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Original Research

Updating the Diabetic Foot Treatment Algorithm: Recommendations on Treatment Using Advanced Medicine and Therapies

February 2018
1044-7946
Wounds 2018;30(2):29–35. Wounds Epub 2017 October 20

Abstract

Objective. Since the last diabetic foot ulcer (DFU) treatment algorithm was published in 2002, new options for diagnostic testing and treatments have been developed. This study seeks to update the DFU treatment algorithm to include new options available in diagnostic testing and treatment.Materials and Methods. A computerized literature search of peer-reviewed articles published between January 2003 and January 2016 was conducted using MEDLINE (PubMed), EMBASE, and the Cochrane Library. Diabetic foot ulcer treatment algorithms were reviewed and changes recommended based on current standards of care, new treatment modalities, and clinical experience. Results. A multidisciplinary approach is recommended to address potential underlying problems. A visual inspection, foot pulse palpation, skin temperature measurement, and shoe gear, gait, orthopedic, neurologic, and vascular exams are recommended. Appropriate offloading and continuing diabetes education are included as treatment for all DFUs. If calluses or increased foot pressure are present, preventative care is necessary to prevent further tissue breakdown. If infection is present, treatment should follow the Infectious Diseases Society of America diabetic foot infection guidelines. As the DFU severity increases, advanced wound dressings and advanced wound therapies should be employed. In acute/chronic and acute/urgent DFUs, debridement, amputation, and skin grafting may be required. Conclusions. Treatment for DFUs should start when a possible pre-ulcer is noticed. This prophylactic treatment may reduce development of more severe DFUs. Once a DFU has developed, care should be optimized for both the patient and the wound bed. While these treatment recommendations are focused solely on DFUs, they may be expanded for use in other foot/leg pressure ulcers.

Introduction

Diabetes is a prominent health burden affecting millions of people in the United States and rates of incidence continue to increase.1,2 In 2012, 21 million Americans had diabetes, with an estimated 8.1 million people undiagnosed and about 1.7 million cases of diabetes diagnosed in the United States each year.1,2 The increased need for care and costs associated with treatment cause financial strain on the health care system as well as the patients.1-4 In 2012, the estimated total cost of diabetes care was $245 billion.2 Of this, $176 billion was spent on direct medical costs, including hospitalization, advanced therapy, and office visits. The remaining $69 billion went towards indirect costs such as disability, loss of work, and premature death.

Over the course of the disease, up to 25% of all patients with diabetes will develop diabetic foot ulcers (DFUs).5 Loss of protective sensation, impaired wound healing, vascular disease, and foot deformity can lead to DFU development. In addition, the side effects of diabetes (eg, increased infection risk and inappropriate pressure distribution over the foot) make DFU healing a challenge. 

Numerous DFU grading systems exist to assist health care providers in identifying DFU severity, including Wagner6; the University of Texas7,8; perfusion, extent, depth, infection, and sensation (PEDIS)9; and site, ischemia, neuropathy, bacterial infection, and depth (SINBAD).10 One of the most commonly used grading systems, including utilization in the authors’ institutions, is the Wagner Grading System.6,11 This article uses the Wagner DFU grading system to determine the severity of DFUs. After determining the severity, the difficult task of developing a treatment plan begins, as a number of treatment options exist for DFUs. Offloading treatments help redistribute foot pressure away from the ulcer.12 Advanced wound dressings allow for wound bed management (ie, moisture balance, infection management, etc.) to promote wound healing.13,14 Negative pressure wound therapy (NPWT) utilizes negative pressure to remove infectious materials, reduce edema, and promote granulation tissue formation.15-17 Negative pressure wound therapy with instillation and dwell time (NPWTi-d) delivers wound cleansers or antiseptics directly to the wound bed.18 For DFUs that require surgical closure, skin grafts, skin substitutes, or biologics can be utilized.19-21 

While previous DFU treatment algorithms do exist, they do not contain a full representation of treatment options currently available. This work seeks to update the DFU treatment algorithm to include new options available in diagnostic testing and treatment.

Materials and Methods

Literature search. A computerized literature search was conducted using MEDLINE (PubMed), EMBASE, and the Cochrane Library to assess the current status of DFU treatment options and treatment algorithms. The search covered peer-reviewed articles published between January 2003 and January 2016. Search terms included diabetic foot ulcer, diabetic foot ulcers, DFU, risk factors, diagnostic, diagnostics, treatment, surgical procedures, off-loading, dressings, skin grafts, skin substitutes, biologics, wound healing, advanced wound therapy, advanced dressings, Wagner DFU classification system, and University of Texas DFU classification system

Developing the algorithm. The authors reviewed the current Wagner and University of Texas DFU classification algorithms and current DFU treatment algorithms. Changes to the algorithms were suggested based on current standard of care, new treatment modalities, and clinical experience with difficult-to-heal DFUs.

Results 

Literature search results. The literature search identified 1083 published articles on DFU treatment options, treatment algorithms, and studies. This published literature was briefly reviewed and served to inform the development of the updated treatment algorithm. 

Changing patient population. The last comprehensive Wagner DFU treatment algorithm was published in 2002.11 Since then, the population has changed and new treatment options have been developed. As science and medicine
continue to advance, the life expectancy of the population also increases. In 2012, about 25% of the US population was > 55 years old.22 A comparison of 2003 and 2012 census data demonstrates the percentage increase in the US population in 3 age categories: 55–59 years, from 5.4% to 6.6%; 60–64 years, from 4.2% to 5.7%; and 65–69 years, from 3.3% to 4.4%.23 This increase in the elderly population presents health care providers with new challenges, including patients with impaired healing and age-related disorders. 

Value-driven health care. The current US health care system is in the process of changing to a value-driven system so that reimbursement and payment costs are tied to patient outcomes. As such, well-documented, evidence-based care will become more important. The advent of the electronic health record (EHR) allows doctors to share patient data to help facilitate a multidisciplinary approach to care, which has been found to be beneficial for patient outcomes.24 Recently, the US health care system has switched to new medical coding requirements; the more detailed International Classification of Diseases, Tenth Revision codes allow for improved documentation of treatment and outcomes by health care providers. 

Advanced treatment modalities. New treatment modalities have been developed since 2002. Wound dressings have been developed to treat various aspects of the wound bed environment, including dressings for highly exudative wounds and dressings that help modulate proteases that inhibit healing (Table 1).25 Advanced wound therapies also have expanded to include NPWTi-d to deliver antiseptics and wound cleansers directly into the wound bed (Table 2).26 In addition, topical application of growth factors onto the wounds may be included in the advanced treatment modalities. These products can include platelet-derived growth factor, fibroblast growth factor, or vascular endothelial growth factor.27

Alternative skin grafting products and techniques are continuing to be developed. Currently available alternative skin grafting products include extracellular matrices; xenografts using porcine dermis, porcine intestinal submucosa, or bovine collagen; synthetic bilayer skin substitutes; acellular skin substitutes; cultured epidermal substitutes; neonatal immortalized keratinocytes; dermal substitutes using newborn foreskin fibroblast cells; and composite skin substitutes with a collagen scaffold, cultured fibroblasts, and stratified cultured keratinocytes. Additionally, autologous cultured skin replacements using cultured keratinocytes or epidermal cells are available.28

While split-thickness or full-thickness skin grafting is an important tool for wound closure, these methods may not be suited for every wound. As another available skin grafting method that uses only the epidermal layer, epidermal skin grafting was first introduced in 1964 when suction was utilized to raise this layer, allowing for its removal.29 In recent years, a commercial device for epidermal graft harvesting has become available that uses heat and negative pressure to raise the epidermal layer into microdomes.30 Harvesting the epidermal microdomes reduces the amount of skin required for grafting. 

Clinical experience. The Wagner DFU grading system remains the most commonly utilized system in health care today. The present authors most often see DFU patients who have failed multiple treatments and are told amputation is the only option remaining. A multidisciplinary approach to patient care reduces the risk of amputation in patients with DFUs.31 In the authors’ experience, a combination of care from vascular, cardiovascular, infectious disease, and endocrinology disciplines as well as pedorthists and wound care specialists provides a full range of care for the patient with a DFU. This multidisciplinary approach allows for treatment of underlying patient comorbidities as well as promotion of wound healing. In patients with hard-to-heal DFUs, treatment with multiple therapies is often necessary.32 If the DFU does not show signs of healing within 4 weeks of treatment initiation, the authors discontinue the current treatment and initiate another treatment method.32

Updated and expanded DFU treatment algorithm

Patient risk factors. Patients with diabetes have a high risk of developing chronic, nonhealing wounds. However, certain patient characteristics put these individuals at risk for development of severe and complex DFUs. Common risk factors for DFU development include a previous amputation, a previous DFU, a foot deformity, neuropathy, vascular disease, and duration of diabetes (Table 3).33 

Preventative care. If the patient is showing signs of calluses or uneven distribution of foot pressure, preventative care is necessary. It is important to treat at this stage in order to prevent tissue breakdown, especially in patients that have been previously treated for a DFU.5 At this early stage, a multidisciplinary approach is recommended to address any potential underlying problems in the patient.34 In addition to the podiatrist, a pedorthist, endocrinologist, vascular specialist, and primary care physician should be involved in patient care. The EHR should be well-documented and shared between all care specialties. A vascular assessment, neurologic exam, and shoe gear exam should be performed.35 Treatment includes appropriate offloading,12 diabetes education, and continued monitoring (Figure). 

Acute/chronic DFUs. Acute/chronic DFUs can range from a superficial ulcer to a deep ulcer with tendon, ligament, joint capsule, and bone involvement with or without an infection. Patients may be in outpatient care throughout the course of treatment. A nutrition assessment should be conducted during the patient evaluation. A clinical exam, including a visual inspection, foot pulse palpation, and skin temperature measurement, should be performed. A neurologic exam to assess foot neuropathy is recommended along with a gait assessment. Also, vascular exams are recommended to identify any potential vascular insufficiency. Noninvasive tests include cutaneous oximetry, ankle-brachial index, toe-brachial index, Doppler ultrasound, pulse volume recording, segmental pressures, and ultrasonography.36 In patients whose noninvasive vascular tests provided unclear results or in patients with prior DFUs, vascular referrals are recommended. Magnetic resonance angiography, computed tomography angiography, and thermography can be performed.36 Noninvasive imaging should be performed to identify any potential changes to the foot and tissue structure. An initial x-ray, followed by a computed tomography scan or magnetic resonance imaging, if needed, is recommended when foot deformity is present (Figure). 

Diabetes education and a care team comprised of a podiatrist, pedorthist, endocrinologist, vascular specialist, interventional cardiologist, interventional radiologist, and wound care specialist are recommended. The types of specialties on this multidisciplinary team may vary depending on where care is given, as some areas may have one department that provides both vascular and tendon surgery. Treatment includes debridement, application of an advanced wound dressing (Table 1),25,37,38 advanced wound therapy (Table 2),26,39,40 skin grafting/skin substitutes, and offloading.12 Offloading options include total contact casts (TCCs), custom sandals, cast walkers, Charcot restraint orthotic walkers, braces, and ankle-foot orthoses. In patients with a high risk of recurrent ulcers and when traditional offloading methods have failed, surgical offloading may be an alternative option.41 

If surgery is required, the goal is to remove all nonviable tissue or bone, provide mechanical balance, and create a functional foot and ankle. If infection is present, treatment should include care following the Infectious Diseases Society of America (IDSA) diabetic foot infection guidelines.9 Extensive debridement is recommended as well as potential revascularization surgery if warranted.

Acute/urgent DFUs. Acute/urgent DFUs range from
a deep ulcer with infection, abscess, osteomyelitis, and joint sepsis to localized gangrene of the foot or more rarely gangrene of the entire foot. Patient care is usually given in an inpatient setting, and the multidisciplinary care team should consist of the podiatric, pedorthic (prior to discharge, if available), orthopedic, vascular, infectious disease, wound care, endocrinology, interventional cardiology, interventional radiology, plastic surgery (if necessary), and diabetic education departments (Figure). 

Treatment should follow the IDSA diabetic foot infection guidelines.9 These urgent DFUs may require amputation (either local digit or foot/limb amputation) depending on the severity of infection or gangrene and degree of vascular insufficiency. Postsurgical treatments should include advanced wound therapies (Table 2),26,39,40 advanced wound dressings (Table 1),25,37,38 and offloading.12 Options for offloading include TCCs, custom sandals, cast walkers, Charcot restraint orthotic walkers, braces, ankle-foot orthoses, and surgical offloading (after other methods have failed).12,41

Discussion

This update on DFU treatment algorithms provides recommendations for preventative care through acute/urgent DFUs. The algorithm includes the most recently available treatment options (offloading, advanced wound dressings, advanced wound therapy, and/or surgery) and recommends a multidisciplinary team through all stages of care. 

Since the DFU treatment algorithm by Frykberg11 was published in 2002, a number of changes and advancements have occurred. The overall population is aging and has longer life expectancies. As such, the need for DFU care in hard-to-heal populations is increasing. The advent of the EHR has allowed for more detailed patient data to be shared among members of the care team. In addition, US health care is changing to require evidence-based treatments and use patient outcomes for reimbursement. 

More advanced wound care dressings and therapies have been developed that help manage the wound bed environment to promote healing. Recent years have seen the emergence of dressings that promote wound healing by managing exudate, maintaining moisture balance, removing infectious materials, and altering protease activity in the wound bed. New options for advanced wound therapy have been created to further manage the wound bed environment. The expansion of NPWT to include instillation and dwell time allows for direct delivery of wound cleansing or antiseptic solutions to the entire wound followed by fluid and infectious material removal during the NPWT phase,26 something that is missing in the surface-only contact of wound dressings. The wound coverage options available for skin grafting also have expanded to include a number of skin substitute products and epidermal skin grafting.28,30 This new variety of products can offer health care providers the option to customize treatments based on wound type, wound location, and the goal of treatment, especially when traditional wound care or skin grafting is not optimal.  

Treatment of DFUs can be difficult, and underlying patient comorbidities and lack of patient compliance can affect healing. Diabetes itself alters healing by disrupting cell response to cytokines and chemokines, angiogenesis, macrophage function, epidermal barrier function, and collagen and granulation tissue formation.42-44 Additional comorbidities such as advanced age, obesity, and malnutrition alter wound healing through delayed inflammation and immune response and increased susceptibility to infection.45 Patient compliance with treatment instructions can greatly influence DFU wound healing; this is especially true with offloading, a cornerstone of DFU treatment. Offloading seeks to redistribute and/or remove foot pressure from the wound; however, studies have indicated that patient compliance with removable offloading devices is low.12,46   

In the course of treating DFUs, the clinician will inevitably come across hard-to-heal ulcers. These wounds either do not respond to treatment at all or exhibit stalled healing after some treatment success. The lack of healing may be attributed to bacterial colonization, elevated protease activity, or increased inflammatory markers in the wound bed.25 Patient healing should be monitored at each stage of treatment, and clinicians should be willing to change therapy if wound improvements are not observed within 4 weeks of treatment initiation.47 In addition, each treatment should be optimized for the patient, wound bed environment, and therapy goals. The authors suggest changing treatment plans after 2-3 weeks of stagnant or worsening DFU conditions.

Limitations

A limitation of this work includes the use of only 1 grading system rather than multiple grading systems. While these treatment recommendations focused solely on the Wagner DFU grading system, they are not limited to this grading system or DFUs only and can be expanded for use in other wound grading systems or foot/leg pressure ulcers.

Conclusions 

Treatment for DFUs should start when a possible pre-ulcer is noticed. Patients should undergo an initial vascular assessment, neurologic exam, and shoe gear exam in order to identify and treat symptoms that can lead to DFU development. If caught early, this prophylactic treatment may reduce the development of more severe DFUs. The authors recommend a multidisciplinary care team for each DFU category in order to ensure that all comorbidities and diabetic symptoms are treated, and appropriate offloading and continuing diabetes education are included as treatment for all DFUs. As the DFUs become more severe, the use of advanced wound dressings and advanced wound therapies optimized for the patient and the wound bed during treatment is recommend. In acute/chronic and acute/urgent DFUs, debridement, amputation, and skin grafting may be required prior to treatment with advanced wound dressings or therapies.

Acknowledgments

From the Anesthesia and Orthopedics and Rehabilitation, Yale University School of Medicine, New Haven, CT; and Dr. William M. School College of Podiatric Medicine, Rosalind Franklin University of Medicine and Science, Center for Lower Extremity Ambulatory Research (CLEAR), North Chicago, IL

Address correspondence to:
Peter Blume, DPM, FACFAS
Anesthesia and Orthopedics and Rehabilitation 
Yale School of Medicine
800 Howard Ave
New Haven, CT 06519
peterb@ctfootandanklesurgery.com

Disclosure: Both authors are consultants for KCI, an Acelity company (San Antonio, TX). Ricardo Martinez and Julie Robertson (Acelity) provided manuscript preparation and editing assistance.

References

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