Table of Contents  

Zoech: Modern management of diabetic foot syndrome

Introduction

Reduction of the amputation rates is one of the primary goals in managing diabetic foot syndrome (DFS). A multidisciplinary team approach to diabetic foot care reduces amputation rates by about 49–85%. Health economic studies have shown that strategies to achieve a 25–40% reduction in the incidence of ulcers or amputation are cost-effective and even cost-saving.

The circumstances and problems leading to amputations in patients with DFS are probably widely underestimated. Up to 70% of all lower-leg amputations are performed on people with diabetes, which means that > 1 million people undergo a lower-limb amputation as a consequence of DFS every year. Every 30 sec, a limb is lost worldwide. The annual incidence of lower-extremity amputations ranges from 46.1 to 93.6 per 100 000 people with diabetes, the exact figure depending on demographic factors and the prevalence of diabetes. In only a few countries is a continuous registration system in place.14

How is diabetic foot syndrome defined?

Diabetic foot syndrome is defined as infection, ulceration or destruction of deep tissues of the foot associated with neuropathy and/or peripheral arterial disease in the lower extremity in an individual with diabetes. A foot lesion is called any abnormality associated with damage to the skin, nails or deep tissues of the foot. Necrosis of the skin and underlying structures with irreversible damage is defined as gangrene.

Goals and strategies

Healing of foot ulcers is limited by multiple factors and, thus, therapeutic strategies require a multifactorial approach (Table 1). Treatment of vascular disease, pressure relief, infection control and wound-bed management are essential components of the multifactorial treatment of diabetic foot ulcers. The cause and site of the ulcer must also be considered in choosing between different treatment strategies. Topical wound management is adjunctive to systematic and surgical treatment. Lifelong observation and continuity of care of people with a foot at risk are essential both in prevention and management.5

TABLE 1

Management of a diabetic foot ulcer5

Goal Strategy
Improve metabolic control Tight blood glucose regulation
 Malnutrition
Treat infection Antibiotics
 Oral
 Parenteral
Culture, biopsy
Radiography, computerised tomography (CT), bone scan, magnetic resonance imaging (MRI)
Non-weight bearing Therapeutic footwear
 Insoles/orthoses
 Contact casting/cast boot
 Crutches
 Wheelchair/bed rest
Improve circulation Non-invasive vascular testing
 Percutaneous transluminal angioplasty (PCTA)
 Vascular surgery
General condition Cardiovascular treatment
Treat retinopathy/nephropathy
Treat malnutrition
Cessation of smoking
Pain control Analgesic agents
Relieve anxiety
Treat oedema Intermittent external compression
Diuretics
Topical treatment Debridement
Dressings
Topical agents
Skin grafting
Foot surgery Incision/drainage
 Corrective surgery
 Amputation
Setting Patient/staff education
Compliance
Support/follow-up
Multidisciplinary

Treatment of diabetic foot syndrome

The principles of care of a diabetic foot ulcer

The principles of care of diabetic foot ulcer are (1) treatment of any associated infection, (2) revascularization if feasible, (3) off-loading, and (4) management of the wound bed in order to promote healing. The important principles are simple: regular inspection, cleansing, removal of debris and/or regular debridement with a scalpel and protection of the regenerating tissue from the environment.6

Wound management and wound bed preparation

Diabetic wounds need to be carefully cleaned and debrided of necrotic tissue and surrounding callus (Table 2). In the case of non-infected wounds, saline is the most appropriate medium. Those with heavy exudate need a dressing that absorbs the moisture, whereas dry wounds heal best in a moist environment. Older evidence supported the use of hydrogels, but there are no recent data to confirm their effectiveness.7 The use of honey is widespread in clinical practice, but only one study has assessed the effect of honey in a controlled trial. This study reported no difference between the use of honey and of povidone iodine.8 To allow careful examination of the wound, dressings should be changed at least daily. Available studies do not support the use of any topical antimicrobials on most wounds. Topical negative pressure therapy may hasten healing of postoperative wounds.9

TABLE 2

Wound management of diabetic foot ulcers – a set of simple interventions5

The wound should be cleaned regularly with water or saline
Exudate should be controlled in order to maintain a moist wound environment; usually a sterile, inert protective dressing is sufficient
Regular debridement with a scalpel

There are currently no data to justify the use of specific treatments or dressing products (including silver-containing dressings or other antiseptic products) in routine management of diabetic foot ulcers. In summary, there is only little evidence to support the choice of any one dressing in preference to any other that promotes healing of chronic diabetic foot ulcers.5

Hyperbaric oxygen

New studies provide further evidence that the use of systemic hyperbaric oxygen (HBO) and not topical oxygen therapy may increase the incidence of healing10,11 and reduces the rate of major amputation in patients with unreconstructable peripheral arterial disease.12

Bioengineered skin and skin grafts

There is a limited number of reports suggesting that bioengineered skin products might hasten wound healing and the evidence to justify their routine use is not strong.13

Application of platelets and stem cells

Some studies of the effectiveness of the supernatant of platelet suspensions have suggested benefit. Jeong et al.14 assessed the use of platelets from ABO- and rhesus-matched blood-bank samples and reported a significant improvement in the healing at 12 weeks compared with a control group. The incidence of healing was surprisingly high.

The clinical effectiveness of topical platelet-derived growth factor (PDGF, becaplermin) or of other growth factors on healing remains to be confirmed.5

Seung-Kyu and colleagues15 reported a retrospective comparison of fibroblast allograft recipients and controls. A significant improvement in healing at eight weeks in the 37 recipients compared with 18 control subjects was reported, but it is possible that selection bias could have influenced the results.

Electrical stimulation and shockwaves

Petrofsky et al.16 compared the use of electrical stimulation with a placebo comprising local warming of the skin. The study was very small and not blinded. A reduction in ulcer area in the intervention group was seen at four weeks.

At present there is no strong evidence for the use of shockwave therapy in DFS. The results of two trials have recently been published. The first randomized 30 patients to receive either shockwave therapy for 72 hours or a sham intervention. There was no difference in healing by 20 weeks.17

The second compared extracorporeal shockwave treatment with hyperbaric oxygen, and reported a significant difference between the two groups, this study may have been methodologically weak.18

Off-loading

Ulcer prevention and prevention of recurrence

Only limited studies of sufficient methodological quality are available regarding the effectiveness of footwear and surgical off-loading in preventing ulceration.

There are indications that therapeutic shoes may reduce ulcer recurrence compared with standard footwear, although one study reviewed found no effect.19

In patients with neuropathic plantar ulceration, surgical off-loading techniques, such as lengthening of the Achilles tendon, in combination with surgical excision, debridement and removal of bone segments, reduce the risk of ulcer recurrence. Surgical procedures such as metatarsal head (MTH) resection and joint arthroplasty may also reduce the risk of ulcer recurrence compared with conservative off-loading treatment.21

Ulcer treatment

Adequate pressure relief is an essential component of successful and consistent healing for the majority of neuropathic diabetic foot ulcers.

Application of a total-contact cast (TCC) is associated with healing of a higher proportion of neuropathic plantar foot ulcers, and at a faster rate, than use of removable walkers or off-loading shoes.22 Similar rates and speed of healing are achieved by the use of alternative off-loading devices, such as cast boots23 or non-removable walkers,24 but it appears that half-shoes, off-loading shoes or extra-depth shoes with Plastazote® (Zote foams Plc., Croydon, UK) insoles are less effective.25 Surgical off-loading techniques significantly reduce healing time, whether or not they are used in addition to TCC treatment, but they do not increase percentage of healed ulcers when compared with use of TCC alone.26 However, MTH resections or trans-metatarsal amputations may cause increased pressure in other areas of the foot residuum.27,28 Exostectomy procedures are relatively reliable methods of treatment for prominent deformities secondary to Charcot's neuro-osteoarthropathy. Regular callus removal contributes to a reduction in plantar pressure,29 whereas the presence of callus has been associated with a relative risk of development of a plantar ulcer.30

A TCC is the most effective treatment of neuropathic, non-ischaemic, non-infected, non-plantar diabetic foot ulcers, whereas cast shoes or cast boots and irremovable walkers may be considered alternative modalities in selected patients. Neither conventional shoes nor a walking brace are recommended for the healing of foot ulcers in diabetic patients.

The infected diabetic foot

Diagnosis

Every diabetic foot wound should be assessed routinely for the presence of infection. The diagnosis of infection in DFS is based on clinical findings of inflammation rather than on the results of wound cultures. Cultures are not necessary in the case of lesions that appear clinically uninfected and, in any case, are difficult to obtain in the presence of cellulitis. Wound cultures are more helpful in optimizing antibiotic selection when taken from deep-tissue specimens, because those obtained from superficial swabs often yield colonizing organisms. Hospitalization is necessary for patients with severe infections and those who need surgical or diagnostic procedures (Table 3). The consensus criterion standard for the diagnosis of osteomyelitis is an aseptically obtained bone sample with histopathological findings of inflammation and microorganisms recovered by culture. Other useful tests for osteomyelitis are probing to bone, erythrocyte sedimentation rate, sequential radiographs and, especially, magnetic resonance imaging (MRI). Nuclear medicine scans and computed tomography (CT) are less helpful.5

TABLE 3

Findings suggesting a serious diabetic foot infection

Wound penetrates into fascia, tendon, muscle, joint and/or bone
Cellulitis is extensive, distant from ulceration or rapidly progressive
Local signs: abscess, crepitus, bullae, induration, discoloration, necrosis/gangrene, ecchymoses
Severe inflammation
Progression while on apparently appropriate antibiotic therapy
Leucocytosis, worsening hyperglycaemia, acidosis, electrolyte abnormalities
Fever, hypotension, confusion, volume depletion

Treatment

Infected diabetic foot ulcers often require surgical therapy. Patients should usually be hospitalized (Table 4) to facilitate control of their metabolic status, administration of parenteral antibiotics, close monitoring of treatment response and sufficient off-loading of the affected area.

TABLE 4

Indications for hospitalization

Metabolic instability
Severe infection
Critical foot ischaemia present
Surgical procedures required
Intravenous therapy needed
Diagnostic tests needed
Failure of outpatient management

Wound care

Patients with infected diabetic foot wounds should be encouraged to be non-ambulatory or to be mobile only with an appropriate off-loading device. TCCs should be windowed to allow visualization of the wound and topical negative-pressure devices without instillation should be changed daily.

Surgery is the cornerstone of treatment of an infected DFS, but only surgeons with adequate knowledge of the anatomy of the foot should operate. Early surgical intervention is associated with better outcomes. Severe infection in an ischaemic limb, an abscess accompanied by compartment syndrome or necrosis, extreme pain or systemic sepsis syndrome necessitate emergent intervention. In many cases, revascularization is needed for an infected ischaemic limb.31 Especially in an ischaemic foot with a dry eschar, it is often best to avoid debriding the necrotic tissue. Surgery may range from minor debridement and drainage to extensive resection. Major amputation should be avoided. When the limb is non-viable, is affected by life-threatening infection, is causing intractable pain or is functionally useless, major amputation should be performed.32,33

Antibiotic therapy

There is no need for antimicrobial therapy in clinically uninfected, superficial wound. In the case of clinically infected wounds, the initial antibiotic therapy is usually empirical and the regimen should always include an antibiotic active against Staphylococcus aureus and aerobic streptococci. In patients with risk factors for methicillin-resistant Staphylococcus aureus (MRSA), an agent effective this organism should be added, and patients who have been previously treated with an antibiotic or have a severe infection may need extended coverage for common Gram-negative bacilli and for Enterococcus species. In the case of necrotic or gangrenous wounds, empirical anti-anaerobic therapy is appropriate. A combination may be appropriate for infections presumed to be caused by more than one organism or when the pathogen has a high potential to develop resistance.

Available data do not favour any specific antibiotic class or agent. When culture and sensitivity results are available, consider a change to a more specific regimen targeted at the isolated pathogens, but if the infection is improving and the patient is tolerating therapy, there may be no reason to change.34 If the infection is not responding or worsening, treatment has to be modified or the need for surgical intervention should be revisited. Two studies have suggested that the risk of major amputation is significantly reduced when minor surgery is deployed early. The risk reduction was 27% to 13% in one study35 and 8% to 0% in the other.36 Agents that have demonstrated clinical effectiveness, alone or in combination, in published prospective studies of diabetic foot infections are listed in Table 5 and factors that influence the choice of antibiotic are shown in Table 6.37

TABLE 5

Agents that have demonstrated clinical effectiveness37

Orally Parenterally
Cephalosporins
Cefalexin Cefoxitin
Ceftizoxime
Penicillin/β-lactamase inhibitor congeners
Amoxicillin/clavulanate Ampicillin/sulbactam, piperacillin/tazobactam
Ticarcillin/clavulanate
Carbapenems
Imipenem/cilastatin
Ertapenem
Fluoroquinolones
Ciprofloxacin Ciprofloxacin
Ofloxacin Ofloxacin
Levofloxacin Levofloxacin
Moxifloxacin Moxifloxacin
Clindamycin
Amdinocillin
Linezolid
Daptomycin
Vancomycin
TABLE 6

Factors that may influence choice of antibiotic therapy for diabetic foot infections

Infection related
Clinical severity of the infection
History of antibiotic therapy within 3 months
Bone infection
Patient related
Allergies to antibiotics
Impaired immunological status
Patient treatment preferences
Renal or hepatic insufficiency
Impaired gastrointestinal absorption
Arterial insufficiency in affected limb
Drug related
Safety profile (frequency and severity of adverse effects)
Drug interactions potential
Frequency of dosing
Formulary availability/restrictions
Cost considerations (acquisition and administration)
Approval for indication
Likelihood of inducing Clostridium difficile disease or antibiotic resistance
Published efficacy data

The optimal duration of antibiotic therapy for diabetic foot infections is unknown, but 1–2 weeks is usually effective.38 In the case of more serious infections, 2–4 weeks' treatment is usually sufficient.39 Antibiotic therapy can be discontinued even if the wound has not healed provided signs of infection have resolved. The aim of the antibiotics is to cure infection, not to heal wounds. Prolonged antibiotic therapy may be necessary for osteomyelitis, for wounds that are deep, large or poorly perfused, or in immunocompromised patients. Only severe infections require parenteral therapy: mild and most moderate infections can be treated with oral antibiotics.

With appropriate treatment, the signs and symptoms of mild infections resolve without the need for amputation. When infection involves deep structures or bone, surgical debridement, bone resection or partial amputation is required. In the hands of an experienced surgeon, most amputations can be foot-sparing.40 In the case of extensive infection, or in medical centres with limited expertise, major amputation rates of up to 50–60% have been reported.37 The presence of limb or foot ischaemia has a negative effect on the outcome, in synergy with infection, and worsens the prognosis.41

Treating osteomyelitis

Among the important factors to consider when treating osteomyelitis are the following: the anatomical site of infection, the local vascular supply, the extent of soft tissue and bone destruction, the presence of systemic signs of infection and the patient's preferences.42 The choice of an antimicrobial agent for osteomyelitis should ideally be based on the results of a bone culture, but, if empirical therapy is necessary, always select a regimen that covers S. aureus. Many cases of diabetic foot osteomyelitis require surgical debridement or resection of bone. Some can be treated successfully by antibiotic therapy alone, but there is need for long-duration therapy, usually 3–6 months.43 If all of the infected bone is surgically removed, a shorter course of antibiotic therapy may be sufficient, depending on the status of the soft tissues.37 Extending post-debridement antibiotic therapy beyond six weeks, or intravenous (i.v.) treatment for longer one week, does not appear to increase the remission rate.44 It is difficult to know when osteomyelitis is cured. Remission includes a drop in the erythrocyte sedimentation rate or C-reactive protein level and healing of any overlying soft-tissue wound.

Surgical procedures

Prior to surgery in patients with diabetes, preoperative medical assessment and management of diabetes and comorbid conditions is necessary. Emphasis must be directed to renal, cardiovascular and/or vascular disease issues. Wounds will not heal without adequate nutrition, and it is essential to assess the nutrition status of patients.

Patients with systemic symptoms should be evaluated for gangrene or deep abscesses, which require urgent surgical intervention. All surgical procedures should be performed by a competent surgeon. These specialists are trained to distinguish between limb-threatening conditions, that need emergent surgery, and non non-limb-threatening presentations for elective or prophylactic surgery. Patients with serious wound infections need emergent surgery, because the risk of tissue loss and amputation is increased by long delays before surgery. Infected wounds must be incised and a drainage for pus established. They need to be explored, necrotic tissue and bone removed and local amputation carried out if necessary. The aggressiveness of the surgical interventions is determined by the nature of the presentation. Early surgical intervention, even for moderate infections, may reduce the risk of lower-extremity amputation. If revascularization of an ischaemic limb is necessary, it should be done as soon as possible. Surgery may also be necessary for loss of mechanical function of the foot and/or when the degree of bone involvement is limb-threatening (Table 7).

TABLE 7

Goals of diabetic foot surgery

Establish dependent drainage
Remove bacteria-laden necrotic soft tissue and/or infected bone
Reduce risk of ulceration and/or amputation
Correct deformity
Preserve function
Restore stability
Prevent major amputation

Ulcer recurrence

In DFS ulcer recurrence remains a problem. Studies have reported between 27–100% rates of recurrence at one and four years respectively.45

Case studies

Debridement

A 71-year-old man with type 2 diabetes mellitus for 11 years and neuropathy developed ulcers on the plantar surface over the first and second ray (Figure 1a and b). The infected DFS had been treated with betadine by a general practitioner. The patient was hospitalized for parenteral antibiotic therapy and surgery. Radiography revealed destruction of the metatarsocuneiform joint of the first ray. Debridement and resection of bony sequestrum was performed and the first toe partially amputated to close the defect.

FIGURE 1

(a) Before debridement. (b) After debridement.

5-2-1-fig1.jpg

Removal of callus

A 67-year-old woman with type 2 diabetes mellitus of 12 years' duration with no peripheral arterial disease but neuropathy underwent amputation of the first toe (Figure 2a and b). She developed two ulcers on the plantar surface. The proximal ulcer was surrounded by callus and after removal the underlying ulcer was superficial. The probe to the bone was positive at the distal ulcer after debridement. The bony sequestrum was removed and a therapy with TCC promoted healing within six weeks.

FIGURE 2

(a) Before removing the callus. (b) After debridement.

5-2-1-fig2.jpg

Severely infected foot treated with negative-pressure wound therapy

A 52-year-old man, being treated for a blister, was admitted to the clinic with a severely infected diabetic foot as the first manifestation of type 2 diabetes (Figure 3). He had no manifest peripheral arterial disease and no neuropathy. Emergent surgery was performed as a limb-saving procedure.

FIGURE 3

(a) On day 2 after primary surgery, prior to second necrectomy. (b) Negative-pressure wound pressure device (NPWT) (V.A.C. Therapy®; Kinetics Concepts Inc., San Antonio, TX, USA) in place on day 18. (c) The wound after two weeks of NPWT. (d) Transplantation of a split-thickness graft, fixed with the (V.A.C. Therapy®) (e) After 10 days the skin is healing. (f ) The situation eight weeks after onset.

5-2-1-fig3.jpg

The necrotic tissue was removed and abscess drainage performed. After a second necrectomy two days after the first surgical intervention, a negative-pressure wound therapy (NPWT) device (V.A.C. Therapy®) was applied for two weeks, with dressings changed every second day. After two weeks, a split-thickness graft was applied. The NPWT was applied again for five days, fixing the skin graft. The skin healed and, eight weeks after onset, the defect was closed.

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