As diabetic foot ulcers plague more patients, wound care management—including a host of new technologies—are driving an increase in office visits.
By Michael Flores, DPM, and Marshall G. Solomon, DPM, FACPM, FACFAS, FFPM RCPS (qlas)
Diabetes mellitus is the leading cause for nontraumatic amputation.1 Since 1980, the number of people with diabetes around the world has nearly quadrupled, from 108 million to nearly 422 million in 2014—and it continues to rise.2 Although first described in 1550 BC, diabetes is among today’s costliest diseases, placing a major strain on our modern healthcare system due to its many complications.3 Given the increasing trend in obesity and the growing aging population (with age-related metabolic changes that favor diabetes), the need for patient care in the office has also increased.
Patients with diabetes, particularly those with long-standing disease or of an older age, suffer with significant deficits in general wound healing, but particularly with wounds on the lower extremities. There is general consensus that wounds with a duration of 4 weeks to 3 months be identified as chronic wounds. Wound care therapy has advanced in such a way that patients with these challenging wounds can be treated as outpatients with weekly in-office visits. This review will examine these advanced wound care therapies, which consist of offloading equipment, biologics, dressings, topical products, and hyperbaric oxygen therapy.
Negative Pressure Wound Therapy
Negative pressure wound therapy (NPWT), also known as vacuum-assisted wound closure, is an advanced wound dressing that applies continuous or intermittent application of sub-atmospheric pressure to the wound site to facilitate healing and collection of wound drainage. NPWT causes physical contraction of complicated wounds and removes soiling, excess interstitial fluid, and slough from the wound bed, thereby optimizing the wound environment for angiogenesis, resulting in granulation tissue formation. It has become the mainstay in treatment of both acute and chronic diabetic foot wounds.4 Typically, NPWT uses black or white foam dressings which are composed of different materials and function in different ways.
The most-often used black foam is an open porous structure made of polyurethane dressing. The black foam dressing is primarily used to treat deep wounds and flaps. Contraindications for black foam use include malignancy of the wound, untreated osteomyelitis, or necrotic tissue.
White foam, on the other hand, is a denser dressing made of polyvinyl alcohol, which helps reduce granulation tissue formation into the dressing thereby decreasing pain on dressing change. White foam dressing also helps protect delicate structures in the wound bed and prevents wound adherence. White foam is indicated for superficial wounds, painful wounds, exposed bone, wounds with established granulation tissue, tunnels, sinus tracts, and areas of undermining. Contraindications include necrotic tissue, untreated osteomyelitis, fistulas to organs or body cavities, placement directly over exposed veins or arteries, and malignancies.5
A recent addition is installation negative pressure wound therapy V.A.C. Veraflo Cleanse Choice™ by KCI. Instillation therapy is a technique that intermittently washes out a wound with liquid solution. The purpose behind this system is to clean the wound bed and promote tissue growth. It has a 3-layer foam with one layer being open-cell reticulated to allow for wound cleansing and removal of thick exudate, fibrin, and infectious material.6 A case series by Arizona Burn Center at Maricopa shows promising results with Veraflo when applied to burns and necrotizing soft tissue.7
Total Contact Cast
One of the basic principles of healing a diabetic foot ulcer is pressure relief with offloading devices. Regardless of creating an optimal environment for a wound to heal, without pressure relief a wound will not resolve. A physician in-office setting has many offloading devices available, but many of them, such as removable casts or controlled, ankle motion (CAM) boots, require daily patient compliance tasks, such as donning and doffing, allowing patients freedom to NOT use them. The long-standing gold standard, the total contact cast (TCC) technique was first developed in the 1930s and was used for treating patients with leprosy deformities.8 The purpose of the TCC was to maintain a patient’s activity level and achieve wound closure at the same time. It continues to be today’s gold standard for offloading diabetic foot ulcerations. TCC is indicated in patients with plantar neuropathic ulcers of the forefoot and midfoot, and to control early stages of Charcot arthropathy.9 It has the advantage of forcing patient adherence during weight-bearing activity that other devices do not offer. The cast absorbs the force that would prevent the wound from healing and distributes the pressure of weightbearing throughout the entire cast reducing significant pressure to the localized area.10 A diabetic foot ulceration utilizing a TCC for offloading with optimal environment can heal, on average, in 6 weeks.11
Although potentially successful, the TCC can also pose risk to patients if applied incorrectly. A neuropathic patient ambulating on a poorly applied TCC is at risk of developing skin breakdown in other areas. A consecutive series by Guyton et al evaluated TCCs applied by a single physician: out of the 398 patients, 22 casts had complications such as ulcerations throughout different parts of the foot and leg.12 In a well-known study, Armstrong et al13 examined several offloading devices (TCCs, removable casts, and half shoes) and found that TCCs were superior in healing diabetic ulcerations in a shorter amount of time. However, TCCs require expert technique and are also time consuming to apply and remove in office, which have led physicians to underutilize them.14 Integralife has developed the TCC-EZ® to counteract the discouragement of applying TCCs. A recent comparative analysis found that this product can be applied by novice casters in less than 14 minutes after 3 training runs.15
The process of wound healing involves a complex biological process that utilizes growth factors to regulate cellular responses for a wound to heal.16 Growth factors are endogenous molecular signals made up of polypeptides that cells use to communicate and respond to progress the wound healing process through stages of migration, proliferation, and differentiation.17 More specifically growth factors play a critical role in influencing the inflammatory response, formation of granulation tissue, and angiogenesis. In chronic wounds, there is a deficiency in growth factors such as fibroblast growth factor-basic (bFGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and transforming growth factor-beta (TGF-β).18 The application of topical growth factors was developed as a way to supplement growth factor deficiency in chronic wounds, and this strategy appears to be promising in diabetic wound care management. Smith-Nephew has developed a recombinant PDGF called Regranex®, which is the only FDA-approved topical growth factor used for the treatment for diabetic neuropathic ulcerations. Fiblast Spray® recombinant human BFGH (RH-BFGF; Kaken Pharmaceutical Co., Ltd., Kyoto, Japan) is used to treat decubitus and skin ulcers including burn and leg ulcers and has been approved in Japan to treat diabetic foot ulcerations.19 Regen-D 150® (Bharat Biotech; Hyderabad, India), Easyef® (CGBio, South Korea), and Heberprot-P® (CubaMedic, Loznica, Serbia) contain 75ug of freeze-dried recombinant human EGF (rhEGF) and are also used to treat diabetic foot ulcerations.20
It’s important to note that topical growth factors are an adjunctive therapy to wound care and not a substitute for proper wound healing principles such as debridement, infection control, and offweighting. The application of supplemental growth factors to chronic wounds which have growth factor deficiencies, appears to be an optimal strategy for treating challenging chronic wounds.
Chronic wounds with extensive tissue loss may exist in a suboptimal environment that may retard wound healing. The longer a wound is exposed to the environment, the higher the risk of infection. Cellular or tissue-based products (CTPs) are effective adjunctive therapies for treating chronic wounds. CTPs accelerate wound healing by providing the necessary cellular products to promote biological repair and tissue regeneration.21 In addition, CTPs provide protective coverings that limit bacterial growth and fluid loss.22 The majority of CTPs are made from collagen and act as scaffolds creating temporary extracellular matrices. This allows for the migration of new blood vessels, cytokines, and growth factors to reach the wound bed, accelerating the wound healing process. The components that make up CTP collagen are derived from human, animals, or synthetic tissues. The main purpose of CTPs is to prepare the wound base for closure via skin graft. It is important to note before applying CTPs that a receptive wound bed be created with a properly debrided wound free of infection and necrotic tissue, no tunnels or sinus tracts, have a granular base with adequate blood flow, moist environment, and pressure relieved. Contraindications to CTPs include allergic reactions to bovine collagen or products that might elicit an allergic response. It’s also important to disclose the composition of the CTP to the patient out of respect for personal, cultural, ethnic, and religious beliefs.
Hyperbaric Oxygen Therapy
Hyperbaric oxygen therapy (HBOT) was first described in the 1940s by Dutch physician Ita Boerma in the treatment of clostridial myonecrosis. Since then, HBOT has been utilized to treat wounds by increasing the oxygen tension in tissue. Wound healing requires a number of biomechanical processes that are oxygen dependent. Local tissue hypoxia increases the risk of wound infection so the goal is to increase the amount of oxygen that reaches the cellular level.23 Hyperbaric chambers accomplish this by increasing the atmospheric pressure up to 3 times that found at sea level. Where 100% oxygen administered at sea-level or normobaric pressure increases the amount of oxygen dissolved in blood fivefold to 1.5 ml/dL (up from 0.3 ml/dL at sea level), increasing the pressure to 3 atmospheres increases the dissolved-oxygen content of the blood to 6 ml/dL. Given that tissues at rest extract 5 – 6 ml/dL of oxygen, the increased concentration provided by HBOT is believed to more than cover resting cellular requirements without robbing oxygen from hemoglobin.23
Hyperbaric oxygen must be administered systemically via inhaling. Treatments for wound healing problems are typically delivered at 2.0 – 2.4 atmospheres absolute (ATA) for 90 – 120 minute intervals. The frequency of treatments depends on the severity and the type of wound. The average number of treatments reported for healing a diabetic foot ulceration varies widely from 4 to 100.24 Increasing oxygen promotes wound metabolism by enhancing fibroblast replication, collagen synthesis, neovascularization, and epithelization. HBOT also improves the host response to bacterial infection by supplying an oxygen source for leukocytes. Selection of HBOT is indicated in those individuals who have decreased oxygen levels in areas that do not have adequate blood supply. Tissue oxygen measurements, such as transcutaneous oximetry, assess oxygen pressure in the tissue and are commonly used to determine proper candidate selection for HBOT. Patients with values less than 34 – 40 mm Hg will not spontaneously heal and may benefit from HBOT.25
Team Approach Helps
The technologies supporting wound management are evolving daily. Such technologies are certainly helpful, but it is also important when treating chronic wounds to establish relationships with other specialties to help take on these challenging medical issues. The principles of wound healing—proper debridement, antibiosis, adequate blood flow, proper nutrition, maximizing the treatment of comorbidities, and pressure reduction, are most successfully addressed with a multispecialty team-based approach. A vascular surgeon will help increase blood flow to a wound; a plastic surgeon can provide soft tissue coverage; infectious disease specialists manage appropriate antibiotic coverage; and primary care physicians and endocrinologists manage nutrition and medical comorbidities. All specialties play a role in providing an environment for wounds to heal.
Michael Flores, DPM, PGY-2 is a podiatric resident at the Beaumont Health Farmington Hills, PM&S/RRA residency program in Farmington Hills, MI, specializing in foot and ankle surgery.
Marshall G. Solomon, DPM, FACPM, FACFAS, FFPM RCPS (Glasg) is a foot and ankle surgeon at the Foot Care Institute of Michigan and the Beaumont Hospital Podiatry Clinic and is the podiatry residency program director at the Beaumont Hospital, Farmington Hills, all in Farmington Hills, Michigan.
LER is proud to partner with the American College of Podiatric Medicine to present clinically relevant peer-reviewed content, curated by Jarrod Shapiro, DPM, FACFAS, FACPM, FFPM RCPS (Glasg).
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- American Diabetes Association. Economic costs of diabetes in the US in 2017. Diabetes Care. 2018;41(5):917-928.
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- Kim PJ, Applewhite A, Dardano AN, et al. Use of a novel foam dressing with negative pressure wound therapy and instillation: recommendations and clinical experience. Wounds. 2018;30(3):S1-S17.
- Matthews MR, Hechtman A, Quan AN, Foster KN, Fernandex LG. The Use of VAC VERAFLO CLEANSE CHOICE in the burn population. Cureus. 2018;10(11):e3632.
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- Armstrong DG, Nguyen HC, Lavery LA, van Schie CH, Boulton AJ, Harkless LB. “Off-loading the diabetic foot wound: a randomized clinical trial.” Diabetes Care. 2001;24(6):1019-1022.
- Fife CE, Carter MJ, Walker D, Thomson B, Eckert KA. Diabetic foot ulcer off-loading: the gap between evidence and practice. Data from the US Wound Registry. Adv Skin Wound Care. 2014;27(7):310-316.
- Ludwig K, Homer V, Jensen J. Ease of application and removal of common total-contact cast systems used in the podiatric medical community. J Am Podiatr Med Assoc. 2019;109(6):445-450.
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