eMedicine Specialties > Vascular Surgery > Medical Topics
Diabetic Ulcers: Treatment & Medication
Updated: Oct 28, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Treatment of diabetic foot ulcers requires management of to a number of systemic and local factors, including:19,20,21,22
- Precise diabetic control is, of course, vital, not only in achieving resolution of the current wound, but also in minimizing the risk of recurrence.
- Management of contributing systemic factors, such as hypertension, hyperlipidemia, atherosclerotic heart disease, obesity, or renal insufficiency, is crucial.23,24
- Management of arterial insufficiency, treatment of infection with appropriate antibiotics, offloading the area of the ulcer, and wound care are also essential.
- 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 footwear,25,9 daily saline or similar dressings to provide a moist wound environment,26 debridement when necessary, antibiotic therapy if osteomyelitis or cellulitis is present,13,14 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 factors,28,29,30,31 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 (vacuum-assisted closure [VAC]).32
- Hyperbaric oxygen therapy is used rarely and is certainly not a substitute for revascularization.33
- 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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Table
| Category | Examples | Description | Applications |
|---|---|---|---|
| Alginate | 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. Alginate rope is particularly useful to pack exudative wound cavities or sinus tracts. |
| Hydrofiber | 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. |
| Debriding agents | Hypergel (hypertonic saline gel) Santyl (collagenase) Accuzyme (papain urea) | Various products provide some degree of chemical or enzymatic debridement. | 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. |
| Hydrocolloid | Aquacel CombiDERM Comfeel Duoderm CGF Extra Thin Granuflex Tegasorb | 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. |
| 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). |
| Low-adherence 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. |
| Transparent film | OpSite Skintact Release Tegaderm Bioclusive | 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). |
| Category | Examples | Description | Applications |
|---|---|---|---|
| Alginate | 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. Alginate rope is particularly useful to pack exudative wound cavities or sinus tracts. |
| Hydrofiber | 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. |
| Debriding agents | Hypergel (hypertonic saline gel) Santyl (collagenase) Accuzyme (papain urea) | Various products provide some degree of chemical or enzymatic debridement. | 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. |
| Hydrocolloid | Aquacel CombiDERM Comfeel Duoderm CGF Extra Thin Granuflex Tegasorb | 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. |
| 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). |
| Low-adherence 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. |
| Transparent film | OpSite Skintact Release Tegaderm Bioclusive | 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). |
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 points.34 Such intervention includes resection of metatarsal heads or ostectomy.35
- 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 gangrene.36,8,37 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 substitutes, and flap closures.38
- 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 substitute.39,27 It is not appropriate for infected ulcers, those that 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:
- 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, 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):
- 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:
- 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 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 (see Diabetes Mellitus, Type 2). For example, hemorheologic agents and antiplatelet agents are sometimes used in the management of underlying atherosclerotic disease. See also Infrainguinal Occlusive 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:
However, there is no conclusive evidence of any direct beneficial effect of either pentoxifylline or cilostazol on the healing of diabetic foot ulcers.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.
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.
Adult
400 mg PO tid with meals; if digestive or CNS adverse effects develop, decrease dose to 400 mg PO bid or discontinue
Pediatric
Not established
Coadministration with cimetidine or theophylline increases effect/toxic potential; pentoxifylline increases effect of antihypertensives
Documented hypersensitivity; cerebral and/or retinal hemorrhage
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal impairment; do not administer this drug without thoroughly reading complete prescribing information
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.
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
Diltiazem, erythromycin, grapefruit juice, itraconazole, ketoconazole, macrolide antibiotics, and omeprazole may increase levels
Documented hypersensitivity; CHF; coadministration with grapefruit juice
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.
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal impairment; do not prescribe or administer without thoroughly reading complete prescribing information
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.
Adult
75 mg PO qd
Pediatric
Not established
Coadministration with naproxen is associated with increased occult GI blood loss; clopidogrel prolongs bleeding time; safety of coadministration with warfarin not established
Documented hypersensitivity; active pathological bleeding, such as peptic ulcer or intracranial hemorrhage
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in patients at increased risk of bleeding from trauma, surgery, or other pathological conditions; caution in patients with lesions with propensity to bleed (eg, ulcers); do not administer this drug without thoroughly reading complete prescribing information
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.
Adult
75-325 mg PO qd
Pediatric
Not established
Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses > 2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs
Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma; due to association of aspirin with Reye syndrome, do not use in children (<16 y) with flu
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause transient decrease in renal function and aggravate chronic kidney disease; caution in patients with severe anemia, with history of blood coagulation defects, or taking anticoagulants; do not administer this drug without thoroughly reading complete prescribing information
More on Diabetic Ulcers |
| Overview: Diabetic Ulcers |
| Differential Diagnoses & Workup: Diabetic Ulcers |
 Treatment & Medication: Diabetic Ulcers |
| Follow-up: Diabetic Ulcers |
| Multimedia: Diabetic Ulcers |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
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Further Reading
Clinical guidelines
Wound, Ostomy, and Continence Nurses Society (WOCN). Guideline for management of wounds in patients with lower-extremity neuropathic disease. Glenview (IL): Wound, Ostomy, and Continence Nurses Society (WOCN); 2004. 57 p. (WOCN clinical practice guideline; no. 3).
National Collaborating Centre for Primary Care. Clinical guidelines for type 2 diabetes. Prevention and management of foot problems. London (UK): National Institute for Clinical Excellence (NICE); 2004 Jun. 104 p.
Lipsky BA, Berendt AR, Deery HG, Embil JM, Joseph WS, Karchmer AW, Lefrock JL, Lew DP, Mader JT, Norden C, Tan JS. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2004 Oct 1;39(7):885-910. 47
Registered Nurses Association of Ontario (RNAO). Assessment and management of foot ulcers for people with diabetes. Toronto (ON): Registered Nurses Association of Ontario (RNAO); 2005 Mar. 112 p.
Keywords
diabetes, ulcers, diabetic ulcers, diabetic dermal ulcer, diabetic dermal wound, diabetic foot wound, diabetic neuropathic ulceration, intractable plantar wound, neuropathic ulceration, neuropathic wound, silver dressings
