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

Under the Guidance of

Dr. R.B. DHADED

M.S (General Surgery)
Professor

DEPARTMENT OF SURGERY
MAHADEVAPPA RAMPURE MEDICAL COLLEGE,
GULBARGA, KARNATAKA
2009

i
 Rajiv Gandhi University of Health Sciences,
Bangalore, Karnataka.

DECLARATION BY THE CANDIDATE

I hereby declare that this dissertation/thesis entitled “STUDY OF

COLLAGENASE AND METRONIDAZOLE IN THE TOPICAL

MANAGEMENT OF DIABETIC FOOT ULCERS” is a bonafide and

genuine research work carried out by me under the guidance of

Dr. R.B. Dhaded, M.R. Medical College, Gulbarga.

Date : Signature of the Candidate

Place : Gulbarga. Dr. Nishant. K

ii
 Rajiv Gandhi University of Health Sciences,
Bangalore, Karnataka.

CERTIFICATE BY THE GUIDE

This is to certify that the dissertation “STUDY OF

COLLAGENASE AND METRONIDAZOLE IN THE TOPICAL

MANAGEMENT OF DIABETIC FOOT ULCERS” is a bonafide

research work done by Dr.Nishant.K in partial fulfillment of the

requirement for the degree of Master of Surgery in General Surgery.

Signature of the Guide

Dr. R.B. Dhaded

M.S (General Surgery)
Professor
Date: Department of Surgery
Place: Gulbarga. M.R. Medical College, Gulbarga

iii
 Rajiv Gandhi University of Health Sciences,
Bangalore, Karnataka.

ENDORSEMENT BY THE HOD, PRINCIPAL/HEAD OF THE

INSTITUTION

This is to certify that the dissertation entitled “STUDY OF

COLLAGENASE AND METRONIDAZOLE IN THE

TOPICAL MANAGEMENT OF DIABETIC FOOT ULCERS” is a

bonafide research work done by Dr.Nishant.K under the guidance of

Dr. R.B. Dhaded Professor, Department of Surgery, M.R. Medical

College, Gulbarga.

Seal & Signature of the Seal & Signature of the

HOD Principal

Dr. S. A. Halkai Dr. Mallikarjun Bhandar

M.S. M.D.
Professor and Head Dean and Principal
Department of Surgery M.R. Medical College,
M.R. Medical College, Gulbarga
Gulbarga.

Date: Date:
Place :Gulbarga. Place : Gulbarga.

iv
 Rajiv Gandhi University of Health Sciences,
Bangalore, Karnataka.

DECLARATION BY THE CANDIDATE

I hereby declare that the Rajiv Gandhi University of Health

Sciences, Karnataka shall have the rights to preserve, use and

disseminate this dissertation/thesis in print or electronic format for

academic/research purpose. .

Signature of the Candidate

Dr.Nishant.K

Date:
Place: Gulbarga

v
 ACKNOWLEDGEMENT

A journey is easier when you travel together. Interdependence is

certainly more valuable than independence. This thesis is the result of
two and a half years of work whereby I have been accompanied and
supported by many people. It is a pleasant aspect that I have now the
opportunity to express my gratitude for all of them.

I dedicate this dissertation to my parents and siblings for

providing the strength, time, unconditioned love, care and especially
for cushioning all my falls in my life and direct me to the path of
success.

I avail this opportunity to express my profound earnest gratitude

to my beloved teacher, guide and mentor, Dr .R.B.DHADED M.S,
Professor of Surgery for his esteemed guidance, unflinching support,
keen surveillance, inestimable aid and continued inspiration. During
the course of my study, I have known him as a sympathetic and
principle- centered person. His overly enthusiasm and integral view on
research and his mission for providing ‘only high quality work not less’
has made a deep impression on me. He has been a source of sustained
illumination to me, with whose valuable guidance and generous
support facilitated me to accomplish this dissertation.

I designate my sincere thanks to the Professor and Head of

Department of General Surgery, Dr.S.A.Halkai for his immense
support.

I would also like to thank all my teachers Dr.M.S.Harsoor,

Dr.S.M.Patil, Dr.M.V.Nisty, Dr.R.G.Devani, Dr.SangannaKollur,
Dr.R.Anil, Dr.S.R.Harwal, Dr.A.V.Mudda, Dr.Umeshchandra,
Dr.Sharad.M.Tanga, Dr.S.S.Karbhari, Dr.Rajshekar Patil,
Dr.V.S.Kappikeri,Dr.Shivakumar.C.R, Dr.Shantha Patil, Dr.Suresh
Patil and Dr.Sanjeev.M.Patil for their immense support.

It is with immense honour and pleasure that I take this

opportunity to thank our Dean, Dr.Mallikarjun.B M.D. for his support,
encouragement and facilities provided during the course of this
dissertation.

Its down in words if I don’t express my sincere and warm

gratitude to my seniors Dr.Balaji, Dr.Basavantrao, Dr.Shravan Shetty
and Dr.Sharanabasava who have been a constant support throughout

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.

I thank Mr. Srinivas Reddy statistician for his invaluable help in

helping me to deal with all the statistical work in this study.

I am also thankful to Mr.Satish Kumar M/s Kotli systems for

providing me an excellent work environment during their past years
and for their cheerful assistance. It is a pleasure to work with them.

The chain my gratitude would be definitely incomplete if I would

forget to thank the first cause of this chain, using Aristotle’s words,
”The Prime Mover, God”. My deepest and sincere gratitude for
inspiring and guiding this humble being.

Date:

Place: Gulbarga Dr.Nishant.K

vii
 ABBREVATIONS

BKA - Below knee amputation

Bp - Blood Pressure
BU - Blood Urea
D.M - Diabetes Mellitus
F - Female
FBS - Fasting Blood sugar
G - Gradual
GTT - Glucose tolerance test
Hb - Hemoglobin
I - Insulin
IR - Irregular
M - Male
N - Normal
NR - Not received
O - Oral
P - Poor
PPBS - Post Prandial Blood sugar
PR - Pulse rate
PVD - Peripheral vascular disease
PVR - Pulse volume recording
R - Regular
Ra - Rapid
Re - Received
S - Spontaneous
SC - Serum creatinine
SD - Standard deviation
SECS - Socio economic status
S.S.G - Split skin grafting
Sl. No - Serial Number
T - Trauma

viii
 ABSTRACT

Background and Objectives:

Diabetes mellitus is recognized to be common in Indians in the Asian subcontinent.

The projection indicates that India will have largest number of diabetic patients by the
year 2025. Diabetes foot is one of the major complications of diabetes mellitus. Foot
problems are the most common cause of admission to the hospital. 15% of the
patients develop foot ulcers during their life times. If untreated they end in lower
extremity amputation. 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. Topical treatment is an important aspect of diabetic foot
ulcers although secondary to surgical and systemic care.

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:

Collagenase with metronidozle is a effective topical applicant in reduction of slough,

promoting granulation tissue formation and reepitheilization. This helps in faster
wound bed preparation for healing, suturing, skin graft and flap in comparison with
conventional treatment with local antiseptics.

Keywords: Diabetic foot ulcers; Collagenase; metronidazole

ix
 TABLE OF CONTENTS

Sl. No. Particulars Page. No.

1. Introduction 1-2

2. Aims and Objectives 3

3. Review of Literature 4-62

4. Materials and Methods 63-65

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.

1 Important Landmark in the History of Diabetes 17th, 18th and 19th 4

Centuries

2 Important Landmark in the History of Diabetes 20th Century 5

3 Age distribution 66

4 Sex distribution 67

5 Diabetes Mellitus 68

6 Duration of Diabetes Mellitus 69

7 Size of the ulcers 70

8 Grade of ulcers 71

9 Presence of necrotic tissue or slough 72

10 Presence of granulation tissue 74

11 Wound Surface Area 76

12 Split Skin Graft 78

xi
 LIST OF FIGURES

Sl. Page.
Particulars
No. No.

1 Muscles of the foot 10

2 Artery and nerve supply of the foot 11

3 Age distribution 66

4 Sex distribution 67

5 Diabetes Mellitus 68

6 Duration of Diabetes Mellitus 69

7 Size of the ulcers 70

8 Grade of ulcers 71

9 Presence of necrotic tissue or slough 73

10 Presence of granulation tissue 75

11 Wound Surface Area 77

12 Split Skin Graft 78

xii
 INTRODUCTION

Diabetes mellitus in characterized by chronic hyperglycemia with disturbances

of carbohydrate, fat and protein metabolism resulting from defects in insulin

secretion, insulin action or both1.

Diabetes is accompanied by a progressive tissue damage secondary to micro

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

blindness and a leading cause of cardiovascular mortality1.

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

2000 and this number is likely to be 71.4 million in 20301.

Diabetic patients suffer from foot ulcers which may eventually lead to

amputation2.

Diabetes mellitus is recognized to be common in Indians in the Asian

subcontinent. The projections indicates that India will have largest number of

diabetic patients by the year 20253.

Diabetes foot is one of the major complications of diabetes mellitus. One in

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

lost due to diabetes, some where in the world4.

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

the ankle in a patient with diabetes irrespective of duration5.

In India, the prevalence of diabetic foot ulcers in clinic population was estimated

to be 3.6%6. Socio-cultural practices such as bare-foot walking and certain religious

practices, use of improper foot wear and lack of knowledge regarding foot care

contributes towards increase in prevalence of foot complications in India7.

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

untreated they end in lower extremity amputation.

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.

Topical treatment is an important aspect of diabetic foot ulcers although

secondary to surgical and systemic care. No hard evidence exists to place any one

approach above another. Collagenase (Enzymatic debriding agent) and metronidazole

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

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.

3
 REVIEW OF LITERATURE

The History of Diabetes

Earliest known record of diabetes mentioned on 3rd Dynasty (1552BC)

Egyptian papyrus by physician Hesy-Ra; mentions polyurea (frequent urination) as a

symptom.

Diabetes described by Arateus in 1st Century A.D. as the melting down of

flesh and limbs into urine.

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.

Up to 11th Century diabetes commonly diagnosed by ‘water tasters,’ who

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

sweetness), ‘mellitus’, is added to the term diabetes as a result.

Table-1
Important Landmark in the History of Diabetes 17th, 18th and 19th Centuries

Date Researcher Observation

17th Century Thomas Willis Diabetic urine contains sugar
18th century Mathew Dobson Diabetic serum contains sugar
1797 John Rolo Coined the term “Mellitus”
1810-20 William Prout Diabetic Coma
1815 Michel Chevreul Excess sugar in DM is glucose
1857 Wilhelm Petters Acetone found in diabetic urine
1869 Paul Langerhan’s Pancreatic islets identified
1874 Adlof Kussmaul Acidotic breathing in diabetic coma
1889 Minkowski & Von Mering Pancreatectomy causes diabetes in
dogs

4
 Table-2
Important Landmark in the History of Diabetes 20th Century

Date Researcher Observation

Hypothetical glucose lowering
1907 Jean de Meyer
hormone named Insulin
Banting, Best, Collip
1922 Isolation & first clinical use of insulin
Macleod
1923 Jr. Murlin Discovered and named glucagons
1955 F. Sanger Sequencing of insulin
1971 Roth et al Discovered insulin receptor
1977 Ulrich Insulin gene cloned

In the year 1998 United Kingdom Prospective Diabetes Study (UKPDS) is

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.

The onset of diabetic foot lesions is due to a combination of peripheral

neuropathy and vasculopathy. This causes decreased sensation in the foot with

intrinsic changes in the foot architecture and decreased tissue perfusion respectively.

Super-added infections results in spreading fascitis, osteomyelitis and gangrene.

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.

Topical treatment of wounds in an important aspect of wound care, although

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,

antibiosis, and debridement. Traditional agents, including hydrogen peroxide,

Dakin’s solution, and povidone-iodine, are more tissue toxic than their common usage

would indicate10.

The Collagenase secreted from clostridium histolyticum is a metalloproteinase

enzyme. It is capable of cleaving native collagen types, I, II, III and IV, this is useful

in diabetic foot ulcers where lot of debridement is needed11.

Metronidazole may be effective in the management of anaerobic skin infection12.

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

provides flexibility and resilience.

The foot and ankle contain13:

• 26 bones (one-quarter of the bones in the human body);

• 33 joints;

• More than 100 muscles, tendons, and ligaments.

• A network of blood vessels, nerves, skin and soft tissue.

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

development of problems elsewhere in the body.

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

sebaceous glands but sweat glands are numerous

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

and nerve endings. Tactile sensation is exceptionally good in the sole.

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

part is known as plantar aponeurosis.

Parts of the Foot:

Structurally, the foot has three main parts:

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

tendons play an important role in supporting the arches.

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.

First layer Second Layer

Third layer
Fourth layer
Figure -1: Muscles of the foot

10
 Figure -2: Arteries of the sole of the foot14,15,16

Nerves of the Sole of the Foot

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

between the big and second toes.

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

posterior tibial venae comitantes.

Medial Plantar Nerve: The medial plantar nerve is a terminal branch of the tibial

nerve. It gives,

1. Muscular branches to the abductor hallucis, flexor digitorum brevis, flexor

hallucis brevis, and the first lumbrical muscle.

2. Cutaneous branches: Plantar digital nerves run to the sides of the medial three

and one-half toes.

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;

cutaneous branches to the skin of the lateral part of the sole.

2. From the superficial terminal branch to the flexor digiti minimi and the

interosseous muscles of the fourth intermetatarsal space.

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.

Artery of the dorsum of the foot:

Dorsalis Pedis Artery: The dorsalis pedis artery begins in front of the ankle

joint as a continuation of the anterior tibial artery. It terminates by passing downward

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.

Lateral tarsal artery. 2. Arcuate artery. 3. First dorsal metatarsal artery.

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.

The lateral branch supplies the extensor digitorum brevis muscle.

Spaces of the Foot:

Infections of the foot can be approached and drained effectively. Grodinsky

has emphasized the clinical importance of the 4 median fascial spaces on the plantar

aspect of the foot and the 2 dorsal spaces.

Four median Plantar Spaces:

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

conjoined long flexor tendons and quadratus plantae.

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

one of the four spaces.

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

long flexor tendons.

Propulsive action of the foot17

Standing immobile: The body weight is distributed via the heel behind and the heads

of the metatarsal bones in the front.

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

joint, using the foot as a lever.

2. By the toes being strongly flexed by the long and short flexors of the foot,

providing the final thrust forward.

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

There are 4 main causes for development of foot lesion in a diabetic

1. Peripheral Neuropathy.

2. Peripheral Vascular disease (PVD).

3. Charcot foot.

4. Infection.

Diabetes mellitus apart from other pathologies primarily affects the vessels &

nerves causing vasculopathy and neuropathy.

1) Neuropathy18

The commonest Diabetic polyneuropathy is distal symmetrical neuropathy, the

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

well-established correlates of diabetic neuropathy include increasing age,

hypertension, and cardiovascular risk factors20,21,22. Vascular and metabolic factors

are both implicated in the pathogenesis of diabetic neuropathy.

Proposed Hypothesis for the Pathogenesis of Diabetic Peripheral Nerve Damage

Chronic Hyperglycemia

Large prospective studies have conclusively demonstrated that chronic

hyperglycemia is implicated in the pathogenesis of diabetic neuropathy as per the

report of The EURODIAB Prospective Study23. The poor glycemic control is related

to the increased prevalence of neuropathy in diabetic patients and that improved

glycemic control may prevent / reverse distal symmetrical neuropathy24,25.

Protein Kinase C. Activation

Diabetes results in hyperactivity of vascular protein kinase C (PKC), in

particular for the Beta-isoform26. Increased synthesis of diacylglycerol (DAG) from

glucose activates PKC. PKC activation is associated with abnormalities in vascular

function seen in preclinical models of diabetes.

Oxidative Stress

Hyperglycemia leads to an increase in free radical generation as a result of

several metabolic derangements, including non-enzymatic glycation and polyol

17
pathway hyperactivity. Oxidative stress may impair nerve function by a direct toxic

effect or by reducing nitric oxide and hence nerve blood flow.

Increased Polyol Pathway Flux:

Polyol Pathway

AldoseRedutase
D Glucose + NADPH + H Sorbitl +NADP

Sorbitol Dehydrogenase
Sorbitol + NADP D- fructose + NADH + H

The hyperglycemia led sorbitol accumulation in the peripheral nerve due to

increased conversion from glucose, via the enzyme aldose reductase. This is

supported by the demonstration of elevated sorbitol levels in diabetic nerves. Elevated

sorbitol levels are associated with depletion of myoinositol, which is important in

phosphoinositide metabolism, and reduction in Na+-K+-ATPase, which plays an

important role in intra and extracellular sodium balance and hence nerve membrane

potential27,28.

Nonenzymatic Glycation

Glucose is highly reactive, and free amino groups on proteins may be

nonenzymatically glycated. From this reversible step there follows a series of

reactions that are progressively irreversible.

Neurotrophic Factors

NGF treatment corrects some aspects of sensory neuropathy related to small-

fiber dysfunction in diabetic rats. Neurotrophic factors in human diabetic neuropathy

18
and the potential use of trophic intervention in diabetic neuropathy remain

undetermined.

Vascular Factors

The importance of microvascular disease in the development of foot ulceration

and in wound healing has long been debated. The view that microvessel disease may

be central to the pathogenesis of diabetic neuropathy is not new29. Several workers

have reported basal membrane thickening of endoneurial capillaries, degeneration of

pericytes, hypoplasia and swelling of endothelial cells, and sometimes vessel closure.

The degree of microvascular disease has been correlated with the severity of

neuropathy30.

Macrovascular disease appears to exacerbate neuropathy, and surgical

restoration of perfusion improves nerve conduction velocity31.

Causative factors for neuropathic Ulcer32

I. Extrinsic Factors II. Intrinsic Factors

Ill-fitting foot wear Limited joint mobility

Bare foot walking Bony prominences

Falls/accidents Foot deformities

Objects inside shoes Neuro arthropathy

Thermal trauma Plantar callus

Injury by sharp objects Scar tissue, fissure

19
2) Diabetic Angiopathy33,34

Disease of blood vessels is a major cause of complications in diabetics. The

vascular lesions are:

I. Macro vascular disease.

a) Atherosclerosis b) Medial calcification c) Diffuse initimal fibrosis.

II. Micro vascular disease.

a) Arteriosclerosis b) Specific Diabetic microangiopathy c) Diabetic Fibrosis

Macro vascular disease:

1. Deranged metabolism of glucose producing sorbitol through polyol pathway.

2. Hyperglycemia, Keen et al conclude that not only are borderline diabetics

more liable to arterial disease than normals but also that this increased risk can

probably be significantly reduced by treatment.

3. The risk of atherosclerosis in a diabetic is seen particularly in patients with

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.

4. Fibrinocoagulopathy: Large deposits of fibrin in the vascular lesions of

maturity onset diabetes and atherosclerosis have been demonstrated by earlier

workers.

5. Atherosclerosis: Degenerative Vascular disease affecting principally the tunica

intima of arteries and composed of fibrosis and or fatty change. Ulceration and

20
 secondary thrombosis commonly occur. This is found more frequently and

with greatest severity in diabetics.

Occlusion of the femoral artery is the most common lesion and

characteristically starts at the region of hiatus in the adductor magnus. Atheroma of

the profunda femoris artery, the major source of blood for thigh muscles, causes

stenosis at its origin. Diffuse disease of any combination of stenosis or occlusion of

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

arteries carries serious threat to the survival of the limbs.

Calcification of the arteries: Calcification of the tunica media of muscular

arteries is a common feature of long-standing diabetes which is the commonest cause

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

relatively unaffected despite major deposits of calcium in the media. Hyperglycemia

has a direct role in the development of this condition.

Microangiopathy:

Parving put forward the haemodynamic hypothesis to explain the development

of microangiopathy in diabetes.

21
 Haemodynamic hypothesis

Increased microvascular blood flow

Endothelial injury response

Microvascular sclerosis

Limitation of maximum hyperaemia

+/-

Impaired autoregulation

The clinical association between retinopathy, neuropathy and nephropathy

suggest a common factor between them, the disease of the small blood vessels.

The typical changes in diabetes are:

I. Thickening of capillary basement membranes

II. Proliferative changes in arterioles arteries:

Cause of micro Angiopathy:

These morbid anatomical changes are the end result of metabolic disturbances

which continued for long period.

The two major initial changes are:

a. Venular dilatation.

b. Increased capillary permeability.

22
The other factors which synergize with this are:

Platelets:

a. Increased platelet adhesiveness.

b. Increase in platelet aggregation.

c. Reduced survival of both platelets and fibrinogen in diabetics.

Red cells:

The effect of increased levels of glycosylated hemoglobin (HbA1C) and 2,3

diaphosphoglycerate (2, 3, D.P.G) causes profound hypoxia. There is also increased

rigidity of red cells.

Plasma:

In patients with severe microangiopathy, there are increased levels of acute

phase reactants and a decrease in albumin level.

Abnormalities of Metabolism:

Alterations in the activity of enzymes which attach carbohydrate to basement

membrane cellular function defects e.g., changes in leukocyte function, alterations in

the activity of lysozomal enzymes.

Risk factors for diabetic micro vascular disease:

• Genetic predisposition of family history.

• Old age, Duration of diabetes-longer duration, Smoking, Hypertension,

23
Hypercholesterolemia, Hypertriglyceridemia, Hyperglycemia.

• Miscellaneous causes like:

o Autoimmune diseases, drugs like Beta blockers.

The two central processes that determine the occurrence and distribution of

gangrene in the affected limb are:

1. Pre-existing arterial insufficiency.

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

Degree of PVD Diabetes Non Diabetes

More common younger Less common older patient

Clinical
patient more rapid less rapid
Male female 2:1 30:1
Occlusion Multi segmental involved Single segment
Vessels adjacent to
Involved Not involved
occlusion
Tibialis, peroneals Small
Vessels involved Aortic/Iliac Femoral
vessels/Arteriole
Patchy areas of Foot and
Gangrene Extensive
toes
In hospital mortality with
3% Significantly less
amputation

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

Charcot’s polyneuropathy (CN) is a progressive condition affecting the bones

and joints of the foot and is characterized by joint dislocation, subluxation, and

pathological fractures of the foot of neuropathic patients, often resulting in a

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

convexity, which results from displacement of the talonavicular joint or from

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

subtalar joints are involved, instability of the hindfoot can result.

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

hospitalization and amputation.

Foot infections usually occur at the site of trauma / ulceration. Thus patients

with peripheral neuropathy / foot deformity are at increased risk for ulceration.

Infection of the plantar space accounts majority of diabetic foot infections

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

established ascending cellulitis, lymphangitis and lymphadenopathy also develop.

Because of the anatomical tight compartment in foot, infection ascends along the

25
tendon sheaths into posterior compartment of the leg, flexorcanal, subsoleal

compartment.

Clinical classification of a diabetic foot infection

Clinical manifestation of infection Infection severity PEDISa Grade

Wound lacking purulence or any

Uninfected 1
manifestations of inflammation

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.

Infection (as above) in a patient who is

systemically well and metabolically
stable which has ≥ 1 of the following
characteristics; cellulites extending >
Moderate 3
2cm, lymphangitic streaking, spread
beneath the superficial fascia, deep tissue
abscess, gangrene and involvement of
muscle tendon joint or bone

Infection in a patient with systemic

toxicity or metabolic instability (e.g.
Fever, chills, tachycardia, hypotesion,
Severe 4
confusion, vomiting, leucocytosis,
acidosis, severe hypoglycemia,
azotaemia)

PEDIS - Perfusion, extent / size, depth / tissue loss, infection, sensation a →

international consensus on the diabetic foot.

26
MICROBIOLOGY38

Cultures of open foot ulcers cannot be used to establish the presence of

infection. Foot ulcers whether infected or not, will contain multiple comensal or

colonizing bacteria, some of which have the potential to become invasive pathogens.

Reliable specimens are those obtained aseptically at surgery, by aspiration of pus, or

by biopsy of the infected tissue across intact skin.

A simple practical classification of foot infections

1. Non-limb threatening.

2. Limb threatening.

In non-limb-threatening infections, particularly those occurring in patients

who have not pevious1y received antimicrobial therapy, Staphylococcus aureus and

Streptococci, particularly group B streptococci, are predominant pathogens. S.aureus

has been isolated from >50% of these patients, and in more than 30% S.aureus is the

only bacterium isolated39

Limb-threatening foot infections are generally polymicrobial. Cultures from

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.

Clinically uninfected ulcers should not be cultured. When infection is present, a

microbiologic diagnosis will usually facilitate, subsequent therapy, particularly in the

setting of limb-threatening infection. After cleansing the skin and debriding any

overlying eschar, specimens for culture should be obtained before initiating therapy

by curettage of the necrotic base of the ulcer44.

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

and specific , especially for deep (eg-bone) infections45,46,47.

Antibiotic Therapy:

Virtually all diabetic foot infections require antimicrobial therapy; but it is

important to remember that while this is a necessary step, it is rarely sufficient48.

Antimicrobial treatment of foot infections in patients with diabetes is begun

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

the infection. Lipsky et al demonstrated that oral therapy with clindamycin or

cephalexin for 2 weeks in patients with previously untreated nonlimb-threatening foot

infection resulted in satisfactory clinical outcome in 96% and 86% respectively.

Selected antibiotic regimens for initial empiric therapy of foot infections in

patients with diabetes mellitus

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

Empiric antimicrobial treatment should be reassessed between days 3 and 5 of

treatment in the light of culture results and clinical response. When therapy is

unnecessarily broad spectrum (effective therapy for the bacteria isolated could be

achieved by less broad – spectrum antimicrobials with possible cost savings,

avoidance of toxicity, or a reduction in selective pressure for emergence of

antimicrobial resistance) and patients have responded clinically. Treatment regiments

should be simplified based on culture data. If a bacterium resistant to the current

therapy has been recovered and yet the clinical response is .satisfactory, treatment

need not be expanded. Alternatively, if the isolate is resistant to treatment, the

response to therapy is unsatisfactory. The wound should be examined for necrotic

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

colonizing flora), antimicrobial therapy should be expanded to treat this isolate as

well as others.

Anaerobic metabolism:

When oxygen becomes either unavailable or insufficient the oxidative

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.

Connective tissue changes:

Diabetes considerably alters the structure and functions of proteins throughout

the body in presence of hyperglycemia, the proteins undergo non-enzymatic

glycosylation. The proteins mostly involved are haemoglobin, Serum proteins,

myelin, etc. Such molecular changes in proteins alter the function (or) physical

properties of tissues which they form.

These tissues then become rigid and inflexible, have increased tensile strength

and become resistant to enzymatic digestion by collagenases. This explains the

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.

Glycosylation of keratin also produce similar structural changes. The changes in

30
protein of skin, subcutaneous tissues aid the sole of diabetics contribute to the

development of neuropathic ulceration. Glycosylated keratin builds up in response to

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

collagen is also resistant to the normal process degradation by collagenases. This

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

base of such ulcers.

Physiology of wound healing49:

Components of wound healing:

Time Processes Cell Type
Coagulation Platelets
Hours
Inflammation Platelets
Neutrophils,
Macrophages

Migration/proliferation Macrophages,
Angiogenesis Fibroblast,
Epithelisation Lymphocytes,
Days Contraction Keratinocytes
Fibroplasia

Weeks Remodeling Fibroblasts

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

synthesis and degradation is defective.

Bio Mechanism of Ulcer Formation:

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

arteriovenus shunting of blood around the capillary bed. In addition neuropathy

destroys “C’, fibers which are responsible for nociceptive response which is the basis

for wheal and flare response of skin to a noxious stimulus.

To this compromised foot, the cumulative effect of glycation and diminished

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

pressure = Force / area must be remembered;

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.

3. Repetitive moderate stresses probably represent the most common cause of

foot ulceration among neuropathic patients.

32
CLINICAL PRESENTATION:

Signs and Symptoms:

a). Neuropathy18:

The signs and symptoms of neuropathy in the diabetic foot and leg include

- Paresthesia, hyperaesthesia, hypoaesthesia, radicular pain, loss of vibratory and

position sense, anhydrosis, and heavy callus formation over pressure points and

trophic ulcers.

Radiographic changes: demineralisation, osteolysis, Charcots joint.

Autonomic Neuropathy Syndromes:

Cardiovascular:

Resting sinus tachycardia without sinus arrhythmia, exercise intolerance,

painless myocardial infraction, and orthostatic hypotension.

Gastrointestinal:

Esophageal dysfunction, Delayed gastric emptying, Diabetic Diarrhoea,

Constipation, Fecal incontinence.

Genitourinary:

Esophageal impotence, retrograde ejaculation with infertility, bladder

dysfunction.

33
Sudomotor:

Facial sweating, heat intolerance, gustatory sweating, distal anhydrosis.

b). Vascular Insufficiency33:

Intermittent claudication, cold feet, nocturnal pain, rest pain, absent pulses,

blanching on elevation, dependent rubor, atrophy of subcutaneous fatty tissues, shiny

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.

• Pulselessness below the block.

• Paralysis

• Poikilothermia.

VARIOUS PRESENTATIONS OF DIABETIC FOOT50:

Common foot problems that diabetic patients encounter are

Nail Problems:

Onychauxis: This is thickening of the nail without deformity, and follows an insult to

the nail bed. Without regular reduction onychogryphosis will develop.

34
Onychogryphosis (ram’s horn nail)

This is thickening of the nail with deformity. The cause is an insult to the nail

bed. Treatment: can be palliative or surgical. Palliative treatment consists of regular

reduction of excessive thickness of the nail plate at 3-monthly treatment intervals.

Onychocryptosis (ingrowing toe nail): This should be removed.

Nail infections:

Paronychia: Inflammation of the nail fold containing Collections of pus which

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.

Patient presents from a symptomatic fungal infection of nails or low grade

paronychia. A swab is sent for microscopy and culture, and appropriate systemic

antibiotics prescribed.

Onychomycosis (fungal nail): This first cause white or yellowish discoloration of a

patch of nail, which subsequently becomes thickened and friable. Infections are

caused by moulds called dermatophytes, or by yeasts, notably Candida albicans.

Onychomycosis can cause chronic pain, Physical disability and secondary bacterial

infection.

Active treatment involves topical or systemic agents. Palliative care involves

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

considered when the infection is causing unpleasant symptoms or distress. Topical

35
Amorolfine nail lacquer and strong iodine BP. Treatment should continue until a new

nail has formed, which may take up to 12 months.

Lesions under the nail:

These can be due to: haematoma, necrosis, melanoma, exostosis.

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,

where an astringent or antiperspirant such as aluminium chloride is helpful.

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

treatment. The recommended treatment for ablation of painful or spreading verrucae

in people with diabetes is cryotherapy with liquid nitrogen. Sometimes surgical

treatment with excision of the wart is required.

Bullae (blisters): These are superficial accumulations of clear fluid within or under

the epidermis which develop following trauma to the skin. Common causes include

unsuitable shoes, failure to wear socks and walking in wet footwear.

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

ascertained and addressed.

36
Bullosis diabeticorum: This is a rare condition where diabetic patients present with

intraepidermal blisters which are not associated with trauma and heal without

scarring. Treatment of bullosis diabeticorurn is as for bullae. This can spread to

draining lymph nodes. Suspicious lesions should be biopsied. Treatment is surgical

excision.

Chilblains (pemiosis): These are localized inflammatory lesions, provoked by cold

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

benzoin BP may be used.

Malignancy: Although skin malignancy is rare in the foot, squamous cell carcinoma,

malignant melanoma and rarely basal cell carcinoma may present in the foot.

Hyperhydrosis: is excessive sweating of the Feet, and may be a particular problem in

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

be due to hyperthyroidism or anxiety.

Hammer toe: A hammer toe is a flexible or rigid deformity characterized by buckling

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

deformity. There is fixed flexion deformity at the interphalangeal Joint, associated

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.

Hallux valgus: Hallux valgus is a deformity of the first metatarsophalangeal joint

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

down under pressure from a tight shoe.

Limited joint mobility (including hallux rigidus)

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

mobility of the first metatarsophalangeal joint results in loss of dorsiflexion and

excessive forces on the plantar surface of the first toe causing callus formation and

ulceration. It is commonly seen in barefooted and sandal wearing populations.

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

of black appearances is discussed under necrosis.

38
Necrosis

Areas of necrosis and gangrene can be identified by the presence of black or

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

with edema involving dorsum of the foot with shiny skin.

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

indicates that there is pus deep in the foot.

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

dorsum of the proximal interphalangeal joint of a clawed toe. Hyperkeratosis or

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

1. Blood investigations : Hb, TLC, DLC, ESR

2. Renal profile: Blood urea, serum creatinine

3. Urine – Albumin, Sugar, ketone bodies & microscopy

II. Special 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

nephropathy no glycosuria will be present with Serum level of 200mg% glucose.

b) Ketonuria: If glucose is present in urine ketone bodies should also be determined

can be detected by Rothera’s acetone test. It is the first sign to be recognised in

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

l2Omg% is indicative of diabetes.

d) Post prandial blood sugar: After overnight fast, the patient is given breakfast of

100gms of carbohydrates or 100gms of glucose load. Then venous blood is checked

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.

Metabolic profile and Glycohemoglobin: Assessment of serum glucose,

glycohemoglobin.

Culture and sensitivity test:

Pus from infected area is cultured for micro organisms and their sensitivity to

various antibiotics is tested so that appropriate antibiotic can be administered to

control the infection.

Radiology of the foot:

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

osteomyelitis are destruction of bone commonly seen at metatarsophalangeal joint or

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,

indicates the presence of a serious anaerobic infection.

Noninvasive vascular laboratory study:

Pulse-volume recording (PVR) or plethysmography: uses pneumatic cuffs

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

overall haemodynamic response to medical or surgical treatment. The ankle-brachial

blood pressure index is potentially unreliable because of arterial calcification.

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

aneurysms, particularly of the aorta or popliteal segments. Unfortunately, Doppler

techniques are not accurate in assessing the haemodynamic consequences of

atherosclerotic peripheral arterial disease involving the extremities. Use of this

technique probably is best left to the discretion of the vascular specialist.

Plain x-ray studies of the diabetic foot may demonstrate demineralization and

Charcot joint and occasionally may suggest the presence of osteomyelitis.

42
 CT scan and MRI: Although an experienced clinician usually can diagnose a

plantar abscess by physical examination alone, CT scan or MRI is indicated if a

plantar abscess is suspected but not clears on physical examination.

Contrast angiography is indicated if haemodynamically significant vascular

disease precludes healing of the ulcer or is causing intractable pain at rest.

Angiography is best ordered by the vascular or endovascular surgeon to ensure that

the study performed actually visualizes the entire segment of the arterial tree to

facilitate the potential vascular procedure.

Magnetic resonance angiography (MRA) is an alternative for patients with

renal compromise and patients who arc allergic to contrast materials.

Other Tests:

A hand-held Doppler scanner may be used to assess arterial signals, to localize

arteries to facilitate palpation of pulses, or to determine the loss of Doppler signal as a

proximal blood pressure cuff is inflated. The latter pressure divided by the upper

extremity systolic pressure is called the ankle-brachial index (ABI) and is an

indication of severity of arterial compromise. Normal ABI averages 1.0. An ABI less

than 0.9 suggest atherosclerotic disease, with a sensitivity of approximately 95%. In

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

heavily calcified, a finding common in diabetic persons.

43
TREATMENT

Classification and Staging52,53,54

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:

1. The Neuropathic foot.

2. The neuroischaernic foot.

Neuropathy is nearly always found in association with ischaemia, so the

ischaemic foot is best called the neuroischaemic foot. In rare cases the foot may

clinically be ischemic without signs of neuropathy, but in practice, the diabetic

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

by differentiating between the neuropathic and the neuroischaemic foot as their

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

if a neuroischaemic foot is wrongly classified as neuropathic, with resulting failure to

do further tests to confirm ischemia and adapt the care plan accordingly, this may lead

to preventable catastrophe and loss of the foot.

Neuropathic foot

The neuropathic foot is a warm, well-perfused foot with bounding pulses and

distended dorsal veins due to arteriovenous shunting. Sweating is diminished so skin

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

is also prone to bone and joint problems which we refer to as Charcot’s

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

be a deceptively healthy pink or red caused by dilatation of capillaries in an attempt to

improve perfusion. The neuroischaemic foot may be complicated by swelling, often

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

develops necrosis in the presence of infection or if tissue perfusion is critically

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

requires good blood flow.

After classification of the diabetic foot, it is necessary to make the appropriate

staging in its natural history. The natural history of the diabetic foot can be divided

into six stages:

45
Stage I : Normal foot.

Stage 2 : High-risk foot.

Stage 3 : Ulcerated foot.

Stage 4 : Infected foot.

Stage 5 : Necrotic foot.

Stage 6 : Unsalvageable 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

demanding urgent and aggressive management. However, each stage demands

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 foot is characterized by no symptoms, including no pain and examination is

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

need addressing to reduce susceptibility to ulceration. Patients without active foot

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:

• Severe chronic ischaemia

• Acute ischaemia.

• There are also specific complications of neuropathy:

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

in the neuropathic foot and on the margin in the neuroischaemic foot.

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

which appear shriveled.

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

diabetic feet at as lower stage as possible.

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.

Wagner Classification of Diabetic Foot lesions:

Grade 0: At risk foot no obvious ulcer, thick callus prominent metatarsal heads, claw

toes or any bony abnormality.

Grade I : Superficial ulcer not clinically infected.

Grade II: Deeper ulcer often infected but no bone involvement.

Grade III: Deep ulcer, abscess formation, bony involvement.

Grade IV: Localized Gangrene.

Grade V: Gangrene of the whole foot.

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

control of the foot to prevent further progression.

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

needs the expertise of a multidisciplinary team including the following:

Podiatrist, Physician, Nurse Orthotist, Radiologist, Surgeon.

48
Strategies for saving the diabetic foot:

• Correction of vascular risk factors.

• Improve the circulation.

• Regular foot Inspections.

• Treatment of foot ulcers.

• Treatment among medical discipline

• Prescribing special shoes.

• Patient Education.

Improving Circulation: A regular walking program will improve walking distance in

80% of the patients. Recently a drug Cilostozole is used. The ultimate treatment for

claudication is vascular surgery is to by-pass narrowed vessels or endarterectomy.

Transcutaneous angioplasty is also useful. The surgical approach to aorto-iliac

occlusive disease is aorto-ilac endarterectomy, bypass grafting and extra-anatomic

reconstructions.

In the patients with simple occlusion of the superficial femoral artery,

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,

a bypass to the distal popliteal artery is done.

Patient Education: The patient should be taught about good diabetic control, foot-

care, dangers of smoking etc, maintenance of records of investigations.By this the

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

for patient wound. These are:

• Surgical /sharp.

• Mechanical.

• Autolytic.

• Enzymatic and biologic.

Surgical/sharp debridement:

Surgical/sharp debridernent is a selective method-of debridement in which the

clinician uses instruments to remove the necrotic tissue from the wound. Although

lasers have been used, most clinicians employ scissors, scalpels, and forceps to

accomplish surgical/sharp debridernent. Knowledge of underlying anatomy and

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

or necrotizing fasciitis), surgical debridement quickest and best way to remove

necrotic tissue this type of debridement should be avoided or used with extreme

caution in patients with clotting disorders or those taking anticoagulants, as

uncontrolled bleeding may occur.

50
 Surgical/sharp debridement is usually painful; therefore, the patient should be

premedicated with systemic analgesics and/or local anesthetics. Likewise, manage

post procedure pain accordingly. If large amounts of tissue are to be removed,

debridement in the operating room under anesthesia may be preferable.

Mechanical debridement:

Mechanical debridement uses force to remove necrotic tissue. This may

include the use of irrigation fluids delivered by pulsed lavage, the agitation of water

during whirlpool therapy, or the removal of tissue with wet-to-dry dressings.

Mechanical debridement is considered a nonselective method of debridement because

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

Quality) presents data indicating that antiseptic solutions, such a povidone-iodine,

sodium hypochlorite (Dakin’s solution), hydrogen peroxide, and acetic acid, can

damage cells needed for healing, such as fibroblasts.

Autolytic debridement

Autolytic debridement can be accomplished by placing occlusive or

semiocclusive moisture-retentive dressings (eg, hydrocolloids or transparent films)

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

should be irrigated with normal saline to remove liquefied debris. Autolytic

debridement with hydrogels may also soften hard, dry eschar for easier mechanical or

surgical debridement. This type of debridement is slow, requiring multiple dressing

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

dressing should be monitored closely; it may be tan-colored. However, purulent

drainage, unusual odor, inflammation, or increased pain is signs of infection that

require immediate treatment. With signs of infection, autolytic debridement should be

discontinued in favor of a quicker method of debridement (usually surgical) and

treatment of the infection. Failure to do so may result in serious wound infections, and

possibly sepsis.

Enzymatic Debridement

Enzymatic debridement uses topical enzymes to remove necrotic tissue by

digesting and dissolving the devitalized tissue in the wound bed. Some enzymes are

selective and recognize only devitalized tissue57 other enzymes are nonselective and

therefore do not distinguish between viable and nonviable tissue.

Two enzymatic debriding agents are currently available, one preparation

contains papain and urea in a cream base, the other is composed of Collagenase in a

petroleum base the papain-urea combination also comes in a formulation with

chlorophyllin-copper complex.

52
 Papain is a proteolytic enzyme derived from the fruit of Carica papaya. It is a

nonspecific cystiene protease, capable of breaking down a variety of necrotic tissue

substrates. Urea’s role is to facilitate papain’s proteolytic action by altering the

structure of proteins58. The papain-urea combination has a pH range of activity of

3.0-12.0. Hydrogen peroxide inactivates papain; therefore, it should not be used to

cleanse the wound if papain is being used for debridernent. Collagenase, derived from

Clostridiurn histolyticum, has optimal enzymatic activity in a pH range of 6 to 8.

This corresponds to the pH range typically found in human wounds59,60. Some

detergents and heavy metal ions (eg, silver and mercury) inactivate this product;

therefore, avoid using drugs such as silver sulfadiazine in conjunction with

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

saline are compatible with collagenase.

Collagenase ointment is a sterile enzymatic debriding ointment containing

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

collagenase ointment is an effective enzymatic debriding agent61.

Some patients may experience a slight transient erythema in the surrounding

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.

Papain-urea and collagenase each have advantages and disadvantages.In an

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.

Collagenase and papain-urea had comparable healing rate in a clinical trial63

Papain-urea produces more exudate from the enzymatic digestion which may irritate

the surrounding skin and require more frequent dressing changes64.

Papain-urea may be most appropriate in situations where large amounts of

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

(rhPDGFBB, REGRANEX) is not being used.

Collagenase enzymatic debriding agents may digest necrotic tissue from the

bottom up; papain-urea preparations, from the top-down. Collagenase is a water

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

Debridement was followed by gradual ganu1ation and epithelialization, which

generally proceeded at a faster rate than was expected in chronic dermal lesions of the

type under treatment67.

In a study by Altman MI, Goldstein L, Horowitz S. The study mention’s that

the collagenase is a well known and established enzyme preparation for wound

debridement and helps in healing of the ulcers68.

Subsequent studies have elucidated the cellular mechanisms involved in this

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

removed, debridernent cannot take place, granulation is slowed, and no supportive

base is available for epithelialization. Collagenase effectively digests undenatured

collagen fibers62, allowing the necrotic plug to be removed. In cell cultures,

Collagenase increased human keratinocyte migration 3-fold and single cell motility up

to 10 fold65. Because of its specificity and selectivity, Collagenase may also be

preferable for maintenance debridement. Falanga57 suggests that Collagenase may

serve as a possible pluripotential wound bed preparation agent. There is evidence that

collagenase selectively reduces necrotic tissue and decreases bacterial burden70,

increases chemotactic attraction of human fibroblasts33, can stimulate granulation

tissue67,71,72 enhances the proliferation and migration of keratinocytes65 and

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-

thickness burn wounds73,74,.

Surgical / sharp, mechanical, autolytic, and enzymatic are the 4 methods of

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

may impede wound healing.

Metronidazole75

It is a nitroimidazole introduced in 1959 for trichomoniasis, and later found to

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

in Bact Fragilis, Fusobacterium, Clostridium perfingens, anaerobic Streptococci and

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.

The mechanism of action of metronidazole is not well understood. After

entering the microorganism by diffusion it is reduced to intermediate compounds

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

mediated immunity to induce mutagenesis and to cause radio sensitization.

The topical metronidazole gel 1% is used in trophic ulcer, malodorous

fungating tumors, Diabetic ulcers, pressure sores etc. It promotes epithelization,

56
accelerates healing, eliminates anaerobes-breaks microbial synergy and reduces

malodor from ulcer site.

Adverse effects:

Anorexia, Nausea, metallic taste and abdominal cramps are most common.

Less frequent side effects are-headache, glossitis, dryness of mouth, dizziness, rashes

and transient neutropenia.

Contraindications - neurological disease, blood dyscrasias, first trimester of

pregnancy though no teratogenic effect has yet been demonstrated, its mutagenic

potential warrants caution

Povidone-Iodine76,77

Iodine it is a rapidly acting, broad spectrum (bacteria, fungi, viruses)

mirobicidal agent; has been in use of for more than a century. Acts by iodinating and

oxidizing microbial protoplasm. A 1: 20,000 solution kills most vegetative forms

within 1 min. Organic matter retards its germicidal action.

Tincture iodine (2% in alcohol) stings on abrasions. It is used in cuts, for

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

sensitive to iodine rashes and systemic manifestations occur in them.

lodophores: These are soluble complexes of iodine with large, molecular organic

compounds that serve as carriers release free iodine slowly. The most popular is

povidone (Polyvinylpyrrolidine) iodine, is nonirritating, nontoxic, non-staining and

57
exerts prolonged germicidal action. Treated areas can be bandaged or occuluded

without risk of blistering. Used on furunculosis, burns, otitis, external ulcers.

Povidone-Iodine: Produced mixed results. Bacterial counts were either decreased or

unchanged. Healing increased in 4 human studies, decreased in 4 animal studies, and

had no-significant effect in 6 studies. Histologic evidence of tissue toxicity was noted

with a 10% povidone-iodine solution. Iodine sensitivity occurs in a small portion of

the population (0.73%)76,77.

Cadexomer Iodine: consistently demonstrates reduction in bacterial counts and

acceleration in wound healing in human studies. Cadexomer iodine, available as an

ointment or dressing, consists of hydrophilic beads of cadexomer starch, which slowly

release iodine into the wound.

Hydrogen Peroxide: Had little effect on wound healing or bacterial control, but its

effervescent effect may be useful in cleansing or debriding wounds. Hydrogen

peroxide is usually diluted to one-half strength, and, then raised off with saline.

Acetic acid: usually decreased a variety of bacteria (including Pseudomonas

aeruginosa, Staphylococcus aureus and Gram-negative rods), yet was not cytotoxic in

the invivo studies reviewed.

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

Partial thickness (Thiersch) Graft: partial thickness or split skin graft

contain epidermis and upper capillary dermis and are re-vascularized by the in-growth

of capillary buds from the underlying tissue.

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

are not disrupted.

Muscle of myo-cutaneous flaps - muscles including over lying skin may be

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

residual foot. Rehabilitation plays an important role after amputation.

59
Transmetatarsal Amputation:

Provided that the plantar skin is uncompromised, the indications for Tran

metatarsal amputations are infection, gangrene of multiple toes or metatarsal heads

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

amputation at the transmetatarsal level.

Symes Amputation

If the infectious or gangreneous process excludes a transmetatarsal

amputation, then the next level considered is an ankle disarticulation or Symes

amputation. Presence of a neuropathic foot is to be a relative contraindication to

Symes Amputation.

Major Below Knee Amputation

When a distal amputation site is precluded below knee amputation is done.

Selection techniques can predict primary healing in 94 %. Contraindications to this

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

Clearly if the infectious process extends to or through the proposed level of

amputation, a more prominent site is selected in the thigh.

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.

Indication: Guillotine amputation is indicated whenever there is presence of

gross sepsis.

Advantages: In presence of sepsis, spreading infection is controlled and later

on amputation can be refashioned.

Disadvantages: As a rule re-amputation must be performed at higher level in

order that the bone end may be covered with soft parts.

There are two major aims when considering a patient for possible amputation.

1. To produce healing by removing a painful and/or infected and therefore

dangerous limb or part of a limb.

2. To restore mobility.

The achievement of the second aim begins preoperatively-when the nature of

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.

In a patient having a below knee amputation the importance of quadriceps function

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,

delaying rehabilitation is problems with the amputation wound.

The conventional conservative approach has been to await healing of the

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

extremes all amputations are performed by a single group of surgeons, immediate

fitting of prosthesis is, undertaken and a coordinated program of aggressive

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

years (from Dec2007).

Inclusion Criteria

a. Patients aged more than 20 years with diabetic foot ulcer.

b. Ulcers of Wagener’s Grade II-IV.

Exclusion Criteria

a. Clinical signs of infection, cellulites.

b. Ulcers of Wagner’s Grade V.

c. X-ray showing osteomyelitis.

d. Doppler showing gross atherosclerotic arterial changes and venous abnormalities

like varicosities.

e. Malnutrition, uncontrolled diabetes.

f. Other clinically significant medical conditions that would impair wound healing

including renal, hepatic, hematological, neurological, and immunological

diseases.

g. Patients receiving corticosteroids, immunosuppressive agents, radiation, or

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

diabetic control, control of infection by initiating appropriate antibiotic based on culture

sensitivity report, surgical debridement, correction of anemia and correction of other

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

granulation tissue appeared. Metronidazole ointment was applied along with it to

promote the growth of healthy granulation tissue.

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

agents and metronidazole ointment were applied.

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

response was evaluated weekly using a visual score.

The visual scores are as follows63

a. The score for the percentage of wound covered by slough and nonviable

(necrotic) tissue are

1. = 76-100% wound covered with nonviable tissue.

2. = 51-75% wound covered with nonviable tissue.

3. = 26-50% wound covered with nonviable tissue.

4. = 11-25% wound covered with nonviable tissue.

5. = 0-10% wound covered with nonviable tissue.

6. = No necrotic tissue

b. The score for the percentage of wound covered by granulation tissue are

1. = No granulation present

2. = < 25% of wound covered by granulation tissue

3. = 25-74% of wound covered by granulation tissue

4. = 75-100% of wound covered by granulation tissue

The reduction of wound size and area measured in cm2

The final parameters and wound characteristics of the two randomized groups

were analyzed and compared.

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

statistically similar between the two group with P >0.05.

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.

P > 0.05 Insignificant

Figure-3 : Age distribution

12

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

with P > 0.05.

Table -4

Sex distribution

Sex Test group( n=40) Control group( n=40)

distribution
No % No %

Male 25 62.5 27 67.5

Female 15 37.5 13 32.5

Total 40 100.0 40 100.0

Inference Sex distribution is statistically similar between the two groups.

χ2 = 0.22 P > 0.05 Insignificant

Figure -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

Diabetes Test group (n = 40) Control group (n =40)

mellitus
No % No %

Present 34 85.0 30 75.0

Newly detected 6 15.0 10 25.0

Inference Distribution of DM is equally likely between the two groups.

χ2 = 1.25 P > 0.05 Insignificant

Figure -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 %

≤ 5 years 14 41.1 6 20.0

5-10 years 8 23.5 14 46.7

10-20 years 9 26.5 9 30.0

> 20 years 3 8.8 1 3.3

Mean ± SD 9.77 ± 6.94 10.29 ± 5.61

Inference Distribution of DM is equally likely between the two groups.

χ2 = 4.80 P > 0.05 Insignificant

Figure-6: Duration of Diabetes Mellitus

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

Test group Control group

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

between the two groups with P > 0.05.

Table -7
Size of the ulcers

Size of the Test group ( n=40) Control group (n = 40)

ulcer (cms) No % No %
≤5 11 27.5 10 25.0
5-10 14 35.0 12 30.0
10-20 13 32.5 15 37.5
> 20 2 5 3 7.5
Mean ± SD 9.82 ± 6.80 10.32 ± 6.39
Inference Size of the ulcers is statistically similar between the two groups.

Z = 0.34 P > 0.05 Insignificant

Figure-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)

Test group Control group

70
Grade of Ulcers

Most of the patients had Grade III and IV ulcers in both test and control groups.

The grade of ulcer is statistically similar between the two groups.

Table -8

Grade of ulcers

Grade of Test group ( n=40) Control group (n = 40)

ulcers
No % No %

II 6 15.0 6 15.0

III 17 47.5 14 35.0

IV 13 27.5 14 35.0

Unstagable 4 10.0 6 15.0

χ2 = 0.73 P > 0.05 Insignificant

Figure-8: Grade of ulcers

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

the Chi-square / Fisher Exact test.

Table -9

Presence of necrotic tissue or slough

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.

Figures in brackets are percentages

Visual score63

1. = 76-100% wound covered with nonviable tissue

2. = 51-75% wound covered with nonviable tissue
3. = 26-50% wound covered with nonviable tissue
4. = 11-25% wound covered with nonviable tissue
5. = 0-100% wound covered with nonviable tissue
6. = no necrotic tissue

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

Score 1 Score 2 Score 3 Score 4 Score 5 Score 6

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

Score 1 Score 2 Score 3 Score 4 Score 5 Score 6

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

A comparative line diagram showing presence of necrotic tissue or

slough in test and control group in each week

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

Presence of granulation tissue

Study Test group (n=40) Control group (n=40)

period 1 2 3 4 1 2 3 4
22 14 4 - 23 13 4 -
Baseline
(55.0) (35.0) (10.0) (57.5) (32.5) (10.0)
11 11 17 1 23 9 8 -
1st week
(27.5) (27.5) (42.5) (2.5) (57.5) (22.5) (20.0)
1 12 17 10 9 17 9 5
2nd week
(2.5) (30.0) (42.5) (25.0) (22.5) (42.5) (22.5) (12.5)
- 3 16 21 1 22 9 8
3rd week
(7.5) (40.0) (52.5) (2.5) (55.0) (22.5) (20.0)
- 1 10 29 - 12 16 12
4th week
(2.5) (25.0) (72.5) (30.0) (40.0) (30.0)
- - 4 36 - - 24 16
5th week
(10.0) (90.0) (60.0) (40.0)
- - 2 38 - - 21 19
6th week
(5.0) (95.0) (52.5) (47.5)
- - - 40 - - 5 35
7th week
(100.0) (12.5) (87.5)
Inference Number of patients with 75-100% wound filled are significantly higher in Test group at
3rdweek 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.

Figures in brackets are percentages

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

Score 1 Score 2 Score 3 Score 4

100%
4 5
8 8
90%
12
80% 16
9 19
13
70% 9 9

60% 35 Control group

Percentage

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

Score 1 Score 2 Score 3 Score 4

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

Line diagram showing comparative study of gradual progress of

granulation tissue in test and control groups

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

per the Chi-square / Fisher Exact test.

Table – 11

Wound Surface Area

Study Test group (n=40) Control group (n=40)

period Wound Surface area (cm2)
> 10 5-10 1-5 Nil >10 5-10 1-5 Nil
Baseline 15 14 11 - 18 12 10 -
(37.5) (35.0) (27.5) (45.0) (30.0) (25.0)
1st week 15 14 11 - 19 12 9 -
(37.5) (35.0) (27.5) (47.5) (30.0) (22.5)
2nd week 15 10 14 1 21 9 10 -
(37.5) (25.0) (35.0) (2.5) (52.5) (22.5) (25.0)
3rd week 13 5 11 11 20 8 10 2
(32.5) (12.5) (27.5) (27.5) (50.0) (20.0) (25.0) (5.0)
4th week 13 6 10 11 21 6 11 2
(32.5) (15.0) (25.0) (27.5) (52.5) (15.0) (27.5) (5.0)
5th week 8 5 6 21 20 6 9 5
(20.0) (12.5) (15.0) (52.5) (50.0) (15.0) (22.5) (12.5)
6th week 3 1 3 33 19 8 4 9
(7.5) (2.5) (7.5) (82.5) (47.5) (20.0) (10.0) (22.5)
7th week 1 - - 39 14 6 5 15
(2.5) (97.5) (35.0) (15.0) (12.5) (37.5)
Inference 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 per the Chi-Square/
Fisher Exact test.

Nil – Flap, Heeled, SSG and Suturing

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%

40% 5 6 6 Test group

30% 5
20% 15 15 15
13 13
3
10% 8 1
3
1
0%
Base line 1st week 2nd week 3rd week 4th week 5th week 6th week 7th week
Followup

Wound surface area >10 5-10 1-5 Nil

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

Wound surface area

>10 5-10 1-5 Nil

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

The comparative line diagram showing shrinking of wound surface and

their final treatment like secondary suturing, SSG, flap and complete
wound healed (Nil)

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

Split Skin Graft

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

Figure-12: Showing Split Skin graft in test and control group

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 III ULCERS

GRADE IV ULCERS

79
 HEALING ULCERS WITH GOOD WOUND BED

FINAL OUTCOME

Skin graft over sole Skin graft over dorsum

Skin graft over dorsum Secondary suture

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

age, diabetic status, nutritional status, and grade of ulcer.

In addition, there was no significant difference between the two groups with

respect to baseline ulcer size and amount of nonviable tissue / slough.

The number of patients with no necrotic tissue is 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.

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

superficially to remove dead tissue only.

The number of patients with 75-100% wound filled by granulation tissue is

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.

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

Malodor from the ulcer site compared to that of control group.

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

OM, Fernandez-Obregon A, Rogers RS et al , A prospective randomized comparative

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

side surgical debridement had cumulative effect in reduction of slough, increase

granulation tissue and faster wound bed preparation.

The test group patients had increased growth of the granulation tissue along with

epithelization which is generally correlated with the development of a granulating wound

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

results than the control group.

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

wound also healed faster this is due to increased epithelization.

83
 CONCLUSION

1. The study was done to give an insight to the depth of diabetic wound

management, as it has become a foremost problem in recent era.

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

wound bed using collagenase and metronidaozole as the agents and

preparing the wound for a healthy bed of granulation tissue to promote a

rapid healing.

3. This is achieved in our study by using collagenase and metronidazole

combination which is proved to be highly effective in reduction of slough,

promoting granulation tissue formation and reepitheilization

4. Collagenase with metronidazole combination proved to be significantly

effective in wound bed preparation in comparision with conventional

treatment with local antiseptics.

84
 SUMMARY

A short introduction to diabetic foot ulcer, its incidence and complications is

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

foot ulcer is revived.

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.

Our study concluded that collagenase with metronidazole is a effective topical

applicant in faster reduction of slough, regeneration of granulation tissue and

Reepitheilization in diabetic foot ulcer.

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

between test group and control group.

1. Chi-Square Test

χ2 = ∑(Oi – Ei)2, where Oi is observed frequency and Ei is expected frequency

Ei

2. Fisher Exact Text

Class I Class 2 Total

Sample 1 a b a+b
Sample 2 c d c+d
Total a+c b+d n

(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:

Occupation: Socioeconomic class:

History

Onset of ulcer: Trauma / Spontaneous

Site of ulcer: Sole-fore foot / heel, dorsum of foot, web space

Wound size : ………………cm2

Duration of ulcer:

Progress: Progress gradual (Or) Rapidly

Pain: Yes/No

Discharge: pus / Serous / Sero-sanguinous

Treatment: Received / Not Received

Diabetic history

History of diabetes Mellitus:

Duration of diabetes Mellitus:

Type of Treatment at Admission: Oral / Inj

Treatment For Diabetes: Regular / Irregular

96
 INVESTIGATIONS

Haematological

Hb% ,PCV , T.C , D.C, E.S.R

B.T ,C.T , Blood grouping

Blood Urea , S.Creatinine

Urine examination: Albumin ,Sugar, Ketones

Doppler studies:

X-Ray of foot:

Pus for Culture Sensitivity:

Clinical features Follow-up

2nd week
Baseline

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

Sl. No - Serial Number

D.M - Diabetes Mellitus
F - Female
M - Male
S.S.G - Split skin grafting
SD - Standard deviation
SECS - Socio economic status
P - Poor
O - Oral
I - Insulin
R - Regular
IR - Irregular
T - Trauma
S - Spontaneous
NR - Not received
Re - Received
G - Gradual
Ra - Rapid
Bp - Blood Pressure
PR - Pulse rate
Hb - Hemoglobin
FBS - Fasting Blood sugar
PPBS - Post prandial Blood sugar
BU - Blood Urea
SC - Serum creatinine
N - Normal

98
 Master Chart (Control Group)
Presence of Necrotic
Urine Presence of Granulation

Duration of stay in the

Clinical History Investigations tissue or strains of Wound surface area (cm2)

Size of ulcer in cms

study period (days)

Analysis tissue
collagen

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

2 Imam Patel 60 M 261133 + 10 R O S R 8 IV G + 8.4 152 216 20 0.9 + - - N N 1 1 2 3 3 4 5 6 1 1 2 2 3 3 3 4 8 8 8 7.2 6 6 4 2 40

3 Dhariyappa 65 M 285566 + 10 IR O T NR 6 III G - 13 148 216 16 0.8 + - - N N 2 2 3 4 5 6 6 6 2 2 3 3 3 4 4 4 6 6 6 4.4 4 3 2 Healed 49

4 Dharmanna 60 M 280334 + 8 IR O S NR 4 II G - 12 184 218 20 1 + - - N N 2 3 4 5 6 6 6 6 2 2 3 3 4 4 4 4 4 4 2 1 1 Healed Healed Healed 40

5 Venkobha 40 M 301980 + 5 R O T R 14 IV G - 12 146 198 20 0.6 + - - N N 1 1 2 2 3 3 4 5 1 1 2 2 3 3 3 4 14 14 14 14 12 12 11 S.S.G 49

6 Laxmikant 35 M 281558 - - - - T R 11 III G + 13 146 222 22 0.8 + - - N N 1 1 2 2 3 4 5 6 1 1 2 2 3 3 3 4 11 11 10 10 8.8 8 7 S.S.G 49

7 Laxmibai 45 F 268786 - - - - S R 3 II G - 11 148 210 20 0.7 + - - N N 3 5 6 6 6 6 6 6 3 3 4 4 4 4 4 4 3 3 2 1 Healed Healed Healed Healed 35

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

9 Sharanabasappa 32 M 265040 + 2 - - S R 12 IV G + 13 140 196 22 1.1 + - - N N 1 1 2 1 3 4 5 6 1 1 2 2 2 3 3 3 12 12 12 11 11 10 10 10 >49

10 Shankareppa Konni 71 M 263525 + 20 R O T NR 10 US G - 9.8 148 198 20 0.9 + - - N N 1 1 2 2 3 4 5 6 1 1 2 2 3 3 3 4 10 10 10 10 10 9 8.6 8 >49

11 Ghamibai 60 F 272641 + 8 IR O S NR 16 IV G - 8.2 150 230 28 0.9 ++ - - N N 1 1 3 4 5 6 6 6 1 1 2 3 3 4 4 4 16 16 16 14 14 12 S.S.G S.S.G 42

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

13 Malappa 28 M 274628 - - - - T R 7 III G + 11 162 240 22 1.1 + - + N N 1 1 2 2 3 3 4 5 1 1 2 2 3 3 3 4 7 8 8 7 6.6 6 4 2 48

14 Shivappa 65 M 290550 + 10 IR O T S 16 IV G - 9.8 152 204 18 1.2 ++ - - N N 1 1 1 3 4 5 6 6 1 1 1 2 2 3 4 4 16 18 18 16.8 16 14 12 S.S.G 48

15 Basavaraj 59 M 253367 + 8 IR O T NR 4 II G - 9.4 148 204 26 0.9 ++ - - N N 3 4 5 6 6 6 6 6 3 3 3 4 4 4 4 4 4 3 3 2 1 suturing suturing suturing 44

16 Malappa 30 M 271456 - - - - T R 6 III G + 13 132 196 14 0.8 + - - N N 2 3 5 6 6 6 6 6 2 2 3 4 4 4 4 4 6 6 5 4 2 1 Healed Healed 45

17 Kalavva 45 F 250870 - - - - S R 18 IV G + 9.2 144 198 12 0.9 ++ - - N N 1 1 2 2 3 3 4 5 1 1 2 2 2 3 3 4 18 20 19 18 18 16.4 Flap Flap 45

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

19 Devindrappa 86 M 254804 + 25 IR O T NR 13 US G - 10 168 218 26 1.3 +++ + + N N 2 3 4 5 6 6 6 6 2 2 3 3 4 4 4 4 13 13 12 12 12 S.S.G S.S.G S.S.G 38

20 Razakmiya 68 M 283346 + 10 R I/O T R 8 IV G + 13 202 278 28 1.4 +++ - + N N 1 1 2 3 4 5 6 6 1 1 2 2 3 3 4 4 8 10 8 8 6 6 S.S.G S.S.G 45

 Master Chart (Control Group)
Presence of Necrotic
Urine Presence of Granulation

Duration of stay in the

Clinical History Investigations tissue or strains of Wound surface area (cm2)

Size of ulcer in cms

study period (days)

Analysis tissue
collagen

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
+

22 Geetha 56 F 253733 + 4 R I/O T R 28 IV G - 8.2 190 250 22 0.9 +++ - - N N 1 1 1 3 4 5 6 6 1 1 1 1 2 3 3 3 28 30 32 32 30 30 28 26 >49

23 Tippanna 62 M 249058 + 15 IR O T NR 5 IV G - 12 203 268 33 1.2 ++ - - N N 1 1 2 1 3 4 5 6 1 1 1 1 2 3 3 4 5 6 8 8 8 7 6.2 S.S.G 48

24 Subashchandra 58 M 249003 + 4 R O T R 6 III G - 12 180 240 28 1 + + - N N 2 2 1 3 4 5 6 6 2 2 2 2 3 3 3 4 6 8 9 9 9 8 8 S.S.G 47

+++
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
+

26 Naganath 63 M 253499 + 10 R I/O S NR 3 II G + 10 170 200 20 0.9 ++ - - N N 3 4 6 6 6 6 6 6 2 3 4 4 4 4 4 4 3 3 2 2 1 Healed Healed Healed 37

27 Veeranna 52 M 285558 + 8 R O S R 8 US G + 9.6 140 190 44 1.5 + - - N N 2 2 3 5 6 6 6 6 2 2 3 3 4 4 4 4 8 8 7 6 4 2 1 Healed 48

28 Mallikarjun 44 M 293219 + 7 R I/O T R 14 III G - 12 130 200 33 0.8 ++ - - N N 1 1 2 3 4 5 6 6 1 1 1 2 2 3 3 4 14 16 16 16 15 14 14 14 >49

29 Subhash 58 M 247256 + 16 R I/O T R 10 IV R + 10 210 280 46 2.2 +++ + - N N 1 1 2 3 4 5 5 6 1 1 2 2 3 3 3 4 10 14 14 14 13 12 11 S.S.G 48

30 Sabavva 72 F 265611 + 14 R I/O S R 5 III G - 8 188 210 18 0.7 ++ ++ - N N 2 2 3 5 6 6 6 6 2 2 2 3 3 4 4 4 5 5 5 4 4 3 2 1 49

31 Sunil 84 M 254466 + 20 IR I/O T R 12 IV R + 13 200 240 22 1.4 ++ - - N N 1 2 3 4 5 5 6 6 1 1 2 2 3 3 4 4 12 16 16 15 14 14 12 S.S.G 47

32 Ladla Sab 70 M 225171 + 12 R O T R 16 US G + 12 270 380 18 1.4 +++ + + N N 1 1 2 2 3 4 5 5 1 1 1 2 2 3 3 4 16 18 20 20 20 18 16 S.S.G 46

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
+

35 Sharanabasappa 46 M 301679 - - - - S NR 6 US G - 14 142 180 18 1 ++ - - N N 3 3 4 5 6 6 6 6 2 3 3 3 4 4 4 4 6 6 4 4 3 1 Healed Healed 45

36 Rukminibai 39 F 270238 - - - - S R 12 US G + 6.5 160 200 22 1.4 +++ - - N N 2 2 2 3 4 5 6 6 2 2 3 3 3 3 4 12 12 12 12 11 10 10 8 >49

37 Kalyanrao 50 M 264587 + 3 R O T R 9 IV G + 9.4 174 230 32 2 +++ + - N N 1 1 2 2 4 5 5 5 1 1 1 2 2 3 3 3 9 10 10 10 10 9 8 8 >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
+

39 Neelamma 55 F 290380 - 9 IR I/O T NR 6 II G + 11 136 180 14 0.8 + - - N N 2 2 3 4 5 6 6 6 2 2 3 3 3 4 4 4 6 6 6 5 4 2 Healed Healed 45

+++
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
+