WHS guidelines update: Diabetic foot ulcer treatment guidelines

There are 22.3 million people in the United States with diabetes, of whom 15–25% are at risk for foot ulceration. Diabetic foot ulcers (DFUs) are a growing health problem. DFUs are a leading cause of infection, amputation, and hospitalization in patients with diabetes mellitus. Guidelines for the treatment of DFUs were published by the Wound Healing Society (WHS) in 2006. However, in the past few years new evidence has emerged that improves our understanding of previous recommendations. The objectives of the WHS DFU guidelines are to systematically evaluate the medical literature to assist clinicians in making health care decisions, identify areas that need additional research, and to clarify controversial diagnosis and treatment strategies. An advisory panel comprised of academicians, clinicians, researchers, and industry representatives was chosen to update the 2006 guidelines. In 2006, in an effort to develop guidelines that could provide clinicians with a reasonable approach to caring for patients, even in the absence of high quality human data, the WHS developed guidelines using a different approach to evidence citations and past approaches to evidence-based guidelines. Most past approaches relied only on publications regarding clinical human studies. Laboratory or animal studies were not cited. We have used well-controlled animal studies that present proof of principle, especially when a clinical series corroborated the laboratory results. Because of this variation, a different system was used to grade the weight of evidence supporting a given guideline. The strength of evidence supporting a guideline is listed as Level I, Level II, or Level III. Since the 2006 guidelines, we sought to capture the highest quality of literature available regarding DFU diagnosis and treatment using a key word search of PubMed, Embase, and Cochrane Library databases. Similarly, the citations of relevant articles were examined by hand. Key terms were generated from the existing guidelines. In this search as opposed to the previous data collection prior to 2006, we used human and disease specific data and limited to meta-analyses, systematic reviews, RCTs, retrospective series reviews, clinical case series, and expert panel recommendations published between January 2006 and present. References prior to 2006 supporting the original guideline recommendations are not included. Therefore, in some cases no additional updated references were included and the support for the guideline recommendation is based on evidence presented in the 2006 guideline. Therefore, no updated references are presented. It was further limited to only English publications. Any relevant additional references found after the formal search were also included. The findings of these articles have been divided into one or more of the appropriate categories as performed in the original guideline Each of the separate guidelines has undergone a Delphi consensus among the panel members. Not all panel members thought they had sufficient expertise to critique all of the separate sections of the guidelines. The first draft was of the guidelines was presented in 2014 for public comment and subsequent drafts revised based on those comments. Evidence Reference: Preamble: Ulcers of the lower extremity may be caused by a variety of conditions, including neuropathy, ischemia, venous hypertension, and pressure. Patients with diabetes develop wounds secondary to neuropathy with or without biomechanical abnormalities, peripheral vascular disease with ischemia, or both. There are over 20 million people in the United States with diabetes, of whom 15–25% are at risk for ulceration. It is imperative that the etiology be established to provide for proper therapy. Guideline #1.1: Clinically significant arterial disease should be ruled out by establishing that pedal pulses are clearly palpable or that the ankle:brachial index (ABI) is > 0.9. An ABI > 1.3 suggests noncompressible arteries. In elderly patients or patients with an ABI > 1.2, a normal Doppler-derived waveform, a toe:brachial index of > 0.7, or a transcutaneous oxygen pressure of > 40 mmHg and/or hyperspectral imaging analysis may help to suggest an adequate arterial flow. Color duplex ultrasound scanning provides anatomic and physiologic data confirming an ischemic etiology for the leg wound. (Level I) Principle: Diabetic ulcers can result from arterial insufficiency or neuropathy. Although clinical history and physical examination can be very suggestive of an ischemic etiology of the lower extremity diabetic ulcers, a definitive diagnosis must be established. When significant arterial disease is present, successful treatment requires that arterial insufficiency be addressed. Updated Evidence: Guideline #1.2: The presence of significant neuropathy can be determined by testing with a 10 g (5.07) Semmes–Weinstein monofilament. (Level II) Principle: Diabetic sensory neuropathy creates an environment in which repetitive trauma, injury and infection are unrecognized by the patient. Several simple clinical techniques can be used to identify sensory neuropathy with loss of protective sensation. The presence of sensory neuropathy can be determined by testing with a 10 g Semmes Weinstein monofilament, 128 Hz tuning fork, vibration perception threshold testing or a good neurological clinical examination for sensory loss. Updated Evidence: Preamble: Diabetic ulcerations on the sole of the foot are often associated with moderate to high pressures because of foot deformity, limited joint mobility, and neuropathy. Off-loading devices reduce pressure on the sole of the foot and often reduce the activity level of the patient. Off-loading the area of high pressure has been the mainstay to heal DFUs and prevent recurrence of foot ulcerations (Level I). Guideline #2.1: Protective footwear should be prescribed in any patient at risk for amputation (significant arterial insufficiency, significant neuropathy, previous amputation, previous ulcer formation, preulcerative callus, foot deformity, evidence of callus formation). (Level II) Protective footwear results in reduction in recurrent ulcerations in high-risk patients with a previous foot ulcer or amputation. (Level I). Principle: The etiology of many foot ulcers involves a biomechanical component. Most treatments do not eliminate the underlying biomechanical etiology of the foot ulcer. Abnormal pressure and shear stress is still present, so long-term off-loading is necessary. By reducing pressure and shear forces on the sole of the foot, repetitive injury to the foot is reduced, and existing wounds can heal or high-risk areas are protected from recurrent ulcers. Updated Evidence: Guideline #2.2: Acceptable methods of offloading include crutches, walkers, wheelchairs, custom shoes, depth shoes, shoe modifications, custom inserts, custom relief orthotic walkers, diabetic boots, forefoot and heel relief shoes, and total contact casts. (Level I) Principle: Relieving pressure on the diabetic wound is necessary to maximize healing potential. Updated Evidence: Preamble: Infection results when the bacteria: host defense equilibrium is upset in favor of the bacteria. Infection plays various roles in the etiology, healing, operative repair, and complications of diabetic ulcers. Guideline #3.1: Remove all necrotic or devitalized tissue by surgical, enzymatic, mechanical, biological, or autolytic debridement. (Level II; detailed discussion of debridement is in Wound Preparation Guidelines). Principle: Devitalized tissue provides a safe haven for bacterial proliferation, a barrier for antibiotics to reach bacterial pathogens. In addition, it limits the body's cellular defenses to fight infection. Removal of devitalized tissue reduces bacterial bioburden. Updated Evidence: Guideline #3.2: If there is suspected infection in a debrided ulcer, or if epithelialization from the margin is not progressing within two weeks of debridement and initiation of offloading therapy, determine the type and level of infection in a debrided diabetic ulcer by tissue biopsy or by a validated quantitative swab technique. (Level II) Principle: High levels of bacteria (≥106 CFU/g of tissue) impede wound healing and surgical wound closure. Reduction of the bacterial bioburden in the wound reduces the risk of clinical infection and improves wound healing. Cultures should be performed to isolate both aerobic and anaerobic bacteria. Updated Evidence: Guideline #3.3: For ulcers with levels of bacteria (>105 CFU/g of tissue) following adequate debridement, topical antimicrobial agent can decrease the bacterial levels. Once in bacterial balance, topical antimicrobial agent should be discontinued to minimize cytotoxic effects and emergence of bacterial resistance organisms. (Level I). Principle: Systemically administered antibiotics do not effectively decrease bacterial levels in granulating wounds, Topically applied antimicrobials can be effective to decrease bacterial levels in granulating wounds. Updated Evidence: Guidelines #3.4: Topical antimicrobial and antiseptic therapies are not effective to improve wound healing (Level I). Principle: New to the guidelines is evidence that topical antimicrobial and antiseptic therapies, while decreasing bioburden, do not improve wound healing. Updated Evidence: Guideline #3.5: For acute diabetic foot infections not confined to the granulating wound, systemic antibiotics are effective. (Level II) Principle: Systemic antibiotics have been demonstrated in most trials to be helpful in treating acute diabetic foot infections. Deep tissue cultures are most helpful in determining antibiotic usage. Updated Evidence: Guideline #3.6: Cellulitis (inflammation and infection of the skin and subcutaneous tissue most commonly due to streptococci or staphylococci) surrounding the ulcer should be treated with systemic Gram-positive bactericidal antibiotics. (Level II) Principle: Edema fluid (plasma) neutralizes the fatty acids of sebum and inactivates the normal bactericidal properties of skin. This renders the skin and subcutaneous tissue susceptible to infection by streptococci or staphylococci. Gram positive bacteria are the most common pathogens in cellulitis in DFUs. Updated Evidence: Guideline #3.7: If osteomyelitis is suspected, appropriate diagnostic measures include bone biopsy, probing the wound area to the bone with a sterile instrument, serial x-rays, MRI, CT and radionucleid scans. (Level II). PET leukocyte screening, and Tc99m WBC labeled-SPECT/CT. (Level II) Principle: Bone underlying a diabetic ulcer is often infected. Biopsy of the bone gives a definitive diagnosis, but less invasive techniques can be useful in establishing a diagnosis with a high degree of specificity and sensitivity. Updated Evidence: Guideline 3.8: If osteomyelitis is suspected, determine the type of bacterial pathogens by bone biopsy (Level II). Principle: Culture-directed antibiotic treatment seems to provide better clinical outcomes than empiric therapy. If diabetic foot osteomyelitis (DFO) is suspected, bone specimens should be obtained to identify the bacterial pathogens and to direct antibiotic therapy. Since the last publication of the WHS guidelines, data has emerged suggesting that culture-directed antibiotic treatment results in enhanced outcomes in osteomyelitis. Therefore, we have added this guideline to suggested treatment approaches to advance treatment of bioburden that results in osteomyelitis. Updated Evidence: Guideline #3.9: Osteomyelitis is best treated by removal of the infected bone, followed by 2–4 weeks of antibiotics. However, when this is not practical, osteomyelitis underlying a diabetic ulcer can be effectively treated with prolonged antibiotic therapy. (Level II) Principle: Osteomyelitis underlying a diabetic ulcer, like osteomyelitis elsewhere, is most effectively treated by debridement of the infected bone. When debridement has been adequate, a 2–4-week course of antibiotics is adequate. If the infected bone is not totally resected, a longer course (at least 6 weeks) is usually required. Updated Evidence: Guideline #3.10: Minimize the tissue level of bacteria, preferably to 105 CFU/g of tissue with no beta hemolytic Streptococci in the ulcer before attempting surgical closure by skin graft, skin equivalent, pedicled, or free flap. (Level II) Principle: A wound containing contaminated foci with greater than 105 organisms per gram of tissue cannot be readily closed, as the incidence of wound infection that follows is 50–100%. Updated Evidence: None. (Detailed discussions of infection control, dressings, and tissue engineering/growth factors are in infection control guidelines, dressings guidelines, and adjuvant agents topical, device, and systemic guidelines). Preamble: Wound bed preparation is defined as the management of the wound to accelerate endogenous healing or facilitate the effectiveness of other therapeutic measures. The aim of wound bed preparation is to convert the molecular and cellular environment of a chronic wound to that of an acute healing wound. Guideline #4.1: Examination of the patient as a whole is important to evaluate and correct causes of tissue damage. This includes factors such as: (A) systemic diseases and medications, (B) nutrition, and (C) tissue perfusion and oxygenation. (Level I) Principle: (4.1.A) A general medical history, including a medication record, will help in identifying and correcting systemic causes of impaired healing. The presence of a major illness or systemic disease and drug therapies such as immunosuppressive drugs and systemic steroids will interfere with wound healing by alterations in immune functioning, metabolism, inflammation, nutrition, and tissue perfusion. Autoimmune diseases such as rheumatoid arthritis, uncontrolled vasculitis, or pyoderma gangrenosum can all delay healing and may require systemic steroids or immunosuppressive agents before local wound healing can occur. Patients undergoing major surgery have a diminished wound-healing capacity as do chronic smokers. Smoking is associated with impaired wound healing and increased risk of infection. Updated Evidence: Principle: (4.1.B) Nutrition must be adequate to provide sufficient protein to support the growth of granulation tissue. The patient's weight, prealbumin level (reflecting recent protein consumption), and serum albumin (reflecting long-term protein consumption) are useful in identifying patients who are outside the norms. Although most diabetic ulcer patients are ambulatory and not at the extremes of nutrition, nutritional support is required if an individual is undernourished. Updated Evidence: Principle: (4.1.C) Wounds will heal in an environment that is adequately oxygenated. Oxygen delivery to the wound will be impaired if tissue perfusion is inadequate. Dehydration and factors that increase sympathetic tone such as cold, stress, or pain will decrease tissue perfusion. Cigarette smoking decreases tissue oxygen by peripheral vasoconstriction. For optimal tissue perfusion, these factors must be eliminated or minimized. Updated Evidence: Guideline #4.2: Initial debridement is required to remove the obvious necrotic tissue, excessive bacterial burden, and cellular burden of dead and senescent cells. Maintenance debridement is needed to maintain the appearance and readiness of the wound bed for healing. The health care provider can choose from a number of debridement methods including surgical, enzymatic, mechanical, biological, or autolytic. More than one debridement method may be appropriate. (Sharp surgical debridement is preferred; Level I). Principle: Necrotic tissue, excessive bacterial burden, senescent cells, and cellular debris can all inhibit wound healing. The method of debridement chosen may depend on the status of the wound, the capability of the health provider, the overall condition of the patient, and professional licensing restrictions. Updated Evidence: Guideline #4.3: Wounds should be cleansed initially and at each dressing using a wound should be with a of and/or (Level Principle: and the wound to wound healing. or is usually should only be used if the is data suggest that a may be useful as may fluid by increased pressure. Updated Evidence: Guideline There should be an and of wound history, and condition of the surrounding and to evaluate wound bed The of wound healing should be to determine treatment is (Level II) Principle: of wound bed preparation are if the ulcer is not healing at the for wound bed preparation need to be The longer the of the ulcer, the more it is to If an ulcer is etiology, patient or of and long-term need to be Updated Evidence: Guideline Patients who to a reduction in ulcer by or more after weeks of should be and other treatments should be (Level II) Principle: in wound area of DFUs over weeks of treatment is a good of effectiveness of and of healing. Updated Evidence: Guideline control improves wound healing. (Level II) Principle: Wound healing is more to be optimal in the of good diabetes Abnormal levels also the of infection and cellular Updated Evidence: Preamble: There are a number of topical therapies available for DFUs. Most dressings are used in with debridement, and infection It is thought that a wound environment and There are that should be when a dressing including the for and wound dressings should not the wound. If the wound and surrounding tissue have contact with wound the local tissue can and impede healing. dressings that are not can cause to the surrounding skin or wound The of health care provider healing and the of dressings should be when determining clinical studies have not that any dressing approach is more effective than to facilitate wound healing. Guideline a dressing that will maintain a wound-healing (Level Principle: A wound environment and while healing of wounds by autolytic debridement. Updated Evidence: Guideline clinical to a wound (Level Principle: dressings are not dressings are as effective as other of wound healing in terms of healing This guideline has not the 2006 recommendations. However, additional on adjuvant agents and dressings is available in Guideline Updated Evidence: None. Guideline a dressing that will the wound and the skin. (Level I) Principle: and contact with wound can the wound and impede healing. Updated Evidence: None. Guideline a dressing that in shear and and not cause additional tissue damage. (Level II) Principle: Wound skin and patient activity can all the of Updated Evidence: None. Guideline a dressing that is effective. (Level I) Principle: Because of dressings are often as the least most However, when determining it is important to into health care provider of and healing as as the of the Updated Evidence: None. Guideline adjuvant agents device, and/or after a patient and ulcer and when there is a of healing in to more (Level I) (Detailed discussions of these are in Principle: therapies and devices may and increase healing in patients or wounds. therapies are and are in in the Updated Evidence: Evidence references are detailed in the Systemic Guidelines). Preamble: The of dressings and offloading are not successful in healing all diabetic ulcers. the surgical have been to diabetic ulcers with of clinical trials operative techniques are but data are available supporting surgery in Guideline improves healing of diabetic forefoot wounds. (Level II) the reduces pressure on forefoot ulcers in patients with limited of the has been associated with a reduction in ulcer recurrence (Level I). Principle: A to increased forefoot the reduces pressure on forefoot ulcers in patients with limited and may be of in healing DFUs. Updated Evidence: Guideline Patients with should be for a and in are associated with a significant in ulcer healing. (Level Principle: In patients with arterial in is associated with an increase in nutrition, and wound healing. Updated Evidence: Preamble: agents have been suggested to be used as to dressings and off-loading in the treatment of diabetic ulcers. adjuvant agents can be divided into topical agents to be applied to the ulcer, devices at ulcer healing, and systemic drugs to the patient. Several of these agents have evidence to guidelines regarding Guideline of growth reduces the to heal and the of ulcers that (Level I) Principle: growth factors are in wound healing. Diabetic foot wounds are in growth of growth factors to wounds can accelerate wound healing. Updated Evidence: Guideline and growth factors have demonstrated with healing. (Level I) Principle: and growth factors are in wound healing. Updated Evidence: Guideline (Level and growth (Level II) have not demonstrated an increase in the of wounds that heal and the healing of DFUs. Principle: There is one systematic and with and that suggest no wound healing Updated Evidence: Guideline pressure wound has been to increase the of wounds that heal and the of wound healing with wound care in diabetic lower extremity wounds. (Level I) Principle: treatment may improve wound healing by reducing bacterial and the of the wound, and should be when other treatments are not effective. Updated Evidence: Guideline and skin improve DFU healing. (Level I) Principle: skin assist in healing DFUs by therapeutic of growth and other that the wound Updated Evidence: Guideline is to accelerate wound closure. (Level I) Principle: of to diabetic foot wounds local tissue perfusion and may protein and bacterial growth to improve wound healing. Updated Evidence: Guideline diabetic ulcer healing (Level I). Principle: has been used in a variety of clinical for repair, and wound healing. for patients with diabetic foot ulcers. Updated Evidence: Guideline oxygen should be used to improve wound healing and reduce major amputation (Level I). Principle: oxygen may increase the of oxygen to a wound in diabetic patients and improve healing. Updated Evidence: Preamble: Diabetic ulcers of the lower extremity are a chronic problem. are Therefore, must be even for ulcers. Guideline Patients with diabetic ulcers should protective footwear to prevent (Level I) Principle: Most treatments do not eliminate the underlying increased pressure on the foot, so offloading is necessary Updated Evidence: Guideline foot care and of the will not reduce the recurrence of diabetic ulceration. (Level I) Principle: There is data regarding the effectiveness of good foot care including proper will reduce in diabetic such as good foot care proper and care should be included as of a care that includes professional foot and therapeutic and Updated Evidence: Guideline of foot with an reduces (Level I). Principle: areas of increased are a of and tissue injury that the of ulceration. By of patients could identify of tissue and reduce activity to the of an ulceration. Updated Evidence: