Professional Documents
Culture Documents
INTRODUCTION
The majority (6080%) of foot ulcers will heal, while 1015% of them will
remain active, and 524% of them will finally lead to limb amputation within a
period of 618 months after the first evaluation. Neuropathic wounds are more
likely to heal over a period of 20 weeks, while neuroischemic ulcers take longer
and will more often lead to limb amputation. It has been found that 4070% of all
nontraumatic amputations of the lower limbs occur in patients with diabetes.
Furthermore, many studies have reported that foot ulcers precede approximately
85% of all amputations performed in diabetic patients. The risk of foot ulceration
and limb amputation increases with age and the duration of diabetes. The
prevention of diabetic foot is crucial, considering the negative impact on a
patients quality of life and the associated economic burden on the healthcare
system.4-6 The factors that delay wound healing in diabetes are multiple and relate
both to the impaired glucose metabolism and to the effect of neurovascular
complications. Diabetic foot ulcers readily become chronic; all too often these
wounds do not heal primarily. Treatment of chronic wounds should be essentially
directed against the main etiologic factors responsible for the wound.
Management is based on the simple principles of eliminating infection, the use of
dressings to maintain a moist wound bed and to absorb exsudate, offloading high
pressure from the wound bed, and debridement to accelerate endogenous healing
and facilitate the effectiveness of topically applied substances.7 Diabetic foot
ulceration is a major health problem and its management involves a
multidisciplinary approach. This review aims to provide a synopsis of the current
management strategies of diabetic foot ulcers, from prevention to the options for
treatment.
II. LITERATURE REVIEW
A DFU is a pivotal event in the life of a person with diabetes and a marker of
serious disease and comorbidities. Without early and optimal intervention, the
wound can rapidly deteriorate, leading to amputation of the affected limb. It
has been estimated that every 20 seconds a lower limb is amputated due to
complications of diabetes. In Europe, the annual amputation rate for people
with diabetes has been cited as 0.5-0.8%, and in the US it has been reported
that around 85% of lower-extremity amputations due to diabetes begin with
foot ulceration.12 Mortality following amputation increases with level of
amputation and ranges from 5068% at five years, which is comparable or
worse than for most malignancies.13
Many studies have shown that planned intervention aimed at healing of DFUs
is most effective in the context of a multidisciplinary team with the patient at
the centre of this care. One of the key tenets underpinning this document is
that infection is a major threat to DFUs, much more so than to wounds of
other etiologies not subject to diabetic changes. A European-wide study found
that 58% of patients attending a foot clinic with a new ulcer had a clinically
infected wound. Similarly a single-centre US study found that about 56% of
DFUs were clinically infected. This study also showed the risk of
hospitalization and lower-extremity amputation to be 56155 times greater for
diabetes patients with a foot infection than those without. Recognizing the
importance of starting treatment early may allow practitioners to prevent
progression to severe and limb threatening infection and potentially halt the
inevitable pathway to amputation.14-16
2.2 Etiology and Pathogenesis of Diabetic Wound
The most significant risk factors for foot ulceration are diabetic neuropathy,
peripheral arterial disease, and consequent traumas of the foot. In most
patients, peripheral neuropathy and peripheral arterial disease (PAD) (or
both) play a central role and DFUs are therefore commonly classified as 17:
Neuropathic
Ischaemic
Neuroischaemic
Other risk factors for foot ulceration include a previous history of foot
ulceration or amputation, visual impairment, diabetic nephropathy, poor
glycemic control, and cigarette smoking. Some studies have shown that foot
ulceration is more common in men with diabetes than in women. Social
factors, such as low socioeconomic status, poor access to healthcare services,
and poor education are also proven to be related to more frequent foot
ulceration. DFUs usually result from two or more risk factors occurring
together. Intrinsic elements such as neuropathy, PAD and foot deformity
(resulting, for example, from neuropathic structural changes), accompanied by
an external trauma such as poorly fitting footwear or an injury to the foot can,
over time, lead to a DFU.18
Fig. 1. Pathway to diabetic ulcer. Modified from the International Working Group
on the Diabetic Foot, International Consensus on the Diabetic Foot
a. Hemostasis
Once the source of damage to a house has been removed and before work
can start, utility workers must cap damaged gas or water lines. So, too, in
wound healing must damaged blood vessels be sealed. In wound healing,
the platelets are the cells that act as utility workers sealing off the damaged
blood vessels. The blood vessels themselves constrict in response to
injury, but this spasm ultimately relaxes. The platelets secrete
vasoconstrictive substances to aid this process, but their prime role is to
form a stable clot sealing the damaged vessel. Under the influence of ADP
(adenosine diphosphate) leaking from damaged tissues, the platelets
adhere to the exposed type 1 collagen. They become activated and secrete
adhesive glycoproteins, leading to platelet aggregation. They also secrete
factors that interact with and stimulate the intrinsic clotting cascade
through the production of thrombin, which in turn initiates the formation
of fibrin from fibrinogen. The fibrin mesh strengthens the platelet
aggregate into a stable hemostatic plug. Finally, platelets also secrete
growth factors such as platelet-derived growth factor, which is recognized
as one of the first factors in initiating the subsequent healing steps. These
growth factors recruit neutrophils and monocytes (initiating the next phase
of wound healing), stimulate epithelial cells and recruit fibroblasts.
Hemostasis occurs within minutes of the initial injury unless the patient
has underlying clotting disorders.
b. Inflammation
Clinically, inflammation (the second stage of wound healing) presents as
erythema, swelling and warmth often associated with pain, the classic
rubor et tumor cum calore et dolore. This stage usually lasts up to 4 days
post injury. In the damaged house analogy, once the utilities are capped
the second job is to clean up the debris. This is a job for unskilled
labourers. In a wound, these unskilled labourers are the neutrophils
(polymorphonucleocytes). The inflammatory response causes the blood
vessels to become leaky, releasing asma and neutrophils into the
surrounding tissue. The neutrophils phagocytose debris and
microorganisms and provide the first line of defence against infection. As
they digest bacteria and debris, neutrophils die and release intracellular
enzymes into the surrounding matrix, which further digest tissue. As fibrin
is broken down as part of this clean-up, the degradation products attract
the next cells involved such as fibroblasts and epithelial cells. They are
aided by local mast cells. The task of repairing a house is complex and
requires someone, such as a contractor, to direct this activity. Similarly,
wound repair requires coordinated cell activity and good cell-to-cell
communication. Cells communicate through soluble proteins call
cytokines and growth factors. These cytokines and growth factors are
released by 1 cell and bind to a receptor on a target cell. Once a cytokine
binds to a target cell it stimulates the cell to move. Growth factors, on the
other hand, stimulate the target cell to either divide and produce more cells
or synthesize and release substances such as collagen, which is required to
form the extracellular matrix. The extracellular matrix also plays an active
role in wound healing by interacting with the cells through receptors called
integrins, leading to platelet activation, epithelial migration and fibroblast
movement. In wound healing, cells known as macrophages act as the
contractors. Circulating monocytes differentiate into macrophages after
they exit the blood vessels and come in contact with the extracellular
matrix. Macrophages are able to phagocytose bacteria and provide a
second line of defence. Macrophages also secrete extracellular enzymes to
degrade necrotic tissue at the wound site. These enzymes belong to a
family of substances called matrix metalloproteases (MMPs). MMPs
require calcium to form a functional shape and zinc for the active site.
c. Proliferation
The proliferation phase starts approximately 4 days after wounding and
usually lasts until day 21 in acute wounds, depending on the size of the
wound and the health of the patient. It is characterized by angiogenesis,
collagen deposition, granulation tissue formation, wound contraction and
epithelialization. Clinically, proliferation is observed by the presence of
pebbled red tissue or collagen in the wound base and involves replacement
of dermal tissues and sometimes subdermal tissues in deeper wounds, as
well as contraction of the wound. In the house analogy, once the site has
been cleared of debris under the direction of the contractor, framers move
in to build the framework of the new house. Subcontractors can now
install new plumbing and wiring on the framework and siders and roofers
can finish the exterior of the house. The framer cells are fibroblasts,
which secrete the collagen framework on which further dermal
regeneration occurs. Specialized fibroblasts are responsible for wound
contraction. The plumber cells are the pericytes, which regenerate the
outer layers of capillaries, and the endothelial cells, which produce the
lining. This process is called angiogenesis. The roofer and sider cells
are the keratinocytes, which are responsible for epithelialization. In the
final stage of epithelialization, contracture occurs as the keratinocytes
differentiate to form the protective outer layer or stratum corneum. In a
healing wound, the cells under the influence of growth factors divide to
produce new cells, which migrate to where they are needed under the
influence of cytokines. There is a balance between the MMPs and TIMPs
so that there is a net production of new tissue. In chronic wounds, in
contrast, in which healing is stalled, cell division and migration are
suppressed, there are high levels of inflammatory cytokines and MMPs,
and low levels of TIMPs and growth factors. Cells are often senescent and
unresponsive to the growth factors. This lack of response is characteristic
of a chronic inflammatory state. It may be caused by an increased bacterial
burden, the presence of devitalized tissue, chronic ischemia or repetitive
trauma.
d. Remodelling
Once the basic structure of the house is completed, interior finishing may
begin. Similarly, in wound repair, the healing process involves
remodelling and realignment of the collagen tissue to produce greater
tensile strength. In addition, cell and capillary density decrease. The main
cells involved in this process are the fibroblasts. Remodelling can take up
to 2 years after wounding. This explains why closed wounds can quickly
breakdown if attention is not paid to the initial causative factors.
Diabetes mellitus affects soft tissue healing via metabolic, vascular, and
neuropathic pathways. Wound healing in diabetes is impaired by factors that
are both extrinsic and intrinsic to the wound and its biology. Extrinsic factors
include repeated trauma or mechanical stress applied to a foot that has been
rendered insensitive due to neuropathy as well as ischemia as a result of macro
or microvascular disease. Thickening of the basement membrane of the
capillaries and arterioles frequently occurs in individuals with diabetes,
resulting in an impaired wound healing and persistent ulcer formation. Factors
that affect the microcirculation in diabetes include stiffened red blood cells
and increased blood viscosity; susceptibility of the tibial and peroneal arteries
to atherosclerosis; high venous back-pressure in the lower extremities that
increases transudation and edema; affinity of glycosylated hemoglobin for
oxygen contributing to low oxygen delivery at the capillary; and impaired
phagocytosis and bacterial killing, which along with neuropathy and ischemia
make the patient vulnerable to infection. Moreover, this population is prone to
develop chronic non-healing diabetic foot ulcers (DFUs). The impaired
healing of both DFUs and acute cutaneous wounds in persons with diabetes
involves multiple complex pathophysiological mechanisms.21
An important role has been attributed to factors intrinsic to the biology of the
chronic wound in diabetes. It has been postulated that hyperglycaemia itself
has a deleterious effect on wound healing through the formation of advanced
glycation end-products (AGEs)which induce the production of inflammatory
molecules (TNF-, IL-1) and interfere with collagen synthesis. Furthermore,
Spravchikov et al. showed that exposure to high glucose is associated with
changes in cellular morphology, decreased proliferation, and abnormal
differentiation of keratinocytes, thus revealing another mechanism by which
hyperglycaemia may affect wound healing in diabetes. Interestingly, the
healing times of leg and foot ulcers are decreased in diabetic patients with
lower HbA1c, thereby emphasizing the clinical correlation between
hyperglycaemia and impaired wound healing. Hyperglycemia can also add to
the oxidative stress when the production of ROS exceeds the anti-oxidant
capacity. The formation of advanced glycation end-products (AGEs) under
hyperglycemia and the interaction with their receptors (RAGE) are associated
with impaired wound healing in diabetic mice as well.22
For the non-specialist practitioner, the key skill required is knowing when and
how to refer a patient with a DFU to the multidisciplinary footcare team
(MDFT). Patients with a DFU should be assessed by the team within one
working day of presentation, or sooner in the presence of severe infection. In
many places, however, MDFTs do not exist and practitioners instead work as
individuals. In these situations, the patients prognosis often depends on a
particular practitioners knowledge and interest in the diabetic foot. Patients
with a DFU need to be assessed holistically to identify intrinsic and extrinsic
factors. This should encompass a full patient history including medication,
comorbidities and diabetes status. It should also take into consideration the
history of the wound, previous DFUs or amputations and any symptoms
suggestive of neuropathy or PAD. Physical examination of the diabetic foot is
based on assessment of the skin and of the vascular, neurological, and
musculoskeletal systems.24 Below are the details of assessment of diabetic
foot ulcer from International Best Practice Guidelines. 25
a. Examination of Ulcers
The dermatological examination includes a visual inspection of the skin of
the legs and feet, particularly the dorsal, plantar, medial, lateral, and
posterior surfaces, as well as a close examination of each toenail. Other
observations to be noted include the presence of peeling skin and
maceration or fissuring of the interdigital skin. The visual inspection may
discover signs of autonomic neuropathy and sudomotor dysfunction. A
physical examination should determine:
e. Identifying Infection
Recognising infection in patients with DFUs can be challenging, but it is
one of the most important steps in the assessment. It is at this crucial early
stage that practitioners have the potential to curb what is often progression
from simple (mild) infection to a more severe problem, with necrosis,
gangrene and often amputation. Around 56% of DFUs become infected
and overall about 20% of patients with an infected foot wound will
undergo a lower extremity amputation.
Most acute infections in patients who have not recently been treated with
antimicrobials are caused by aerobic Gram-positive cocci, especially
staphylococci. More chronic infections, or those occurring after antibiotic
treatment are often polymicrobial, with aerobic Gram-negative bacilli
joining the aerobic Gram-positive cocci. Obligate anaerobes may be
isolated with proper techniques, usually as co-pathogens with aerobes, in
ischaemic or necrotic wounds. Tissue specimens or deep swabs should
therefore be cultured for both aerobic and anaerobic organisms. Cultures
should not be taken from clinically non-infected wounds as all ulcers will
be contaminated; microbiological sampling cannot discriminate
colonisation from infection.
Where necrosis occurs on the distal part of the limb due to ischaemia and
in the absence of infection (dry gangrene), mummification of the toes and
auto-amputation may occur. In most of these situations, surgery is not
recommended. However, if the necrosis is more superficial then the toe
can be removed with a scalpel.
Plain x-rays can help to confirm the diagnosis, but they have a relatively
low sensitivity (early in the infection) and specificity (late in the course of
infection) for osteomyelitis. The National Institute for Health and Care
Excellence (NICE) in the UK and IDSA recommend that if initial x-rays
do not confirm the presence of osteomyelitis and suspicion remains high,
the next advanced imaging test to consider is magnetic resonance imaging
(MRI). If MRI is contraindicated or unavailable, white blood cell scanning
combined with a radionuclide bone scan may be performed instead. The
most definitive way to diagnose osteomyelitis is by the combined findings
of culture and histology from a bone specimen. Bone may be obtained
during deep debridement or by biopsy.
In people with diabetes, even minor trauma can precipitate a chronic ulcer.
This might be caused by wearing poorly fitting footwear or walking
barefoot, or from an acute injury. In some cultures the frequent adoption of
the prayer position and/or sitting cross-legged will cause ulcerations on the
lateral malleoli, and to a lesser extent the dorsum of the foot, in the mid-
tarsal area. The dorsal, plantar and posterior surfaces of both feet and
between the toes should be checked thoroughly for breaks in the skin or
newly established DFUs. that occurs most often in the foot and in people
with diabetes. Nerve damage from diabetes causes decreased sensation,
muscle atrophy and subsequent joint instability, which is made worse by
walking on an insensitive joint. In the acute stage there is inflammation
and bone reabsorption, which weakens the bone. In later stages, the arch
falls and the foot may develop a rocker bottom appearance (Figure 8).
Early treatment, particularly offloading pressure, can help stop bone
destruction and promote healing. Corrective foot surgery to offload
pressure areas may be considered where structural deformities cannot be
accommodated by therapeutic footwear
Addressing the physical cause of the trauma. As well as examining the foot,
practitioners should examine the patient's footwear for proper fit, wear and
tear and the presence of any foreign bodies (such as small stones, glass
fragments, drawing pins, pet hairs) that may traumatise the foot. When
possible and appropriate, practitioners should check other footwear worn at
home and at work (eg slippers and work boots).
1. Tissue debridement
There are many methods of debridement used in the management of DFUs
including surgical/sharp, larval, autolytic and, more recently, hydrosurgery
and ultrasonic. Debridement may be a one-off procedure or it may need to be
ongoing for maintenance of the wound bed. The requirement for further
debridement should be determined at each dressing change. If the wound is
not progressing, practitioners should review the current treatment plan and
look for an underlying cause of delayed healing (suchas ischaemia, infection
or inflammation) and consider patient concordance with recommended
treatment regimens (such as not wearing offloading devices or not taking
antidiabetic medication). Debridement should be carried out in all chronic
wounds to remove surface debris and necrotic tissues. It improves healing by
promoting the production of granulation tissue and can be achieved surgically,
enzymatically, biologically, and through autolysis.
Sharp debridement
Surgical debridement, known also as the sharp method, is performed by
scalpels, and is rapid and effective in removing hyperkeratosis and dead
tissue. Particular care should be taken to protect healthy tissue, which has a
red or deep pink (granulation tissue) appearance. Using a scalpel blade with
the tip pointed at a 45 angle, all nonviable tissue must be removed until a
healthy bleeding ulcer bed is produced with saucerization of the wound edges.
If severe ischemia is suspected, aggressive debridement should be postponed
until a vascular examination has been carried out and, if necessary, a
revascularization procedure performed. No one debridement method has been
shown to be more effective in achieving complete ulcer healing. However,
inpractice, the gold standard technique for tissue management in DFUs is
regular, local, sharp debridement using a scalpel, scissors and/or forceps. The
benefits of debridement include:
Removes necrotic/sloughy tissue and callus
Reduces pressure
Allows full inspection of the underlying tissues
Helps drainage of secretions or pus
Helps optimise the effectiveness of topical preparations
Stimulates healing.
Enzymatic debridement
It can be achieved using a variety of enzymatic agents, including crab-derived
collagenase, collagen from krill, papain, a combination of streptokinase and
streptodornase, and dextrans. These are able to remove necrotic tissue without
damaging the healthy tissue. Although expensive, enzymatic debridement is
indicated for ischemic ulcers because surgical debridement is extremely
painful in these cases. Enzymatic debridement is based on the application of
topical agents on the ulcer. These agents are usually applied once daily. Their
action is based on the necrotic tissue degradation using proteolytic digestive
enzymes such as streptokinases, trypsin, papain, fibrinolysin-DNase,
collagenase, papain-urea and streptodornase. Data from clinical studies have
shown conflicting results about the efficacy of these topical agents, thus, their
additional benefits to standard wound care remains unclear. Putting into
consideration the need of long time application, as well as, the high cost, their
use is usually limited to slowly soften large eschars or debridement of some
decubitus ulcerations in sensate limbs. In order to improve efficacy of these
agents, a scalpel blade is applied to crosshatch eschars
Biological debridement
It has been applied recently using sterile maggots. Maggots have the ability to
digest surface debris, bacteria, and necrotic tissues only, leaving healthy tissue
intact. Recent reports suggest that this method is also effective in the
elimination of drug-resistant pathogens, such as methicillin-resistant
Staphylococcus aureus, from wound surfaces. Fly can achieve relatively rapid,
atraumatic removal of moist, slimy slough, and can ingest pathogenic
organisms present in the wound. The decision to use larval debridement must
be taken by an appropriate specialist practitioner, but the technique itself may
then be carried out by generalist or specialist practitioners with minimal
training. Larval therapy has been shown to be safe and effective in the
treatment of DFUs. However, it is not recommended as the sole method of
debridement for neuropathic DFUs as the larvae cannot remove callus. A
recent review of debridement methods found some evidence to suggest that
larval therapy may improve outcomes when compared to autolytic
debridement with a hydrogel.
Hydrosurgical debridement
This is an alternative method of wound debridement, which forces water or
saline into a nozzle to create a high-energy cutting beam. This enables precise
visualisation and removal of devitalized tissue in the wound bed.
Autolytic debridement
This is a natural process that uses a moist wound dressing to soften and
remove devitalised tissue. Care must be taken not to use a moisturedonating
dressing as this can predispose to maceration. In addition, the application of
moisture-retentive dressings in the presence of ischaemia and/or dry gangrene
is not recommended. Autolytic debridement involves the use of dressings that
create a moist wound environment so that host defense mechanisms
(neutrophils, macrophages) can clear devitalized tissue using the bodys
enzymes. Autolysis is enhanced by the use of proper dressings, such as
hydrocolloids, hydrogels, and films. Autolysis is highly selective, avoiding
damage to the surrounding skin.
Off-loading of the ulcer area is extremely important for the healing of plantar
ulcers. Retrospective and prospective studies have shown that elevated plantar
pressures significantly contribute to the development of plantar ulcers in
diabetic patients. In addition, any existing foot deformities may increase the
possibility of ulceration, especially in the presence of diabetic peripheral
neuropathy and inadequate off-loading. Furthermore, inadequate off-loading
of the ulcer has been proven to be a significant reason for the delay of ulcer
healing even in an adequately perfused limb. The value of ulcer off-loading is
increasing, as it has been reported that the risk of recurrence of a healed foot
ulcer is high if the foot is not properly off-loaded (in the high-pressure areas),
even after closure of the ulcer. The most effective method of off-loading,
which is also considered to be the gold standard, is the nonremovable total-
contact cast (TCC). It is made of plaster or fast-setting fiberglass cast
materials, has relatively low costs, and permits restricted activity.
Nonremovable TCCs are indicated for the effective off-loading of ulcers
located at the forefoot or midfoot. Severe foot ischemia, a deep abscess,
osteomyelitis, and poor skin quality are absolute contraindications to the use
of a nonremovable TCC. Nonremovable TCCs work by distributing the
plantar pressures from the forefoot and midfoot to the heel. They allow
complete rest of the foot whilst also permitting restricted activity.
Nonremovable TCCs also reduce edema, and compliance with treatment is
necessarily high. There are a number of removable cast walkers (RCW),
which usually have a lightweight, semirigid shell that helps support the limb
whilst also providing full-cell protection. The sole is of a rocker type, offering
off-loading of the forefoot during standing and walking. The foot base is wide
and there is enough room for dressings. In some RCWs, overlapping air cells
provide intermittent pneumatic compression for edema reduction. In other
RCWs, there are additional layers of foam or other soft material, offering total
contact.
A modification of RCWs is an instant total-contact cast (ITCC), where there is
a wrapping layer of cohesive tape or plaster bandage around the RCW. The
aim of the ITCC is to combine the efficacy of a TCC with the easy application
of a RCW. Half shoes are another solution for patients who cannot tolerate
other methods of off-loading, although they provide less pressure relief than a
cast boot and are difficult to walk in. Therapeutic shoes, custom insoles, and
the use of felted foam are alternative methods to off-load wounds located on
the forefoot, and can reduce pressure at the site of ulceration by 450%.
4. Dressings
Ulcers heal more quickly and are often less complicated by infection when in
a moist environment. The only exception is dry gangrene, where the necrotic
area should be kept dry in order to avoid infection and conversion to wet
gangrene. A wounds exudate is rich in cytokines, platelets, white blood cells,
growth factors, matrix metalloproteinases (MMPs), and other enzymes. Most
of these factors promote healing via fibroblast and keratinocyte proliferation
and angiogenesis, while others, such as leukocytes and toxins produced by
bacteria, inhibit the healing process. Moreover, it has been reported that local
concentrations of growth factors [platelet-derived growth factor-beta (PDGF-
beta), transforming growth factor-beta] are low in patients with chronic ulcers.
The ideal dressing should be free from contaminants, be able to remove excess
exudates and toxic components, maintain a moist environment at the wound-
dressing interface, be impermeable to microorganisms, allow gaseous
exchange, and, finally, should be easily removed and cost-effective. Various
dressings are available that are intended to prevent infection and enhance
wound healing, and several studies support their effectiveness for this purpose.
However, most of these studies were performed in wounds and not in diabetic
ulcers/ Available data on their use in diabetes are scarce, and therefore further
randomized clinical trials are needed to support the existing evidence for their
benefit in diabetic ulcers.
Most dressings are designed to create a moist wound environment and support
progression towards wound healing. They are not a substitute for sharp
debridement, managing systemic infection, offloading devices and diabetic
control. Moist wound healing has the potential to address multiple factors that
affect wound healing. It involves maintaining a balanced wound environment
that is not too moist or too dry. Dressings that can help to manage wound
exudate optimally and promote a balanced environment are key to improving
outcome. However, a dressing that may be ideal for wounds of other
aetiologies may be entirely inappropriate for certain DFUs. The dressing
selected may have a considerable effect on outcome and, due to the varying
complexities of DFUs, there is no single dressing to suit all scenarios. Many
practitioners are confused by the great range of dressings available.
Impressive claims are rarely supported by scientific studies and there is often a
lack of highquality evidence to support decision making. One inherent
problem is whether the characteristics of each wound randomised to a specific
dressing in a trial correspond to the characteristics that the dressing was
designed to manage. Many dressings are designed for non-foot areas of the
body and may be difficult to apply between or over the toes or plantar surface.
In addition, most practitioners have historically had little specific, practical
guidance on selecting dressings.
The status of the diabetic foot can change very quickly, especially if infection has
not been appropriately addressed. The need for regular inspection and assessment
means that dressings designed to be left in situ for more than five days are not
usually appropriate for DFU management.
Practitioners should also consider the following questions. Does the dressing:
Stay intact and remain in place throughout wear time?
Prevent leakage between dressing changes?
Cause maceration/allergy or sensitivity?
Reduce pain?
Reduce odour?
Retain fluid?
Trap exudate components?
Is the dressing:
Comfortable, conformable, flexible and of a bulk/weight that can be
accommodated in an offloading device/footwear?
Suitable for leaving in place for the required duration?
Easy to remove (does not traumatise the surrounding skin or wound bed)?
Easy to apply?
Cost effective?
Likely to cause iatrogenic lesions?
2. Growth Factors
PDGF-beta (becaplermin; available as Regranex; Ortho-McNeil
Pharmaceutical, Inc., Titusville, NJ, USA; and Janssen-Cilag International
NV, Beerse, Belgium) has been developed as a topical therapy for the
treatment of noninfected diabetic foot ulcers. It is applied in the form of a
once-daily gel along with debridement on a weekly basis. Initial studies have
indicated a significant positive effect of becaplermin on ulcer healing;
however, more recent studies have reported an increased incidence of cancer
in patients treated with becaplermin, especially at high doses. Consequently,
the US Food and Drug Administration has published a warning of an
increased risk of cancer if more than three tubes of becaplermin are used.
6. MMP Modulators
Matrix metalloproteinases regulate the extracellular matrix components.
During normal wound healing, there is a balance between the construction and
the destruction of the extracellular matrix. In chronic wounds, a high
expression of MMP-2 in fibroblasts and the endothelium is detected and is
believed to favor destruction. Thus, downregulation of MMP-2 expression
may enhance the healing process. DerMax (Tyco Healthcare Group Lp,
North Haven, CT, USA) is a dressing containing metal ions and citric acid,
and its topical application is associated with a lower expression of MMP-2 by
fibroblasts and endothelial cells. Metal ions inhibit the production of reactive
oxygen species by polymorphonuclear cells, and citric acid acts as a scavenger
of superoxide anions. One pilot study provided encouraging results. Certainly,
randomized trials are necessary in order to establish the role of DerMax in the
treatment of diabetic ulcers.
9. Hyperbaric Oxygen
There is strong evidence that fibroblasts, endothelial cells, and keratinocytes
are replicated at higher rates in an oxygen-rich environment. Moreover,
leukocytes kill bacteria more effectively when supplied by oxygen. It is also
known that fibroblasts from diabetic individuals show diminished cell
turnover in comparison with those from nondiabetic persons. Based on these
data, the idea was that the administration of oxygen at high concentrations
might accelerate wound healing in diabetes. Treatment with hyperbaric
oxygen therapy involves the intermittent administration of 100% oxygen at a
pressure greater than that at sea level. It is performed in a chamber with the
patient breathing 100% oxygen intermittently while the atmospheric pressure
is increased to 23 atmospheres for a duration of 12 h. A full course involves
3040 sessions. A small amount of data suggests significant reduction of the
ulcer area as well as reduction of the risk for major amputation. Hyperbaric
oxygen can be applied as an adjunctive therapy for patients with severe soft-
tissue foot infections and osteomyelitis who have not responded to
conventional treatment. Adverse effects include barotrauma to the ears and
sinuses, pneumothorax, transient changes in visual acuity, and seizures.
Furthermore, a recent systematic review by the National Institute for Health
and Clinical Excellence (NICE) Guidelines Development Group in the UK
concluded that the available data are insufficient to demonstrate that
hyperbaric oxygen therapy is cost-effective.
10. Amputations
Amputations are urgent or curative. Indications for an amputation include the
removal of infected or gangrenous tissue, controlling infection and creating a
functional foot or stump that can accommodate footwear or a prosthesis. The
preservation of leg length aids ambulation and decreases energy expenditure.
Yet the surgical site should heal primarily. A closed toe and metatarsal
amputation typically leave the patient with a functional foot for walking. If the
healing of a toe is in doubt, metatarsal amputations should be used liberally
after revascularisation. Piecemeal amputations should be avoided. In situations
involving extensive tissue loss and precluding a functional foot, as well as
when there are non-healing wounds despite patent revascularisation and for
controlling sepsis, amputation below the knee is necessary. According to the
IDF guideline, amputation should not be considered unless a detailed vascular
assessment has been performed by vascular staff. Amputation may be
indicated in the following circumstances:
Ischaemic rest pain that cannot be managed by analgesia or
revascularisation
A life-threatening foot infection that cannot be managed by other
measures
A non-healing ulcer that is accompanied by a higher burden of disease
than would result from amputation. In some cases, for example,
complications in a diabetic foot render it functionally useless and a well
performed amputation is a better alternative for the patient.
Around half of patients who undergo an amputation will develop a further DFU
on the contralateral limb within 18 months of amputation. The threeyear
mortality rate after a first amputation is 2050%. In a six-year follow-up study,
almost 50% of patients developed critical limb ischaemia in the contralateral limb,
but the severity of the DFU and amputation level was significantly lower than in
the unilateral limb. This may have been due to prompt intervention made possible
by increased patient awareness. Patients at high risk for ulceration (such as
patients who have undergone an amputation for a DFU) should be reviewed 13
monthly by a foot protection team. At each review patients' feet should be
inspected and the need for vascular assessment reviewed. Provision should be
made for intensified footcare education, specialist footwear and insoles, and skin
and nail care. Special arrangements should be made for people with disabilities or
immobility1. The Scottish Intercollegiate Guidelines Network (SIGN)
recommends specialist diabetes podiatrist input for patients with a history of
amputation and ulceration. Although amputation incidence may not reflect the
quality of local healthcare delivery, there is a need for more consistent delivery of
diabetes care, with the involvement of an MDFT and patient education.
III. CONCLUSION