Supported by a grant from

Robert J. Snyder, DPM, CWSRobert S. Kirsner, MD, PhDRobert A. Warriner III, MD, FACA, FCCP, FCCWS, ABPM/UHMLawrence A. Lavery, DPM, MPHJason R. Hanft, DPM, FACFASPeter Sheehan, MD

Consensus Recommendations OnAdvancing The Standard Of CareFor Treating Neuropathic Foot Ulcers In Patients With Diabetes

Supplement to April 2010

This supplement is provided as a courtesy to the readers of WOUNDS.

WOUNDS

2

Robert J. Snyder, DPM, CWS*. Dr. Snyder is the Medical

Director of the Wound Healing Center at University Hospital in

Tamarac, Fla. He is an Adjunct Professor at the Temple University

School of Podiatric Medicine in Philadelphia. Dr. Snyder is in pri-

vate practice in Tamarac, Fla.

Robert S. Kirsner, MD, PhD. Dr. Kirsner is the Director of

the University of Miami Hospital Wound CURE Center in

Miami. He is a Professor and the Vice Chairman of the Depart-

ment of Dermatology at the University of Miami Miller School

of Medicine.

Robert A. Warriner III, MD, FACA, FCCP, FCCWS,

ABPM/UHM. Dr. Warriner is Chief Medical Officer of Diversi-

fied Clinical Services in Jacksonville, Fla. He is the Emeritus Med-

ical Director and Founder of the Southeast Texas Center for

Wound Care and Hyperbaric Medicine at the HCA Conroe Re-

gional Medical Center in Conroe, Texas.

Lawrence A. Lavery, DPM, MPH. Dr. Lavery is a Professor in

the Department of Surgery at the Texas A&M Health Science

Center College of Medicine.

Jason R. Hanft, DPM, FACFAS. Dr. Hanft is the Director of

Research for the Podiatric Residency Program and is the Director

of Podiatric Education at the South Miami Hospital in Miami. He

is in private practice at The Foot and Ankle Institute of South

Florida in Miami.

Peter Sheehan, MD. Dr. Sheehan is the Chair of the Car-

diometabolic Risk Committee of the American Diabetes Asso-

ciation. He is a consultant at Sanford Health USD Medical

Center in Sioux Falls, S.D. Dr. Sheehan is in private practice in

New York City.

*Corresponding author: Please address correspondence to: Robert J. Sny-

der, DPM, CWS, 7301 N. University Drive, Suite 305, Tamarac, FL

33321; e-mail: drwound@aol.com

Consensus Panel Members

Potential Conflicts Of InterestDr. Snyder has disclosed that he has received speaker honoraria

and served as a consultant or paid advisory board member for Ad-

vanced BioHealing. Dr. Snyder is the Medical Director of Systa-

genix Wound Management.

Dr. Hanft has disclosed that he has received speaker honoraria

and served as a consultant or paid advisory board member for Ad-

vanced BioHealing.

Dr. Kirsner has disclosed that he has received speaker honoraria

from Advanced BioHealing and Organogenesis.

Dr. Lavery has disclosed that he has received speaker honoraria

from KCI and Advanced BioHealing. Dr. Lavery serves as a con-

sultant or paid advisory board member for Chronic Disease Spe-

cialists, and has stock ownership in Chronic Disease Specialists.

Dr. Sheehan has disclosed that he has received research grant

funding from Tissue Repair Company, PamLab and Sanofi-Aven-

tis. Dr. Sheehan is the Director of Greystone Pharmaceuticals and

is a consultant or paid advisory board member for Advanced Bio-

Healing, Heal Or and ev3. Dr. Sheehan is also a consultant for

Sanford USD Medical Center, US Biotest, Izun, Hypermed and

Calretex. Dr. Sheehan is also a member of the Speakers’ Bureau

for ev3, Bristol-Myers Squibb/Sanofi-Aventis, Merck and

Organogenesis.

Dr. Warriner has disclosed that he has received speaker hono-

raria from Systagenix Wound Management.

Acknowledgments: This activity is supported by a grant from Advanced BioHealing. The authors thank Amy M. Horton,

PharmD, for editorial and manuscript assistance. The authors also thank David J. Margolis, MD, PhD, for editorial assistance.This supplement is provided as a courtesy to the readers of WOUNDS. This supplement was not subject to the peer review

process of WOUNDS.

3

Abstract: Neuropathic foot ulcers are a common and serious complication of diabetes mellitus. The presence of an unhealed

diabetic foot ulcer (DFU) increases the risk of infection, amputation and death. Low rates of DFU healing remain a challenge.

Recognizing these issues, a consensus panel recently was convened to review the evidence and practicalities for the evaluation

and treatment of patients with neuropathic DFUs. This consensus panel seeks to provide clinicians with the clinical markers, ev-

idence and recommendations that, used in conjunction with orderly decision-making and good clinical judgment, will advance

the standard of care for the treatment of neuropathic DFUs.

Key Words: advanced therapy, amputation, diabetic foot ulcer, debridement, hyperbaric oxygen therapy, infection control, livingskin equivalents, offloading, strain rate, wound bed preparation, wound classification systems

Index: Ostomy Wound Management. 2010;56(suppl 4):S1–S24.

Consensus Recommendations On Advancing TheStandard Of Care For Treating Neuropathic Foot Ulcers In Patients With DiabetesRobert J. Snyder, DPM, CWS; Robert S. Kirsner, MD, PhD; Robert A. Warriner III, MD, FACA, FCCP,FCCWS, ABPM/UHM; Lawrence A. Lavery, DPM, MPH; Jason R. Hanft, DPM, FACFAS; and PeterSheehan, MD

4

INTRODUCTIONDiabetes mellitus represents a group of chronic diseases charac-

terized by high levels of glucose in the blood resulting from de-

fects in insulin production, insulin action or both. Worldwide,

the number of cases of diabetes has been estimated to be 171

million and this number is projected to reach 366 million by

2025.1 Patients with diabetes are at risk for developing serious

health problems that may affect areas of the body including the

eyes, feet, skin, heart and kidneys. Among these health concerns,

foot ulceration is one of the most common complications. The

annual incidence rate for foot ulcers is 1% to 6.84% in individ-

uals with diabetes with a lifetime risk of 15% to 25%.2-6

The development of diabetic foot ulcers (DFUs) is thought to

result primarily from either peripheral arterial disease (PAD)

and/or peripheral neuropathy in addition to factors like defor-

mity, callus and trauma.4,5,7-9 However, the severity of PAD, in-

fection and deficiencies in the effective treatment of DFUs are

linked with secondary medical complications such as os-

teomyelitis and amputation. Approximately 15% of DFUs result

in lower extremity amputation.5,9 Diabetic foot ulcers are a con-

tributing factor in more than 85% of all diabetes-related lower

extremity amputations.8,10

The significant morbidity and mortality associated with dia-

betes is well known. A recent 10-year, prospective, population-

based study found a history of DFU to be a significant

independent predictor of mortality in patients with diabetes.11

This study found patients with diabetes with a history of DFU

had a 47% increased risk of mortality in comparison to patients

with diabetes who did not have a history of DFU. The five-year

mortality rates for patients with neuropathic and ischemic DFUs

were 45% and 55% respectively.12

The economic burden of DFUs and the complications aris-

ing from them are enormous. The estimated annual cost of care

for a patient with a DFU is $15,309 (1995 dollars) and direct

costs for a lower extremity amputation range from $22,700 to

$51,300 (2001 dollars).13,14 One of the most important cost-

saving considerations in caring for the patient with a DFU is

expeditious and complete wound healing to avoid complica-

tions such as amputation. Standard management strategies for

healing this malady typically have included preparation of the

wound bed, debridement, infection control, revascularization

and offloading. Despite the use of standard management strate-

gies, healing rates of DFUs remain low.

Clinical Decisions And Evidence-Based Medicine

Evidence-based medicine is defined as “the conscientious, explicit,

and judicious use of current best evidence in making decisions

about the care of patients” that integrates “individual clinical ex-

pertise with the best available external clinical evidence from sys-

tematic research.”15

Evidence-based medicine often involves searching published sources

for evidence to help guide an answer to a given clinical question. The

evidence often is obtained from sources such as PubMed

(http://pubmed.gov) or peer-reviewed sources like the Cochrane Col-

laboration (http://www.cochrane.org/). The practitioner then needs to

critically evaluate the evidence for its validity, importance and usefulness

in clinical practice.

Levels of evidence are used to rank the strength and validity of

the evidence from basic research to systematic reviews and meta-

analyses (see Figure 1). The treating clinician can subsequently in-

tegrate the critical evaluation of evidence with clinical expertise

and the patient’s individual problems and needs. The evidence ob-

tained from clinical trials is just one factor and must be interpreted

in light of individual patient factors, including the impact of co-

morbidities not addressed in clinical trials, economic issues and

psychosocial issues, in order to come to a clinical decision. Quite

often, the best level of evidence (ie, randomized controlled trial)

is not available on which to base a decision so all levels of evidence

must be considered.

Clinical guidelines and algorithms are readily available for as-

sisting in care decisions. Such guidelines, usually the result of

multidisciplinary teamwork, provide fast, accessible resources for

clinicians to make patient care decisions. Although they may vary

in regard to strength of scientific evidence, these guidelines and

Randomized Controlled Double Blind Studies

Systematic Reviewsand Meta-analyses

Cohort Studies

Case Control Studies

Case Series

Ideas, Editorials, Opinions

Animal research

In vitro (’test tube’) research

Case Reports

Figure 1. The Level Of Evidence Pyramid

Adapted from Sackett DL, Rosenberg WM, Gray JA, Haynes RB,Richardson WS.Evidence based medicine: what it is and what it isn't.BMJ. 1996;312(7023):71-2.

5

algorithms carry the weight of the governmental agencies, pro-

fessional organizations, universities, and authors who release

them.16 Table 1 lists several resources for guidelines and algo-

rithms specific to DFUs.

However, a systematic literature review of quality of care in the

United States revealed that 30% to 40% of patients are not being

treated according to evidence-based guidelines, and 20% to 30%

of care is either inappropriate, unnecessary or potentially danger-

ous.17 These data illustrate that there are apparent barriers to the

adoption of treatment guidelines and gaps exist between research

and clinical practice.

Recognizing these issues, a multidisciplinary panel of experts in

the field of wound care in patients with diabetes was recently con-

vened to review and discuss the evidence and practicalities for a

variety of modalities for DFU evaluation and treatment. The goal

of this panel was to provide straightforward and practical ap-

proaches for clinicians to adopt when treating patients with DFUs,

thus working to close the loop between research and practice.

In formulating these recommendations, the panel debated the

merits and disadvantages of these approaches, and held each to the

highest level of evidence available. They recognized that while ev-

idence-based guidelines may provide an ideal approach, clinicians

must consider and address the unique set of challenges inherent

to each individual patient.

ASSESSMENT OF THE DFUThe panel recognizes that a multidisciplinary team approach is

most advantageous for the treatment of the neuropathic ulcer in

patients with diabetes, and this is viewed as the standard of care.18

Furthermore, this approach should be considered as part of a con-

tinuum of care including acute care, home health care, subacute

intervention and the clinician’s office or wound care center.

However, the panel recognizes that multidisciplinary teams

are not always available. In these settings, referral to other spe-

cialists should be based on clinical judgment. The guidelines

listed in this section comprise the most important components

of the initial wound evaluation. Clinicians should be open to

additional testing beyond what is delineated below if clinical

impression warrants.

A comprehensive foot and ulcer evaluation for patients with dia-

betes encompasses several criteria. These key components include a

patient history and physical examination, laboratory screening, nu-

tritional evaluation, and a neurologic, musculoskeletal and vascular

assessment.19Wound history, a description and measurements of the

wound should be included in the evaluation. The clinician should

be looking for factors that may have led to wound formation and

may impair healing. Foot ulcers in patients with diabetes that exhibit

“stalled” healing after two to four weeks should be re-evaluated.

History And Physical Examination

A complete history and physical must be performed as part of an ap-

propriate evaluation. Information pertinent to the patient with a

DFU includes: the duration of diabetes, degree of glycemic control,

the presence of other diabetes-associated comorbidities and other

illnesses that may affect wound repair such as end-stage renal disease,

pulmonary disease, or cardiovascular disease (hypertension, dyslipi-

demia, myocardial infarction, transient ischemic attacks, angina, or

valvular heart disease). A review of systems and family history should

also be considered.

Clinicians also should assess factors such as the initial wounding

event, history of recurrent wounding, previous wound healing

problems, prior diagnostic testing, prior therapies and response,

functional impact of the wound on the patient, and a sufficient

social history to define potential adverse impact on an optimal

plan of care.

Table 1. Some Resources For Guidelines And Algorithms ForThe Care Of Patients With Diabetic Foot Ulcers

Association for the Advancement of Wound Care

www.aawconline.com

American College of Cardiology

www.acc.org/

American College of Footand Ankle Surgeons

www.acfas.org

American Diabetes Association

www.diabetes.org

American Orthopaedic Foot and Ankle Society

www.aofas.org

American Pharmaceutical Association

www.pharmacist.com

Cochrane Collaboration www.cochrane.org

Infectious Diseases Society of America

www.idsociety.org

International WorkingGroup on the Diabetic Foot

www.iwgdf.org

Wound Healing Society www.woundheal.org

Wound, Ostomy, Continence Nurses Society

www.wocn.org

6

Laboratory Screening

Since wound healing can be delayed by complications like anemia

and renal insufficiency, complete blood count and

creatinine/blood urea nitrogen tests may be included as part of

the baseline evaluation for patients with chronic wounds.20 If deep

tissue infection or osteomyelitis is suspected, erythrocyte sedimen-

tation rate (ESR) and C-reactive protein (CRP) testing may be

considered as secondary markers.21,22

Hemoglobin A1C. Although there is no concrete evidence

linking hemoglobin A1C to impaired wound healing, this test

should be used to assess the degree of glycemic control as an

overview of the patient’s disease state.23 Although optimal cut-

offs are still in debate, the American Diabetes Association (ADA)

generally recommends an A1C goal of <7% for adults with di-

abetes.24 Hemoglobin A1C should be ordered by the wound

care specialist if one has not been recently performed by the

patient’s internist or endocrinologist.

Lipid profile. A multitude of patients with diabetes who have

concomitant neuropathic ulcers are at high risk for developing or

have been diagnosed with cardiovascular disease.25 Therefore, it is

important to reduce dyslipidemia, hypertension and other cardio-

vascular risk factors. In this regard, evaluation of the patient’s lipid

profile (cholesterol, HDL and LDL) and homocysteine levels re-

mains critical, and wound specialists should work closely with the

patient’s primary care physician or cardiologist for any significant

change in this panel.

Nutritional Assessment

Although albumin is considered a gold standard for assessing

long-term nutritional status, there is little evidence to suggest

that it either predicts DFU healing or that correction of a low

albumin level improves healing.26 In patients with diabetes, low

albumin may be a marker for poor renal function rather than

poor nutrition.

Prealbumin has a shorter half-life when compared to albumin

and therefore may be a more appropriate marker in evaluating

protein deficiency. This test can be performed frequently to ascer-

tain whether a particular nutritional intervention is effective.26

If malnutrition is suspected, a dietary questionnaire should be

completed at screening by the patient and evaluated by the clini-

cian.27 Although no specific evaluation was recommended by the

panel, clinicians should choose the tool that works best for their

daily clinical practice.

Considerations include:

• Height

• Weight

• Unintentional change in weight > 10 lbs over the past six months

• Persistent or recurrent diarrhea

• Alcohol intake greater than three drinks per day

• Current dietary supplements including over-the-counter

vitamins

• Mouth, tooth or swallowing problems

• Tube feeding or TPN

• Limited access to food, missing two meals/day for more than two

days out of the week

• Morning fasting blood sugar

Responses may prompt further laboratory studies and nutritional

referral.27

Lifestyle/Psychosocial

Quality of life. General quality-of-life scoring systems exist but

may not be practical in day-to-day clinical practice because of their

length and complexity. Although the panel cannot recommend a

particular quality-of-life screener, a basic line of questioning should

be used at initial evaluation and subsequent visits to help guide

treatment decisions. For example: Do you have pain? How do you

feel? Do you feel worse or better? Are you working? What are

your daily activities? Are you able to carry out daily activities?

Smoking.Although there is little direct research on the effect

of smoking on healing of DFUs, there is some evidence that

chronic smoking has a negative impact on endothelial and smooth

muscle microcirculation in the skin, which could impair healing.28

This evidence, in addition to the known macrovascular and end-

organ complications associated with smoking, makes smoking ces-

sation a goal in the treatment of any DFU.

Additional factors include alcohol consumption and the pres-

ence of depression or other mental illness because these may affect

adherence with treatment recommendations.29,30

Neurologic Screening

There are several techniques that can be used to assess sensory func-

tion during neuropathic screening. The current recommendation

supported by the ADA advocates the use of the 10-g monofilament

in addition to one of the following techniques: pinprick sensation,

vibration perception with a 128-Hz tuning fork, ankle deep tendon

reflexes or vibration perception threshold testing.24The use of a 128-

Hz tuning fork and 10-g monofilament tests on the foot is recom-

mended by the consensus panel to assess neuropathy.

Vascular Evaluation

There is no universal noninvasive test that can completely evaluate

vascular health.31 However, a combination of testing, used where

7

indicated and appropriate, can support the assessment of vascular

supply in patients with diabetes. The panel recommends a tiered

testing approach to assist clinicians in evaluating DFUs. At screen-

ing, one or more measurements may be appropriate given the clin-

ical impression, equipment requirements and operator expertise.

These measurements include palpation of pulses, ankle brachial

index (ABI) and/or toe brachial index (TBI).

Palpation of pulses. Palpation of peripheral pulses, including

the femoral, popliteal and pedal vessels (dorsalis pedis and posterior

tibial), should be part of the routine physical examination. Al-

though the panel recognizes that palpation of pulses is subject to

a degree of variability among clinicians, it can provide evidence

for the presence of vascular disease but not necessarily its absence.32

In this regard, palpation of pulses is an inadequate screening tool for

PAD in patients with diabetes in the setting in which pulses are

present or absent.33

Ankle brachial index (ABI). The ADA recommends the

ABI as a reproducible and quantitative test for vascular evalu-

ation.32 Simple to perform, the ABI measures the patency of

the lower extremity arterial system using a hand-held Doppler

probe and a blood pressure cuff. The ABI is calculated as a ratio

of systolic blood pressure measured in the dorsalis pedis and

posterior tibial arteries of the ankle, taking the highest of the

two, divided by the systolic blood pressure in the brachial ar-

tery measured at the arm of a patient in a supine position for

five minutes.

Diagnostic interpretation indicates that low ABI ratios are as-

sociated with a high vascular risk (see Table 2).32 Normal values

range from 0.91 to 1.30 and ratios < 0.91 or > 1.30 could be

indicative of PAD. These individuals require further evaluation.

However, the ABI should be performed with an understanding

of the limitations of this test in patients with diabetes. For ex-

ample, results may be normal because the patient may be in a

transitional stage of diabetes. Conversely, an ABI value of >1.30

may be spurious secondary to medial arterial calcification in

this patient population.31

Toe brachial index.As the applicability of ABI may be po-

tentially limiting given that some patients with diabetes may de-

velop calcification in lower limb arteries that may result in a

falsely high ankle pressure, the TBI can be substituted. Clinicians

should remember that the TBI measurement requires specialized

equipment not commonly found in clinical settings and addi-

tional technical expertise.34 The TBI has shown to be superior

to the ABI in patients with medial arterial calcification and a

normal TBI (greater than 0.7 is normal) can exclude the pres-

ence of arterial disease.35 This outcome may well reduce con-

cerns of underdiagnosis in patients with diabetes and early stages

of incompressible vessels because a normal ABI does not neces-

sarily exclude systemic vascular disease.

If there is a high clinical index of suspicion that the wound is

ischemic or for individuals at high risk for PAD, a referral for sec-

ondary tier evaluations may include segmental pressure volume

and skin perfusion pressure (SPP) as well as transcutaneous oxy-

gen measurement (TCPO2), evaluation of lower limb indices and

waveforms (ie, segmental pressure volume recording). Tertiary

approaches for more aggressive care may include referral to a

vascular specialist for angiography and other interventions.

Segmental pressure volume. Segmental pressure pulse vol-

ume recording is considered a secondary tier approach for as-

sessing vascular health and is primarily used for patients with

poorly compressible vessels, or those with a normal ABI with

suspicion of peripheral vascular disease.32 Segmental pressure

volume is based on the principle that obstruction is proximal

to the level at which the pressure drops. To localize arterial le-

sions, systolic blood pressure cuffs are placed at several intervals

on the legs (thigh, calf and ankle) and pressures are recorded.

The shape of the observed pulse waveform is used to determine

the presence, severity and general location of vascular disease.36

Skin perfusion pressure (SPP). A laser Doppler measurement

that uses a blood pressure cuff at the ankle, SPP indicates the presence

(or lack thereof) of perfusion in the lower limbs. In essence, SPP is a

measure of cutaneous capillary circulation. Although SPP requires

specialized equipment, it has been shown be more sensitive than other

techniques for detecting lower extremity peripheral arterial disease.37

Transcutaneous oxygen measurement (TCPO2).TCPO2

measures oxygen tension in areas adjacent to a wound and has

been suggested as a diagnostic tool for assessing the probability of

wound healing. Two evidenced-based reviews support TCPO2 as

a screening tool for a wound population at high risk for vascular

Table 2. Diagnostic Interpretation Of Ankle-Brachial Index

Resting ABI Severity

0.91-1.30 Normal

0.70-0.90 Mild obstruction

0.40-0.69 Moderate obstruction

< 0.40 Severe obstruction

> 1.3 Poorly compressible

Adapted from American Diabetes Association. Peripheral arterial diseasein people with diabetes. Diabetes Care. 2003;26:3333-3341.

8

disease.38,39 When clinically indicated, TCPO2 should be used to

validate referral for vascular status and be used in conjunction with

hyperbaric oxygen (HBOT) intervention. Drawbacks of this test

may include variability secondary to technician experience and

technique although this can be true with other tests of perfusion

as well.39

Imaging.Although angiograms, duplex ultrasound, magnetic

resonance angiography, carbon dioxide angiography and com-

puted tomography angiography are not recommended as initial

screening tools, such methods may be necessary in further eval-

uation of these patients once clinical suspicion is ascertained. In

an observational study of 104 patients with a normal pulse, nor-

mal ABI or normal TCPO2, who were consecutively evaluated

with arteriography, 99% had hemodynamically significant le-

sions in the presence of an ulcer.33

Therefore, the panel agrees that if there is a high degree of

clinical suspicion of vascular disease, vascular consultation and

angiography should be considered to evaluate arterial disease

when an intervention is being considered in patients with dia-

betes who have non-healing wounds.

Additionally, the panel strongly suggests that if there is a high

clinical suspicion of critical limb ischemia, the patient should

be referred for a consult with a vascular specialist with whom

the clinician can have a dialogue concerning the potential for

wound healing, and help foster decisions regarding which pro-

cedures (ie, open procedures versus endovascular interventions)

would be most appropriate.

Foot And Ulcer Evaluation

The complete wound history is critical. Clinicians should re-

view and consider factors including: the initial wounding event;

history of recurrent wounding; previous wound healing prob-

lems; prior diagnostic testing, therapies and response; and the

functional impact of the wound on the patient. A sufficient so-

cial history is also helpful in defining potential adverse impacts

on an optimal plan of care.

The foot and ulcer examination should include:

• assessment of dermatologic changes in the surrounding skin in-

cluding callus, musculoskeletal deformity and muscle wasting;

• documentation of ulcer characteristics including location,

shape, and size of the wound (measurement of length, width,

and depth);

• clinical utilization of a probe to check for sinus tracts and a

positive probe-to-bone test;

• determination of the condition of the wound edges, wound

bed, wound base, periwound skin, and exudates; and

• determination of the presence of necrosis and wound

associated pain.40-42

Screening for complications, such as cellulitis, gangrene, os-

teomyelitis or Charcot deformity (neuropathic osteoarthropathy),

also should be performed. Wound depth, as measured by those

wounded anatomic structures (ie, dermis, fascia, muscle or bone), ap-

pears to be the most important clinical measurement of delayed heal-

ing.43Ankle mobility is also a key factor to assess with plantar ulcers.44

The panel recommends that both be evaluated by the clinician.

The Wound, Ostomy and Continence Nurses Society offers

further guidance for wound assessment that may prove helpful to

the clinician.42

• Determine localized inflammation by palpation and

dermal thermometry.

• Determine if edema is dependent or pitting, localized or

generalized, or bilateral or unilateral.

• Assess perfusion status by assessing skin temperature,

capillary refill, venous refill and color changes.

• Assess for ischemic skin changes including purpura, atro-

phy of subcutaneous tissue, shiny, taut skin, hair loss and

dystrophic nails.

• Assess musculoskeletal/biomechanical status for foot de-

formities, muscle weakness or gait abnormalities.

Wound Classification Systems

While several wound classification systems are available, there are

two well-established systems: the Wagner and the University of Texas

classifications. Although both systems provide descriptions of ulcers,

each has its own set of advantages and drawbacks.

The Wagner system uses six wound grades (scored 0 to 5) to assess

ulcer depth (see Table 3).45 However, the system is limited in its abil-

ity to identify and describe vascular disease and infection as inde-

pendent risk factors.46 For instance, superficial wounds that are

infected or dysvascular cannot be classified by this system.

The University of Texas system uses a matrix of grades (scored 0

to 3) and scales (scored A to D) to assess ulcer depth along with the

presence of wound infection and lower extremity ischemia.47 The

system allows identification of vascular disease and infection as in-

dependent factors regardless of ulcer anatomic depth (see Table 4).

Although the Wagner system is more widely implemented by health

care providers, is used in evaluation for hyperbaric oxygen therapy,

and may be required for reimbursement, the consensus panel favors

the University of Texas system because it has been shown to be a

better predictor of clinical outcome.48

The implementation of any wound classification system, when

used appropriately (ie, with a presenting grade in place – no

9

retroactive assessment), is a stride forward for patient data collec-

tion and quality reporting provided the ulcer measures are con-

sistent. However, a complete wound description should be

included so a clear picture of what the clinician is observing is

available to other specialists who may read the chart.

Infection Evaluation

Clinical assessment of wound infection in DFUs is imperative to

prevent complications such as amputation. Heat, pain, redness and

swelling are classic symptoms of wound infection. However, pa-

tients with diabetes are typically immunocompromised with an

impaired neuroinflammatory response and often fail to mount a

physiological response to infection. Therefore, clinicians should

look for secondary signs of infection including exudates, delayed

healing, friable granulation tissue, discolored granulation tissue,

foul odor, pocketing at the wound base and wound breakdown.49

Although clinical examination remains the standard for diag-

nosing skin, wound and soft tissue infection, recent evidence sup-

ports the use of erythrocyte sedimentation rate and C-reactive

protein as potential markers for infection in bone.50,51These factors

may help assist in diagnosing osteomyelitis along with evidence of

a positive probe-to-bone test and chronicity.52 Bone histology and

culture are the gold standard in diagnosing osteomyelitis.53 How-

ever, the consensus panel does not recommend routine culture as

a method to diagnose skin or soft tissue infections unless there are

clinical signs of infection, protracted healing and sensitivities are

required for appropriate antibiotic selection.

Radiography

Plain film radiography represents an important initial assessment

tool for evaluating infection, foreign bodies and deformity. Radi-

ographs of the affected foot represent the gold standard.53 How-

ever, if clinically indicated, bilateral radiographs should be

considered as a method for comparison.

Table 3. Wagner Classification System

Grade Lesion

0 No open lesions: may have deformity or cellulitis

1 Superficial ulcer

2 Deep ulcer to tendon or joint capsule

3 Deep ulcer with abscess, osteomyelitis or joint sepis

4 Local gangrene — forefoot or heel

5 Gangrene of entire foot

Adapted from Wagner FW. The dysvascular foot: a system for diagno-sis and treatment. Foot Ankle. 1981;2:64-122.

Table 4. University Of Texas At San Antonio Diabetic Wound Classification System

Wound depth

0 1 2 3

APre- or postulcerative lesionwith complete epithelialization

Superficial wound. No involvementof tendon, bone or capsule.

Wound penetrates to tendon or capsule.

Wound penetrates to boneor joint.

BPre- or postulcerative lesionwith complete epithelializationand infection

Superficial wound. No involvementof tendon, bone or capsule. Presence of infection.

Wound penetrates to tendon or capsule with infection.

Wound penetrates to bone or joint with infection.

CPre- or postulcerative lesionwith complete epithelializationand ischemia

Superficial wound. No involvementof tendon, bone or capsule. Presence of ischemia.

Wound penetrates to tendon or capsule withischemia.

Wound penetrates to boneor joint with ischemia.

DPre- or postulcerative lesionwith complete epithelialization,infection and ischemia

Superficial wound. No involvement of tendon, bone or capsule. Presence of infectionand ischemia.

Wound penetrates to tendon or capsule withinfection and ischemia.

Wound penetrates to bone or joint with infection and ischemia.

Adapted from Lavery LA, Armstrong DG, Harkless LB. Classification of diabetic foot wounds. J Foot Ankle Surg. 1996;35:528-531.

Presence of infection/ischemia

10

Radiologic changes may lag behind the clinical presentation of

osteomyelitis as long as two weeks.53 Magnetic resonance imaging

is the most specific and sensitive noninvasive test to evaluate os-

teomyelitis, and may be clinically indicated, especially if there is a

positive probe-to-bone test.54 Other osteomyelitis testing strategies

to consider are the Ceretec or Indium white blood cell scans (eg,

if the patient has a pacemaker).53 A triple-phase bone scan lacks

specificity and often is inaccurate in this patient population be-

cause it is entirely blood flow dependent. Although the triple-

phase bone scan is not recommended as a primary tool for

diagnosing osteomyelitis in patients with diabetes, it may be useful

as part of a dual-peak imaging analysis to gather anatomical per-

spective when compared to the Ceretec or Indium scans.53

Screening For Hyperbaric Oxygen Therapy (HBOT)

There is sufficient evidence for the use and applicability of

HBOT therapy in persistently ischemic or infected DFUs, but

HBOT should be used in combination with optimization of

perfusion, aggressive local wound care, and systemic antibiotic

therapy when indicated. Selecting patients for HBOT is assisted

by demonstration of local periwound hypoxia by transcutaneous

PO2 study (PtcO2 <50 mm Hg with = 30 mm Hg defining crit-

ical limb ischemia) and demonstration during HBOT that there

is sufficient periwound blood flow to raise the PtcO2 to a level

= 200 mm Hg.55,56 Additional considerations for HBOT in di-

abetic limb salvage are recalcitrant osteomyelitis and progressive

necrotizing infection.56

TREATMENTSince prolonged healing times increase the risk for morbidities,

infections, hospitalization and amputation, expeditious wound clo-

sure is the primary goal in DFU treatment. Moist wound healing

is a well-known precept that should be considered and utilized

for neuropathic ulcers in patients with diabetes.57 Selection of an

appropriate dressing should depend on the type of wound, its ap-

pearance, the amount of exudate and bioburden, and the absence

or presence of pain.58 In patients not responding to standard care,

early adoption of advanced care may be more cost-effective than

continuing standard care practices for decreasing the incidence of

lower extremity amputation.3,8

Management Of Arterial Disease

Emerging research suggests that individuals with multiple under-

lying comorbidities who are not candidates for open interventions

may benefit from endovascular techniques such as balloon angio-

plasty with or without stenting, artherectomy and excimer laser

therapy.59-61 Although the data with these techniques is not as ro-

bust as the data for distal bypass surgery, these endovascular inter-

ventions have created a window of opportunity for ulcer healing.

However, many specialists still subscribe to bypass surgery as being

more durable and therefore the preferred method of treating vas-

cular disease in the lower extremities in patients with diabetes.

They believe that endovascular interventions should be employed

predominantly in large vessels although endovascular intervention

has been successful in small vessels, and has been used increasingly

in below the knee disease. In this regard, the panel consents that

this topic is still controversial and long-term studies would be re-

quired to reach a definitive position.

Addressing The Wound Environment

Chronic wounds differ biochemically from acute ones and are

commonly complicated by impediments to healing such as local

ischemia, necrotic tissue and heavy bacterial loads.62 Continued

recruitment of macrophages and neutrophils fosters a prolonged

inflammatory response leading to the production of excessive

inflammatory cytokines and matrix metalloproteinases

(MMPs).63 This noxious environment perpetuates cellular senes-

cence, growth factor deficiencies, faulty receptor site function

and poor cell proliferation.

Therefore, addressing this abnormal wound envirionment may

include debridement, control of infection and inflammation, mois-

ture control and excision of wound edges and periwound callus

when appropriate.64

Debridement may be surgical/sharp, enzymatic (ie, collagenase),

autolytic (ie, occlusive), mechanical (wet-to-dry dressing, lavage)

or biologic (larval).64 Out of these types of debridement, surgical

debridement is the gold standard and is the most studied.65 Sharp

debridement represents the operational definition for purposes of

this manuscript and may be excisional or selective in nature.

Excisional debridement involves the surgical removal of clearly

identifiable tissue (ie, skin, subcutaneous tissue, tendon, fascia, mus-

cle or bone) by cutting outside or beyond the wound margin in

whole, or in part. Selective debridement involves the removal of

devitalized tissue including slough, fibrin, exudates, crusts and

other non-tissue materials from wounds. Selective debridement

also includes the removal of specific, targeted areas of unidentifi-

able devitalized tissue along the wound margin.66

The rationale behind debridement in the preparation of the

wound bed is to change the wound physiology. This involves the

removal of non-viable tissue, MMPs and biofilm, and the excision

of wound edges and periwound callus in order to stimulate the

production of growth factors. Ironically, evidence supporting de-

11

bridement as a primary treatment regimen to improve healing

rates is sparse. The evidence primarily consists of self-reporting

from treating physicians and post-hoc analysis of RCTs.65,67,68

Steed and colleagues evaluated debridement frequency as a

secondary endpoint to a double-blind randomized control trial

in patients with chronic neuropathic DFUs (N = 118) treated

with platelet-derived growth factor.65 All patients had aggressive

sharp debridement of DFUs before randomization and repeat

debridement of callus and necrotic tissue as needed. Across the

six treatment centers, 83% of patients who received frequent

debridement (81% of visits) healed compared with 20% who

received less frequent debridement (15% of visits). A potential

flaw of the study may have been its focus on center outcomes

as opposed to individual ulcer outcomes, and could reflect other

factors such as the general consistency of the center in following

the clinical trial protocol rather than the separate effect of de-

bridement alone.

In a randomized, controlled trial of a bilayered human skin equiv-

alent, Saap and Falanga rated the adequacy and performance of sur-

gical debridement.67The researchers found that patients with higher

scores (3–6) on the debridement performance index were 2.4 times

more likely to heal than those who had lower scores (0–2).

A post hoc analysis of two controlled, prospective, randomized piv-

otal trials of topical wound treatments evaluated surface area changes

and wound closure probabilities for 366 venous leg ulcers (VLUs)

and 310 DFUs over 12 weeks.68 Both VLUs and DFUs had a higher

median wound area reduction with debridement (34% and 24%,

P=0.019 and P=0.317, respectively), but an effect on healing was

not demonstrated.

Wound debridement has been proposed to be performed at

weekly intervals or as often as needed based upon the formation

of necrotic or fibrinous tissue.69 Anecdotally, if the ulcer bed is

clean, shows beefy red granulation tissue, is free of infection and

has no abnormality of the wound edge, debridement may not be

required. Conversely, Falanga and colleagues suggest that mainte-

nance debridement should be considered even in the face of a

seemingly healthy wound bed if the wound is not showing evi-

dence of closure.69

Despite the fact that debridement is universally accepted in the

care and treatment of neuropathic ulcers and chronic wounds, the

panel agrees there is very little high-quality evidence validating this

practice. This procedure, albeit an important part of any treatment

algorithm, is still considered intuitive and should be performed after

clinical evaluation. When debridement is considered, surgical de-

bridement is recognized as the gold standard and is recommended

by the panel.

Infection Control

Bacterial contamination or colonization of a DFU does not nec-

essary mean it is infected. All wounds are colonized and there is

no operational guide to what level of bacteria leads to pathology.

When feasible, foot ulcer infection in patients with diabetes should

be diagnosed clinically (see Table 5) based on host response to in-

fection as demonstrated by the presence of purulent secretions or

at least two principal symptoms of inflammation (redness, warmth,

swelling and pain or tenderness).21,22

Optimal treatment decisions can be made only after deter-

mining the causative organism. Tissue cultures have remained

the gold standard of bacterial identification for many years.

Deep tissue specimens produce better results than superficial

swabs, especially when osteomyelitis is suspected.66,70 However,

quantitative biopsy of deep soft tissue is not routinely performed

based on lack of availability and is therefore not recommended

by the consensus panel.

Table 5. Clinical Infection Classification Of A Diabetic Foot Ulcer

Clinical manifestations of infection Infection severity

Wound lacking purulence or any manifestations of inflammation

Uninfected

Presence of ≥ 2 manifestations of inflammation (purulence or erythema, pain,tenderness, warmth or induration), but anycellulitis/erythema extends < 2 cm aroundthe ulcer, and infection limited to the skin or superficial subcutaneous tissues; no otherlocal complications or systemic illness.

Mild

Infection (as above) in a patient who is systemically well and metabolically stable but who has ≥ 1 of following characteristics: cellulitis extending >2 cm,lymphangitic streaking, spread beneath the superficial fascia, deep-tissue abscess, gangrene, and involvement of muscle, tendon, joint or bone.

Moderate

Infection in a patient with systemic toxicity or metabolic instability (eg, fever, chills, tachycardia, hypotension, confusion, vomiting, leukocytosis, acidosis, severe hyperglycemia, or azotemia)

Severe

Adapted from Lipsky BA, Berendt AR, Deery HG, et al. Diagnosis andtreatment of diabetic foot infections. Clin Infect Dis. 2004;39:885-910.

12

Although the panel does not specifically recommend one cul-

turing method, sharp debridement followed by culture using the

Levine technique has been shown to be accurate and consistent

with quantitative biopsy.71The Levine technique involves rotating

a culture swab in one area of the ulcer bed with gentle pressure,

thereby extracting fluid from the underlying tissue.72

Newer but not universally available diagnostic tests with greater

sensitivity have been developed that can better identify infections

or pathogens within hours instead of days.70 For instance, a poly-

merase chain reaction assay can detect gram-positive, gram-negative

and anaerobic organisms. An oligonucleotide array can detect genes

involved with resistance and toxins, and can also identify some spe-

cific species by their genotype. The clinical utility of these is not yet

clear. Finally, magnetic resonance imaging (MRI) is an emerging

technique for detecting infections in soft tissue and bone.

Infections in DFUs are usually polymicrobial, predominantly

comprising aerobic, gram-positive, cocci organisms.70 Staphylococcus

aureus is the most common pathogen found in chronic, non-healing

DFUs.70,72 Osteomyelitis often underlies an infected DFU. The bone

can be cultured and biopsied. However, less invasive diagnostic tech-

niques such as X-ray, MRI or computed axial tomography scans

also may be of benefit.66 Osteomyelitis can be difficult to cure.

Whenever feasible, the bone should be debrided. Intravenous an-

tibiotic therapy should be utilized for a maximum of two weeks if

all infected bone has been resected, four to six weeks after debride-

ment, and for several months if oral antibiotic therapy is used.66 In-

fectious disease consult should be considered in these cases.

The panel recommends diagnosing infection based on clinical

presentation. Quantitative biopsy of deep tissue specimens for culture

is not primarily recommended but the Levine swab technique may

be helpful for quantitative analyses.71,72

Offloading

From a practical standpoint, more widespread adoption of effec-

tive offloading modalities would make the most positive im-

provement in DFU treatment. Clinical studies have shown that

fewer wounds heal with offloading methods such as therapeutic

shoes, pads or custom insoles as compared to more aggressive

techniques like cast walkers and total contact casts (TCCs).74,75

There is little evidence that wheelchairs, bed rest or crutches fa-

cilitate wound healing.76

True offloading is crucial to decreasing pressure and strain

rate.77 Pressure is the force applied over a surface and is measured

as force per unit of area.78 Strain rate is force divided by time. The

duration of stress is very important in determining strain. The re-

lation between the shear stress and the rate of strain is linear.77

Many patients with DFUs are obese and suffering from atten-

dant comorbidities. Obese patients suffering from DFUs put 2 to

2.5 times their body weight on the wound with each step, and the

elastic modulus of skin is about 10 cm per kilogram squared.79

That means a 400-lb patient exceeds the maximum skin elasticity

by about threefold with each step.

Decreasing the strain rate, not just pressure, may improve wound

healing. The easiest way to decrease force over time is to decelerate

the foot into the ground and shorten the time the foot is on the

ground. However, most patients with DFUs are so neuropathic

that they do not decelerate the foot into the ground and strike

more rapidly than those without neuropathy.77

The literature supports the following devices as having repro-

ducible ability to heal wounds: TCC or instant total contact casting

(iTCC); cast walkers (eg, DH, Bledsoe, 3-D, CAM); Charcot Re-

straint Orthotic Walker (CROW)/total contact brace; patellar ten-

don-bearing (PTB) braces; and ankle-foot orthoses (AFOs) in

shoes.80-82 These methods work because they decelerate the foot

into the ground and decrease the weightbearing if they are used

for walking.

The key to effective offloading is to have an ankle brace or a

facsimile fixed to the foot bed. The TCC is the ideal method

for most patients and is supported by the highest level of evi-

dence.83-86 Molding the bottom of the cast to the bottom of the

foot causes the entire sole to participate in the force distribu-

tion, resulting in lower pressures. One non-randomized, single

center comparison study assessed the treatment of 1,350 diabetic

foot ulcers with either TCC, 3-D walkers with custom insoles

or custom healing sandals.87Within five weeks, the percentages

of closures were as follows:

TCC — 88%

3-D walkers with custom insoles — 63%

Custom sandals with three layers of foam — 55%

The results show superior healing with the TCC. However,

the other offloading modalities in this study provided rates of

healing better than those seen without offloading.87 Clinician

comfort with TCC is a barrier to its acceptance but training in-

services can smooth the transition to everyday practice.88

The key in casting is to increase the padding in high-risk

areas. Clinicians should ensure a well-molded cast, which allows

for no ankle motion (to transfer all forces to the tibia) and is

less likely to create secondary ulcerations.

Reimbursement issues are potential barriers to adoption.

However, there is time and effort to be saved by ensuring pa-

tients have better healing rates more quickly. If TCC is not avail-

able for any reason, there are ways to improvise and make

13

removable casts non-removable in order to ensure adherence.

Sometimes referred to as an instant TCC, plaster application

over a properly fitted CAM walker can be very effective.89 An-

other option is to staple together the ends of hook and loop

closures to assess adherence. If the staples are removed, the pa-

tient has removed the device.

Not all patients are appropriate candidates for a TCC or a

CROW walker. These devices are cumbersome relative to size

and weight. They also may not be appropriate for frail individ-

uals, patients with motor difficulties or morbidly obese pa-

tients.90,91 An option for these individuals is an AFO with felted

foam. Clinicians who are not entirely comfortable with TCC

or iTCC can opt for a CAM walker that can be obtained by

prescription from any durable medical equipment supplier.

The primary disadvantage of these removable devices is that

they are just that — removable. There is a probability that these

removable devices will be worn while the patient works (likely

seated) during the day and subsequently removed when the patient

is at home at night.82,89 However, this is when most of the patient’s

weightbearing will occur and may, therefore, render the removable

device useless. In addition, if the patient improperly dons a remov-

able device, the wearing of it may not be effective.

Pressure and strain rate reduction are imperative in healing

DFUs in people with neuropathy. The panel members agree that

total contact casting is the gold standard for offloading DFUs but

recognize this application may not be practical for some clinicians.

Fortunately, clinicians have many other effective offloading devices

available to them and their patients (see Figure 2).90 Given frequent

non-adherence with removable devices, the panel recommends

careful patient counseling.

Hyperbaric Oxygen Therapy (HBOT)

HBOT has been shown to reduce amputation rates in a prospec-

tive, randomized controlled clinical trial when compared to stan-

dard therapy that included aggressive revascularization,

debridement, treatment of infection and glycemic control.92 These

patients were severely ischemic, had underlying osteomyelitis (or

both) with threatened amputation below or above the knee at

presentation. Similar results have been reported in a small RCT

as well as a large (1,144 patients) cohort.93,94 The Wound Healing

Society clinical practice guidelines for diabetic foot ulcer care has

given HBOT in this setting a IA level of evidence.66 A Cochrane

review of HBOT trials found that HBOT may reduce the number

of major amputations in patients with diabetes and chronic foot

ulcers.95 Kalani and colleagues showed long-term durability with

limb salvage for patients receiving HBOT in this setting.96

Medicare has established the following guidelines for coverage

of HBOT for patients with diabetic foot ulcers.97

• Type I or Type II DM, lower extremity wound due to DM

• Wagner grade III or higher

• Failed standard wound care (no measurable signs of healing

for 30 days)

• Wound must be re-evaluated every 30 days during HBOT

therapy course

• Continued HBOT therapy will not be covered if there are

no measurable signs of healing during the 30-day period

Advanced Therapies

Good wound care practices are necessary to promote timely

and complete DFU healing. Despite management with good

wound care, many DFUs do not heal completely, become

chronic or infected.3,98 Major costs associated with managing

DFUs include hospitalizations due to osteomyelitis and ampu-

tation. Therefore, the economics of treatment point to healing

the ulcer and preventing these complications.

Margolis and colleagues evaluated the rate of neuropathic

ulcer healing in 10 control groups from prospective clinical tri-

als via meta-analysis.98 Control groups used good wound care,

which included debridement, offloading and either saline-

moistened gauze or placebo gel and gauze. Six-hundred and

twenty-two (n=622) patients were assessed; 172 in the 20-week

end point group and 450 in the 12-week end point group.

Weighted mean healing rates were 24.2% (95% CI 19.5–28.8%)

for the 12-week end point and 30.9% (95% CI 26.6–35.1%)

for the 20-week end point.

These surprisingly poor healing rates elucidate the challenges

of healing chronic wounds despite appropriate conservative

wound management and fosters the notion that advanced

wound therapies may be required to treat ulcers that fail to

progress with good wound care alone.

The importance of utilizing advanced therapies and products

such as human skin equivalents (HSEs), wound modulators and

growth factors is well documented.3,66,99,100 Clinicians, however,

continue to use these therapies as “last resorts” and may not

be sure when it is appropriate to use them earlier in the wound

healing process.

It has been increasingly suggested that after four weeks of stan-

dard DFU care, the wound should be reassessed for progress and

reduction in ulcer size should be used as a predictive marker.3,100

Sheehan and colleagues assessed the ability of the four-week

healing rate to predict complete healing over a 12-week pe-

riod. Sheehan and co-workers did a post hoc analysis of data

Continued on page 16

14

Figure 2. Offloading options.

Total Contact Cast CROW BootPrefabricatedWalker

DH OffloadingWalker

IPOS Shoe Ortho Wedge

Dorsal Digit

• • • • • •

Plantar Digit

• • • • • •

Plantar Metatarsal

• • • • • •

Medial Metatarsal

• • • • • •

Lateral Metatarsal

• • • •

Heel

15

PostOp Shoe Healing Sandal Reverse IPOS L’nard Splint PTB Brace MABAL Shoe

•

• •

• •

• •

• •

• • • •

Adapted from Snyder RJ, Lanier KK. Offloading difficult wounds and conditions in the diabetic patient. Ostomy Wound Management. 2002;48(1):22-35.

16

from a large prospective multicenter trial of 203 patients with

diabetes and foot ulcerations.100 (This analysis included patients

receiving an active treatment and control.) The midpoint be-

tween the percentage area reduction (PAR) from baseline at

four weeks in patients healed versus those not healed at 12

weeks was found to be 53%. Subjects with a PAR in ulcer size

greater than 53% in four weeks had a 12-week healing rate of

58% whereas those with a reduction in ulcer area less than 53%

in four weeks had a healing rate of only 9% (P <0.01).100

It was concluded that the PAR in foot ulcer area after four

weeks is a robust predictor of healing at 12 weeks and could serve

as a pivotal clinical decision point in the treatment algorithm of

diabetic foot ulcers for early identification of patients who may

not respond to standard care and may require advanced therapies.

Foremost, this study created a negative predictive value for those

ulcers that would not heal in 12 weeks.100

Snyder and co-workers found similar results by conducting post

hoc analyses of control participant data extracted from two previ-

ously published randomized, controlled trials of a human fibrob-

last-derived dermal substitute for treating DFUs.101 The total study

population size was 250 patients. Analyses showed that a 50% PAR

at four weeks was significantly associated with healing at 12 weeks

independent of baseline ulcer area (P < 0.001).

The lead author notes that additional analyses indicated that

approximately one-tenth or fewer of DFUs with a PAR < 50%

at weeks 2, 3 or 4 were healed by week 12 (12%, 9% and 4%

respectively) whereas more than half of the DFUs with at least

50% PAR measurements at weeks 2, 3 and 4 were healed by

week 12 (58%, 55% and 54% respectively).

Therefore, previous recommendations to re-evaluate wound

care at four weeks continue to hold true. In addition, it has

been recommended that the failure to reduce the size of an

ulcer after four weeks, despite standard wound care, should

prompt consideration of an advanced therapy.3

In addition to percent area reduction, several other wound-

specific characteristics (duration of wound, baseline wound

size, and location of the wound) have been predictive of DFU

healing.102,104The value of understanding the possible outcomes

associated with prognostic factors should not be underesti-

mated. A recent study demonstrated improved DFU healing

rates by merely providing clinicians with computer generated

prognostic data based on the ulcer baseline measurements and

changes in wound size at four weeks.104 No guidance for ad-

justing treatment was given with the prognostic data.

In a recent review of optimal treatment strategies for dia-

betic foot ulcers, Armstrong and colleagues advocated the use

of an active therapy such as a bioengineered skin substitute to

stimulate healing in non-responding wounds after four weeks

of treatment.12

Only a small handful of wound care technologies have proven

their value in accelerating DFU healing in prospective, randomized

trials. These include: becaplermin (Regranex®, Systagenix Wound

Management), a topical gel containing recombinant human

PDGF; and two living skin equivalents in the form of a bilayered

skin substitute (Apligraf®, Organogenesis) and a human fibroblast-

derived dermal substitute (Dermagraft®, Advanced BioHeal-

ing).62,99,105,106 These clinical trials involved well-perfused and

non-infected, partial to full thickness DFUs. Before these therapies

are applied, the wound should be clean and free of infection. Other

advanced modalities (with less rigorous trial data) that may be ef-

fective include vacuum-assisted wound closure and electrical stim-

ulation among others.107,108

Any incremental improvement in healing the wound and

avoiding serious complications — especially amputation — can

have a dramatic impact on overall health-care utilization costs.

The panel recognizes the prognostic value of 50% percent

area reduction of the wound at four weeks and recommends

utilization of this parameter as a clinical decision point for the

use of advanced therapies in healing DFUs. Use of advanced

modalities, when indicated, should be viewed as the new stan-

dard of care and these advanced modalities should not be a ‘last

resort’ in the treatment of DFUs. There are, however, certain

patients, who may benefit from even earlier intervention with

advanced therapies while others may require other interven-

tions first (ie, revascularization) to optimize the success of

wound healing.

Amputation

The decision to amputate when a wound has penetrated

through the dermis and affects tendon or bone is a difficult

one. Five-year mortality rates after lower extremity amputation

(LEA) range from 50% to 76%.109,110 Approximately 85% of

lower limb amputations in patients with diabetes are preceded

by ulceration.

Whether an amputation is minor (ie, occurring distal or

through the tarsometatarsal joint) or major (ie, proximal to the

tarsometatarsal joint), it is sometimes the best therapeutic op-

tion for the patient. Some studies using quality-of-life (QOL)

indicators have shown slightly better mean QOL scores with a

healed amputation than with a chronically open wound.111

In summary, patients and their treating clinicians would pre-

fer not to seek amputation as a primary endpoint. However, if

Continued from page 13

17

other therapies are not appropriate or do not prove effective,

one may consider amputation. Other key considerations in-

clude the patient’s quality of life and medical status. The alter-

natives and rationale of amputation should be discussed in

depth with the patient.

CONCLUSIONNeuropathic diabetic foot ulcerations are one of the most com-

mon complications in patients with diabetes. The economic

burden of DFUs is high and secondary complications of infec-

tion and amputation contribute most to the costs. Expeditious

and complete wound healing is the definitive goal in treating

DFUs. Standard management strategies include preparation of

the wound bed, debridement, infection control and offloading.

Despite the use of these strategies, healing rates of DFUs re-

main low.

The approaches of this consensus panel are designed to pro-

vide straightforward and practical management paths for clini-

cians to adopt when treating patients with DFUs, but clinicians

must recognize the unique challenges presented by individual

patients and adjust treatment approaches accordingly.

Assessment should include a comprehensive foot and ulcer

evaluation with key components of a patient history and phys-

ical examination, laboratory screening, nutritional evaluation,

and a neuropathic and vascular assessment. Wound status history

and a complete and accurate description of the wound, includ-

ing measurements of length, width, and depth, need to be in-

cluded in the evaluation.

Treatment should include appropriate preparation and

maintenance of the wound bed with special attention paid to

debridement, offloading and infection control. Clinicians must

take a holistic approach to healing DFUs and decision-making

is a proactive process that requires ongoing reassessment. When

wound healing stalls, early adoption of advanced therapies is

advocated to accelerate wound healing and decrease compli-

cations, and should be considered the new standard of care. n

18

ASSESSMENTHistory and Physical Exam

General• Determine the duration of diabetes and quality of glycemic control• Determine the presence of comorbidites (eg, end-stage renal disease, pulmonary disease, hypertension, hy-percholesterolemia, hyperlipidemia, myocardial infarction, transient ischemic attacks, angina or valvularheart disease)• Laboratory tests

• complete blood count and creatinine/blood urea nitrogen • HbA1c• lipid profile • prealbumin

• Dietary questionnaire• Quality of life questions• Smoking cessation

Neurologic exam: Vibration perception with a 128-Hz tuning fork and 10-g monofilament tests

Vascular exam: use a tiered approach as indicated or appropriate• 1º palpation of pulses, ankle brachial index (ABI), and/or toe brachial index (TBI)• 2º (if suspicion of vascular insufficiency) refer for segmental pressure volume and skin perfusion pressure(SPP) and transcutaneous oxygen measurement (TCPO2)• 3º refer for vascular consultation and angiography in patients being considered for intervention

Foot and ulcer evaluation• Determine:

• initial wounding event, history of recurrent wounding, previous wound healing problems • prior diagnostic testing, prior therapies and response• functional impact of the wound on the patient • sufficient social history to define potential adverse impact on treatment plan

• Assess dermatologic changes including callus, musculoskeletal deformity and muscle wasting• Document ulcer characteristics including location, shape and size of the wound (measurement of length,width and depth)• Clinical utilization of a probe to check for sinus tracts and a positive probe to bone test • Determine condition of the wound edges, wound bed, wound base, periwound skin and exudates• Determine presence of necrosis and wound associated pain

Wound classification: University of Texas system is recommended, Wagner system may be required for re-imbursement. Prognosis may be related to anatomically deeper wounds.

Consensus Panel Summary Of RecommendationsUse a multidisciplinary team approach to assessment and treatment.

19

Infection• Classic signs: heat, pain, redness and swelling • Secondary signs: exudates, delayed healing, friable granulation tissue, discolored granulation tissue, foulodor, pocketing at the wound base, and wound breakdown • Probe-to-bone test • If osteomyelitis is suspected, 2º markers are erythrocyte sedimentation rate and C-reactive protein • Not recommended: routine culture as an evaluation method unless an infection is apparent or sensitivities arerequired for appropriate antibiotic selection

Radiography • Plain film radiography• If the clinician suspects osteomyelitis (especially if there is a positive probe-to-bone test)

• MRI to evaluate for osteomyelitis• Other testing may include Ceretec or Indium white blood cell scans. While a triple phase bone scanlacks specificity, it may be used in conjunction with these tests for dual peak imaging.

TREATMENT

Debridement: Cold steel surgical debridement initially and then as needed based on condition of the wound (maintenance)

Infection control• Bacterial colonization ≠ infection• Infection is diagnosed from clinical findings whenever possible. Purulent secretions are present or > two orat least two principal symptoms of inflammation (eg, redness, warmth, swelling and pain or tenderness). • Given that patients with diabetes are typically immunocompromised, clinicians should also look for secondarysigns of infection including exudates, delayed healing, friable granulation tissue, discolored granulationtissue, foul odor, pocketing at the wound base and wound breakdown. • Culture:

• Levine swab technique• Quantitative biopsy (for bone only) • Testing (not universally available) via polymerase chain reaction assay, oligonucleotide array

Offloading• Total contact cast (TCC) • Instant TCC • See Figure 2.

Advanced therapies· Use 4-week treatment end point to assess need for advanced therapies· If wound is not progressing toward healing (percent wound area reduction < 50%), then advanced therapiesshould be considered· All previous assessment and treatment standards should continue to be utilized

20

References

1. Wild S, Roglic G, Green A, et al. Global prevalence of diabetes. Estimates for theyear 2000 and projections for 2030. Diabetes Care. 2004;27(5):1047-1053.

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23

There exists a number of challenges in diagnosing and treating

diabetic foot ulcers (DFUs). Between the myriad comorbidities

that can contribute to stalled healing and striving to ensure the

best multidisciplinary care, it can be difficult for physicians to stay

abreast of the latest research let alone incorporate these findings

into the management of these patients in the clinic.

This consensus panel seems to have found a middle ground be-

tween evidence-based medicine and the practical realities of the

day-to-day pragmatic practice. For example, the panelists discuss

the supporting research behind total contact casting as well as this

technique’s practical limitations. They also explore the pros and

cons of alternative offloading techniques and modalities.

The consensus panel also reviews new tools for diagnosing in-

fection and pathology in DFUs, and considers the increasingly

emerging evidence about the earlier use of advanced therapies.

This practical yet evidence-based guide should go a long way

toward facilitating improved outcomes in healing chronic ulcers

in patients with diabetes.

— David G. Armstrong, DPM, MD, PhD,

Professor of Surgery

Director, Southern Arizona Limb Salvage Alliance (SALSA)

University of Arizona College of Medicine

Tucson, Ariz.

Expert Commentary The chronic complications of diabetes in the lower limbs now

represent the most prevalent cause of lower extremity amputation

(LEA). It has been estimated worldwide that a lower limb is lost

because of diabetes every 30 seconds and the prevalence is bound

to rise in relation to the projected increased incidence of type 2

diabetes in the near future.1

Far from being a local problem, the diabetic foot is the conse-

quence of the systemic involvement of both the vascular and pe-

ripheral nervous system in the lower extremity. It has been

demonstrated to be a marker of mortality for patients with diabetes

with a frequency, which has been compared to some of the most

severe types of cancer.2

Such a complex and evolutive pathology deserves a thorough

assessment, which encompasses both systemic and local character-

istics, and an integrated therapeutic approach, which addresses both

the vascular, neurologic and infective components. Revasculariza-

tion, surgical treatment and offloading (and systemic antibiotic

therapy when appropriate) are the cornerstones of therapy and

ensure healing in more than 90 percent of the cases when they

are applied in a timely manner.3

Increasing the knowledge and promoting an advancement of

the standards of care for the diabetic foot (through consensus rec-

ommendations such as these) is crucial to developing a stronger

medical understanding of this still neglected aspect of the compli-

cations of diabetes, which are often managed with empiricism and

still end frequently in dramatic consequences.

— Alberto Piaggesi MD

Head, Diabetic Foot Section

Depatment of Endocrinology and Metabolism

University of Pisa

Italy

References

1. Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, et al. The global burden of dia-

betic foot disease. Lancet. 2005 Nov 12;366(9498):1719-24.

2. Armstrong DG, Wrobel J, Robbins JM. Guest Editorial: are diabetes-related wounds

and amputations worse than cancer? Int Wound J. 2007 Dec;4(4):286-7.

3. Schaper NC, Apelqvist J, Bakker K. The international consensus and practical

guidelines on the management and prevention of the diabetic foot. Curr Diab

Rep. 2003 Dec;3(6):475-9

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