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Guidelines regarding negative wound therapy (NPWT) in the diabetic foot

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Guidelines Regarding Negative
Table of Contents
Pressure Wound Therapy (NPWT)
in the Diabetic Foot: Introduction/Abstract . . . . . . . . . . . . . . . . . . . .1S
Results of the Tucson Expert
Consensus Conference (TECC) Pathophysiology and Epidemiology of
on V.A.C.® Therapy Diabetic Foot Ulcers . . . . . . . . . . . . . . . . . . . . . . .1S

Chair/Editor Basic Science and Mechanism of Action of

David G. Armstrong, DPM, MSc Negative Pressure Wound Therapy . . . . . . . . . . . .7S
Director of Research, Department of Surgery, Podiatry Section, Southern
Arizona Veterans Affairs Medical Center, Tucson, Arizona
Indications and Contraindications of Use for
Negative Pressure Wound Therapy
Authors
in the Diabetic Foot . . . . . . . . . . . . . . . . . . . . . . . . .10S
David G. Armstrong, DPM, MSc
Director of Research, Department of Surgery, Podiatry Section, Southern
Arizona Veterans Affairs Medical Center, Tucson, Arizona
Appropriate Perioperative Use of Negative
Pressure Wound Therapy for Diabetic Foot
Christopher E. Attinger, MD
Professor of Plastic and Orthopedic Surgery, Georgetown University Wounds Following Peripheral Arterial
Hospital, Washington, DC
Revascularization . . . . . . . . . . . . . . . . . . . . . . . .14S
Andrew J. M. Boulton, MD, FRCP
University Department of Medicine, Manchester Royal Infirmary,
Manchester, United Kingdom
Appropriate Use of Negative Pressure
Wound Therapy in Reconstructive
Robert G. Frykberg, DPM, MPH Surgery of the Diabetic Foot . . . . . . . . . . . . . . . . .19S
Associate Chief, Podiatry Section, Department of Surgery, Carl T. Haden
VA Medical Center, Phoenix, Arizona

Robert S. Kirsner, MD
Important Questions and Answers
Associate Professor, Department of Dermatology, University of Miami on the Use of Negative Pressure
School of Medicine, Miami, Florida
Wound Therapy . . . . . . . . . . . . . . . . . . . . . . . . .23S
Lawrence A. Lavery, DPM, MPH
Associate Professor of Surgery, Department of Surgery, Texas A & M
University/Scott & White Medical Center, Temple, Texas References . . . . . . . . . . . . . . . . . . . . . . . . . . . .25S

Joseph L. Mills, MD These guidelines are sponsored by an educational grant

Professor of Surgery, Chief, Division of Vascular Surgery, University of
Arizona School of Medicine, Tucson, Arizona
HMP Communications
Copyright © 2004, All Rights Reserved
83 General Warren Blvd. • Malvern, PA 19355
Phone 800.237.7285 • Fax 610.560.0501
from Kinetic Concepts Inc., San Antonio, Texas.
THIS ARTICLE WAS WRITTEN BY INDEPENDENT CLINICAL EXPERTS. SOME OF THE
INFORMATION REPRESENTS THE VIEWS AND OPINIONS OF THESE EXPERTS
BASED ON THEIR PRACTICE AND EXPERTISE. THIS ARTICLE MAY CONTAIN CERTAIN
INFORMATION THAT MAY BE CONSIDERED OFF-LABEL CLAIMS. KCI DOES NOT
PROMOTE ANY OFF-LABEL CLAIMS OR APPLICATIONS AND ENCOURAGES THE
CLINICIAN TO CONSULT SPECIFIC INDICATIONS, CONTRAINDICATIONS, PRE-
CAUTIONS, SAFETY TIPS, AND CLINICAL GUIDELINES FOR V.A.C. THERAPY CON-
TAINED IN PRODUCT LITERATURE AND INSTRUCTIONS FOR USE.
 I N T R O D U C T I O N

Guidelines Regarding Negative Wound Therapy (NPWT)

in the Diabetic Foot

A
bstract: The purpose of these guidelines is to the summarize consensus of
a multidisciplinary expert advisory panel convened to determine appropri-
ate use of negative pressure wound therapy (NPWT), also known as
Vacuum-Assisted Closure® or V.A.C.® Therapy, in the treatment of diabetic foot wounds. The Tucson Expert
Consensus Conference (TECC) on V.A.C. Therapy was convened in an effort to guide the direction for future
research either to confirm or refute current consensus while providing practical guidance to the clinician cur-
rently treating diabetic foot wounds. The consensus committee discussed and commented on the following ten
key questions regarding NPWT: 1) How long should NPWT be used in the treatment of a diabetic foot wound?
2) Should NPWT be applied to a wound that has not been debrided? 3) How should the patient using NPWT
be evaluated on an outpatient basis? 4) When should NPWT be applied following lower-extremity bypass?
5) When should NPWT be applied after incision and drainage of infection? 6) How should NPWT be used
in patients with osteomyelitis? 7) How should nonadherence (i.e., noncompliance) be defined in the patient
on NPWT? When should NPWT be discontinued in this population? 8) How should NPWT be used in com-
bination with other modalities? 9) Should small, superficial, noninfected wounds be considered for NPWT?
10) How should we define success in future studies of NPWT?

Ostomy/Wound Management 2004;50(4 Suppl B):3S–27S

This supplement is being reprinted with permission from Ostomy/Wound Management and distributed to the readers of Podiatry Today.

Diabetic Foot Ulceration:
Pathophysiology and Epidemiology
The world is facing a major epidemic of diabetes.
There are 190 million people with diabetes in the
world today. Over the next 22 years, this number is
expected to increase 72 percent worldwide to nearly
325 million people. Specifically, in the United States,
diabetes is expected to increase 60 percent over the
next 22 years, while in Europe diabetes is expected to
increase a modest 16 percent. Australasia is expected
to increase 59 percent, South America 88 percent, and
Africa, Middle East, and Asia a tremendous 98 per-
cent. India is the world capital of known diabetes;
there are currently more people with diabetes in India
than there are people living in the United Kingdom,
which is over 50,000,000. The highest prevalence of
diabetes is in the Pima Indians’ community in
Arizona where up to 50 percent of the residents have
diabetes. There is an increasing number of young
people and children with type 2 diabetes especially
among ethnic minority groups. This increase in dia-
betes is mainly attributed to modernization or west-
ernization of the world’s societies.1

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Guidelines Regarding Negative Pressure Wound Therapy in the Diabetic Foot
Pathophysiology. Neuropathy. Dr. Paul Brand
once said, “God’s greatest gift to mankind is pain.”
A lack of pain is what leads to many of the lower-
limb complications often seen with diabetes.
Diabetic neuropathy is a complication associated
with diabetes that can lead to foot ulcers. Those at
greatest risk of developing foot ulcers include those
who have past histories of foot ulcers, those who
have undergone amputations, or those with
microvascular complications. As early as 1887, it
became clear to the medical community that dia-
betes may play an active role in the causation of per-
forating ulcers. An article published in Lancet in
18872 stated it was abundantly evident to the author
in his clinical observation that the cause of the per-
forating ulcers was a
degeneration of peripher-
al nerves. Yet there is a Twenty percent of persons
paradox in diabetic neu-
ropathy because some
with diabetes will develop
individuals experience foot ulcers...
severe pain with pre-
served sensation while
others experience much less pain and loss of sensa-
tion and still others have no symptoms whatsoever.
Twenty percent of persons with diabetes will
develop foot ulcers, and the vast majority of these
ulcers are initially due to neuropathy. Neuropathic
ulcers are frequently complicated by infection. In a
study by Reiber,3 investigators reviewed several
cases to determine key component causes that
resulted in the diabetic foot ulceration. Investigators
found that while a single component cause may be
important in the development of ulceration, it
would not cause ulceration on its own; however,
when combined with other component causes ulcer-
ation would develop. This study showed that the
most important component cause of diabetic ulcera-
tion was neuropathy, which was present in 4 out of
5 subjects (78%). Other causative factors include
infection and ischemia. It is mandatory that physi-
cians treating diabetic patients with foot problems
4S
determine which components of this etiologic triad
(neuropathy, infection, ischemia) are contributing to
the foot ulcer in each patient. It is estimated that 80
percent of diabetic ulcers are potentially preventable.
In the United Kingdom Prospective Diabetes Study
(UKPDS),4 11 percent of the subjects had neuropathy
at the time of diagnosis of diabetes. What this means
is that diabetic foot problems may present themselves
to surgeons, podiatrists, or primary care physicians as
diagnostic features of diabetes. Neuropathy may be
asymptomatic in over half of the patients.
In a UK population-based study of type 2 dia-
betes published in 1994, 42 percent of the 811 sub-
jects included in the study had clinical evidence of
neuropathy and 11 percent had vascular disease.5
The investigators, there-
fore, conservatively esti-
mated that over 50 percent
of the older type 2 diabetes
patients are at risk for foot
problems. In a prospective
study, investigators
showed that diabetic neu-
ropathy does indeed lead to foot ulceration. This
observational study consisted of 469 patients who
were screened when a new diabetes center was
opened in 1988.6 The subjects were assessed by
vibration perception using a Bio-Thesiometer, which
is a hand-held device that semiquantitatively meas-
ures vibration perception. Subjects also received foot
care education. Investigators followed the patients
to determine who developed foot ulcers. The results
of this study showed that those patients with no
neuropathy (vibration perception threshold [VPT] of
less than 15) had an annual risk of developing an
ulcer below one percent. Those subjects with defini-
tive neuropathy (VPTs of more than 25) had a seven-
fold increase risk or a five-percent annual risk of
developing foot ulcers. This study was later repeat-
ed and included multiple centers in North America
and Europe with over 1000 diabetic subjects with
definite neuropathy but no past history of ulcers and
 Results of the Tucson Expert Consensus Conference on V.A.C.® Therapy
no evidence of peripheral vascular disease. The sub-
jects were seen every three months by the investiga-
tive podiatrist or a specialist nurse. The annual risk
of first ulcers in this group of subjects was over
seven percent.7 The data from this study can be used
for power calculations for further studies.
Investigators in this study also showed that electro-
physiology was the best predictor of foot ulcers. For
more sophisticated studies where nerve function is
measured, electrophysiology is a good surrogate
marker for risks of the endpoint of neuropathy.8
In the ongoing population-based Northwest
Diabetes Foot Care Study (N.W. UK), there are
16,000 patients and six healthcare districts being
studied. For this study,
investigators are using a
simple neuropathy dis-
ability score (NDS), which ...the most important
comprises sensory modal-
ities of vibration, pin- component cause of
prick, and hot and cold diabetic ulceration [is]
rods. The NDS is calculat-
ed from each of these
neuropathy.
modalities and the pres-
ence or absence of ankle
reflex scores.9 If the
patient has loss of vibration and pinprick sensation,
loss of temperature perception, and absent ankle
reflex, the patient scores a 5, with a maximum score
of 10 for both legs. Subjects in this study are seen
once by a research podiatrist and are followed up in
primary care. Subjects are followed up two years
later by investigators. Out of the 10,000 subjects
studied so far, 291 developed ulcers during this time.
In this group of patients, ulcers were more common
in male patients, which is typical in Europe and
North America. This study suggests that the best
predictor of risk of ulcers was the NDS. If the patient
scored 6 or higher, he or she had an annual risk of
ulceration of six percent. If the patient scored less
than 6, he or she had a one-percent annual risk of
ulceration.10
Neuropathy on examination is usually symmetrical;
the symptoms are usually bilateral but they may be
more severe on one side. Most often, however, symp-
toms are symmetrical. Often, when diabetic neuropa-
thy rapidly progresses, the physician may attribute the
symptoms to another cause.
Epidemiology. Globally, there appears to be a
steady increase in major amputations although there
have been some regional differences. Studies in the UK
reported an increase in amputation despite the St.
Vincent Declaration to reduce amputations by 50 per-
cent. Likewise, there is no evidence of a decrease in
amputations.11 Sweden, however, has been successful
in reducing the number of amputations. All Swedish
citizens carry cards with
them that contain their
medical data. This allows
Sweden to have very accu-
rate databases, and togeth-
er with well-organized dia-
betes care, this has proba-
bly resulted in a fall in the
amputation rate.12
The prevalence of foot
ulceration in the various
studies worldwide is
important to consider. For example, in a study from
Sweden in 1990, the subjects had a prevalence of foot
ulcers of less than one percent and a population aged
15 to 50 with type 1 diabetes. However, in a study from
the United Kingdom, 1.4 percent of the patient popu-
lation in the study had active ulcers, and this study
comprised active and a history of ulcers; in other
words 4.8 percent of the population had ulcers previ-
ously or during the study. In the developing world,
like South Africa, especially in Algeria, 12 percent of
the patient population has active ulcers and 6.7 percent
were amputees. The US has a high rate of amputation,
which is at 8.1 per 1000 persons with diabetes. More
recent data from the San Antonio population base data
set shows the incidence of ulceration to be about 6.8
per 1000 persons with diabetes per year.13,14
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Guidelines Regarding Negative Pressure Wound Therapy in the Diabetic Foot

A HMO US population retrospective study pub- were diabetic foot problems. Twenty percent of the
lished in 1999 estimated the outpatient cost of a foot foot lesions in Tanzania resulted in amputation.
ulcer over two years to be $28,000, which did not Investigators showed in 1995 that diabetic foot ulcers
include inpatient treatment.13 Worldwide, particularly are much less common among Indian sub-continent
in developing countries, diabetes is increasingly com- Asian patients in the Manchester region. Investigators
mon. In some islands in the Caribbean, over 20 per- believe this is due to the following two reasons: 1)
cent of the population have diabetes. In Brazil, it is Muslims, who are prevalent in these areas, remove
estimated that 7.6 percent of the population has their shoes and socks and wash their feet many times
diabetes.15,16 a day for religious practice, which means they are
China has a population of 1.25 billion and only a more apt to notice any problems; and 2) patients from
few foot clinics. Senegal has one foot clinic, but Brazil Indian Subcontinent Asia often have hypermobility of
now has 52 foot clinics joints, which is associated
across the country.17 There with reduced foot pressure.
are progressive develop-
Those patients with Subsequently, in 2002,
ments in some African investigators showed that
countries, such as known risk factors [of amputations are four times
Cameroon, Senegal, South diabetic foot ulceration] more common in Europe
Africa, Sudan, and compared to Asian persons
Tanzania—representatives require much more frequent with diabetes in the North
of which were present at follow-up, regular West of England.10
the recent International There is an ongoing
Diabetic Foot Meeting.
education, and podiatric study on neuropathy to
This means researchers care in order to reduce the determine why there are
will be able to finally differences. In a paper pub-
obtain some data from
all too high incidence of lished in Diabetes Care, 1665
these areas. As discussed diabetic foot ulceration in persons with diabetes
at the PAHO (Pan enrolled in a health man-
the United States.
American Health agement program.13 This
Organization), which took study showed incidence of
place in 2003, there is a very high prevalence of type 2 ulcerations to be 6.8 percent and incidence of ampu-
diabetes and neuropathy in the Caribbean and tations to 0.6 percent. This study showed that ampu-
Central America. There are very few diabetes foot tation rates are greater in Mexican Americans.
services in these areas, and each has a high amputa- According to a study by Reiber, who investigated
tion rate. A retrospective study from Trinidad investi- outpatient foot ulcer episodes in the Veteran’s
gated 187 major amputations and found the vast Administration in 2001, the rate of foot ulcer episode
majority (over 80%) were due to diabetic foot prob- was very high in VA patients with diabetes.19
lems. Sixty-three percent of the amputations were The US Centers for Disease Control and
above-the-knee amputations. Peripheral vascular dis- Prevention (CDC) surveillance system is the largest
ease was rare compared to neuropathy, 27 percent vs. telephone server in the world, servicing 44 states.
92 percent, respectively. According to data obtained from this system, 12 per-
A recent paper in Diabetic Medicine in 200218 showed cent of adults with diabetes have a history of foot
that 15 percent of all hospital admissions in Tanzania ulcers. There are limitations to this study, which

6S
 Results of the Tucson Expert Consensus Conference on V.A.C.® Therapy
include that it is based on self reporting. In other
words, subjects may or may not even know what a
foot ulcer is.20
Certain ethnic groups are considered to be at
greater risk of ulceration, including Mexican
Americans, Hispanics, and Blacks, while other eth-
nic groups appear to be at lower risk. The incidence
of diabetic foot ulcers is likely to increase. Foot ulcer-
ation is a major burden for the economies of devel-
oping countries.20
The risk factors for diabetic foot ulcers appear to
be well described, although there has been much
neglect of psychological aspects of diabetic neuro-
pathic foot complications.21 The important physical
factors to look for on clinical examination include
neuropathy, peripheral vascular disease, foot defor-
mity, and other microvascular complications. Those
patients with known risk factors, including past his-
tories of foot ulceration or amputation, require much
more frequent follow-up, regular education, and
podiatric care in order to reduce the all too high inci-
dence of diabetic foot ulceration in the United States.
Basic Science and Mechanism of
Action of Negative Pressure Wound
Therapy (NPWT)
The NPWT device (Vacuum Assisted Closure®,
V.A.C.® Therapy, Kinetic Concepts Inc., San Antonio,
Texas) consists of a sterile, open-foam cell dressing
that is cut to fill a wound defect. The foam is sealed
to the wound by an adhesive dressing, and an evac-
uation tube is applied to the foam. The end of the
tube not placed through the foam is attached to a
pump outside of the wound so subatmospheric or
negative pressure can be applied uniformly to all tis-
sue within the wound.
In theory, applied negative pressure will stimu-
late development of granulation tissue in a previ-
ously nonhealing wound leading to epithelization.
The proposed process by which the NPWT device
accomplishes this is by uniformly drawing the
wound edges closed by applying controlled local
negative pressure. This pressure removes interstitial
fluid, which allows tissue decompression, removes
infectious materials, and provides a closed moist
wound healing environment. Thus, given the action
of NPWT, it is possible that the following mecha-
nisms occur: provision of a moist wound healing
environment; improved management of exudate;
improved bacterial burden within the wound;
increased wound temperature; and physical stimula-
tion of cells.
Moist wound healing (occlusion). NPWT applies
occlusion to the wound bed, which, theoretically,
creates a moist wound healing environment.
Advantages of a moist wound bed include promo-
tion of rapid epithelization of acute wounds,
enhanced healing of chronic wounds, reduced pain,
and reduced chance of infection. The most simple
outcome of this is that moisture in the wound bed
prevents the epithelium from having to migrate and
digest crust. In the moist wound bed, the epithelium
has a smoother pathway to reepithelize the surface
of the wound. Additionally, in this more aqueous
milieu, growth factors are more active, more avail-
able, and more easily synthesized within a moist
environment compared to a desiccated environment.
There may be more available matrix materials as
well, and moist wounds maintain their lateral volt-
age gradient, or so called wound healing potential,
more effectively than wounds that are dried.22
Some clinicians may fear that the use of occlusive
dressings leads to infection. This fear may be due to
the fact that when occlusive dressings are placed on
chronic wounds, they induce an exudative phase.
NPWT, however, obviates the exudate by its nega-
tive pressure. In the literature, there are less reported
infections with the use of occlusive dressings.23
Exudate management. Exudate can be detrimen-
tal to wound healing because it contains excess
amounts of proteases, primarily matrix metallopro-
teinases, and lesser amounts or inactivity of their
inhibitors. One study24 suggests that exudate from
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Guidelines Regarding Negative Pressure Wound Therapy in the Diabetic Foot
wound fluid from human pressure ulcers contains
elevated proteases and this is associated with poor
healing; another study25 suggests that acute wound
fluid stimulates cell growth; and yet another26 sug-
gests chronic wound fluid inhibits cell growth. In the
study of acute wound fluid,25 investigators found
application of acute wound fluid stimulated both
fibroblast and endothelial cells when applied in cul-
ture. In a study that investigated wound fluid from
venous ulcers,27 it was found that the wound fluid
from venous ulcers induced a senescent phenotype
in neonatal fibroblasts. It rapidly changed these
healthy, active, neonatal fibroblasts in culture to
senescent phenotype, which are characterized by an
irreversible arrest of growth, a resistance to cell
death, and a modification of cell function, so cells
grow less well. Platelet-derived growth factor, a
potent stimulus of cells, in culture rapidly stimulates
the growth of fibroblasts taken from acute wounds
and from the dermis, but in contrast, fibroblasts
from chronic wounds are not stimulated to the same
extent, and this is associated with senescent pheno-
type. Because of this idea of cellular senescence,
therapies like debridement, grafting, applying new
autologous or allogeneic cells to a wound, and appli-
cation of NPWT may prove very beneficial to
wound healing.
In addition to removing fluid that contains an
imbalance of matrix metalloproteinases and their
inhibitors, there may be other benefits of NPWT in
regards to removing fluid. Localized edema occurs
in response to tissue injury, and this localized edema
then results in an increase in interstitial pressure.
This increased interstitial pressure then causes
occlusion of the microvasculature and lymphatics.
This leads to decreased nutrients and decreased oxy-
gen delivery. A greater accumulation of metabolic
waste and increased bacterial colonization leads to a
release of protein-degrading enzymes. These pro-
tein-degrading enzymes may then cause capillary
damage and hypoxia, which lead to a decrease in
collagen matrix formation and an oxidative burst.
8S
This oxidative burst is important in destroying neu-
trophils, the presence of which leads to inflamma-
tion and a subsequently more proteolytic environ-
ment.28 NPWT creates an increase in diffusion gradi-
ents, which then facilitates the removal of this excess
interstitial fluid and improves some of those param-
eters. In a study of a porcine model of 25 pigs,29 the
investigators placed laser Doppler probes inside the
wounds they created and then studied blood flow.
They found when they applied negative pressure in
25mm of mercury (Hg) increments up to 400mmHg
for 15 minute intervals, the optimal pressure for
improved blood flow was 125mmHg, which had
four times the blood flow in both the subcutaneous
tissue and muscle. In fact, there was a bell-shaped
curve, and at 400mmHg the blood flow was reduced
below baseline. Interestingly, this increase in blood
flow declined after 5 to 7 minutes, so it occurred rap-
idly, slowly decreased, and then required at least
two minutes without pressure if the pressure was
applied again. If a rest period of two minutes was
not given, the peak in increased blood flow was not
seen This was the basis of the five-minute on/two-
minute off intermittent cycle that was established for
the use of NPWT when blood flow, healing, and
improved granulation tissue were the desired
outcomes .
Other models looked at a combination of subat-
mospheric pressure (NPWT) and hyperbaric oxygen
in a rabbit ischemic full-thickness wound healing
model.30 The investigators randomized rabbit ears to
one of four treatment groups: NPWT alone, NPWT
plus hyperbaric oxygen (daily for 2 ATMs [atmos-
phere O2] for 90 min), a sham control NPWT, and a
sham control NPWT plus the hyperbaric oxygen.
Pathologists performed semiquantitative evaluation
looking at granulation tissue and epithelization. The
NPWT device increased the healing in the rabbit
ischemic model, while HBO did not improve out-
comes when added to NPWT.
Infection control. With regard to the concept that
NPWT helps control bacterial burden, one study29
 Results of the Tucson Expert Consensus Conference on V.A.C.® Therapy
involved five pigs with acute wounds that were
inoculated with 108 infecting organisms.
Investigators applied 125mmHg to some of these
wounds and then harvested full-thickness biopsies
from each of these wounds every 24 hours for bacte-
rial burden. They found that between Days 4 and 5,
NPWT wounds had a decrease in the bacterial load
(105), while the control wounds not receiving NPWT
continued to have elevated levels of bacteria.
It has been suggested that the presence of higher
bacterial loads within wounds delay healing.31 If a
reduction of bacterial burden is achieved with
NPWT, the result may have a beneficial effect on
healing.
Wound heating. Chronic wound fluid is inhibito-
ry to cells, and if that fluid is heated, it reverses the
inhibitory effect. Some cli-
nicians have used devices,
such as Warm-Up® thera- NPWT...obviates the
py (Augustine Medical,
Eden Prairie, Minnesota),
exudate by its negative
to warm wounds, in effect pressure.
perhaps reversing the
chronic wound fluid. A
small, randomized trial in 10 patients with diabetic
foot ulcers32 showed better healing compared to a
control group when they received Warm-Up thera-
py. A simpler alternative to raising the temperature
of a wound is the use of an occlusive dressing. By
using an occlusive dressing, NPWT may also warm
the wound and provide this beneficial effect for
healing.
Physical stimulation of cells. In 1892, Julius
Wolfe noted that bone changed shape in response to
physical stress. Subsequent to that a German histol-
ogist, Richard Thoma, extrapolated Wolfe’s observa-
tion to soft tissues and found that the development
of blood vessels is governed by dynamic forces act-
ing on their walls as follows: An increase in velocity
of blood flow causes dilation of the lumen; an
increase in lateral pressure of the vessel walls causes
it to thicken; and an increase in end pressure causes
formation of new capillaries. This is the law of ten-
sion stress,33 and it postulates that gradual traction
on living tissues creates stresses that can stimulate
and maintain regeneration or active growth of cer-
tain tissue structures. In other words, slow, steady
forces metabolically activate tissues.
There are two conceptual ways to think about
this. To study the effects of mechanical stress, one
can perform in-vitro cellular experiments looking at
cell proliferation and gene and protein expressions,
or one can also perform in-vivo experiments looking
at tissue expansion as a model or tension experi-
ments in both animals and humans. In 1978,
Folkman, the father of angiogenesis,34 suggested that
altered cell shape affects cell proliferation, again
consistent with the idea of Wolf and Thoma. Since
then work has shown that
mechanical stress stimu-
lates aortic endothelial
cells to proliferate.35 In
these experiments, using a
bovine model, vacuum-
operated stress provided
10 repeated cycles of elon-
gation, which elongated cells by 10 percent.
Relaxation was then applied, and it was found
endothelial cells do proliferate in response to this.
There are several hypotheses about the transla-
tion of physical stress to cell proliferation. In addi-
tion to endothelial cells, there has been work using
keratinocytes.36 When basal cells are stressed, they
alter their shape and their nuclei become hyper-
chromatic and have mitotic figures, which ultimate-
ly lead to increases in proliferation. The mechanical
stress increases deoxyribonucleic acid (DNA) syn-
thesis, which causes proliferation. Changes in soft
tissue may also be induced, and increases in protein
production, collagen, DNA synthesis, and matrix
materials in response to stress has been reported. In
vivo, demonstration of tissue response to stress
(stretching) has been found using tissue expanders.
When placed in saphenous arteries and veins in ani-
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Guidelines Regarding Negative Pressure Wound Therapy in the Diabetic Foot

mal studies, it has resulted in the vessels elongating chemical signal cascades, and gene transcription.
84 percent.37 When these tissue expanders were These models also suggest that cyclical forces are
placed beneath sciatic nerves in rats, the nerves elon- superior to continuous forces.
gated in a dose-dependent fashion. When 20mmHg When NPWT is applied to patients, the foam in
was applied, 30-percent expansion was seen, and the wound bed collapses, which transmits a negative
when 40mmHg was applied, 40-percent expansion force to surrounding tissues. This force deforms the
was noted over a 14-day period. The electrical poten- extracellular matrix in cells, and by doing this, it cap-
tial in this case of nerve expansion did not change. In italizes on this tension stress effect. This results in
a model simulating activating tyrosine kinas-
wound healing, tissue es, transporting genes,
expanders were placed in As shown in several stimulating calcium
rodents subcutaneously. studies, NPWT can prepare release, and inducing
Maximum load, energy early growth response
absorption, and more wound beds for grafting or genes.
organized collagen orien- for delayed primary Through the aforemen-
tation resulted in the areas tioned mechanisms,
expanded compared with
closure very effectively and numerous studies suggest
control areas. is also useful for those that NPWT may improve
In women undergoing healing by providing a
breast reconstruction
patients who are not moist wound healing
using tissue expansion, suitable surgical environment, improving
biopsies taken prior to management of exudate,
and after the tissue expan-
candidates. 40,41
improving bacterial bur-
sion found the number of den within the wound,
basal and suprabasal keratinocytes significantly increasing wound temperature, and physically
increased after expansion.38 stimulating cells.
One popular hypotheses to explain the events
depicted above is called the Tensegrity Model.39 It is Indications and
suggested that cellular conversion of the stress Contraindications for NPWT
occurs by way of molecular, chemical, and genetic
responses through secondary messengers. Cells In 1997, Argenta and Morykwas conducted stud-
maintain structure and regulate response to extracel- ies on NPWT and showed that there was enhanced
lular forces via their cytoskeleton. This cytoskeleton granulation tissue formation and improved bacteri-
connects throughout the cell and connects the nucle- al clearance when compared with control dress-
us to the cytoplasm through receptors of the inte- ings.35 There also appeared to be increased flap sur-
grins. Integrin receptors mediate this reaction and vival. Some of the therapeutic benefits of NPWT
work through clusters called focal adhesions, which that were postulated by Morykwas29 as well as
is a group of anchoring complexes. When cells gen- Argenta and Morykwas in 199740 included aggres-
erate either internal or receive external forces these sive reduction in local or interstitial edema, increas-
are applied to integrins, a local intracellular trans- es in local blood flow, evacuation of excessive
duction response is activated that leads to focal drainage, decreased bacterial colonization, and con-
adhesion assembly, cytoskeletal strengthening, verting an open wound to a controlled closed

10S
 Results of the Tucson Expert Consensus Conference on V.A.C.® Therapy
wound, which allows less frequent dressing
changes and protects the wound from the patient
and his or her surroundings. Therapeutic benefits
also included providing a moist wound healing
environment, which has become the standard of
therapy.
Indications. The V.A.C.® system is cleared by the
US Food and Drug Administration (FDA) for pro-
motion of healing in wound types, including pres-
sure ulcers, other types of chronic wounds, acute
and traumatic wounds, in conjunction with meshed
grafts and flaps, and partial-thickness burns. This
therapy is adjunctive for managing large defects and
heavily draining wounds because of its ability to
control exudate from unhealthy wounds after
debridement. As shown in several studies, NPWT
can prepare wound beds for grafting or for delayed
primary closure very effectively and is also useful
for those patients who are not suitable surgical
candidates.40.41
Though NPWT can be used on any size wound, it
is especially useful on deep, complicated, nonheal-
ing wounds of mixed etiologies. In 2002, in a retro-
spective review of 31 patients at two wound centers,
NPWT was applied to large wounds following sur-
gical debridement until achieving 100-percent gran-
ulation tissue.41 The wounds were medium sized at
28cm2 with a general duration of 25 weeks. The
investigators’ outcomes were time to closure, pro-
portion, and healing at the same level of initial
debridement without requiring a more proximal
amputation. They also assessed complications.
About 90 percent of these wounds healed at the ini-
tial level at a mean of eight weeks. NPWT duration
was a mean of approximately five weeks but most
often was used for two weeks. Multimodal thera-
pies, including split-thickness skin grafts, were then
used to facilitate closure after the wound had been
prepared with NPWT. Complications were wound
maceration under and around the dressing and, on
one occasion, cellulitis. There was one deep space
infection, and several patients had to have below-
Indications of Negative
Pressure Wound Therapy
The V.A.C.® system is cleared by the US Food and Drug
Administration for promotion of healing in wound types,
including:
• Chronic wounds
• Acute and traumatic wounds
• In conjunction with meshed grafts and flaps
• Partial-thickness burns.
knee amputations. This represents a general clinical
perspective on the types of patients on whom
NPWT can be used and what can be expected.
Benefits. Improvement of graft take. In many clini-
cal applications, NPWT will be used not to affect pri-
mary closure but to enhance the progression of
wounds in preparation for early surgery. The modal-
ity can also stabilize flaps, grafts, and traumatic
wounds in preparation for eventual closure. Initially,
some clinicians feared that suction from NPWT
might disturb a graft from its recipient bed, but the
negative pressure actually compresses and enhances
the take of the skin graft. Another benefit of NPWT
in this situation is to prevent fluid accumulation
underneath the graft. In a study by Schneider, et al.,42
investigators used a nonadherent porous dressing
between the graft and the dressing for skin grafts.
This created an interface between the graft and the
dressing that applied continuous pressure to the
graft against the recipient bed. The investigators left
the dressing in place for three or four days until the
graft had taken.
Wound bed granulation. In conjunction with the basic
tenets of wound healing and appropriate wound care
(including debridement), NPWT can stimulate angio-
genesis.43–46 By applying negative pressure uniformly to
all points of a wound, NPWT will assist in wound con-
traction and the development of new tissue, not just in
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Guidelines Regarding Negative Pressure Wound Therapy in the Diabetic Foot
Potential Benefits of Negative
Pressure Wound Therapy
• Reduces local or interstitial edema
• Increases local blood flow
• Evacuates excessive drainage
• Improves graft take
• Assists in granulation
• Reduces number of dressing changes
• Useful as an adjunctive therapy (e.g., with skin
substitutes or in heavily exuding wounds)
the diabetic foot but for patients who are nonoperative
(e.g., those who are too sick to go to the operating room
for closure). Although use over bone, tendon, or hard-
ware was an early contraindication to NPWT there are
now reports in the literature that support its use with
exposed deep structures.40,47 NPWT in these wounds
may enhance angiogenesis and granulation tissue for-
mation to the point that they may be successfully graft-
ed or closed. Some clinicians will apply NPWT in the
operating room; however, it is necessary to wait until
hemostasis is achieved along with adequate drainage
and resolution of acute infection before applying this
therapy.
In a study on both animals and humans by Genecov,
et al.,48 investigators covered half the donor sites with
NPWT dressing and half with a simple polyurethane
occlusive dressing. Biopsies were taken every other
day from the animal model and on Days 4 and 7 for the
human model. They found NPWT donor site wounds
had epithelized significantly faster, while there was no
difference in the degree of pain in the human studies.
Ease of dressing changes. An additional benefit is the
ease of applying these dressings. NPWT allows
reduced hands-on care, meaning the dressing changes
can be performed every 48 hours rather than every 12
12S
hours unless infected (12–24 hours for infected
wounds). The device can be applied at home or in
alternative care settings. It can be changed more fre-
quently if there is concern about what is taking place
under the dressing in the early stages. More than one
wound can be treated at a single time by using con-
necting foam bridges or Y connectors. A minimum of
22 hours a day of active therapy is important since
these dressings should not be left on a wound without
the therapy being active (either continuous or
intermittent).
As adjunctive therapy. NPWT is most often used
adjunctively with other agents or modalities. A brief
review by Espensen, et al.,49 described multimodal
therapy using a tissue substitute in concert with
NPWT. Increasingly common is the use of NPWT as a
means to promote take of these skin substitutes.
Usually there is some type of nonadherent dressing
applied between the graft and NPWT dressing.
One abstract that was presented at the American
Podiatry Association meeting in 2003 reviewed a retro-
spective experience in one center where investigators
reviewed 22 patients with 23 wounds on whom NPWT
had been applied and compared these patients to 24
patients who chose standard therapy.50 This was not a
comparative trial; rather, it was a historical review.
NPWT was continued until the wound was filled or
prepared for eventual closure. Patients were followed
daily as inpatients; once they left the hospital, they
were followed weekly as outpatients. Patients were fol-
lowed either until healed or one year after initial sur-
gery. With the patients on standard therapy (moist
saline dressings), the wounds took longer to fill as well
as to heal; there were significant differences between
groups for both parameters. This is also consistent with
other current prospective, randomized literature. The
investigators also looked at the complications, but they
did not specifically enumerate which complications
they were studying. Such complications, however,
would include infections or having to go back to sur-
gery or perform further revisions and amputations.
Again, there are significantly fewer complications in
 Results of the Tucson Expert Consensus Conference on V.A.C.® Therapy
NPWT-treated group compared to the control group
and significantly fewer additional surgeries necessary
in the actively treated group. The investigators also
looked at the readmission days as well as the number
of readmissions. Generally, they found that NPWT
patients required fewer admissions and fewer days in
the hospital because they were able to be treated as out-
patients or in a skilled nursing care center much soon-
er than the other patients. This data is not yet
published.50
Contraindications and precautions. Most of the
conditions of concern when using NPWT are “relative
limitations.” These are factors that the treating physi-
cian and nursing staff need to consider when imple-
menting therapy and should monitor during the
course of treatment. Some concerns involve patients
with untreated osteomyelitis, nonenteric fistulas, pres-
ence of necrotic tissue, exposed blood vessels or arter-
ies, untreated infection, anticoagulation therapy,
malignancy, recent surgery with the potential for hem-
orrhage, and poor compliance.
Infection. NPWT is a common adjunctive treatment
in wounds after surgical debridement as a result of
infection. When used in conjunction with adequate
debridement and appropriate antibiotics, there are no
contraindications to using NPWT in this scenario.
Necrotic, nonviable tissue should be removed from the
wound before implementing NPWT. If this is done,
NPWT is effective in enhancing wound closure in
patients with treated osteomyelitis or soft-tissue
infections.
Anticoagulation therapy. There are certain precau-
tions the treating physician and nursing staff should
take when using NPWT in persons that are being
treated with anticoagulation therapy. Laboratory
parameters should be regularly evaluated to make
sure anticoagulation therapy is in a therapeutic
range, and patients should be monitored for peri-
wound bruising or bloody drainage in the NPWT
canister. If there is bruising, the treating physician
should consider decreasing NPWT pressure while he
or she continues to monitor the adjacent tissue.
Contraindications and Precautions of
Negative Pressure Wound Therapy
NPWT should not be used in the in the presence of
following conditions:
• Malignancy in the wound
• Untreated osteomyelitis
• Necrotic tissue with eschar
• Nonenteric and unexplored fistulas
• Over exposed blood vessels or organs.
The following precautions should be carefully considered
when using NPWT:
• Patients with active bleeding, difficult wound
hemostasis, or who are on anticoagulants require close
monitoring.
• When placing the dressing in proximity to blood vessels
or organs, ensure vessels or organs are adequately
protected with overlying fascia, tissue, or other
protective barriers.
• Greater care should be taken with respect to weakened,
irradiated, or sutured blood vessels or organs.
• Bone fragments or sharp edges could puncture a
barrier, vessel, or organ.
• Wounds with enteric fistulas require special precautions
to optimize NPWT.
Malignancy. Using NPWT in patients with untreat-
ed malignancy is contraindicated. However, NPWT
can be used as part of surgical reconstruction in
patients being treated for soft-tissue and bone malig-
nancies. In many instances, NPWT can be imple-
mented immediately following surgical excision of
the lesion while the pathologist is evaluating the
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Guidelines Regarding Negative Pressure Wound Therapy in the Diabetic Foot
wound margins and determining the final
diagnosis.
Potential for hemorrhage. Care should be taken when
treating patients with the potential for postoperative
hemorrhage, such as in the cases of patients with
adjacent bypass grafts, large areas of exposed bone
(e.g., in subtotal calcanectomies and open fractures),
or surgical wounds with the potential for bleeding.
When the treating physician has a concern about the
potential for postoperative bleeding, it would be pru-
dent to wait for 1 to 3 days after surgery before initi-
ating NPWT. Once therapy is initiated, the wound
should be monitored for signs of increased bleeding
or bloody drainage in the NPWT canister by the nurs-
ing staff. If excessive bleeding is identified, NPWT
should be discontinued until hemostasis is achieved.
Poor patient compliance. Patient selection is a pivotal
aspect of successful NPWT. Patients and their families
must be willing and able to sleep, ambulate, and rest
during the day with NPWT in place. NPWT has been
used effectively in patients with dementia in super-
vised settings in the home, hospital, and extended
care facility.
Basic in-home ambulation. Until recently, weight-
bearing while using NPWT was thought to be poten-
tially dangerous for the neuropathic patient. The
small NPWT unit (V.A.C. Freedom® system) can be
worn around the waist and offers an ideal opportuni-
ty to allow patients to take care of activities of daily
living and still achieve the benefits of topical negative
pressure therapy. Without allowing some degree of
activity, most patients would be relegated to bedrest
or prolonged hospitalization.
A technique known as “bridging”51 can be used to
connect forms from the plantar wound (where tubing
would normally cause excessive pressure) to the dor-
sum or side of the foot. The tubing can then exit the
proximal or anterior aspect of a removable cast walk-
er (Active Offloading Walker, Royce Medical,
Camarillo, California, USA). This entire construct can
then be wrapped in a cohesive bandage. This allows
the patient to walk in a protected fashion with NPWT
14S
in place while ensuring adherence to pressure
offloading. This device has been dubbed an “instant
VCC.”52 Recent data suggest that it does not impart a
clinically significant amount of increased pressure to
the plantar aspect of the foot provided that NPWT is
applied within the removable cast walker as
described above.52
Appropriate Perioperative Use of
NPWT for Diabetic Foot Wounds
Following Peripheral Arterial
Revascularization
There are three enduring myths regarding the dia-
betic foot: Myth 1) Diabetic foot ulcers and gangrene
are caused by a unique form of microangiopathy;
Myth 2) Surgeons should not make long incisions on
persons with diabetes because they will not heal; and
Myth 3) Leg bypass operations do not work on per-
sons with diabetes. None of these myths are true. The
overwhelming majority of patients undergoing arteri-
al reconstruction will heal their incisions and their
wounds, even persons with diabetes, if certain basic
principles are followed: debridement of necrotic tis-
sue, control of infection, and presence of adequate
blood flow.53
When treating a diabetic individual with a foot
ulcer, the first determination the responsible clinician
must make is whether or not invasive infection is
present. Next, the responsible clinician must deter-
mine if tissue necrosis is present. If either one of these
two conditions is present, the wound will usually
require drainage or debridement. Before debride-
ment, however, the clinician must determine if the
vascular supply is sufficient to allow healing. Finally,
the clinician will need to manage the neuropathy
and/or bony deformity, if present.
In the case of an ischemic wound, aggressive
debridement other than that required to gain control
of any infection should not take place until proper
arterial blood flow has been established. This is par-
ticularly the case when dealing with areas of dry gan-
 Results of the Tucson Expert Consensus Conference on V.A.C.® Therapy

grene. Ischemia is an issue that must be addressed or Critical limb ischemia. The Society for Vascular
healing may not occur. In advanced cases with con- Surgery has defined critical limb ischemia as the
comitant infection and ischemia, the wounds must be presence of ulceration or gangrene with an ankle
debrided and revascularized as soon as possible. systolic pressure of less than 60mmHg, toe or
As discussed earlier, when treating diabetic foot metatarsal pulse volume recordings (PVRs) that are
ulcers, infection, neuropathy, and ischemia are the nonpulsatile, or toe pressure less than 40mmHg.55 In
three most important factors to consider. The miscon- Europe, there is a slightly different definition, which
ception that persons with diabetes have a unique is the presence of ischemic rest pain for more than
form of microangiopathy that causes them to lose two weeks in a patient with an ankle pressure less
their lower limbs is based on a single amputation than 50mmHg or a toe pressure less than 30mmHg.
study54 performed over 40 years ago. Subsequent However, most persons with diabetes do not have
investigations that have ischemic rest pain because
carefully analyzed either of the presence of neu-
arteriographic, physiolog- The overwhelming ropathy.56 When reviewing
ic, or histologic studies the North American surgi-
only show definitively that
majority of patients cal literature, bypass
there is abnormal capillary undergoing arterial patency and limb salvage
basement membrane rates appear to be better
thickening in persons with
reconstruction will heal than in Europe, in part
diabetes. Does this histo- their incisions and their because of the different
logic finding contribute to definitions of critical limb
or cause ulcers in the
wounds, even persons with ischemia. There is a dis-
absence of other factors? diabetes, if certain basic tinction between sub-criti-
The answer is probably
principles are followed: cal ischemia and critical
not. Does it prevent ulcers ischemia.57 Patients with
from healing once patients debridement of necrotic sub-critical ischemia have
have been successfully tissue, control of infection, rest pain or very low ankle
revascularized? No. pressures but no tissue
What is different in a and presence of adequate loss. Patients with critical
person with diabetes? blood flow. ischemia have very low
Histologically, atheroscle- ankle pressures and tissue
rosis in persons with dia- loss. This distinction is clin-
betes is identical to those without diabetes. The ically important because about 20 percent of patients
major distinction is disease distribution: atheroscle- with sub-critical ischemia maintain limb salvage at
rosis patients without diabetes tend to have aortoili- one year without any reconstructive surgery. When
ac occlusive disease, while persons with diabetes dealing with patients who have true critical limb
tend to have tibioperoneal disease. The reasons for ischemia (rest pain and a toe pressure less than
this difference in atherosclerotic disease distribution 40mmHg or tissue loss and a toe pressure less than
are uncertain. People with diabetes also frequently 40mmHg), only five percent of such patients will
have pedal and digital artery sparing. maintain limb viability at one year without revascu-
Histopathologically, the atherosclerotic process is larization. This distinction is clinically important since
the same. virtually all functional patients with critical limb

15S
Guidelines Regarding Negative Pressure Wound Therapy in the Diabetic Foot
ischemia will require amputation if a revascularization
procedure is not performed. However, there are select,
frail, high-risk patients with sub-critical ischemia who
have the potential for limb salvage as long as careful
foot care, proper footwear, avoidance of foot trauma,
and close follow up by their physicians occur.
Revascularization. The traditional term applied to
assess a surgical revascularization is assisted primary
graft patency. About 20 to 30 percent of lower-extremi-
ty vein grafts following implantation will develop a
fibrotic stenosis (myointimal hyperplasia) that reduces
graft blood flow and may result in graft thrombosis if
not recognized and corrected. Such graft-threatening
lesions can be detected through serial duplex surveil-
lance, and if a critical lesion is identified, it can be
addressed with a limited operative revision or angio-
plasty. If the vascular surgeon performs such interven-
tions on patent grafts before thrombosis has occurred,
the long-term prognosis is quite favorable, with
approximately 80 percent of such revised grafts
remaining patent at five-year follow-up. Assisted pri-
mary patency reflects the results of such intervention
on patent, but failing, grafts. The limb salvage rate is
often higher than the graft patency rate because
patients with initially successful grafts are often able to
heal their ischemic foot wounds and toe or forefoot
amputations before their grafts thromboses.55
The vascular group at the University of Arizona has
studied graft flow resistance and outflow resistance by
duplex assessment in patients who have undergone
lower-extremity bypass. In general, graft resistances
do not appear to differ in persons with diabetes vs.
persons without diabetes. In a smaller subset of 30
lower-limb bypass patients with diabetes and end-
stage renal disease (ESRD), such patients appear to
exhibit higher graft outflow resistances either due to
fixed distal microvascular disease or altered vasomo-
tor tone. Renal failure patients also appear to have
more calcification and more pedal arch arterial occlu-
sive disease than patients without ESRD. This prob-
lem partially may explain the decreased limb salvage
rates in patients with ESRD, some of whom even
16S
require amputation for nonhealing ulcers despite
bypass graft patency.
In experienced hands, when an adequate vein con-
duit is employed, there appears to be little difference
in graft patency whether the distal graft is anasto-
mosed to the popliteal artery or a more distal tibial
artery target if required. Because of the disease pattern
previously alluded to, many diabetic individuals who
require revascularization can undergo short bypasses
because they often have normal vessels angiographi-
cally and physiologically down to the level of the knee
joint. The major occlusive problem frequently is in the
infrapopliteal vessels, with relative sparing of the per-
oneal and pedal arteries. For such patients, diabetes
does not adversely affect graft patency. If the surgeon
performs a popliteal artery to pedal artery bypass
using the saphenous vein from the calf, and a wound
problem occurs in the saphenectomy site that results
in exposure or infection of the underlying bypass
graft, it could prove disastrous. Harvesting the vein
conduit from the thigh in such cases avoids this poten-
tial disaster.
Generally speaking, if the foot pulses are palpable,
the vascular supply is adequate for healing. However,
a normal popliteal pulse does not mean the foot has
normal circulation. There is even a small subset of
patients in whom foot pulses can be detected but
whose wounds will not heal. An arteriogram often
will reveal severe tibial disease in these cases. Once
these patients are revascularized, their wounds heal. It
is also possible to have a patent anterior tibial artery
with a palpable dorsalis pedis pulse in a patient in
whom the pedal arch is not continuous with the hind-
foot/posterior tibial circulation. In this circumstance,
the clinician may still feel a dorsal pedal pulse, but
blood flow may be inadequate to the hindfoot or heel
if the posterior tibial artery is occluded; this pattern of
disease is not uncommon in renal failure patients. If a
diabetic foot ulcer that has been properly debrided is
not healing, it is usually because either the infection
has not been controlled or the vascularity is
inadequate.
 Results of the Tucson Expert Consensus Conference on V.A.C.® Therapy
According to Pomposelli,58 dorsal pedal bypasses
achieve good results when used to manage heel ulcers
and infections. However, the clinician must determine
which part of the foot is ischemic. If a dorsalis pedis
pulse is present in a foot with a toe or forefoot prob-
lem, this procedure will probably work. If the problem
is in the heel or midfoot, discontinuous circulation
may be present. For most diabetic ulcer patients,
whether or not the pedal arch is patent is not impor-
tant. For a subset of patients with heel ulcers, howev-
er, it does matter and will require careful assessment
by the clinician.60 In patients with proximal posterior
tibial occlusion, if the pos-
terior tibial artery reconsti-
tutes distally even if the It is the opinion of the
arch is discontinuous, a TECC panel that NPWT
hindfoot lesion will heal if
the posterior tibial artery is is...particularly useful on
revascularized. In some major saphenectomy
such patients, if angiogra-
phy reveals minimal plan-
harvest incision problems
tar collaterals from the dis- as well as on fasciotomy
tal posterior tibial artery, a
free flap may be required
wounds.
to heal a hindfoot lesion. In
these cases, when performing a bypass, the surgeon
should keep in mind that a plastic surgeon later may
have to apply a free flap.
If pedal pulses are absent and toe PVRs are non-
pulsatile or arterial digital pressures are less than
60mmHg in a person with diabetes with a foot ulcer,
an arteriogram should be performed. Unless a
patient previously has had multiple, failed bypasses,
an identifiable target artery for reconstruction can
almost always be found, although the target artery
may be at the level of the malleolus or below.
A group from the University of Arizona recently
investigated patients who underwent intra-inguinal
bypass for critical limb ischemia60 The investigators
found that the reporting methods used for scientific
journals (e.g., mortality, graft patency, and limb sal-
vage) do not truly reflect what happens to these
patients after revascularization. Although these tra-
ditional outcome measures are important, other less
traditional outcomes are also worthy of note, such as
how many times the index limb required reoperative
surgery, how many patients required readmission to
the hospital, and how long it took them to heal their
wounds. These considerations have been systemati-
cally underestimated. The University of Arizona
group also wanted to determine a way to better ana-
lyze patient risk factors in order to determine what
the highest risk factors were for adverse outcome
(e.g., readmission, reoperation, delayed healing).
Investigators, therefore,
reviewed the records of
318 consecutive patients
who had undergone 305
vein grafts and 13 pros-
thetic bypasses for lower-
extremity ischemia. The
following endpoints were
analyzed: Did the patient
require reoperation within
three months? Was the
patient readmitted to the
hospital within six
months of bypass? How long did it take the patient
to heal? These endpoints may seem arbitrary, but
most would agree that if a physician told a patient
up front that the patient was going to require multi-
ple operations and readmissions for the next 3 to 6
months, the patient might choose another course of
action, including amputation. If limb-salvage
patients require such intensive ongoing therapy, per-
haps the treatment regimen should be improved
In the same study,60 72 percent of patients met the
definition of critical limb ischemia and 84 percent
required bypass to a below-knee popliteal, tibial, or
pedal vessel. The perioperative complications that
occurred in the first 30 days were complications with
the bypass site (saphenectomy, 11%; graft thrombo-
sis, 3%) and systemic complications (myocardial
infarction, 4%); only three deaths (<1%) occurred in
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Guidelines Regarding Negative Pressure Wound Therapy in the Diabetic Foot
the whole series. With respect to the nontraditional
outcomes, however, 50 percent of the patients
required at least one additional surgery within three
months of their initial procedures; 22 percent need-
ed minor toe or forefoot amputations to obtain a
healed foot. When dealing with dry gangrene, blood
flow must first be restored for 5 to 10 days before
any tissue should be removed. This allows nonvi-
able and viable tissue to clearly demarcate. Fifteen to
twenty percent needed debridements that required a
return to the operating room; this percentage does
not include additional debridements carried out in
the clinic. Ten percent of the patients received skin
grafts, eight percent
required revision of their
grafts, and eight percent
A recent report...suggests
had to go back to the ...that NPWT does
operating room for
saphenectomy or other
accelerate healing times in
harvest wound problems. persons with diabetes who
Only three percent of the
318 patients lost their legs
have undergone foot
being treated in the first debridement or open
six months following
forefoot infection.
bypass.
A multivariate analysis
was then performed to determine the risk factors for
reoperation within three months. The only risk fac-
tor that panned out using the multivariate analysis
was whether the subjects’ initial bypasses were done
for critical limb ischemia. Regarding hospital read-
mission rate, almost half of the debridements were
done on an outpatient basis. The mean number of
hospital admissions was almost two per patient, and
these were longer stays than the initial visit. Two-
thirds of the readmissions were because of limb
ischemia, and one-third resulted from cardiac mor-
bidity or pneumonia. These types of encountered
problems were not caused by a lack in skill by the
surgeons or clinicians, but rather because patients
with critical limb ischemia and large foot wounds
require intense, ongoing care. The two risk factors
18S
for readmission that were identified by multivariate
analysis were critical limb ischemia and renal fail-
ure; both were highly statistically significant. Finally,
wound healing time was another factor investigated
in the study. For the patients with ischemic tissue
loss, 137 subjects had complete records, and almost
half of them healed completely in three months. For
that early healing subset, the mean healing time was
45 days. However, 54 percent of these patients took
longer than three months to heal their index
wounds. These data were skewed somewhat by a
relatively small number of patients who took a very
long time to heal, including some who never healed
during the study period.
The major risk factor for
delayed healing was dia-
betes mellitus.
In this analysis60 of a
large group of patients
requiring lower-limb
revascularization, the risk
factors for reoperation
within three months were
65 ischemic tissue loss and
native American ethnicity;
the risk factors for read-
mission within six months were ischemic tissue loss
and end-stage renal failure; the only independent
risk factor for delayed wound healing was diabetes.
Responsible clinicians should, therefore, inform
revascularization patients that the surgery will help
their foot ulcers heal; however, they should expect
about 3 to 6 months of therapy before complete heal-
ing occurs following the revascularization. Some
patients with advanced ischemia and severe infec-
tions should expect about 6 to 12 months of therapy
before healing can be expected. Patients should
know this information before limb-salvage surgery
is initiated.
Negative pressure wound therapy. If one is
going to take proper care of persons with diabetes
who have foot ulcers and infections, therapies in
 Results of the Tucson Expert Consensus Conference on V.A.C.® Therapy
addition to bypass surgery must be considered.
NPWT is an adjunctive therapy. One goal of NPWT
when dealing with a diabetic foot ulcer is to get the
wound bed prepared as expeditiously as possible
so that it can be closed using another technique,
such as a split-thickness skin graft (STSG). It is not
necessarily the purpose of NPWT to obtain com-
plete wound healing. The clinician should try to
save as much of the foot as possible; the clinician
does not want to have to keep debriding the wound
and removing more tissue in order to close the
wound. This is where NPWT is most useful. It is
the opinion of the TECC panel that NPWT is also
particularly useful on major saphenectomy harvest
incision problems as well as on fasciotomy
wounds. NPWT is also an effective technique for
securing skin grafts. A report by Scherer, et al.,61
suggests that NPWT versus standard bolster dress-
ing on skin grafts reduced the need for repeat skin
grafting.
In the Joseph study,62 there were 24 patients with
chronic nonhealing wounds, predominantly pres-
sure ulcers. Investigators in this study compared
NPWT to standard care (wet-to-moist dressings).
The wound evaluators were blinded. Investigators
analyzed wound depth, which correlates with ulti-
mate healing, and histology. The histologic exami-
nation revealed more granulation tissue in NPWT-
treated wounds with less inflammation versus the
standard care group.
In a study by DeFranzo, et al.,63 investigators
evaluated complex wounds. The study included 75
patients with lower-extremity wounds with
exposed bone, tendon, or orthopedic hardware.
Investigators were able to heal 71 out of 75 of the
patients using NPWT. Without NPWT, some of
these patients undoubtedly would have required
major reconstructions, such as free flaps.
An important principle to consider when using
NPWT on diabetic foot wounds is that ischemic
wounds should be evaluated carefully prior to
treatment with NPWT. Revascularization must
occur prior to applying NPWT when dealing with
profoundly ischemic wounds.
Another important principle to consider is in the
treatment of infected wounds with NPWT, for the
most effective treatment, purulence or invasive soft-
tissue infection present in the wound should be
eliminated or controlled. The infection does not
need to be completely eradicated, but it should be
under control, and the wound should appear
healthy without purulence or tissue necrosis.
Treating a wound with exposed bone is acceptable.
Osteomyelitis should be treated medically or surgi-
cally prior to or concomitant with the use of NPWT.
Once NPWT has been applied, the clinician
should remove NPWT in 24 hours to re-evaluate the
wound. If the wound looks good, without macera-
tion or infection, then NPWT can be re-applied and
the clinician can then change it every other day.
Dressing changes for infected wounds should be
performed every 12 to 24 hours.
When using NPWT, especially on an outpatient
basis or in a skilled nursing facility, there is some
risk that NPWT is not being used properly.
Ancillary personnel thus require adequate NPWT
training.
Since experts have identified specific subsets of
patients who take longer to heal, including those
with diabetes mellitus or renal failure, such patients
may benefit from early initiation of NPWT. A recent
report from the Milwaukee group by Eginton, et
al.,64 suggests in fact that NPWT does improve heal-
ing times in persons with diabetes who have under-
gone foot debridement or open forefoot infection.
Appropriate Use of NPWT in
Reconstructive Surgery of the
Diabetic Foot
A multidisciplinary approach to diabetic foot
reconstruction is necessary to achieve salvage rates of
95 percent or higher. The reconstruction should be
biomechanically sound to prevent recurrent rate foot
19S
Guidelines Regarding Negative Pressure Wound Therapy in the Diabetic Foot
ulceration. Because there is no formula for success-
ful diabetic foot reconstruction, it is critical to initial-
ly salvage all potentially viable tissue and then use it
creatively to rebuild a functional foot. Mayfield, et
al.,19 has shown that the more of the foot one man-
ages to salvage, the longer the patient life expectan-
cy will be. That may be, in part, because the longer
the foot, the less the energy required for ambulation.
Proper debridement, infection control, adequate
blood supply, and use of grafts or flaps when neces-
sary are key additional factors to successful foot
reconstruction. Use of NPWT during the process
helps prepare the wound to either heal by secondary
intention or to be closed by simple reconstructive
means. If the wound is to be skin grafted, NPWT
provides the ideal dressing to achieve the highest
possible take rate. Use of
NPWT in foot recon-
struction has enabled
clinicians to solve com-
[According to] Mayfield, et
plex wound problems al.,...the more of the foot
(exposed bone, joints,
and tendons), which in
one manages to salvage,
the past required micro- the longer the patient life
surgery, with more sim-
ple solutions.
expectancy will be.
Debridement. The
first step to successful
foot reconstruction, assuming adequate blood flow
has been achieved (see the perivascular reconstruc-
tion section in these guidelines), is debridement. The
debrided wound should be free of all necrotic tissue
and debris and should have at its base clean, healthy,
bleeding tissue. During debridement, the clinician
should only remove dead tissue while preserving all
other tissue. The clinician should be aggressive
enough to ensure that all necrotic tissue is removed,
but gentle enough surgically to avoid damaging the
viable tissue left behind. If dissection is required, the
clinician should use a surgical blade and skin hooks
rather than pickups and cautery to avoid damaging
the normal tissue. Since that peripheral tissue is the
20S
future source of new tissue growth, the more intact
it is after the debridement, the better it will be able
to promote future healing.
As mentioned previously, the clinician should be
very aggressive when debriding necrotic tissue.
Thoughts about future reconstruction should not
affect the amount of tissue that needs to be debrid-
ed. What is dead has to go. The process should con-
sist of taking serial thin slices of tissue until normal
looking tissue appears. The presence of clotted veins
in the skin, fat, or muscle indicates that the local cir-
culation to that area is obstructed and the tissue is
almost certainly not viable. The presence of stringy
fascia or tendon indicates nonviability, and the tis-
sue should be shaved to shiny hard tendon or fascia.
The presence of soft grey bone indicates dead bone,
and the bone should be
sawed, burred, or rongered
back to clean hard bone
with punctuate bleeding at
the surface. Odor is an
excellent indicator of
whether a wound has been
adequately debrided or not.
As long as there is a persist-
ent odor, further debride-
ment is needed. When the
odor is gone, the debrider
can feel comfortable that the wound has been ade-
quately debrided.
Deep tissue cultures should be obtained during
the debridement, and broad spectrum antibiotics
should be started thereafter. If cellulitis is present,
the cutaneous border of erythema should be delin-
eated with a magic marker and the time should be
noted. The wound can then be checked within the
next six hours to see whether the cellulitis is resolv-
ing. If the infection has spread beyond the outlined
border, then either the wound debridement was
inadequate or the antibiotics are inappropriate and
further debridement and/or antibiotic adjustments
need to be carried out.
 Results of the Tucson Expert Consensus Conference on V.A.C.® Therapy
The wet-to-dry dressing provides an alternative
option to surgical debridement. In this method,
saline-moistened gauze is placed upon the wound
and allowed to dry. Upon removing the dressing, the
necrotic tissue that has adhered to the gauze will
also be removed from the wound bed.
Unfortunately, this method also removes healthy,
adherent, underlying tissue including the new tissue
formation. This dressing then only should be used in
the presence of necrotic tissue. Because this dressing
regimen is very painful in the sensate patient, it only
should be used in the insensate population. Because
most persons with diabetes are insensate, wet-to-dry
dressing is an acceptable option that initially can be
used to debride dirty wounds.
Maggot therapy is another nonsurgical debride-
ment option. The maggots are sterilized with radia-
tion so they cannot progress to the pupae stage.
Using this debridement method, the maggots are
placed in the wound bed and covered with an semi-
occlusive (i.e., permeable to air) dressing. They are
left in place for one to two days. The maggots will
only break down and digest the necrotic tissue while
the healthy tissue is left intact. The maggots sterilize
the wound in the process and are effective against
methicillin-resistance Staphylococcus aureus (MRSA)
or vancomycin-resistant enterococci (VRE) wound
infections. This method is best applied to patients
who are awaiting revascularization and in whom the
margins of dead vs. live tissue are unclear or to
patients who are too sick to go into the operating
room for surgical debridement. This method of
debridement should not be used in cases of over-
whelming osteomyelitis because the maggots are not
as effective in debriding bone.
Infection control. Antibiotic-impregnated beads
that are used in osteomyelitis are also effective as
topical dressings on debrided infected wounds.
Vancomycin and tobramycin are mixed into methyl-
methacrylate and then small beads are fashioned out
of the resulting mixture. Other antibiotics, such as
doxycycline, which has additional wound healing
properties, could be used as well. The beads are
placed on the wound bed and covered with an
occlusive dressing. The dressing is changed every 2
to 3 days. The beads can be rinsed in normal saline
and reapplied. The bacterial count decreases rapidly
to less than 105 bacteria, and wound is ready for clo-
sure when signs of healing appear. These beads are
available in Europe in pre-made form and are ready
to apply off the shelf.
Adequate blood flow. Optimal blood flow must
be achieved prior to performing reconstructive sur-
gery. The clinician should not initiate reconstruction
until new granulating tissue, neo-epithelization at
the wound edge, and wrinkled skin at the wound
borders are present. If the patient has been revascu-
larized, it takes 4 to 10 days for the new blood flow
to have maximal effect at the wound’s edge. The
timing of debridement and revascularization in the
dysvascular patient is tricky because one only wants
to remove dead tissue, and that can be hard to iden-
tify under ischemic conditions. If wet gangrene is
present, debridement should precede revasculariza-
tion. If the wound is relatively stable, debridement
should be initiated after revascularization when
there are signs that the new blood flow is having an
effect on the wound (e.g., presence of new granula-
tion). If dry gangrene is present, the gangrenous
edges will have to be monitored closely for the
development of wet gangrene so that further necro-
sis does not occur. See the peripheral arterial revas-
cularization section in these guidelines for further
instruction.
Skin grafts. A skin graft is a very effective way
to heal a chronic ulcer. However, it should not be
applied immediately following initial debridement
because the bacterial milieu of the wound may be
inhospitable. After the wound site is debrided, NPWT
should be applied until the wound has developed a
healthy, well-vascularized granulation bed. Then, if
further coverage is necessary, the skin graft can be
applied. Skin grafts require clean, healthy, granulat-
ing beds in order to be effective.
21S
Guidelines Regarding Negative Pressure Wound Therapy in the Diabetic Foot

When applying a skin graft, the following factors preparation, and use of NPWT as a topical dressing.
are critical to ensure a good take: avoiding infection, A study comparing the effectiveness of NPWT to
ensuring good adherence of the graft to the underly- bolster dressings as a dressing for fresh skin grafts
ing bed, avoiding a seroma or hematoma to develop demonstrated a 97-percent primary complete skin
between the skin graft and the wound bed, and graft take using NPWT therapy versus 81-percent
avoiding shearing forces to detach the skin graft for the group dressed with bolster dressings.62
from the underlying wound bed. To ensure a higher Skin grafts can also be used in inhospitable
skin graft take rate, the clinician should curette or wound beds (bone or tendon) provided the wound
shave down the existing granulation tissue to bed has adequately been prepared. The application
remove any bacteria that may still lie within its of a collagen lattice framework covered with a thin
interstices. The skin graft should be meshed (1:1 or silicone sheet (Integra®, Integra Life Sciences,
1.5:1) to prevent a seroma Plainsboro, New Jersey,
or hematoma from build- USA) for three weeks
ing up between the skin NPWT has revolutionized allows vascularization of
graft and the underlying collagen network from the
wound bed. The graft is
soft-tissue reconstruction normal wound periphery.
then placed on the wound of the foot and ankle The exposed bone or ten-
bed and its position is don is debrided and pulse
secured by a few strategi-
because it has enabled the irrigated. The sheet of the
cally placed stitches or clinician to close wounds collagen lattice framework
staples. Following graft is meshed and then placed
by simple techniques that
application, a nonadher- on the debrided wound. It
ent dressing (petrolatum- in the past would have is secured with a few
impregnated gauze or sil- required complex pedicled strategically placed
icone mesh) is placed on sutures or staples. It is
the skin graft. NPWT is or microsurgical free flaps. then covered with a sheet
then placed on top of the of silver ion and the
mesh and continuous suc- NPWT device is placed on
tion is applied for the next 3 to 5 days. NPWT con- top as a bolster type dressing. NPWT is placed on
forms perfectly to the underlying wound bed and continuous suction and is changed every 2 to 3 days
thus ensures good contact of the skin graft to the for the next three weeks. During that time, collagen
underlying wound bed regardless of the latter’s con- lattice turns pink/red as it develops a vascular net-
tour or depth. NPWT continuously absorbs any work. The silicone sheet is then removed and cov-
fluid that may appear, thereby preventing fluid ered with a thin skin graft. The technique described
build up that could disrupt the contact of the graft to above is applied to ensure good skin graft take. The
the wound bed. NPWT ensures such good contact use of the collagen lattice framework to develop a
between the skin graft and the underlying bed that it hospitable wound bed for eventual skin grafting has
is hard for shear forces from normal motion to cause allowed wounds to heal with a simple skin graft that
any disruption. Finally, NPWT helps to control the in the past have required complex flap reconstruc-
bacterial count of the area. tion.
Clinicians can expect up to a 95-percent skin graft The Ilizarov frame has proved to be very effective
take with adequate debridement, proper wound in salvaging infected Charcot joints. When there are

22S
 Results of the Tucson Expert Consensus Conference on V.A.C.® Therapy
open wounds, underlying joints, bone, and/or ten-
don are exposed. This, in the past, would have
required a free flap to adequately cover the wound,
which was a formidable undertaking because it had
to be performed within the confines of a metal
frame. Now, small local fasciocutaneous flaps can be
rotated to cover the exposed bone and tendon and a
skin graft can be used to cover the rest of the wound.
NPWT is applied over the entire skin-grafted area
for 3 to 5 days. Using this technique, one can expect
a greater than 90-percent successful wound closure
rate. This provides a very simple solution to wound
problems that in the past either required micro-
surgery or led to a below-the-knee amputation.
When NPWT is used after adequate debridement
in a well-vascularized bed, it prepares the wound for
closure by secondary intention, delayed primary
closure, skin graft or flap coverage. NPWT shrinks
the wound, reduced bacterial colonization, and pro-
motes the formation of healthy granulation tissue.
NPWT can then be used as a bolster-type dressing
over skin grafts to insure a higher skin-graft take.
NPWT has revolutionized soft-tissue reconstruction
of the foot and ankle because it has enables the clini-
cian to close wounds by simple techniques that in
the past would have required complex pedicled or
microsurgical free flaps.
Important Questions and Answers
on the Appropriate Use of NPWT
1. How long should NPWT be used in treat-
ment of a diabetic foot wound?
In most cases, NPWT may be used to achieve a
healthy granular bed after which other modalities or
surgical procedures may be considered. There may
be instances when NPWT can be used to complete
closure/healing by secondary intention (e.g., when a
patient is too sick to undergo additional procedures
or the patient refuses additional surgical
intervention).
2. Should NPWT be applied to a wound that
has not been debrided?
No. A neuropathic diabetic foot wound must be
adequately debrided and pressure offloaded in
order for NPWT or any other wound healing modal-
ity to be effective in the diabetic foot. While an initial
debridement prior to application of NPWT is
mandatory, debridement prior to each subsequent
application of NPWT is not always indicated. The
clinician should be guided by wound appearance
and the presence of non-viable tissue.
3. How should the patient using NPWT be
evaluated on an outpatient basis?
Regular evaluation by the responsible clinician
should be performed to evaluate for wound
progress. Failure of improvement in the wound over
a 2- to 4-week period should signal the requirement
for reevaluation of the current NPWT, including the
potential for occult ischemia, inadequate debride-
ment, inadequate pressure offloading, or presence of
infection.
4. When should NPWT be applied following
lower-extremity bypass?
While there are few data to guide a clinician in
this area, NPWT may be applied to a wound distal
to a bypass graft following a revascularization pro-
cedure provided there is no evidence of residual
infection, active bleeding, or necrotic tissue. When
dealing with the presence of an exposed vascular
graft, preferred alternatives are to reroute the graft
or to use local flap or coverage techniques. If these
are not applicable then NPWT could be applied
cautiously and under the close supervision of the
attending surgeon.
5. When should NPWT be applied after
incision and drainage of infection?
It is the opinion of this committee that NPWT
should not be applied immediately after an incision
and drainage procedure. The wound should gener-
23S
Guidelines Regarding Negative Pressure Wound Therapy in the Diabetic Foot
ally be evaluated for a positive response for at least
24 hours prior to application of NPWT. In the
instances when immediate application is
employed, the wound should be evaluated fre-
quently (every 12 hours) for the first 2 to 3 days.
6. How should NPWT be used in patients
with osteomyelitis?
NPWT is not a treatment for osteomyelitis.
Osteomyelitis in the diabetic foot may be surgically
resected or suppressed medically. These options
should be used before or concomitant with NPWT.
It is useful to obtain granulation and coverage after
medical or surgical treatment of osteomyelitis in
the foot. In these situations, the use of NPWT is
favorable.
7. How should nonadherence (i.e., non-
compliance) be defined in the patient on
NPWT? When should NPWT be discontin-
ued in this population?
Nonadherence with NPWT is defined as a fail-
ure of the patient to follow the advice given when
provided with the instrument. Patients who histor-
ically demonstrate their inability or unwillingness
to participate in their own care generally should
not be treated with NPWT. As with many wound
care modalities, NPWT is an expensive device and
should be reserved for patients who are likely to
adhere to the guidelines to its use. Adequate
adherence to care means the patient is using the
device appropriately 24 hours a day and receiving
changes every 48 hours or 12 to 24 hours if the
wound is infected. Choosing the appropriate
NPWT device for the appropriate patient may
improve adherence; however, ultimately adherence
to care is the patient’s responsibility. Repeated
events of nonadherence to this modality are
grounds for choosing an alternate technology or
approach to wound care.
24S
8. How should NPWT be used in combina-
tion with other modalities?
There are few data to guide the clinician in the
choice for combination wound therapy. However,
many clinicians choose to augment NPWT with
other adjunctive agents. The members of the TECC
and other investigators have had experience with
“combination therapy,” which includes but is not
limited to NPWT’s use with bioengineered skin, sil-
ver dressings, other various antimicrobial agents,
and cytokine therapy. Furthermore, there is emerg-
ing evidence that NPWT may improve survival of
split-thickness skin grafts.
9. Should small, superficial, noninfected
wounds be considered for NPWT?
Patients that clinically may be at higher risk for
failure to heal, such as patients with wounds that
are larger, deeper, and have prolonged courses of
previous therapy or a long duration, are more like-
ly to be candidates for primary NPWT use. Smaller
superficial wounds without infection or ischemia,
if responding well to adequate debridement and
offloading, generally are not candidates for pri-
mary use of NPWT. In general, the superficial, non-
infected, nonischemic wound that is progressing
well with adequate debriding and offloading does
not require NPWT.
10. How should we define success in future
studies of NPWT?
Randomized, controlled trials on NPWT need to
be done with primary and secondary endpoints.
While a primary endpoint to any randomized con-
trol trial should be time to complete epithelization or
prevalence of healing at that time point between the
two groups, the other endpoints may be valuable in
guiding potential benefits of NPWT. Secondary end-
points may include the following: rate of healing,
time to a complete wound bed preparation/healthy
granular bed, requirement for further procedures,
quality of life, pain reduction, cost of care, the level
 Results of the Tucson Expert Consensus Conference on V.A.C.® Therapy
of nursing care required, rate of healing, proportion
of peritherapeutic complications, and proportion of
amputation at given time points. Ideally the evalua-
tions of active and control groups should be evalu-
ated by observers blinded to therapy.
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