infection may cause local pain or discomfort due to the release of pre-inflammatory mediators by the bacteria and the host, but it is much more likely that pain is indicative of infection in the deeper compartment. When infection occurs close to the surface, signs and symptoms of infection or increased bacterial burden may include exuberant friable or bright red granulation, increased exudate, odor, or new areas of breakdown (slough) within the existing ulcer area.32 Pain along with significant swelling and warmth, new areas of breakdown or ulcer enlargement, and probing to bone are all more likely with deep infection. Some patients with diabetes may have decreased inflammatory response that delays healing. The following equation is a reminder that PWD may have a decreased immune response (host resistance) and this may increase the effect of bacteria in a chronic wound.33 Infection = (Organisms x Virulence)/Host resistance Topical therapies with low toxicity, antibacterial properties, and absorptive properties are now available in the form of cadexomer iodine and ionized silver dressings. Traditional antibiotics may not absorb exudate, and other antiseptics can be toxic to granulation tissue; using such agents systemically may lead to bacterial resistance. Moisture balance. Moisture balance in diabetic foot ulcers is best achieved through moisture-absorptive dressings. Excess moisture will lead to macerated callus around the edge of the wound and may favor bacterial proliferation.34 Moisture should be controlled and the callus debrided. Foams, hydrofibers, and calcium alginates are absorptive; hydrogels prevent dehydration of the surface. Some of these dressings have the benefit of newer antibacterial combinations such as ionized silver. If the wound edges are macerated, protection around the outer rim can be accomplished using any of five products: 1. Zinc oxide paste 2. Petrolatum 3. Film forming acrylates 4. Windowed hydrocolloid and film dressings 5. Soft silicone dressings.35 Pressure relief. If callus is excessive, pressure relief has probably not been optimized. The gold standard is the contact cast but it is not suggested for heel ulcers.36 Pneumatic walkers or deep-toed shoes with orthotics are other alternatives. If hemorrhage or blisters appear, friction and shear due to movement between the plantar surface and the offloading device need to be checked. Conclusion Pain is not common in patients with diabetic foot ulcers due to the high incidence of neuropathy. When pain does occur, it may herald limb-threatening complications. The clinician should assess the cause and correct it as soon as possible, as most diabetic lower extremity amputations are preventable.37,38 Even when pain is absent, effective wound care (eg, atraumatic dressing removal through use of soft silicones) remains important to prevent the onset of complications. - OWM

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