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Study of Collagenase and Metronidazole in The Topical Management of Diabetic Foot Ulcers
Study of Collagenase and Metronidazole in The Topical Management of Diabetic Foot Ulcers
By
DR. NISHANT. K
Dissertation Submitted to
Rajiv Gandhi University of Health Sciences, Karnataka,
Bangalore
In partial fulfillment of the requirements for the Degree of
MASTER OF SURGERY
IN
GENERAL SURGERY
DEPARTMENT OF SURGERY
MAHADEVAPPA RAMPURE MEDICAL COLLEGE,
GULBARGA, KARNATAKA
2009
i
Rajiv Gandhi University of Health Sciences,
Bangalore, Karnataka.
ii
Rajiv Gandhi University of Health Sciences,
Bangalore, Karnataka.
iii
Rajiv Gandhi University of Health Sciences,
Bangalore, Karnataka.
College, Gulbarga.
Date: Date:
Place :Gulbarga. Place : Gulbarga.
iv
Rajiv Gandhi University of Health Sciences,
Bangalore, Karnataka.
academic/research purpose. .
Dr.Nishant.K
Date:
Place: Gulbarga
v
ACKNOWLEDGEMENT
vi
my dissertation work. I am also grateful to my colleagues Dr Rohan
Shah, Dr.Peeyush, Dr. Lalchand, Dr Santosh, Dr.Krishna, Dr.Rajeev and
Dr.Swamy for their overwhelming encouragement, valuable hints and
timely help and my juniors Dr.Sharanu, Dr.Anup, Dr. Amaresh and
Dr.Avinash who have always been at my side and provided me with
valuable insights.
Date:
vii
ABBREVATIONS
viii
ABSTRACT
Objective:
To study the efficacy of topical agents like Collagenase ointment and Metronidazole
gel in the management of diabetic foot ulcers and comparison of the results over the
conventional treatment with local antiseptics.
Methods:
The study was a prospective, parallel group, comparative trial. Patients admitted with
diabetic foot ulcer in Basaveshwar Teaching and General Hospital, attached to M.R
Medical College, Gulbarga. The number of patients included in the study was 80, Out
of which, 40 Test group-Topical dressings of collagenase and metronidazole were
applied with bedside surgical debridement whenever indicated and 40 Control group-
Conventional Topical dressings with bedside surgical debridement. Patients were
followed up and ulcer status was noted using visual score.
Results:
The reduction of slough is as early as 3rd week in the test group than the control
group. The number of patients with 75-100% wound filled with granulation tissue is
as early as 3rd week in test group than the control group where it took more than 4
weeks. The number of patients who underwent secondary suturing, skin graft and
flap are significantly higher and also as early as 3rd week in test group than the control
group.
Conclusion:
ix
TABLE OF CONTENTS
1. Introduction 1-2
5. Results 66-80
6. Discussion 81-83
7. Conclusion 84
8. Summary 85
9. Bibliography 86-95
10. Annexures
x
LIST OF TABLES
Sl. Page.
Particulars
No. No.
3 Age distribution 66
4 Sex distribution 67
5 Diabetes Mellitus 68
8 Grade of ulcers 71
xi
LIST OF FIGURES
Sl. Page.
Particulars
No. No.
3 Age distribution 66
4 Sex distribution 67
5 Diabetes Mellitus 68
8 Grade of ulcers 71
xii
INTRODUCTION
and macrovascular complications. It is the leading cause of end stage renal disease, a
major cause of non traumatic amputations, responsible for 30% of the preventable
The prevalence of diabetes is rapidly rising all over the globe at an alarming
rate. According to the world health organization, at least 171 million people world
wide have diabetes. The figure is likely to double by 2030. The WHO predicts that
developing countries will bear the brunt of this epidemic in 21st century1.
WHO reports show that 32 million people had diabetes in India in the year
Diabetic patients suffer from foot ulcers which may eventually lead to
amputation2.
subcontinent. The projections indicates that India will have largest number of
every six people with diabetes will have a foot ulcer during his /her life time. Every
year 4 million people with diabetes develop a foot ulcer. Every 30 seconds a leg is
1
In developing countries, foot problems may account for upto 40% of health care
resources4.
In order to estimate accurately the occurrence of diabetic foot ulcers and risk
factors associated with this diabetic complication. The international consensus on the
diabetic foot currently defines a diabetic foot ulcer as a full-thickness wound below
In India, the prevalence of diabetic foot ulcers in clinic population was estimated
practices, use of improper foot wear and lack of knowledge regarding foot care
Foot infection is the most common reason for hospitalization accounting to upto
25% of admissions. 15% of the patients develop foot ulcers during their life times. If
Diabetic foot ulcers should be treated aggressively to improve the quality of life,
control infections, maintain patients health, prevent amputations and to reduce health
care costs.
secondary to surgical and systemic care. No hard evidence exists to place any one
are being used as one of the topical modalities of treatment of diabetic foot ulcer. In
this context, no study has been conducted in our setup and hence the study has been
taken up.
2
AIMS AND OBJECTIVES
Metronidazole gel in the management of diabetic foot ulcers and comparison of the
3
REVIEW OF LITERATURE
symptom.
Notable Indian physicians Susruta and Charaka first reported the association
of polyurea with a sweet tasting substance in the urine in Sanskrit literature during 5th
to 6th century.
drank the urine of those suspected of having diabetes; the urine of people with
diabetes was thought to be sweet-tasting. The Latin word for honey (referring to its
Table-1
Important Landmark in the History of Diabetes 17th, 18th and 19th Centuries
4
Table-2
Important Landmark in the History of Diabetes 20th Century
published. UKPDS results clearly identify the importance of good glucose control and
good blood pressure control in the delay and/or prevention of complications in type
2-diabetes.
neuropathy and vasculopathy. This causes decreased sensation in the foot with
intrinsic changes in the foot architecture and decreased tissue perfusion respectively.
About 400y B.C., Hippocrates wrote, “in case of ulcer, it is not expedient to
stand” especially if ulcer be situated on the leg”. This holds good for diabetic foot
ulcer. The management of diabetic foot ulcer needs multi disciplinary approach. The
standard therapy of diabetic foot ulcers include systemic control of diabetic mellitus,
infection and local control by debridement, pressure relief and protective dressing9.
secondary to surgical and systemic care. Dressing materials come in many forms to
suit wound types and preferences. No hard evidence exists to place any one approach
above another. All wounds deserve individualized attention and care plans.
5
Likewise, a plethora of solutions exist to augment dressing materials in cleansing,
Dakin’s solution, and povidone-iodine, are more tissue toxic than their common usage
would indicate10.
enzyme. It is capable of cleaving native collagen types, I, II, III and IV, this is useful
6
ANATOMY OF FOOT
The human foot combines mechanical complexity and structural strength. The
ankle serves as foundation, shock absorber and propulsion engine. The foot can
sustain enormous pressure (several tons over, the course of a one-mile run) and
• 33 joints;
These components work together to provide the body with support, balance
and mobility. A structural flaw or malfunction in any one part can result in the
Skin14,15,16
The skin of dorsum of the foot (hirsute) is thin and highly flexible, containing
hair follicles, sweat glands and scanty sebaceous gland. Hairs are sparse and thick. It
is less then 2mm thick and few fibrous septa penetrate to deeper facial structures. The
plantar skin (glabrous) is 5mm thick especially over those points which bear weight
viz. heel, ball of big toe and lateral margins of the sole. It has no hair follicles or
7
Hypodermis is composed of loose areolar connective tissue, most of this is
collagenous and elastic fibers running parallel to the surface of the skin but some are
continuous with the fibers of dermis. Hypodermis is well supplied with blood vessels
The subcutaneous tissue in the sole as in the palm differs from that of the rest
of body in being more fibrous, tough and stingy. Fibrous septa divide the tissue into
small loculi which are filled with fluid fat under tension. This makes a shock
absorbing pad especially over the heel and over the tips of toes.
Deep fascia: On the dorsum of the foot (fascia dorsalis pedis) is the thin
layer continuous above with the inferior extensor retinaculum and at the sides of the
foot; it blends with plantar aponeurosis, anteriorly it ensheathes the dorsal tendons.
Plantar aponeurosis: Cover the whole length of the sole. It arises posteriorly
from the medial and lateral tubercles of the calcaneous and from the back of that bone
below the insertion of the tendo-calcaneous. It spreads out over the sole and is
inserted by five slips into each of the five toes. A very dense and strong intermediate
The forefoot: Is composed of the five toes (called phalanges) and their
connecting long bones (metatarsals). Each toe (phalanx) is made up of several small
bones. The big toe (hallux) has two phalanges, two joints (interphalangeal joints) and
two tiny, round sesamoid bones that enable it to move up and down. The other four
8
toes each have three bones and two joints. The phalanges are connected to the
metatarsals by five metatarsal phalangeal joints at the ball of the foot. The forefoot
bears half the body’s weight and balances pressure on the ball of the foot.
The midfoot: forms the font’s arch, and serves as a shock absorber. The bones
of the midfoot are cuboid, first, second, third cuneiform and navicular, connected to
the fore foot and the hind foot by muscles and the plantar fascia.
The hind foot: Is composed of three joints and links the midfoot to the ankle
(talus). The top of the talus is connected to the two long bones of the lower leg (tibia
and fibula. forming a hinge that allows the foot to move up and down. The heel bone
(calcaneus) is the largest bone in the foot. It joins the talus to form the subtalar joint,
which enables the foot to rotate at the ankle. The bottom of the heel bone is cushioned
by a layer of fat.
The Arches: The foot has three arches. The medial longitudinal arch is
composed of the calcaneus, talus, navicular cuneiforms, and the first three
metatarsals. The lateral longitudinal arch is composed of the cuneiforms, cuboid and
the fourth and fifth metatarsals. The transverse arch is composed of the cuneiforms
the cuboid and the five metatarsal bases. The arches of the foot are maintained not
only by the shapes of the bones as well as by ligaments; in addition, muscles and
Muscles, Tendons, and Ligaments: There are 20 muscles in the foot that
give the foot its shape by holding the bones in position and expand and contract to
impart movement. The muscles in the sole of the foot are categorized into four layers:
Muscles in the first layer include Flexor digitorum brevis, Abductor hallucis and
9
Abductor digiti minimi. In the second layer are tendon of Flexor hallucis longus,
Flexor digitorum accessorius and the Lumbricals. In the third layer are Flexor hallucis
brevis, Adductor hallucis and Flexor digiti minimi brevis. In the fourth layer are
peroneous longus tendon, Tendon of the tibialis posterior, 4 dorsal interossei and 3
plantar interossei.
Third layer
Fourth layer
Figure -1: Muscles of the foot
10
Figure -2: Arteries of the sole of the foot14,15,16
11
Medial plantar artery: This terminal branch of the posterior tibial artery
arises beneath the flexor retinaculurn. It ends by supplying the medial side of the big
toe. During its course it gives off numerous muscular, cutaneous, and articular
braches.
Lateral Plantar Artery: Is the larger of the terminal branches of the posterior
tibial artery. During its course, it gives off numerous muscular, cutaneous, and
articular branches. The plantar arch gives off plantar digital arteries to the adjacent
sides of the lateral four toes and the lateral side of the little toe.
Dorsalis Pedis Artery: On entering the sole between the two heads of the first
dorsal interosseous muscle, the dorsalis pedis artery immediately joins the lateral
plantar artery, gives the first plantar metatarsal artery, which supplies the cleft
Veins of the Sole of the Foot: Medial and lateral plantar veins accompany the
corresponding arteries, and they unite behind the medial malleolus to form the
Medial Plantar Nerve: The medial plantar nerve is a terminal branch of the tibial
nerve. It gives,
2. Cutaneous branches: Plantar digital nerves run to the sides of the medial three
12
Lateral Plantar Nerve: The lateral plantar nerve is a terminal branch of the tibial
nerve.
Branches:
1. From the main trunk to the quadratus plantae and abductor digiti minimi;
2. From the superficial terminal branch to the flexor digiti minimi and the
3. From the deep terminal branch supplies the aductor hallucis; the second, third
and fourth lumbricals; and all the interossei, except those in the fourth
intermetatarsal space.
Dorsal venous arch: The dorsal venous arch lies in the, subcutaneous tissue over
the heads of the metatarsal bones and drains on the medial side into the great
saphenous vein, and on the lateral side into the small saphenous vein. The great
saphenous vein leaves the dorsum of the foot by ascending into the leg in front of the
medial malleolus. The small saphenous vein ascends into the leg behind the lateral
malleolus.
Dorsalis Pedis Artery: The dorsalis pedis artery begins in front of the ankle
into the sole between the two heads of the first dorsal interosseous muscle, where it
joins the lateral plantar artery and completes the plantar arch. The Branches: Are 1.
13
Nerve supply of the dorsum of the foot:
Deep Peroneal Nerve: It divides into terminal, medial and lateral branches.
The medial branch supplies the skin of the adjacent sides of the big and second toes.
has emphasized the clinical importance of the 4 median fascial spaces on the plantar
1. The first space is located between the plantar aponeurosis and the flexor
digitorum brevis.
2. The second space is situated between the flexor digitorum brevis and the
3. The third space is found between the flexor digitorum longus (with its
associated lumbricals muscles) and the oblique head of the abductor hallucis.
4. The fourth and deepest space is situated between the oblique head of the
abductor hallucis muscle and the 2nd and the 3rd metatarsal bones and their
interosseous muscles.
These spaces are bound both laterally and medially by dense connective tissue
septa an infection may travel from one space to another. The sheaths of the entire
flexor tendon extend from the toes and proximal to the distal head of the metatarsal
14
bones; therefore infection within these sheaths either may remain local or break into
The 3rd layer of the sole of the foot is enclosed inferiorly by the plantar fascia
and superiorly by the metatarsal and small muscles and ligaments of the foot. It is
continuous distally into the toes through the lumbricals and web space along with the
Standing immobile: The body weight is distributed via the heel behind and the heads
Walking: As the body weight is thrown forward, the weight is borne successively on
the lateral margin of the foot and the heads of the metatarsal bones. As the heel rises,
the toes are extended at the metatarso-phalangeal joints and the plantar aponeurosis is
pulled on thus heightening the longitudinal arches. The body is then thrown forwards
1. By the actions of the gastrocnemius and soleus (and plantaris) on the ankle
2. By the toes being strongly flexed by the long and short flexors of the foot,
The lumbricals and interossei contract and keep the toes extended so that they
do not fold under pressure because of the strong action of the flexor digitorum longus.
In this action, the long flexor tendons also assist in Plantar flexing the ankle joint.
15
PATHOGENESIS OF DIABETIC FOOT
1. Peripheral Neuropathy.
3. Charcot foot.
4. Infection.
Diabetes mellitus apart from other pathologies primarily affects the vessels &
1) Neuropathy18
main initiating factor for foot ulceration, affecting about 30% of all diabetic
people.19,20 About one-fourth (nearly 28%) of type I diabetic patients developed distal
16
symmetrical neuropathy. Its incidence parallels the duration and severity of
hyperglycemia in both type I and type II diabetes. Age, duration of diabetes, and poor
glycemic control being major determinants; also retinopathy and albuminuria. Less
Chronic Hyperglycemia
report of The EURODIAB Prospective Study23. The poor glycemic control is related
Oxidative Stress
17
pathway hyperactivity. Oxidative stress may impair nerve function by a direct toxic
Polyol Pathway
AldoseRedutase
D Glucose + NADPH + H Sorbitl +NADP
Sorbitol Dehydrogenase
Sorbitol + NADP D- fructose + NADH + H
increased conversion from glucose, via the enzyme aldose reductase. This is
important role in intra and extracellular sodium balance and hence nerve membrane
potential27,28.
Nonenzymatic Glycation
Neurotrophic Factors
18
and the potential use of trophic intervention in diabetic neuropathy remain
undetermined.
Vascular Factors
and in wound healing has long been debated. The view that microvessel disease may
pericytes, hypoplasia and swelling of endothelial cells, and sometimes vessel closure.
The degree of microvascular disease has been correlated with the severity of
neuropathy30.
19
2) Diabetic Angiopathy33,34
more liable to arterial disease than normals but also that this increased risk can
early onset requiring high insulin doses. The work of Peters and Hales 1965,
Nikkila et al (1965) has led to the postulate that raised plasma insulin is
possibly atherogenic.
workers.
intima of arteries and composed of fibrosis and or fatty change. Ulceration and
20
secondary thrombosis commonly occur. This is found more frequently and
the profunda femoris artery, the major source of blood for thigh muscles, causes
the arteries between the aorta and ankle occurs. The diabetic more frequently have
multiple occlusions of the Popliteal and its branches which limits the application of
reconstructive arterial surgery. Hence this pattern of atherosclerosis affecting the leg
of these changes. The distinguishable feature is its relatively regular, tiny, speckled
appearance and commonly affects the vessels of the foot. Tunica intima may be
Microangiopathy:
of microangiopathy in diabetes.
21
Haemodynamic hypothesis
Microvascular sclerosis
+/-
Impaired autoregulation
suggest a common factor between them, the disease of the small blood vessels.
These morbid anatomical changes are the end result of metabolic disturbances
a. Venular dilatation.
22
The other factors which synergize with this are:
Platelets:
Red cells:
Plasma:
Abnormalities of Metabolism:
23
Hypercholesterolemia, Hypertriglyceridemia, Hyperglycemia.
The two central processes that determine the occurrence and distribution of
2. The regional increased tissue turgor and metabolic rate resulting from
inflammatory reaction.
Some inherent differences follows in PVD of diabetes and non diabetes patients are as
The involvement of smaller vessels makes vascular surgery less useful and
more unsuccessful. The most common type of bypass was tibioperoneal. In a study by
Sicard G.H., Walker W.B and Anderson,C.B. 10% of bypass surgery in diabetes was
Aorta - Femoral, 30% was Femoro-Popliteal, while nearly 60% was Tibia-Peroneal.
24
3) Charcot foot35,36
and joints of the foot and is characterized by joint dislocation, subluxation, and
debilitating deformity. Bone and joint damage in the tarsometatarsal joints and mid-
tarsal joints leads to two classical deformities: the rockerbottom deformity, in which
there is displacement and subluxation of the tarsus downwards, and the medial
tarsometatarsal dislocation. Both are often associated with a bony prominence which
is very prone to ulceration and healing is notoriously difficult. When the ankle and
4) Infection37
Foot infection occur frequently in persons with diabetes and the occurrence of
infection is an event that most often leads to more serious sequelae particularly
Foot infections usually occur at the site of trauma / ulceration. Thus patients
with peripheral neuropathy / foot deformity are at increased risk for ulceration.
Majority of infections start with infected ulcers on the planar aspect of the foot
interdigital infections and nail bed infections. In the initial stage there is usually an
area of localised cellulites, then infection progresses and once deep space infection is
Because of the anatomical tight compartment in foot, infection ascends along the
25
tendon sheaths into posterior compartment of the leg, flexorcanal, subsoleal
compartment.
Presence of ≥2 manifestational
inflammation (Purulence or erythema,
pain, tenderness wormth or induration),
but any cellulites or erythema extending
Mild 2
≤ 2cm around the ulcer and infection
limited to the skin or superficial
subcutaneous tissues, no other local
complications or systemic illness.
26
MICROBIOLOGY38
infection. Foot ulcers whether infected or not, will contain multiple comensal or
colonizing bacteria, some of which have the potential to become invasive pathogens.
1. Non-limb threatening.
2. Limb threatening.
who have not pevious1y received antimicrobial therapy, Staphylococcus aureus and
has been isolated from >50% of these patients, and in more than 30% S.aureus is the
these infections yield on average 4.1-5.8 bacterial species per culture. Both gram-
positive cocci and gram-negative rods are commonly isolated from a single lesion,
and in 40% of Infections both aerobic and anaerobic organisms are recovered40,41,42,43.
setting of limb-threatening infection. After cleansing the skin and debriding any
overlying eschar, specimens for culture should be obtained before initiating therapy
27
Most clinicians obtain cultures by rolling a swab over the wound. While the
results of some studies suggest that these types of specimens give results similar to
those of deep tissue biopsies, most investigation have found swabs to be less sensitive
Antibiotic Therapy:
empirically and thereafter revised based on the results of cultures, which were
obtained prior to therapy and on occasion during therapy, and the clinical response of
28
Infections Antimicrobial regimen
Non-limb threatening Cephalexin 500mg p.o q6h
Clindamycin 300mg p.o. q8h
Amoxicillin-calvulanate (8751125mg) one q12h
Dicloxacillin 500mg p.o. q6h
Levofloxacin 500-750 mg p.o. qd
Limb threatening Ceftriaxone Ig IV dialy plus clindamycin 450-600 mg
IV q8h
Ciprofloxacin 400mg IV q12h plus clindamycin 450-
600 mg IV q8h
Ampicillin/sulbactam 3g IV q6h
Ticarcillin/clavulanate 3.1 g IV q4-6h
Piperacillintazobactam 3.375 g IV q4h of 4.5 g IV q6h
Fluoroquinolonec IV plus metronidazole 500mg IV
q6h
Life threatening Imipenem cilastatin 500mg IV q6h
Piperacillintazobactam 4.5g IV q6h plus gentamicin
1.5 mg/kb IV q8h
Vancomycin I g IV q12h plus gentamicin plus
metronidazole
treatment in the light of culture results and clinical response. When therapy is
unnecessarily broad spectrum (effective therapy for the bacteria isolated could be
therapy has been recovered and yet the clinical response is .satisfactory, treatment
29
tissue that has not been debrided, the adequacy of arterial circulation should be
assessed, and because the resistant organism might be a pathogen (rather than
well as others.
Anaerobic metabolism:
phosphorylation cannot take place. Thus under anaerobic conditions by for the major
portion of the pyruvic acid is converted into lactic acid which diffuse readily Out of
the cells into extracellular fluid & even in to intracellular fluids of other less active
cells. Thus lactic acid represents a type of “sinkhole” into which the glycolytic end
products can disappear thus allowing glycolysis to proceed for longer than would
otherwise be possible.
myelin, etc. Such molecular changes in proteins alter the function (or) physical
These tissues then become rigid and inflexible, have increased tensile strength
clinical features like stiff and syndrome, Dupuytren’s contracture etc Collagen is a
major component of vessel wall and basement membrane Thus changes in connective
tissue proteins can partly explain the vascular changes in diabetes mellitus.
30
protein of skin, subcutaneous tissues aid the sole of diabetics contribute to the
pressure and cannot be removed from superfical layer of the sole as readily as usual
leading to areas of hyperkerotosis which proceed to cavitation under the skin. This
also explains the excessively had that much of surrounds the established ulcer and that
tends to cover the opening of the ulcer. The changed collagen in the skin
subcutaneous tissue will make these layers inflexible and rigid. Thus they breakdown
and ulcerate more readily in response to high horizontal shear force. The cross linked
contributes to the poor wound healing in diabetes and explains the common:
observation of the abnormal persistence of collagen rich fasciae and tendons in the
Migration/proliferation Macrophages,
Angiogenesis Fibroblast,
Epithelisation Lymphocytes,
Days Contraction Keratinocytes
Fibroplasia
A major feature of diabetic neuropa9lic ulcer is that even after all the factors
responsible for the development or persistence of the ulcer have been dealt with, a
31
very prolonged time is required for healing to take place. A major reason for impaired
wound healing in diabetics is the fact that collagen metabolism with respect to both
Motor neuropathy results in claw toes and prominent pressure points over the
metatarsal heads. This when combined with sensory neuropathy, the stage is set for
unperceived pressure injury to the foot. The autonomic neuropathy causes loss of
sweat and oil gland activity results in dry skin that easily cracks fissures. In addition
to these non vascular effects neuropathy can directly impair effective perfusion due to
destroys “C’, fibers which are responsible for nociceptive response which is the basis
perfusion due to macro angiopathy results in ulceration. The insensitive foot can be
injured by external forces in three main ways. Before going into them simple equation
1. A constant pressure maintained for several hours may cause ischemic necrosis.
2. A high pressure for a short period of time wills ca direct mechanical damage.
32
CLINICAL PRESENTATION:
a). Neuropathy18:
The signs and symptoms of neuropathy in the diabetic foot and leg include
position sense, anhydrosis, and heavy callus formation over pressure points and
trophic ulcers.
Cardiovascular:
Gastrointestinal:
Genitourinary:
dysfunction.
33
Sudomotor:
Intermittent claudication, cold feet, nocturnal pain, rest pain, absent pulses,
skin, loss of hair on foot and toes, thickened nails, gangrene, blue toe syndrome, acute
vascular occlusion.
In Acute Vascular occlusion, the six “Ps” in the lower extremity are
• Pain.
• Pallor.
• Paresthesia.
• Paralysis
• Poikilothermia.
Nail Problems:
Onychauxis: This is thickening of the nail without deformity, and follows an insult to
34
Onychogryphosis (ram’s horn nail)
This is thickening of the nail with deformity. The cause is an insult to the nail
Nail infections:
should be drained. Though less common on the feet than on the hands, it occur mainly
in the great toe. This may be bacterial or Candidial which is present in web space.
paronychia. A swab is sent for microscopy and culture, and appropriate systemic
antibiotics prescribed.
patch of nail, which subsequently becomes thickened and friable. Infections are
Onychomycosis can cause chronic pain, Physical disability and secondary bacterial
infection.
regular debulking and thinning of the nail using scalpel. This approach is usually
sufficient for most fungal nail infections and active treatment should only be
35
Amorolfine nail lacquer and strong iodine BP. Treatment should continue until a new
Fissures: Fissures are moist or dry cracks in epidermis at sites where skin is under
tension. Deep fissures may involve dermis. Fissures can occur in dry skin. The
treatment is an emollient, such as E45 cream, olive oil or coco butter or in wet skin,
Verrucae: Warts may occur anywhere on the foot and may be single or multiple, and
appear as round flattened papules or plaques. Most will resolve within 2 years without
Bullae (blisters): These are superficial accumulations of clear fluid within or under
the epidermis which develop following trauma to the skin. Common causes include
Small flaccid bullae can be cleaned and covered with a sterile non-adherent
dressing Large bullae (over 1 cm in diameter) and all tense bullae should be lanced
with a scalpel and drained before dressing aspiration with a syringe is less useful
because the hole frequently seals. Fluid accumulates again and unrelieved hydrostatic
pressure causes extension of the blister. The cause of b1isters should always be
36
Bullosis diabeticorum: This is a rare condition where diabetic patients present with
intraepidermal blisters which are not associated with trauma and heal without
excision.
and injudicious reheating. Chilblains are frequently found on the toes. Initially they
are white due to vasoconstriction, but usually present as dusky red swellings which
are intensely pruritic in the acute stages. In the cyanotic phase compound tincture of
Malignancy: Although skin malignancy is rare in the foot, squamous cell carcinoma,
malignant melanoma and rarely basal cell carcinoma may present in the foot.
patients who live in tropical climates with high humidity. The skin becomes white,
macerated and rubbery in texture and prone to blistering and fungal infections. It may
of the toe. The toe takes on the configuration of a swan’s neck. In people with diabetic
neuropathy, hammer toes are commonly caused by weakness of the small intrinsic
muscles (interossei and lumbricals) of the foot, which can no longer stabilize the toes
on the ground. Muscle imbalance results in the affected toes sitting slightly back and
up on the metatarsal head. This deformity results in increased pressure over the
metatarsal head, over the prominent interphalangeal joint and at the tip of the toe.
37
Claw toes: Claw toes are similar to hammer toes, but with more buckling and greater
with callus and ulceration of the apex and dorsal aspect of the interphalangeal joint.
Although claw toes may be related to neuropathy, they are often unrelated, especially
when the clawing is unilateral and associated with trauma or surgery of the forefoot.
Claw toes may rarely result from acute rupture of the plantar fascia.
with lateral deviation of the hallux and a medial prominence on the margin of the foot.
This site is particularly vulnerable in the neuroischaemic foot and frequently breaks
Limited joint mobility can affect the feet as well as the hands. The range of
motion is diminished at the subtalar and first metatarsophalangeal joints. Limited joint
excessive forces on the plantar surface of the first toe causing callus formation and
Ischemia
The foot may have a pale white appearance in severe ischemia, especially on
elevation. In acute ischemia, the foot is pale, often with purplish mottling. The cause
38
Necrosis
brown devitalized tissue. Such tissue may be wet (usually related to infection) or dry.
Major Infections:
I). Cellulitis: Patients presents with cellulitis of the foot involving distal half or whole
of the foot because of necrotising skin and subcutaneous, these patients manifests
2) Abscess: Abscess may be localized to single toe or multiple toes or in the deep
spaces of the sole. Patients may present with or without pain sometimes even abscess
pointing. The most important signs are swelling and redness which can be seen on the
dorsum of the web spaces of the foot. However the most characteristic sign is
separation of the toes due to diffuse edema of the deep tissues of the foot and always
3) Ulcer: Ulcer may present on the dorsal or plantar aspect of the foot. Plantar ulcers
also called as trophic or penetrating ulcer. They are typically painless and occur over
areas that normally carry weight. The earliest change is an area of hyperkeratosis
often over a metatarsal head. The commonest site for an ulcer of the toe is on the
inflammation may precede the breakdown of skin and the development of a small
ulcer.
4) Gangrene: Areas of gangrene may occur on parts of the foot that are exposed to
pressure. The common sites are heel, the malleoli and the areas of first metatarsal
39
head medially, and the base of the fifth metatarsal. Small areas of gangrene may also
occur on the parts of the foot not subject to pressure because of embolism of
atheromatous debris. Gangrenous patches may form in the interdigital clefts. If the
infection follows, it may spread through tissue which, because of poor blood supply,
is unable to confine the process so that further necrosis leads to wet gangrene. The
gangrene may be localized to single toe or multiple toes or extend to whole of the
foot.
INVESTIGATIONS51:
The following investigations are done for the diagnosis, and treatment of the
diabetic foot:
I. Routine investigations
a) Glycosuria:
Results from hyperglycemia, when blood glucose level reaches 180 mg%
(Renal threshold). Renal threshold increases with increase in age and in diabetic
ketosis.
40
c) Fasting blood sugar: Hyperglycemia is most decisive indication of diabetes. It is
estimated by Folin Wu or Somgy’s Nelson method. Fasting blood sugar more than
d) Post prandial blood sugar: After overnight fast, the patient is given breakfast of
for glucose levels every half hour for two hours. If it exceeds l80mg% is indicative of
diabetes mellitus.
e) Glucose tolerance test: The ability of the body to dispose of an additional load of
glucose is known as glucose tolerance test (G.T.T). It can distinguish normal subject
who should have good glucose tolerance from diabetic who does not.
glycohemoglobin.
Pus from infected area is cultured for micro organisms and their sensitivity to
X-ray of the foot should be taken if there is any suspicious infection deep to
the foot, e.g. abscess or oteomyelitis. The signs which suggest the presence of
in the interphalangeal joint of the great toe. Sequestrum and subperiosteal new bones
formations are common. A small amount of gas in the tissues or in the abscess cavity
41
may be seen. Large amounts of subcutaneous gas especially if it extends to the leg,
encircling the thighs, calves, ankles, feet and occasionally, toes to sense segmental
volume changes with each pulse beat. The resulting tracings provide useful
information about the haemodynamic effects of the arterial disease at each level. In
severe disease, tracings at the Transmetatarsal level may become nearly flat. PVR is
noninvasive and rapid and, therefore, may be repeated frequently to help assess the
Imaging Studies:
Duplex scanning can provide images of arteria1 segments that help localize
the extent of disease, and simultaneous Doppler measurement of flow velocity can
help estimate the degree of stenosis. Duplex scanning is quite useful in visualizing
Plain x-ray studies of the diabetic foot may demonstrate demineralization and
42
CT scan and MRI: Although an experienced clinician usually can diagnose a
the study performed actually visualizes the entire segment of the arterial tree to
Other Tests:
proximal blood pressure cuff is inflated. The latter pressure divided by the upper
indication of severity of arterial compromise. Normal ABI averages 1.0. An ABI less
general, an ABI below 0.3 suggests a poor chance for healing of distal ischemic
ulcerations. Unfortunately, ABI often is falsely elevated if the underlying arteries are
43
TREATMENT
After completing the basic assessment, it will now be possible to classify the
diabetic foot. For practical purposes, the diabetic foot can be divided into o distinct
entities:
ischaemic foot is best called the neuroischaemic foot. In rare cases the foot may
ischemic foot is treated in the same way as the neuroischaemic foot, and thus, we
have continued with the two main divisions. It is essential to classify the diabetic foot
management will differ in many respects. Usually there will be no doubt as to which
category the foot should be placed in. However, if the examiner has any doubt as to
the correct classification, then the foot should be regarded as neuroischaemic, because
do further tests to confirm ischemia and adapt the care plan accordingly, this may lead
Neuropathic foot
The neuropathic foot is a warm, well-perfused foot with bounding pulses and
44
and any callus tend to be hard and dry and prone to fissuring Toes are flexed and the
arch of the foot may be raised Ulceration commonly develops on the sole of the foot,
associated with neglected callus and high plantar pressures. Despite the good
circulation, necrosis can develop secondary to severe infection. The neuropathic foot
osteoarthropathy.
Neuroischaemic foot:
The neuroischaemic foot is a cool, pulseless foot with poor perfusion and
almost invariably also has neuropathy. The colour of the severely ischaemic foot can
secondary to cardiac failure or renal impairment. Ischaemic ulcers are commonly seen
around the edges of the foot, including the apices of the toes and the back of the heel,
and are associated with trauma or wearing unsuitable shoes. The neuroischaemic foot
diminished.
Even if neuropathy is present and plantar pressures are high, plantar ulceration
is rare. This is probably because the foot does not develop heavy callus, which
staging in its natural history. The natural history of the diabetic foot can be divided
45
Stage I : Normal foot.
This simple staging system covers the entire spectrum of diabetic foot disease
but it emphasizes the development of the foot ulcer in stage 3 as pivotal event
specific treatment.
Stage 1: At this stage, the patient does not have the risk factors of neuropathy,
ischemia, deformity, callus and swelling rendering him vulnerable to foot ulcers. The
normal.
Stage 2: The patient has developed one or more of the risk factors for foot ulceration
including neuropathy, ischemia, deformity, callus and swelling. These risk factors
ulceration but a history of ulceration should be regarded as very high risk. Within
stage 2 there are specific conditions which are non ulcerative but require treatment.
These include:
• Acute ischaemia.
46
• Neuropathic fractures.
• Charcot’s osteoarthropathy
• Painful neuropathy.
Stage 3: The foot has a skin breakdown. Although this is usually an ulcer, it is
important not to underestimate some apparently minor injuries such as blisters, skin
fissures or razes, all of which have a propensity to become ulcers if they are not
treated correctly and fail to heal quickly. Ulceration is usually on the plantar surface
Stage 4: The foot has developed infection with the presence of purulent discharge or
cellulitis which can complicate both the neuropathic foot and the neuroischaemic foot
Stage 5: Necrosis has supervened. In the neuropathic foot, infection is usually the
cause. In the neuroischaemic foot, infection is still the most common reason for tissue
destruction although ischaemia contributes. In some cases ischaemia alone can lead to
necrosis of a previously intact foot, with slow onset of dry necrosis and necrotic toes
Stage 6: The foot cannot be saved and will need a major amputation. Reasons for
major amputation: Extensive necrosis which has destroyed the foot. Severe infection
which puts the life at risk Agonizing ischaemic pain which cannot be relieved.
The simple staging based on natural history system used to make an initial assessment
of the diabetic foot at whatever stage in the natural history it might be. The stage sets
the place in the natural history and also determines treatment. The aim is to keep all
47
Other classifications of the diabetic foot such as ‘the Wagner system, the University
of Texas system and the Nottingham’s SAD system are essentially classifications of
ulcers and do not cover the whole natural history of the diabetic foot.
Grade 0: At risk foot no obvious ulcer, thick callus prominent metatarsal heads, claw
Multidisciplinary Management:
The aim in managing diabetic foot problems is always to keep the patient at as
low a stage as possible. At each stage of the diabetic foot it is necessary to take
Primary Treatment of Foot Ulcers: When the examination reveals a foot at stage 3, 4
or 5, there is a need for a great sense of urgency: treatment should begin without
delay. No one person can take control of the diabetic foot. Successful management
48
Strategies for saving the diabetic foot:
• Patient Education.
80% of the patients. Recently a drug Cilostozole is used. The ultimate treatment for
reconstructions.
autogenous saphenous vein by pass from the common femoral artery to the popliteal
artery is done. For patients with significant disease in the above knee popliteal artery,
Patient Education: The patient should be taught about good diabetic control, foot-
patient can prevent, injury to insensitive foot and detect foot lesions earlier.
49
Surgical Management:
Debridement55:
The clinician can choose from among several options for debridement suitable
• Surgical /sharp.
• Mechanical.
• Autolytic.
Surgical/sharp debridement:
clinician uses instruments to remove the necrotic tissue from the wound. Although
lasers have been used, most clinicians employ scissors, scalpels, and forceps to
proficiency with surgical instruments are essential Knowing what is being excised and
when to stop is critical. One challenge is differentiating yellow slough from tendons.
If in doubt, the clinician should avoid cutting. It is indicated whenever the goal is too
quickly remove large amounts of necrotic tissue the patient can tolerate this
teryention. When time is of the essence (as with infected wounds with systemic sepsis
necrotic tissue this type of debridement should be avoided or used with extreme
50
Surgical/sharp debridement is usually painful; therefore, the patient should be
Mechanical debridement:
include the use of irrigation fluids delivered by pulsed lavage, the agitation of water
both viable and nonviable tissues are removed during the process.
Wet-to-dry dressings are time consuming. They are done 3 times a day.
Maceration to surrounding wound skin is also a potential problem. Despite this, wet-
to-dry dressings are one of the most frequently prescribed (and overused) methods of
debridement in the acute care settings56. Normal saline is safe and should be used in
most situations. The pressure ulcer treatment guideline from the Agency for Health
Care Policy and Research (AHCPR; now the Agency for Hea1hcare Research and
sodium hypochlorite (Dakin’s solution), hydrogen peroxide, and acetic acid, can
Autolytic debridement
over the wound and allowing the natural wound fluids to soften eschar, proteolytic
51
enzymes within the wound fluids digest and liquefy necrotic tissue. The dressing
should be left in place for 2 to 3 days. When the dressing is removed, the wound
debridement with hydrogels may also soften hard, dry eschar for easier mechanical or
applications and irrigations over days or weeks. However, it is usually pain-free and
less stressful to the patient. Autolytic debridement is not appropriate for effected
wounds or very deep cavity wounds that require packing. The wound fluid under the
treatment of the infection. Failure to do so may result in serious wound infections, and
possibly sepsis.
Enzymatic Debridement
digesting and dissolving the devitalized tissue in the wound bed. Some enzymes are
selective and recognize only devitalized tissue57 other enzymes are nonselective and
contains papain and urea in a cream base, the other is composed of Collagenase in a
chlorophyllin-copper complex.
52
Papain is a proteolytic enzyme derived from the fruit of Carica papaya. It is a
cleanse the wound if papain is being used for debridernent. Collagenase, derived from
detergents and heavy metal ions (eg, silver and mercury) inactivate this product;
collagenase. Avoid using metal ions or acidic solutions for cleansing the wound due
to the metal ion and low pH.Hydrogen peroxide, sodium hypochlorite, and normal
collagenase in petrolatum. Its labeled Indications include debriding dermal ulcers and
severely burned areas. Dermal ulcer’s include pressure ulcers, arterial ulcers, venous
ulcers and Diabetic ulcers. There are no recent clinical trials that compare
collagenase ointment with placebo in burns or decubitus ulcers. Published studies are
poorly controlled and unblinded. Although not well done these studies suggest that
tissue if Collagenase is not confined to the wound area. Do not store this drug above
77°F (25°C): Enzyme (collagenase) has once-a-day application; the other (papain-
53
urea) may need once or twice-a-day application. Both agents can be used with
infected wounds.
invitro study of the active ingredients of these agents. papain-urea was found to digest
fibrin but not elastin; the opposite was true of collagenase, which digested elastin but
not fibrin60.
Papain-urea produces more exudate from the enzymatic digestion which may irritate
necrotic tissue must be debrided rapidly, important viable tissues (eg, tendons and
large blood vessels) are not in direct contact with the agent, the affected area is either
insensate or any burning and pain can be effectively managed57,63 and becaplermin
Collagenase enzymatic debriding agents may digest necrotic tissue from the
soluble proteinase that specifically attacks and breaks down collagen65,66. Although
Collagenase may deride obviously visible necrotic tissue more slowly than papain –
urea, it is more selective in the number of substances it digests62. It does not affect
cell viability in cell culture media, and it carries less risk of pain or discomfort. In
chronic wounds, keratinocytes are not able to migrate over a wound covered by eschar
or other necrotic debris and may proliferate at the edge of the wound, possibly
creating a rolled edge and stalling healing. Some evidence suggests that collagenase
54
enhances keratinocyte migration over granulation tissue. In an early study evaluating
the use of Cl.histolyticum for the debridement of dermal ulcers and pressure ulcers67,
the time required for complete debridement of the treated lesions averaged 10.5 days
generally proceeded at a faster rate than was expected in chronic dermal lesions of the
the collagenase is a well known and established enzyme preparation for wound
clinical finding. A study by Grinnell et al69 suggests that until the anchoring
undenatured collagen fibers are severed, thereby allowing the necrotic plug to be
Collagenase increased human keratinocyte migration 3-fold and single cell motility up
serve as a possible pluripotential wound bed preparation agent. There is evidence that
endothelial cells in cell cultures, and may stimulate angiogenesis. Two clinical studies
report significantly less pain with collagenase (when compared with control
55
treatments) in 60 patients with diabetic foot ulcer and 79 patients with partial-
debridement most commonly used in clinical practice today. The goal of debridement
is to remove necrotic debris and fibrous tissue, an important facet of wound bed
preparation. Research also suggests that debridement can remove senescent cells that
Metronidazole75
be high active ameobicide. It has broad spectrum cidal activity against protozoa
including Giardia lamblia .In addition to the above two, many anaerobic bacteria such
the helminth, Dracunculus medinesis are sensitive. It does not affect aerobic bacteria.
Clinically significant resistance has not developed among the parasites for which it is
used.
which cause cytotoxicity, probably by damaging DNA. Its selectively high activity
against anaerobic organisms has suggested interference with electron transport form
NADPH or other reduced substrates. Metronidazole has been found to inhibit cell
56
accelerates healing, eliminates anaerobes-breaks microbial synergy and reduces
Adverse effects:
Anorexia, Nausea, metallic taste and abdominal cramps are most common.
Less frequent side effects are-headache, glossitis, dryness of mouth, dizziness, rashes
pregnancy though no teratogenic effect has yet been demonstrated, its mutagenic
Povidone-Iodine76,77
mirobicidal agent; has been in use of for more than a century. Acts by iodinating and
painting in surgery, ring worm etc., Mandel’s paint (1.25% dissolved with the help of
pot.iodide forming soluble 13 - ions) is applied on sore throat. A non staining iodine
ointment (Iodex 4%) is popular as antiseptic and counterirritant. Some individuals are
lodophores: These are soluble complexes of iodine with large, molecular organic
compounds that serve as carriers release free iodine slowly. The most popular is
57
exerts prolonged germicidal action. Treated areas can be bandaged or occuluded
had no-significant effect in 6 studies. Histologic evidence of tissue toxicity was noted
Hydrogen Peroxide: Had little effect on wound healing or bacterial control, but its
peroxide is usually diluted to one-half strength, and, then raised off with saline.
aeruginosa, Staphylococcus aureus and Gram-negative rods), yet was not cytotoxic in
Silver Compounds: have been effective in reducing bacterial loads without adverse
effects on wound healing. In fact, several in vivo studies show acceleration of wound
healing.
58
The use of antiseptics in wounds remains an area of controversy. Slow-release
Cadexomer iodine preparations and some of the newer silver dressings may provide
the safest and most effective alternative for bacterial control and wound management.
Skin Grafting78,79
contain epidermis and upper capillary dermis and are re-vascularized by the in-growth
Full thickness (Wolfe) graft: full thickness grafts contain complete dermis
and epidermis and have advantage of natural skin color in addition to reduced
tendency to contracture.
Skin and muscle flaps: cutaneous flaps may be of random or axial pattern,
including deep fascia into a cutaneous flap. This allows greater extension and
mobility because of the blood vessels perforating the subcutaneous adipose tissue that
transposed as an axial pattern flap and is particular value in covering the bare bone
Micro vascular free flaps: - the micro vascular bundle of an axial pattern flap may be
anastomosed by micro vascular surgery to a donor pedicle in another area of the body.
AMPUTATION80,81
The aim of the treatment is not merely healing but walking on a healed foot or
59
Transmetatarsal Amputation:
Provided that the plantar skin is uncompromised, the indications for Tran
and extension of the infection process proximal to the metatarsal phalangeal crease,
but not up to the distal third/middle third junction of the forefoot compromise of the
plantar skin & deep forefoot infections are the primary contraindications to an
Symes Amputation
Symes Amputation.
level are an infectious or gangrenous process that extends to within five centimeter of
tibial tuberosity or that involves the proposed skin flaps (especially the posterior flap).
In below knee amputation there is increased rate of healing, decreased hospital stay,
decreased rehabilitation time, control of stump edema and early post operative stump
protection with the use of immediate or early (71to 10 days) post operative prosthetic
techniques.
60
Above Knee Amputation
Guillotin Amputation;
The limb is cut off in one transverse plane without formation of flaps. All the
tissues of the limb are divided at same level and the bone end is left exposed on the
cut surface.
gross sepsis.
order that the bone end may be covered with soft parts.
There are two major aims when considering a patient for possible amputation.
2. To restore mobility.
the operation is discussed. An approximate time table for fitting of the prosthesis may
be given. This depends on local policies and the availability of limb fitting facilities.
61
must be emphasized the greatest contribution to rehabilitation is made by the surgeon,
who carefully and meticulously performs the operation because a major factor,
wound and then refer the patient to a specialist in limb fitting and rehabilitation who
undertakes the subsequent management often at the another center. At the other
rehabilitation is begun.
62
MATERIALS AND METHODS
Study Design
The study was a prospective, parallel group, comparative trial. Patients admitted
with diabetic foot ulcer in Basaveshwar Teaching and General Hospital, attached to M.R
Medical College, Gulbarga. The number of patients included in the study was 80, Out of
which 40 were in the test group and 40 were in the control group. Study duration was 2
Inclusion Criteria
Exclusion Criteria
like varicosities.
f. Other clinically significant medical conditions that would impair wound healing
diseases.
chemotherapy within one month prior to entry into the study were also excluded.
63
The selected patients underwent screening for a period of one to two weeks, to
stabilize the wound and institute appropriate medical and surgical line of treatment like
medical illness.
After the initial screening period the eligible patients who required bed side
debridement were divided randomly into test group and control groups.
1. Test group: Received Collagenase ointment with bed side surgical debridement
when ever required for wounds / ulcers which had slough in the floor and till
2. Control group: Received bed side surgical debridement with conventional local
antiseptics.
The test medication was applied to test group once daily, using a tongue
depressor, enough medication was applied over the entire surface of the slough and only
superficial slough was removed using bed side surgical debridement when ever required.
Treatment of control group was done with bed side surgical debridement when
ever required and conventional topical antiseptics, other than the enzymatic debridement
64
Wounds were treated once daily until complete debridement or up to seven
weeks. The amount of nonviable tissue, degree of wound granulation, and overall wound
a. The score for the percentage of wound covered by slough and nonviable
6. = No necrotic tissue
b. The score for the percentage of wound covered by granulation tissue are
1. = No granulation present
The final parameters and wound characteristics of the two randomized groups
65
OBSERVATION AND RESULTS
Age distribution
Most of the patients fell in the age group between 40 years to 70 years. The mean
± SD for test group is (57.0 ± 14.85) and control is (55.5 ± 14.45), so age distribution is
Table – 3
Age distribution
Test group Control group
Age in years
No. of Cases % No. of Cases %
20-30 2 5 3 7.5
31-40 2 5 4 10.0
41-50 9 22.5 8 20.0
51-60 12 30 10 25.0
61-70 9 22.5 10 25.0
71-80 4 10 3 7.5
>80 2 5 2 5.0
Total 40 100. 0 40 100.0
Mean ± SD 57.0 ± 14.85 55.55 ± 14.45
Inference Age distribution is statistically similar between the two groups.
10
Number of cases
6
Test group
Control group
4
0
20-30 31-40 41-50 51-60 61-70 71-80 >80
Age in years
66
Sex distribution
The male and female ratio of the test group is 62.5%: 37.5% and the control group
is 67.5%: 32.5%. Hence sex distribution is statistically similar between the two groups
Table -4
Sex distribution
27
30 25
25
Number of cases
20 15
13
15 Test group
Control group
10
0
Male Female
Sex distribution
67
Diabetes Mellitus Status
Most of the patients in test (85%) and control (75%) group had previous history of
diabetes mellitus. The newly detected groups are only 15% and 25% in test and control
groups respectively.
Table -5
Diabetes Mellitus
34
35 30
30
25
Number of cases
20
Present
15 10
Newly detected
6
10
0
Test group Control group
Diabetes mellitus
68
Duration of DM
It is observed in our study most of the patients presented with diabetes mellitus of
duration with Mean ± SD of test group 9.77 ± 6.94 and control group 10.29 ± 5.61, thus
showing long duration of diabetes mellitus patients are prone for diabetic foot ulcers.
Table -6
Duration of Diabetes Mellitus
Duration of Test group Control group
Diabetes
mellitus No % No %
16
14 14
14
12
Number of cases
10 9 9
8
8
6
6
4 3
2 1
0
≤ 5 years 5-10 years 10-20 years > 20 years
Duration of Diabetes mellitus
69
Size of the ulcers
The mean size of the ulcer was 9.82 to 10.32 cm. The mean ± SD of the size of
ulcer in test group (9.82 ± 6.80) and in control group (10.32 ± 6.39) is statistically similar
Table -7
Size of the ulcers
15
16 14
13
14 12
11
12 10
Number of cases
10
6
3
4 2
0
≤5 5-10 10-20 > 20
Size of the ulcer (cms)
70
Grade of Ulcers
Most of the patients had Grade III and IV ulcers in both test and control groups.
Table -8
Grade of ulcers
II 6 15.0 6 15.0
IV 13 27.5 14 35.0
18 17
16 14 14
13
14
12
Number of cases
10
6 Test group
8 6 6
Control group
6 4
0
II III IV Unstagable
Grade
71
Presence of necrotic tissue or slough
The number of patients with no necrotic tissue are significantly higher in the test
group at 3rd week follow up (P< 0.001), at 4th week (P < 0.001), at 5th week (P< 0.001), at
6th week (P < 0.001) and at the 7th week (P <0.01) when compared to control group as per
Table -9
Study Test group (n=40) visual score of slough covering Control group (n=40) visual score of slough
Period the ulcer covering the ulcer
1 2 3 4 5 6 1 2 3 4 5 6
Base line 22 11 6 1 - - 23 10 7 - - -
(55.0) (27.5) (15) (2.5) (57.5) (25.0) (17.5)
1st week 10 10 7 7 5 1 20 9 5 3 3 -
(25.0) (25.0) (17.5) (17.5) (12.5) (2.5) (50.0) (22.5) (12.5) (7.5) (7.5)
2nd week 1 9 7 3 11 9 6 17 6 4 2 5
(2.5 (22.5) (17.5) (7.5) (27.5 (22.5) (15.0) (42.5) (15.0) (10.0) (5.0) (12.5)
3rd week - 2 5 10 0 23 2 12 9 4 5 8
(5.0) (12.5) (25.0) (0) (57.5.) (5.0) (30.0) (22.5) (10.0) (12.5) (20.0)
4th week - - 2 4 4 30 - 1 14 8 4 13
(5.0) (10.0) (10.0) (75.0) (2.5) (35.0) (20.0) (10.0) (32.5)
5th week - - - 2 3 35 - - 4 11 9 16
(5.0) (7.5) (87.5) (10.0) (27.5) (22.5) (40.0)
6th week - - - - 1 39 - - - 6 11 23
(2.5) (97.5) (15.0) (27.5) (57.5)
7th week - - - - - 40 - - - - 8 32
(100.0) (20.0) (80.0)
Inference Number of patients with No Necrotic tissue are significantly higher in Test group at 3rd week follow up
(P < 0.001), at 4th week (P < 0.001), at 5th week (P < 0.001), at 6th week (P < 0.001) and at the 7th week (P
<0.01) when compared to control group as per the chi-square / Fisher Exact test.
Visual score63
72
Figure-9: Showing the presence of necrotic tissue or slough in Test and Control
group
100% 1 1
6 5
90% 9
80%
7
23
70% 11
11 30
60% 7
Percentage 35
50%
39 40 Test group
3
40% 10
7
10
30% 22
4
20%
10 9
5 4
10% 3
1 2 2 2 1
0%
Base line 1st week 2nd week 3rd week 4th week 5th week 6th week 7th week
Followup
100% 3
5
7 8
90% 3
2 13
5 16
80% 4
5
10 23
70%
6
9 4 4
60% 32
P ercentage
50% 8 9
9
Control group
40% 17
30% 23 11
20 11
12 14
20%
8
10% 6 6
4
2 1
0%
Base line 1st week 2nd week 3rd week 4th week 5th week 6th week 7th week
Followup
100
90
80
70
60
Percentage
Test
50
Control
40
30
20
10
0
Baseline 1st week 2nd week 3rd week 4th week 5th week 6th week 7th week
Graph showing Score 6-No necrotic tissue during the study period
73
Presence of granulation tissue
The number of patients with 75-00% wound filled with granulation tissue are
significantly higher in Test group at 3rd week follow up (P<0.001), at 4th week
(P < 0.001), at 5th week (P<0.001), at 6th week (P<0.001) and at the 7th week
(P<0.05) when compared to control group as per the Chi-Square / Fisher Exact test.
Table – 10
Visual score63
1. = no granulation present
2. = < 25% of wound filled
3. = 25-74% of wound filled
4. = 75-100% of wound filled
74
Figure-10: Showing the gradual progress of granulation tissue
in Test and Control group in each week
100% 1
4
90% 10
80%
17 21
14
70%
29
Percentage
60%
17 36 38
50% 40
11 Test group
40%
30% 22 16
20% 12 10
11
10%
3 4 2
1 1
0%
Base line 1st week 2nd week 3rd week 4th week 5th week 6th week 7th week
Followup
100%
4 5
8 8
90%
12
80% 16
9 19
13
70% 9 9
50% 16
17
40%
23 23 22 24
30% 21
20%
12
9
10% 5
1
0%
Base line 1st week 2nd week 3rd week 4th week 5th week 6th week 7th week
Followup
100
90
80
70
60
Percentage
50
40
30
20
10
0
Base line 1st week 2nd week 3rd week 4th week 5th week 6th week 7th week
Graph showing score 4- 75-100% wound filled during the study
Test Control
75
Wound Surface Area
The number of patients with No wound surface (Nil) are significantly higher in
Test group at 3rd week follow up (P< 0.05), at 4th week (P <0.05), at 5th week (P < 0.05),
at 6th week (P < 0.001) and at the 7th week (P<0.001) when compared to control group as
Table – 11
76
Figure-11: Showing shrinking of wound surface and their final treatment
like secondary suturing, SSG, flap and complete wound healing (Nil)
100% 1
90% 11 11 11 11
14
80%
21
70%
60% 11 10 33
Percentage
14 14
10 39
50%
100% 2 2
5
90% 10 9 10 9
10 11 15
80% 9
4
70%
12 9
60% 12 8 6
6 8
Percentage
5
50% Control group
6
40%
30% 21 21
19 20 20 19
18
20% 14
10%
0%
Base line 1st week 2nd week 3rd week 4th week 5th week 6th week 7th week
Followup
120
100
80
Percentage
60
40
20
0
Base line 1st week 2nd week 3rd week 4th week 5th week 6th week 7th week
Graph showing Nil - Flap, Heeled. SSG & Suturing during the study
Test Control
77
Split Skin Graft
Patients in test group are subjected to the skin graft as early as 3rd week, were as
the patients in control group underwent skin graft only in 5th week. At the end of 6th
week totally 21 patient in test group underwent S.S.G compare to the control group were
only 3 patients.
Table -12
Test Control
1st week Nil Nil
2nd week Nil Nil
3rd week 5 Nil
4th week 9 Nil
5th week 17 1
6th week 20 3
7th week 21 13
25
21
20
20
17
Number of cases
15
13
Test
Control
10 9
5
5
3
1
0 0 0 0 0 0
0
1st week 2nd week 3rd week 4th week 5th week 6th week 7th week
78
DIABETIC FOOT ULCERS
GRADE II ULCERS
GRADE IV ULCERS
79
HEALING ULCERS WITH GOOD WOUND BED
FINAL OUTCOME
80
DISCUSSION
The number of patients studied was 80 and randomly divided into test group (40)
and control group (40). Both the test and control groups were matched regarding their
In addition, there was no significant difference between the two groups with
group at 3rd week follow up (P< 0.001), at 4th week (P <0.001), at 5th week (P <0.001), at
6th week (P < 0.001) and at the 7th week (P<0.01) when compared to control group.
There is minimal loss of viable tissue in the test group compared to that of control group
this is because the number of bedside surgical debridements required is less and done
significantly higher in Test group at 3rd week follow up (P<0.001), at 4th week
(P <0.001), at 5th week (P <0.001), at 6th week (P <0.001) and at the 7th week (P< 0.05)
The number of patients with no wound surface (nil) is significantly higher in Test
group at 3rd week follow up (P<0.05), at 4th week (P <0.05), at 5 week (P <0.05), at 6th
week (P < 0.001) at the 7th week (P < 0.001) when compared to control group. In
81
addition to the above observation test group has experienced less pain and reduced
The duration of hospital stay was less in test group compared to control group.
The patients treated with Collagenase and metronidazole gel had faster reduction
of slough / necrotic tissue and increased granulation tissue, compared to study by Alvarez
study of collagenase and papain-urea for pressure ulcer debridement, where it showed
that the papain urea debridement ointment is more effective than the collagenase in the
3rd and 4th week recording the reduction of slough, increasing the growth of granulation
tissue. In our study patients showed similar improvement in 3rd and 4th week.
This study demonstrated that enzymatic collagenase debridement along with bed
The test group patients had increased growth of the granulation tissue along with
bed. All this are done with visual score so it cannot be determined whether there was an
increase in granulation tissue production resulting from the treatment or that more
granulation was visible after debridement. But patients in test group produced better
The test group patients also experienced less pain than the control group because
the need for the bed side surgical debridement is less than the control group.
82
The test group patients also experienced less pain than the control group because
the need for the bed side surgical debridement is less than the control group.
The test group patients under went skin grafting, secondary suturing and flap as
early as 3rd week than control group because of faster wound bed preparation. The
83
CONCLUSION
1. The study was done to give an insight to the depth of diabetic wound
2. The goal of this study was to enhance the wound / ulcers to be devoid of
necrotic tissue and debris and to remove the senescent cells from the
rapid healing.
84
SUMMARY
given with an account of the historical aspect of diabetes mellitus. The literature in
respect of clinico-pathology and diagnostic aspect and the management of the diabetic
Both the test and control group were matched regarding their age, diabetic status,
nutritional status, and grade of ulcer. In addition, there were no significant differences
between the two groups with respect to baseline ulcer size and amount of nonviable tissue
/ slough.
The reduction of slough is as early as 3rd week in the test group than the control
group.
The number of patients with 75-100% wound filled with granulation tissue is as
early as 3rd week in test group than the control group where it took more than 4 weeks.
The number of patients who underwent secondary suturing, skin graft and flap
are significantly higher and also as early as 3rd week in test group than the control group.
This helps in faster wound bed preparation for healing, suturing, skin graft and
Flap.
85
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Statistical methods:
Chi-square and Fisher exact test have been used to test the significance of frequencies
of presence of necrotic tissue, Presence of granulation tissue and wound surface area
1. Chi-Square Test
(a+b)! (c+d)!(a+c)!(b+d)! 1
Fisher Exact Test statistic = ∑ p =
n! ∑ a!b!c!d!
95
PROFORMA
Case no : Hospital no :
Name : DOA :
Age : DOD :
Sex : Address :
Religion:
History
Duration of ulcer:
Pain: Yes/No
Diabetic history
96
INVESTIGATIONS
Haematological
Doppler studies:
X-Ray of foot:
3rd week
4th week
5th week
6th week
7th week
1st week
1Presence of necrotic
tissue or strands of
collagen
Visual scores 1. = 76-100%, 2. =51-75 %, 3. 26-50%, 4. 11-25%, 5. = 0-10%, 6. No
necrotic tissue covering the ulcer
2. Presence of Granulation
tissue
Visual scores 1. = 76-100%, 2. =51-75 %, 3. 26-50%, 4. 11-25%, 5. = 0-10%, 6.
No necrotic tissue covering the ulcer
3. wound surface area
(cm2)
4. Salutyl applied (for
days)
5. Metrogyl applied(for
days)
97
KEY TO MASTER CHART
98
Master Chart (Control Group)
Presence of Necrotic
Urine Presence of Granulation
Grade of ulcer
Hospital No.
Progress
Doppler
Duration in years
Treatment R NR
Treatment R/IR
X-ray
Sl.
Pain
Age
Sex
Oral / Insulin
Ulcer onset
Name
2nd week
2nd week
2nd week
Base line
Base line
Base line
3rd week
3rd week
3rd week
4th week
5th week
6th week
7th week
4th week
5th week
6th week
7th week
4th week
5th week
6th week
7th week
1st week
1st week
1st week
No.
Alumbin
Ketone
PPBS
Sugar
Hb%
FBS
DM
BU
SC
1 Basammma 51 F 265560 + 16 IR O T R 12 III G + 10 132 196 18 0.8 +++ - - N N 1 2 1 2 3 4 5 6 1 1 2 2 3 3 3 4 12 12 12 11 10 10 10 S.S.G 42
8 Amruth 28 M 263797 - - - - T R 4 III G - 12 140 190 16 0.7 + - - N N 3 5 6 6 6 6 6 6 3 3 4 4 4 4 4 4 4 4 2 1 Healed Healed Healed Healed 38
12 Chandamma 48 F 281949 + 6 R O T R 2 II G + 13 148 198 20 0.8 + - - N N 3 5 6 6 6 6 6 6 3 3 4 4 4 4 4 4 2 2 1 Healed Healed Healed Healed Healed 15
18 Hallerao 65 M 246458 + 20 R O S NR 2 III G - 9.4 132 198 22 1.2 ++ - - N N 2 4 6 6 6 6 6 6 2 3 4 4 4 4 4 4 2 2 1 Healed Healed Healed Healed Healed 15
Grade of ulcer
Hospital No.
Progress
Doppler
Duration in years
Treatment R NR
Treatment R/IR
X-ray
Sl.
Pain
Age
Sex
Oral / Insulin
Ulcer onset
Name
2nd week
2nd week
2nd week
Base line
Base line
Base line
3rd week
3rd week
3rd week
4th week
5th week
6th week
7th week
4th week
5th week
6th week
7th week
4th week
5th week
6th week
7th week
1st week
1st week
1st week
No.
Alumbin
Ketone
PPBS
Sugar
Hb%
FBS
DM
BU
SC
+++
21 Shantabai 65 F 259068 + 7 R O S R 20 III G + 11 250 300 38 1.5 + + N N 1 2 2 3 3 4 5 5 1 1 2 2 3 3 3 4 20 22 22 22 20 18 18 S.S.G 48
+
+++
25 Tippibai 44 F 245627 - - - - S NR 12 IV R + 7.6 280 380 33 1.2 + + N N 1 1 2 2 3 4 4 5 1 1 2 2 2 3 3 4 12 14 14 12 12 10 8 8 49
+
33 Shivamma 66 F 257601 + 9 R I/O S R 2 III G - 12 144 200 32 1 + ++ - N N 3 3 4 6 6 6 6 6 2 3 3 4 4 4 4 4 2 2 1 1 Healed Healed Healed Healed 30
+++
34 Vijaylaxmi 67 F 244592 + 6 IR O T R 17 IV R + 7.5 310 410 54 2.4 - - N N 1 1 2 2 3 4 5 5 1 1 1 2 2 3 3 3 17 20 20 20 20 18 18 18 >49
+
+++
38 Tayappa 48 M 273726 + 5 R O T R 24 III R + 12 230 320 44 1.4 + + N N 1 1 1 2 3 4 4 4 1 1 1 2 2 3 3 4 24 26 26 26 26 24 23 S.S.G 48
+
+++
40 Shivanna 74 M 242865 + 12 IR I/O T NR 22 III G - 13 210 320 56 1.3 - - N N 1 1 1 2 2 4 4 4 1 1 1 2 2 3 3 3 22 22 24 26 26 26 25 26 >49
+