a clinical study on management of postoperative pain …

A CLINICAL STUDY ON MANAGEMENT OF POSTOPERATIVE PAIN AND QUALITY

OF LIFE OF OSTEOARTHRITIS PATIENTS AFTER TOTAL KNEE ARTHROPLASTY

A Dissertation submitted to

THE TAMIL NADU Dr. M.G.R. MEDICAL UNIVERSITY

Chennai-600032

In partial fulfilment of the requirements for the award of degree of

MASTER OF PHARMACY

IN

PHARMACY PRACTICE

Submitted by

Ms. H. KALAIVANI

REG. NO: 261540452

Under the Guidance of

Dr. T. TAMILSELVAN, M. Pharm., Ph.D.,

Professor and Head

DEPARTMENT OF PHARMACY PRACTICE,

SWAMY VIVEKANANDHA COLLEGE OF PHARMACY,

ELAYAMPALAYAM, TIRUCHENGODE,

NAMAKKAL (DT)-637205, TAMIL NADU

OCTOBER-2017

SWAMY VIVEKANANDHA COLLEGE OF PHARMACY

Elayampalayam, Tiruchengode-637205

Namakkal (Dt.), Tamilnadu.

Phone: 04288-234417

Fax: 04288-234417

Dr. G. MURUGANANTHAN, M. Pharm., Ph.D.,

Principal

CERTIFICATE

This is to certify that the Dissertation entitled “A CLINICAL STUDY ON

MANAGEMENT OF POSTOPERATIVE PAIN AND QUALITY OF LIFE OF

OSTEOARTHRITIS PATIENTS AFTER TOTAL KNEE ARTHROPLASTY” submitted

to The Tamilnadu Dr. M.G.R. Medical University, Chennai, is a bonafide project work of

H. KALAIVANI (Reg No: 261540452), carried out in the Department of Pharmacy

Practice, Swamy Vivekanandha College of Pharmacy, Tiruchengode in partial fulfilment

for the degree of Master of Pharmacy under the guidance of Dr. T. TAMILSELVAN,

M.PHARM., Ph.D., Professor and Head, Department of Pharmacy Practice during the

academic year of 2016 – 2017.

Dr. G. MURUGANANTHAN, M. Pharm., Ph.D.,

Place:

Date:




Phone: 04288-234417

Fax: 04288-234417


Professor and Head, Department of Pharmacy Practice

CERTIFICATE

This is to certify that the Dissertation entitled “A CLINICAL STUDY ON

MANAGEMENT OF POSTOPERATIVE PAIN AND QUALITY OF LIFE OF

OSTEOARTHRITIS PATIENTS AFTER TOTAL KNEE ARTHROPLASTY” submitted

to The Tamilnadu Dr. M.G.R. Medical University, Chennai, is a bonafide project work of

H. KALAIVANI (Reg No: 26154042)carried out in the Department of Pharmacy

Practice, Swamy Vivekanandha College of Pharmacy, Tiruchengode in partial fulfilment

for the degree of Master of Pharmacy under the guidance of Dr. T.TAMILSELVAN,

M. Pharm., Ph.D., Professor and Head in the Department of Pharmacy Practice during

the academic year of 2016 – 2017.


Place:

Date:




Phone: 04288-234417

Fax: 04288-234417

H. KALAIVANI

Reg. No: 261540452

DECLARATION

I hereby declare that the dissertation entitled “A CLINICAL STUDY ON MANAGEMENT

OF POSTOPERATIVE PAIN AND QUALITY OF LIFE OF OSTEOARTHRITIS

PATIENTS AFTER TOTAL KNEE ARTHROPLASTY” submitted to The Tamil Nadu Dr.

M.G.R. Medical University, Chennai, is a record of independent work carried out in the

Department of Pharmacy Practice, Swamy Vivekanandha College of Pharmacy,

Tiruchengode in partial fulfilment for the degree of Master of Pharmacy Under the

guidance of Dr. T. TAMILSELVAN, M. Pharm., Ph.D., Swamy Vivekanandha College

of Pharmacy, Tiruchengode. This work is original and has not been submitted earlier for

the award of any other degree or diploma of this or any other university.

H. KALAIVANI

Reg. No: 261540452

Place:

Date:




Phone: 04288-234417

Fax: 04288-234417

EVALUATION CERTIFICATE

This is to certify that the dissertation entitled “A CLINICAL STUDY ON MANAGEMENT

OF POSTOPERATIVE PAIN AND QUALITY OF LIFE OF OSTEOARTHRITIS

PATIENTS AFTER TOTAL KNEE ARTHROPLASTY” submitted to The Tamilnadu Dr.

M.G.R. Medical University, Chennai, is a bonafide project work of H. KALAIVANI

(Reg. No. 261540452), carried out in the Department of Pharmacy Practice, Swamy

Vivekanandha College of Pharmacy, Tiruchengode in partial fulfilment for the degree of

Master of Pharmacy under the guidance of Dr. T. TAMILSELVAN, M. Pharm., Ph.D.,

Swamy Vivekanandha College of Pharmacy, Tiruchengode.

Internal Examiner External Examiner

Examination Centre: Swamy Vivekanandha College of Pharmacy.

ACKNOWLEDGEMENT

A journey is easier when you travel together. Interdependence is certainly

more valuable than independence. This thesis is the result of one whole year 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 them.

First and foremost I bow down before lord almighty for his splendid blessings

and care in completing my project work and throughout my life till this very second. I

render my sincere thanks to our honourable chairman and secretary, ‘Vidhyaratna’ Prof. Dr. M. Karunanithi., B. Pharm., M.S., Ph.D, D.Litt., our executive director, Dr.

S. Arthanareeswaran, MBBS., MD for providing all facilities for my study and rendering

his noble hand in the upliftment of women education in all the disciplines.

First of all, I would like to express my heartfelt appreciation to my guide and

Head of the department of Pharmacy Practice, Dr. T. Tamilselvan. M.Pharm., Ph.D.,

thank for his willingness to offer continuous guidance, support and encouragement,

which are driving forces for me to complete this thesis. His vast knowledge, his attitude

of research and skill of presentation have been an invaluable resources to me. He is an

admirable professor and will always be a role model for me.

It is difficult to overstate my gratitude to Dr. G. Murugananthan, M.Pharm.,

Ph.D., Principal of our institution. His enthusiasm and integral view on research and his

mission for providing ‘only high – quality work and not less’, has made a deep

impression on me. I owe him lots of gratitude for having me shown this way of research.

I sincerely express my gratitude to Dr. S. Kumaravel., MS (Ortho).,

(Fellowship Arthroplasty) And Dr. Jayaprakash M.B.B.S., DNB., (Anaesthesia)

Consultant Anaesthetist, Vivekanandha Medical Care Hospital, Elayampalayam for

permitting us to carry out this project in the hospital.

Also their valuable and important advices, encouragement which gave confidence

to carry out this project successfully.

I would be unwise if i forget to express my sincere thanks and gratitude to

Mr. S. AnandKumar, M.Pharm., Mr. D. Joseph Stalin, M.Pharm., Mrs. T. Kumutha,

M.Pharm., Dr. Anuphilip, PharmD., Mrs. P. Parkavi Rani M.Pharm., Department of

Pharmacy Practice, for their support advise and help for this project.

I remain thankful to our lab assistant Mrs. Poongodi for her help during my project

work. I remain greatly in debeted to my beloved Parents and Sister for their precious

love, affection, prayers and moral support which guided me in the right path and are

also the backbone for all successful endeavours in my life.

Also I would like to thank the Tamilnadu Dr. MGR Medical University for providing

a nice environment for learning.

I would like to thank my friends especially NithyaRaju, Swetha, Saranya,

Jennifar, Bittu P Kurian, Abirami, Arun alphones Thomas, Hesly Rajan, Sabith,

Suganeswari, Poorana Pushkalai, Jayaprakash, Venkatesh, Nandhini.

I express my whole hearted thanks to all those who gave their helping hands in

completing my project successfully.

CONTENTS

S. No

CONTENTS

PAGE NO

1.

INTRODUCTION

1

2.

REVIEW OF LITERATURE

29

3.

AIM & OBJECTIVES

41

4.

PLAN OF STUDY

42

5.

METHODOLOGY

43

6.

RESULTS

47

7.

DISCUSSION

59

8.

CONCLUSION

64

9.

REFERENCES

65

ANNEXURES

10.

ANNEXURE I (Ethical Approval: Ref No: SVCP/IEC/JAN/2016/12)

11.

ANNEXURE II Informed Consent Form English

12.

ANNEXURE III Informed Consent Form Tamil

13.

ANNEXURE IV Data Entry Form

14.

ANNEXURE V VAS Scale

15.

ANNEXURE VI KOOS Pain Questionnaire

16.

Certificates of Conferences and Seminars Attended

LIST OF TABLES

TABLE.

No TITLE PAGE NO

1.

Age Wise Distribution Among the Study Population 47

2. Gender Wise Distribution Among the Study Population 48

3. BMI Among the Study Population 49

4. Comparison of NSAIDs Vs Pregabalin with NSAIDs on VAS 50

5. Effect of NSAIDs for Osteoarthritis Patients After TKA 51

6. Effect of Pregabalin with NSAIDs for Osteoarthritis Patients

After TKA using KOOS questionnaire 52

7. Comparison of NSAIDs Vs Pregabalin with NSAIDs on Pain 53

8. Comparison of NSAIDs Vs Pregabalin with NSAIDs on

Symptoms 54


Activities and Daily Living 55


Sport and Recreation Function 56


Quality of Life 57

12. Comparison of Effectiveness of Group A & Group B 58

LIST OF FIGURES

FIGURE

No TITLE PAGE NO

1.

Schematic Diagram of Risk factors of Osteoarthritis

7

2.

Radiographic findings of Before and After TKA 9

3.

Visual Analogue Scale 27

4.

Age Wise Distribution Among the Study Population 47

5. Gender Wise Distribution Among the Study Population 48

6. BMI Among the Study Population 49

7. Comparison of NSAIDs Vs Pregabalin with NSAIDs on VAS 50

8. Effect of NSAIDs for Osteoarthritis Patients After TKA 51

9. Effect of Pregabalin with NSAIDs for Osteoarthritis Patients

After TKA using KOOS questionnaire 52

10. Comparison of NSAIDs Vs Pregabalin with NSAIDs on Pain 53


Symptoms 54


Activities and Daily Living 55


Sport and Recreation Function 56


Quality of Life 57

15. Comparison of Effectiveness of Group A & Group B 58

ABBREVIATIONS

ACR American College of Rheumatology

ADL Activity And Daily Living

BMI Body Mass Index

COX – 2 Cyclooxygenase 2

DMORDs Disease Modifying Osteoarthritis Drugs

KOOS Knee Injury And Osteoarthritis Outcome Score

MRI Magnetic Resonance Imaging

NP Neuropathic Pain

NSAIDs Non Steroidal Anti Inflammatory Drugs

OTC Over the Counter Drugs

OA Osteoarthritis

Preg Pregabalin

QOL Quality of Life

SRF Sport And Recreation Function

TKA Total Knee Arthroplasty

VAS Visual Analogue Scale

WOMAC Western Ontario and McMaster Universities Osteoarthritis Index

A CLINICAL STUDY ON MANAGEMENT OF POSTOPERATIVE PAIN AND QUALITY

OF LIFE OF OSTEOARTHRITIS PATIENTS AFTER TOTAL KNEE ARTHROPLASTY

ABSTRACT

Aim: To assess the management of postoperative pain and the Quality of Life of

osteoarthritis patients after total knee arthroplasty.

Methods: This Prospective observational study was conducted in the Department of

Orthopaedics. Totally 96 patients were divided in to two groups. Group A consist 50

patients with the treatment of NSAIDs and Group B consist 46 patients with the

treatment of Pregabalin with NSAIDs. The pain scores were evaluated baseline, first

and second follow up using VAS. Knee injury and Osteoarthritis Outcome Score

questionnaire were used to assess pain, symptoms, ADL, SRF and QOL of

Osteoarthritis patients after TKA. The study subjects were followed once in 30 days for

3 months and they were asked to answer the same questionnaire. The effect of the

treatment was assessed by comparing the baseline score with follow up score. All

results were analysed using computerized statistical package of graph Pad instat

Version 3.10.

Results: Our study result shows that the pain relief in Group B in VAS at second follow

up 2.56 ± 0.34 and KOOS score at second follow up of Pain 92.73 ± 3.45, Symptoms

89.23 ± 3.59, Activities of daily living 94.97 ± 2.71, and quality of life 81.56 ± 5.29 was

improved and statistically significant when compared to Group A . The mean difference

of second follow up Sport and recreation function 92.60 ± 2.52 was not statistically

significant. (p < 0.01)

Conclusion: The study concluded that pregabalin with NSAIDs group patient showed

the better improvement in symptoms, activities of daily living and quality of life within

short duration as compared to NSAIDS used patients. Regular patient counselling,

maintenance of diet and exercise with good patient compliance may improve the quality

of life of patients in day to day activities.

Key words: Osteoarthritis, Total knee arthroplasty, Pregabalin, NSAIDs.

Introduction

A Clinical Study on Management of Postoperative Pain and Quality of Life of

Osteoarthritis Patients After Total Knee Arthroplasty Page 1

1. INTRODUCTION

Osteoarthritis is a common, progressive disorder affecting primarily weight

bearing diarthrodial joints, characterized by progressive deterioration and loss of

articular cartilage, osteophyte formation, pain, limitation of motion, deformity and

disability.1 Osteoarthritis is one of the most prevalent condition resulting to disability

particularly in elderly patients.2 An estimated 10% to 15% of all adults over 60 have

some degree of OA, with prevalence higher than men.

The Prevalence of OA is increasing due to population ageing and an increase in

related factors such as obesity. According to the United Nations, by 2050 people aged

over 60 will account for more than 20% of the world’s population. Of that 20%, a

conservative estimate of 15% will have symptomatic OA, and one third of these people

will be severely disabled. This means that by 2050, 130 million people will suffer from

OA worldwide, of whom 40 million will be severely disabled by the disease.3

About 13% of women and 10% of men aged 60 years and older have

symptomatic knee OA. The proportions of people affected with symptomatic knee OA is

likely to increase due to the aging of the population and rate off obesity or overweight in

the general population. Prevalence of knee OA in men is lower compared with women.

This was shown in a meta-analysis of males and females in which the incidence of knee

OA in males and females aged < 55 years was lower than females. Females particularly

those ≥55 years, tended to have more severe OA in the knee but not in other sites. The

results of this study demonstrated sex differences incidence of knee OA particularly

after menopausal age. In prospective study in which data where provided by

Introduction



radiographs, physical performance assessment and interviews in 1996 and again in the

follow up visits. Middle aged women had a high prevalence of moderate to severe knee

osteoarthritis. The prevalence rates of knee OA vary according to study population s

well s the methods applied for diagnosis. The prevalence rate was significantly with age.

Symptomatic knee OA was significantly more common in rural compared to urban and

suburban populations.2

1.1.2 EPIDEMIOLOGY

Global statistics reveal over 100 million people worldwide suffer from OA, which

is one of the most common cause of disability. In addition, younger individuals may be

susceptible to injury induced OA. More than 50% of the populations around the world

show X- ray evidence of OA in one of the joints, thus demonstrating the high incidence

of this disease. As per a recent report published in the Times of India (2010) regarding

OA, over 40% of the Indian population in the age group of 70 years or above suffer from

OA. Nearly 2% of these undergo severe knee pain and disability.

As per a recent statement quoted by Piramal healthcare limited in a nationwide

campaign against chronic diseases, “India is expected to be the chronic disease capital,

with 60 million people with arthritis, by 2025. Currently 80% of the persons affected by

OA already report having some movement limitation, and 20% report not being able to

perform major activities of daily living; with an 11% of the total population reporting the

need of personal care.4

Introduction



1.1.3 ETIOLOGY

Osteoarthritis has multifactorial etiologies, which occurs due to interplay

between systemic and local factors. The etiology of this debilitating disease in which

several responsible genes are linked for its occurance. Sports participation, injury to the

joint, obesity and genetic susceptibility predispose adolescent athletes to the development

of premature osteoarthritis. Old age female gender, overweight and obesity, knee injury,

repetitive use of joints, bone density, muscle weakness and join laxity all play roles in the

development of joint OA.2

Primary Osteoarthritis:

Primary Osteoarthritis is a chronic degenerative disorder related to but not

caused by aging. The pathophysiology of osteoarthritis involves a combination of

mechanical, cellular and bio chemical processes. The interaction of these process leads

to changes in the composition and mechanical properties of the articular cartilage.

Cartilage is compose of water, collagen and proteoglycans. As a person ages, the water

content of the cartilage decreases as a result of a reduced proteoglycan content, thus

causing the cartilage to be less resilient. Without the protective effects of the

proteoglycans, the collagen fibers of the cartilage can become susceptible to

degradation and thus exacerbate the degeneration. Inflammation of the surrounding

joint capsule can also occur, through often mid (compared to what occurs in rheumatoid

arthritis). This can happened has breakdown products from the cartilage are released in

to the synovial space, and the cells lining the joint attempt to remove them. New bone

formation, called “Spurs” or osteophytes, can form on the margins of the joints, possibly

Introduction



in an attempt to improve the congruence of the articular cartilage surfaces. These bone

changes, together with the inflammation, can be both painful and disabling.6

Secondary Osteoarthritis

This type of OA is caused by other factors but the resulting pathology is the same

as for primary OA.

Congenital or developmental disorders of joints

Mechanical :

Limp length discrepancy, malalignment, hyper- laxity, Ehlers –

Danlossyndrome, Marfan’s syndrome

Inflammatory:

Rheumatologic diseases, i.e., Rheumatoid arthritis, SLE, all chronic forms

of arthritis.

Traumatic:

Injury to joints or ligaments, post – surgical.

Infective:

Septic arthritis, Lyme disease

Metabolic :

Haemochromatosis and Wilson’s disease, Gout, Calcium crystal

deposition, alkaptonuria

Endocrine:

Diabetes, Acromegaly, Hypothyroidism, Obesity.

Neuropathic arthopathy

Introduction



Miscellaneous:

Haemophilia, Osteonecrosis.6

1.1.4 RISKFACTORS

There are many factors that can increase the risk of osteoarthritis and it’s often

combination of these that leads to the condition.

Age:

Osteoarthritis usually starts from the late 40’s onwards. We don’t fully

understand why it’s more common in old people, but it might be due to factors like

weakening of the muscle, but body being less able to heal itself or gradual wearing out

of the joint with time.

Gender:

Osteoarthritis of the knee is twice as common in women as in men. It’s

most common in women over the age of 50, although there’s no strong evidence that

it’s directly linked to the menopause. It’s often associated with mild arthritis of the joints t

the ends of the fingers, which is also more common in women.

Obesity:

Being overweight is an important factor in causing osteoarthritis,

especially in the knee. It also increases the chances of osteoarthritis becoming

progressively worse.

Introduction



Joint Injury:

Normal activity and exercise don’t cause osteoarthritis, but very hard,

repetitive activity or physically demanding jobs can increase the risk. Injuries to the knee

often lead to osteoarthritis in later life. A common cause is a torn meniscus or ligament,

which can result from a twisting injury. A torn meniscus is common injury in footballers

and an operation to remove the damaged cartilage or repair cruciate ligaments also

increases the risk of osteoarthritis in later life.

Genetic factors:

Genetic factors play a major part in osteoarthritis of the knee. If you have

a parent, brother or sister with knee osteoarthritis then you’ll have a greater chance of

developing it yourself. We don’t know a lot about the genes that cause the increased

risk, but we do know that a number of genes will have a small effect rather than one

particular gene being responsible.

Other type of joint disease:

Sometimes osteoarthritis is a result of damage from different kinds of

rather joint disease, such as gout, that occurred in earlier years.

Although there’s no evidence that different conditions such as cold or wet

weather actually cause or worsen osteoarthritis, many people find that their pain and

stiffness may be because nerve fibers in the capsule of affected joints are sensitive to

changes in atmospheric pressure.7

Introduction



Fig. 1. Schematic diagram of risk factors for Osteoarthritis 5

1.1.5 PATHOPHYSIOLOGY:

Osteoarthritis is usually begins with damage to articular cartilage through injury

excessive joint loading from obesity or other reasons or joint instability or injury.

Damage to articular cartilage increases activity of chondrocytes in attempt to

repair damage, leading to increased synthesis of matrix constituents with cartilage

LOCAL RISK FACTORS

Obesity

Occupation

Physical activity/ Sports

Injury

SYSTEMIC RISK FCTORS

Age

Gender

Genetic &hormones

Diet

SEVERITY OF

OSTEOARTHRITIS

SYMPTOMS OF OA

PAIN

JOINT STIFFNESS

MUSCLE WEAKNESS

DISABILITY

Introduction



swelling. Normal balance between cartilage breakdown and resynthesis is lost, with

increasing destruction and cartilage loss.

Subchondral bone adjacent to articular cartilage undergoes pathologic changes

and releases vasoactive peptides and metallopepteinases (MMPs). Neovascularization

and increased permeability of adjacent cartilage occur, which contribute to cartilage loss

and chondrocyte apoptosis.

Cartilage loss causes joint space narrowing and painful, deformed joints.

Remaining cartilage softens and develops fibrillations, followed by further cartilage loss

and exposure of underlying bone. New bone formations at joint margins distant from

cartilage destruction are thought to help stabilize affected joints.

Inflammatory changes can occur in the joint capsule and synovium. Crystals or

cartilage shards in synovial fluid may contribute to inflammation. Interleukin –1,

prostaglandin E2, tumor necrosis factor – α (TNF- α) and nitric oxide in synovial fluid

may also play a role. Inflammatory changes result in synovial effusions and thickening.

Pain may result from distension of the synovial capsule by increased joint fluid,

micro fracture, periosteal irritation, or damage to ligaments, synovium or the meniscus. 1

1.1.6 DIAGNOSIS

The diagnosis of Osteoarthritis is made with reasonable certainly based on the

patient’s history, nature and severity of pain. It can also be diagnosed to measure the

amount of movement in the joint. X- Rays may confirm the diagnosis. An X – ray of the

knee narrowing of the joint space is a good indicator of OA. The main characteristics of

Introduction



OA are changes in the subchondral bone. The radiographic hall marks of primary OA

include asymmetrical joint space narrowing or loss, subchondral sclerosis (increased

bone formation around the joint), subchondral cyst formation and osteophytes. The

initial radiographs may not show all of the findings. However, in early OA, minimal no

uniform joint space narrowing may be the only radiographic finding.

Figure 2: Radiographic findings of before and after TKA

In some cases, for further clarity and better diagnosis the Magnetic resonance

imaging (MRI) scan may be necessary. This allows the clinician to see whether any

damage to the soft tissue has taken place within the joint.

In certain cases, a blood sample like Normal Erythrocyte Sedimentation Rate

(ESR) may be necessary to rule out the presence of other types of arthritis.

For knee OA, patient must have knee pain and radiographic osteophytes in

addition to one more of the following:

1. Age more than 40 years

2. Morning stiffness lasting 30 min or less

3. Crepitus on motion

4. Bony enlargement

Introduction



5. Bony tenderness

6. Palpable joint warmth 1, 4,6

1.1.7 TREATMENT

NON PHARMACOLOGICAL TREATMENT:

Currently different non pharmacological treatments are available for cur of

osteoarthritis. Weight reduction is one of the first and unproblematic measures that can

be taken to reduce knee osteoarthritis

Educate patient about disease process and extent, prognosis and

treatment. Promote dietary counseling, exercise and weight loss program for overweight

patients.

Cold and heat treatments and an exercise program helps maintain range

of motion and reduce pain and need for analgesics.

Assistive and orthotic devices (canes, walkers, braces, heel cups, insoles)

can be used during exercise or daily activities.

Surgical procedures (e.g. Osteotomy, arthroplasty, joint fusion) are

indicated for functional disability and severe pain unresponsive to conservative

therapy.1

Introduction



PHARMACOLOGICAL THERAPY

Treatment goals for the management of Osteoarthritis to reduce pain,

stiffness, and maintenance or improving function of the knee, retarding the disease

progression of joint damage and improvement of Quality of life.

A range of oral analgesics, topical treatments and intra articular injections

can be used to reduce pain and improve function in patients can be used to reduce

pain and improve function in patients with osteoarthritis of the hip and knee.

The American college of Rheumatology (ACR) has issued the guidelines for

pharmacological treatment of osteoarthritis of the hand, hip and knee. For knee OA,

the ACR conditionally recommends using one of the following

1. Acetaminophen / Paracetamol

2. Oral NSAID’s

3. Topical NSAID’s

4. Tramadol

5. Intra- articular corticosteroid injections.

The American College of Rheumatology (ACR) conditionally recommends

against using chondroitin sulfate, Glucosamine or topical capsaicin for knee

osteoarthritis. The ACR has no recommendations regarding the use of intra- articular

hyaluronates, duloxine and opioid analgesics.1, 8

Acetaminophen, aspirin and Non-steroidal anti-inflammatory drugs (NSAID’s) are

commonly used as pain relief medicines to treat OA. Excessive use of NSAID’s can

lead to gastric complications, ulcers increased risk for hospitalization, adverse effects

Introduction



and death. Glucosamine and chondroitin sulfate are two nutritional supplements that

have been reported to cure arthritis. As glucosamine and chondroitin are produced with

in the body and are used inn repair of cartilage.

Intra – articular hyaluronic acid as a long history of injections in to the joints f

arthritic animals to improve their performance (therapy is called as

“viscosupplementation”). Hyaluronic acid is a lubricating substance with in the joint

which may be lost during osteoarthritis. It has been approved by US food and Drug

Administration as a device for the treatment of OA in humans in 1997 although thought

to have worked with arthritis, it was found that intra articular hyaluronic acid at best has

a small effect in the treatment of knee osteoarthritis compared with an intra- articular

placebo.

The use of opioids should be limited to the patients who have contraindications

or have ineffective response to acetaminophen and NSAID’s. Tramadol is the most

commonly used agent alone or in combination for the treatment of moderate to severe

Osteoarthritic pain. Codeine is also effective for Osteoarthritic pain. Opioids can cause

hyper somnolence, constipation and rarely delirium – especially in the older patients.

Therefore close monitoring is required when using these agents. Non tramadol opioids

should not be routinely used, even if osteoarthritic pain is severe due to risk of adverse

events.4,6

Introduction



Topical creams:

Topical creams are used as adjuvant therapy. It is substitute

therapy for oral medications for osteoarthritic pain. Topical medications like balms,

creams, oils, gels, patches, solution forms – lotions, ointments. Most are available in

OTC medications. Commonly DICLOFENAC is mostly used topical NSAID’s

preparation. Dry skin is most common adverse effects. Topical CAPSAICIN is effective

t 0.025% four times a day or 0.075% twice a dayfor OA pain.

OTC topical pain medications are:

Counter irritants – contain menthol, eucalyptus oil, or oil of wintergreen

and work by irritating the skin where it is applied.

Salicylates – are the main ingredients in topical analgesics. Creams

which contain salicylates offer pain relief and reduce joint inflammation.6.

Other drugs:

Glucosamine: Glucosamine and chondroitin are members of a group of dietary

supplements often termed “complementary agents”, “disease – modifying agents” or

“disease modifying osteoarthritis drugs” (DMOADs). They are derived from animal

cartilage or crab shells. They relieve knee pain and perhaps repair the cells that line the

joint. The effect is possibly the result of its anti-inflammatory activity, synthesis of

proteoglycans, and inhibition of the synthesis of proteolytic enzymes. It also stimulates

synovial production of hyaluronic acid.6

Introduction



Diacerein: An oral interleukin - 1α inhibitor is reported to have slow acting, but

persistent, symptomatic relief in patients with osteoarthritis.Diaceretin treatment of OA

showed that it may be an alternative therapy for OA in patients who cannot take

paracetamol or NSAID’s because of adverse effects or lack of benefit. Diarrhea is the

most common side effect.

Good pain control after surgery is important to prevent negative outcomes such as

tachycardia, hypertension, myocardial ischemia and decrease in alveolar ventilation, poor

wound healing and insomnia. Pain has been found to be one of the three most common

medical causes of delayed discharge of after ambulatory surgery, the other two being

drowsiness and nausea/ vomiting.9

Total Knee Arthroplasty (TKA) is an effective treatment for end stage knee

osteoarthritis, but the optimal management of postoperative pain remains controversial.

TKA is often cited as one of the most painful known procedures. Approximately 20% of

the patients with OA of the knee do not want to undergo TKA because of the expectancy

of high levels of pain. After total knee arthroplasty, the pain may also inhibit early

rehabilitation to mobilize the knee joint.

Different types of local anesthetic application can successfully treat TKA pain in

older days. Although opioids can continuous epidural analgesia remain the major options

for the postoperative pain management of TKA, they have some undesirable side effects.

Epidural analgesia is technically demanding, and the patients require close monitoring

after the surgery because complications such as hypotension, nausea and vomiting. The

Introduction



administration of opioids do not consistently provide adequate pain relief and often cause

sedation, confusion, and delirium, constipation, nausea, vomiting and pruritus.

Epidural infusions containing local anesthetics (with or without an opioid) provide

superior analgesics but are associated with hypotension, urinary retention, motor block

limiting ambulation and spinal hematoma secondary to anticoagulation. In general,

patients undergoing TKA are aged over 55 yrs and most often have accompanying health

problems such as, diabetes, hypertension, and cardiac diseases which restrict high

dosage opioids use. Although the femoral nerve block is an alternative and effective

treatment to reduce postoperative pain.10, 11.

NSAID’s are often considered to be the preferred first line treatment for OA. Use of

non – opioid drugs during the preoperative period can reduce excess intra operative

opioid use. The use of preoperative NSAIDs and COX – 2 inhibitors also has a significant

effect on opioid requirements following surgery. This has been referred to as an “opioid

sparing effect”. The clinical significance of this may be the reduction of opioid related side

effects, improved analgesia and better patient satisfaction. The primary site of action of

NSAIDs and COX – 2 inhibitors are in the periphery where they inhibit prostaglandin

synthesis and stimulation of nociceptors.

In addition of NSAIDs and COX – 2 inhibitors, anti neuropathic drugs as playing a

role in the treatment of postoperative pain. Such drugs as gabapentin and pregabalin,

intended for seizures and neuropathic pain syndromes, can inhibit central neuronal

sensitization. Pregabalin was also found to have a synergistic effect with COX –

2ninhibitors in clinical studies involving patient undergoing spinal fusion. The combination

Introduction



of the two drugs reduced postoperative pain, morphine consumption at 24 hrs and opioid

induced side effects. Improvements in outcome were greater when these drugs were

used in combination than either of the drugs used alone.17.

Acetaminophen is generally prescribed for treating the pain associated with OA.

Tramadol also acts as a serotonin and norepinephrine reuptake inhibitor where it is

essentially employed in OA to reduce the moderate to severe pain associated with the

disease.180

Osteoarthritis is a both inflammatory and neuropathic pain. Patients with

neuropathic pain are challengeto manage. Pregabalin was developed for management of

NP (Neuropathic pain).12The new pharmacological products to treat Postoperative pain

management include extended release epidural morphine and analgesic adjuvants such

as Capsaicin, Ketamin, Gabapentin,Pregabalin, dexmedetomidine and tapentadol.9

Perioperative Pregabalin may reduce postoperative pain and opioid use. Among

total knee arthroplasty patients, pregabalin 300 mg daily reduced acute pain, chronic pain

and opioid use. A Meta-analysis found that pregabalin reduced postoperative pain and

reduced analgesic drug intake, but only at doses ≥ 300mg daily.13

Pregabalin is anα2δ ligand that modulates the activity of voltage gated calcium

channels. In the US, pregabalin is indicated for the treatment of neuropathic pain

associated with diabetic peripheral neuropathy with spinal cord injury, post therapeutic

neuralgia, fibromyalgia and as adjunctive therapy for adult patients. In the European

country, Pregabalin is indicated for peripheral and central neuropathic pain, epilepsy and

generalized anxiety disorder. To further examine the safety and efficacy of pregabalin in

Introduction



the postoperative setting, three separate, large, multicenter, randomized, placebo

controlled trials of pregabalin as an adjunctive treatment for postoperative pain were

conducted in patients following inguinal hernia repair (Post - IHR), following total knee

arthroplasty (Post - TKA), following hysterectomy (Post hysterectomy).14

1.2 DRUG MONOGRAPH

1.2.1 ACETAMINOPHEN

Category/ class:

Analgesic and Antipyretic.

Dose:

Osteoarthritis: 1000 mg orally 4 times daily for four weeks, total 4000 mg /

day.

Pain : Mild to Moderate: 650 mg orally every 4 – 6 hours as needed. Max

3250 mg / 24 hrs

Pain : Moderate to Svere: in combination with opioid medications: 50

kg ≥ 1000mg IV every 6 hrs, 50 kg ≤ 15 mg/ kg IV every 6 hrs,

Mechanism of Action:

Acetaminophen is a centrally acting analgesic and antipyretic with minimal

anti – inflammatory properties. The mechanism of action of acetaminophen

in reducing pain is unknown but may be due to an inhibition of central

Introduction



prostaglandin synthesis (specifically cyclooxygenase (cox) – 2) and an

elevation of the pain threshold. Acetaminophen reduces fever by inhibiting

the formulation and release of Prostaglandins in the CNS and by inhibition

endogenous pyrogens at the hypothalamic thermo regulator centre

Adverse drug Reaction:

Common:

Dermatologic: Pruritis (5 % or greater)

Gastrointestinal: Constipation, Nausea, Vomiting

Neurologic: Headache, Insomnia

Psychiatric: Agitation

Respiratory: Atelectasis

Serious:

Dermatologic: Generalizedexanthematouspustulosis, acute

Stevans – Johnson syndrome, toxic epidermal necrosis.

Hepatic: Liver failure

Respiratory: Pneumonitis

Introduction



Indication:

FDA – Labeled indications:

Fever

Pain (mild to moderate)

Pain (moderate to severe), in combination with opioid

medications

Non- FDA Labeled indications:

Migraine

Osteoarthritis

Vaccines adverse reaction; prophylaxis.

Contraindication:

Acute and Severe hepatic disease

Hypersensitivity to acetaminophen or any other components of the

product

Severe hepatic Impairment.

Drug interaction:

Major:

Imatinib

Isoniazid

Pixantrone

Pneumococcal 13 – valent vaccine, Diphtheria conjugate

Introduction



Moderate:

Acenocoumarol

Carbamazepine

Fosphenytoin

Lixisenatide

Phenytoin

Warfarin

Zidovudine.

Pregnancy Category:

Category C.

1.2.2 ACECLOFENAC

Category/ class:

Non-steroidal Anti-inflammatory Drugs (NSAIDs).

Dose:

Pain and inflammation in Rheumatoid arthritis, Osteoarthritis and

Ankylosing spondylitis: 100 mg twice daily by orally.


Introduction



Aceclofenac, a phenylacetic acid derivative is a potent inhibitor of

cyclooxygenase enzyme, involved in the production of prostaglandins,

causing marked anti inflammatory and analgesic properties.

Absorption:

Rapidly and completely absorbed from the GI tract. Time to peak

plasma concentration: 1-3 hr.

Distribution:

Penetrates into the synovial fluid. Volume of Distribution: approx: 25

L. plasma protein binding: > 99%

Metabolism:

Metabolism into 4’-hydroxyaceclofenac

Excretion:

Via urine. Plasma elimination half- life : approx 4 hr.


Alveolitis, Aseptic meningitis, Hepatic damage, Interstitial fibrosis

associated with NSAIDs can lead to renal failure, Pancreatitis, Papillary

necrosis associated with NSAIDs can lead to renal failure, Pulmonary

eosinophilia, Stevans – Johnson syndrome, Toxic epidermal necrosis,

visual disturbances.

Introduction



Indication:

Pain and inflammation in Rheumatoid arthritis,

Osteoarthritis

Ankylosing spondylitis

Contraindication:

Hypersensitivity to aceclofenac or other NSAIDs, ischemic heart disease,

moderate to severe renal and severe hepatic impairment.

Drug interaction:

Interacts with digoxin, lithium, methotrexate, cyclosporine, diuretics,

phenytoin, warfarin.

Pregnancy Category:

Category N (FDA has not yet classified the drug into a specified

pregnancy category).

Introduction



1.2.3 PREGABALIN 15, 16

Category/ class:

Anxiolytics

Anticonvulsants

Neuropathic pain

Gamma aminobutyric Acid

Dose: (from Beers criteria):

Diabetic Peripheral neuropathy – Neuropathic pain

Initial 50mg orally three times a day and max dose 100 mg

orally three times a day.

Fibromyalgia

Initial 75 mg orally twice daily; may increase to 150 mg twice

daily; max 225 mg twice daily.

Neuropathic Pain - Spinal cord injury

Initial 75 mg orally twice daily; may increase to 150 mg twice

daily; may further increase to 300 mg orally twice daily for

sufficient pain relief after 2 – 3 weeks of treatment.

Partial Seizure; Adjunct

Initial no greater than 75 mg orally two times daily or 50 mg

orally three times daily; max dose of 600 mg / day in divided

dose.

Introduction



Post therapeutic neuralgia

Initial 75 mg orally two times daily or 50 mg orally three

times daily; may be increased to 300 mg/day.

Generalized anxiety disorder

300to 600 mg orally daily usually given in 3 divided doses.

Or 150 to 600 mg orally daily.

Postoperative Pain

Optimal dosage has not been established, 150 mg to 600

mg per day orally has been used in clinical trials or 150 to

300 mg orally 2 hours period to surgery or 1 hour prior to

induction of anesthesia.

Restless legs syndrome

300 mg orally once daily, given 1 to 3 hours before bed time.


Pregabalin is an analogue of the neurotransmitter GABA. It binds potently

to the α2δ submit resulting in modulation of Ca channels and reduction in

the release of several neurotransmitters, including glutamate,

norepinephrine, Serotonin, dopamine, calcitonin gene related peptide and

substance P.

Absorption:

Rapidly absorbed.

Bio Availability: Approx. 90%.time to peak.

Plasma Concentration: W/ in 1.5 hr.

Introduction



Distribution:

Volume of distribution: 0.5 L/ Kg. Not bound to plasma protein.

Metabolism:

Negligible metabolism

Excretion:

Via urine (app. 98%) as unchanged drug.

Elimination half- life: 6.3 hr.


Common

Cardiovascular: Peripheral edema

Endocrine metabolic: Increased Appetite, Weight gain

Gastrointestinal: Constipation, Xerostomia

Neurologic: Asthenia, Ataxia, Dizziness, Headache, Incoordination,

Somnolence and Tremor.

Ophthalmic: Blurred vision, Diplopia.

Psychiatric: Disturbance in thinking, Euphoria

Respiratory:Nasopharyngitis.

Other: Fatigue.

Serious

Hepatic: Jaundice

Immunologic: Hypersensitivity reaction

Musculoskeletal: Increased creatine kinase level.

Introduction



Psychiatric: Suicidal thoughts.

Other: Angioedema.

Indication:

FDA Labeled indication:

Diabetic Peripheral neuropathy – Neuropathic pain

Fibromyalgia

Neuropathic Pain - Spinal cord injury.

Partial Seizure; Adjunct

Post therapeutic neuralgia

Non FDA Labeled indications:

Generalized anxiety disorder

Postoperative Pain

Restless legs syndrome.

Contraindication:

Contraindicated in patients with Hypersensitivity

Drug interaction:

Calcifediol

Orlistat

Pregnancy Category: Category C.

Introduction



1.3 PAIN SCORES

In this study, determine the efficiency of pain treatments and to compare the success

rates between each group.

Visual Analogue Scale (VAS)

Knee Injury and Osteoarthritis Outcome Score (KOOS)

1.3.1 VISUAL ANALOGUE SCALE (VAS)

The visual analogue scale is undimensional measure of pain intensity, which has been

widely used in diverse adult population including those with arthritic disease.19wherein

zero denoted “no pain” and 10 mm denoted the “worst pain” at the end of painless time

and 24 hr after the operation by VAS tables and follow up the every month up to 6

months postoperatively.10 (Annexure V)

Figure 3: Visual Analogue Scale (VAS)

Introduction



1.3.2 KNEE INJURY AND OSTEOARTHRITIS OUTCOME SCORE (KOOS)

The knee injury and osteoarthritis outcome score is an extension of the Western Ontario

and McMaster Universities Osteoarthritis Index (WOMAC). The KOOS reflects the

increasingly younger and more active demographic of people undergoing Total Knee

Artroplasty (TKA). The KOOS is a 42 – item self-report questionnaire that has 5

reported dimensions: Pain (9 items), other Symptoms (7 items), Activities of Daily Living

(ADL) (17 items), Sport and Recreation Function (SRF) (5 items), and knee related

Quality of life (QOL) (4 items). The scoring system of the KOOS utilizes a 5 point likert

scale, with anchors of zero (no problems) to 4 (extreme problems). Scores are

transformed to a 0 to 100 scale with zero representing extreme knee problems and 100

representing no knee problems.20 (Annexure VI)

Literature Review



2. LITERATURE REVIEW

Fei Li et al., (2017) conducted a study to evaluate the efficacy of pregabalin for

the management of postoperative pain in primary total knee and hip arthroplasty. A

meta-analysis the results found to be postoperative side effects such as nausea,

vomiting, pruritus and dizziness. When comparing the pregabalin group to be placebo

group after TKA and THA. Concluded from this study was pregabalin improve pain

control at 24 and 48 hrs with rest, reduce morphine consumption, improve the knee

flexion degree, decrease the incident rate of nausea, vomiting, and pruritus and

increase the incident rate of dizziness after TKA and THA.21

Chao Han et al., (2017) conducted a study to examine the evidence of

pregabalin effectiveness and safety in total knee arthroplasty and concluded as the

administration of pregabalin is not only efficacious in the reduction of narcotic

requirements and incidence of some adverse effect, but also workable for the

improvement of passive knee flexion range after TKA.22

Yingdelong Mao et al., (2016) studied the efficacy of preoperative

administration of gabapentin/ pregabalin in improving pain after total hip arthroplasty

and concluded as gabapentin, or pregabalin can decrease the cumulative morphine

consumption and decrease the occurrence of nausea however further trials are needed

to assess the efficacy of pain control by gabapentin or pregabalin.23

Literature Review



Rajshree Mishra et al., (2016) studied is to evaluate postoperative analgesic

benefit and efficacy in patients administered with oral gabapentin or pregabalin as

premedication for laparoscopic cholecystectomy under general anesthesia, the patients

were randomly allocated in three groups. Groups A, B, and C received 2 capsules of B

complex, 3 capsules of 300 mg gabapentin each, and 2 capsules of 75 mg pregabalin,

respectively, each in 30 patients of each group, 1 h before induction of anesthesia and

concluded that pregabalin group had lower VAS score, prolonged timing of first rescue

analgesic, and less opioids consumption than the gabapentin group. Both

gabapentinoids had better postoperative analgesic profile than placebo.26

Xu Jianda et al., (2016) to investigate the effects of preemptive analgesia on the

inflammatory response and rehabilitation in TKA. 75 patients with unilateral primary

knee osteoarthritis were conducted in this prospective study. All patients were randomly

divided in to 2 groups MMA with/ without preemptive analgesia group as concluded

preemptive analgesia added to multimodal analgesia regime improved analgesia,

reduced inflammatory reaction and accelerated functional recovery at the first week

postoperatively, but not improved long term function.24

Dr. Keith holt et al., (2016) studied pain management after knee replacement

and says that the pregabalin is a pre-operative pain modifying agent and this is the most

commonly used for post-operative pain. It’s most beneficial in the first 2 to 3 days. After

that with someone exceptions it fails to reduce the dosage of other analgesics and now

pregabalin may then prove very helpful.25

https://www.ncbi.nlm.nih.gov/pubmed/?term=Mishra%20R%5BAuthor%5D&cauthor=true&cauthor_uid=27212747

Literature Review



Neil K Singla et al., (2015) conducted a study on pregabalin for the treatment of

postoperative pain: results from three controlled trials using different surgical models.

Totally 3 categories of surgical procedures was done one category of Post TKA patients

are selected in 307 patients were randomly selected to treatment and shows that there

were no significant differences between pregabalin and placebo with respect the

primary pain intensity measure in each of the three clinical trials. These study

encompass a large dataset (1,233 patients in total) and their results should be

considered when assessing pregabalin’s effectiveness in postoperative pain.14

J. T. YaDeau et al., (2015) studied about the drug pregabalin and pain after total

knee arthroplasty: a double-blind, randomized, placebo-controlled, multidose trial and

concluded as the pregabalin had no beneficial effects, but increased sedation and

decreased patient satisfaction and also this study does not support the routine

perioperative pregabalin for total knee arthroplasty patients.27

Sawan H et al., (2014) conducted a study on pregabalin reduces opiod

consumption and improves pain after total knee arthroplasty, even in patients who are

previous users of chronic pain medications shows that pregabalin in the context of

multimodal pain management may be associated with reduced opiod consumption and

other medical complications in patients undergoing TKA, including previous users of

chronic pain medications.30

Literature Review



Seiji Ohtori et al., (2013) studied the efficacy of meloxicam and pregabalin for

pain in knee osteoarthritis patients were divided in to 3 groups in to meloxicam,

pregabalin and meloxicam+pregabalin groups and pain scores are evaluated before and

after 4 weeks after drug application using Visual analogue scale and WOMAC and

reveals that a combination of meloxicam plus pregabalin was effective for OA pain in

OA patients. Furthermore, this study suggests that OA pain is a combination of

inflammatory and neuropathic pain components.12

Mohsen Mardani-Kivi et al., (2013) studied Celecoxib as a pre-emptive

analgesia after arthroscopic knee surgery; a triple-blinded randomized controlled trial to

examine the therapeutic effects of celecoxib in reducing pain following the arthroscopic

knee surgeries: anterior cruciate ligament (ACL) reconstruction and partial

meniscectomy and concluded that celecoxib as a pre-emptive analgesia agent is

effective in decreasing acute postoperative pain and 24 h opioid consumption in

patients undergoing arthroscopic knee surgery.29

Hance Clarke et al., (2012) studied the prevention of chronic postsurgical pain

using gabapentin and pregabalin: a combined systematic review and meta-analysis was

concluded by the perioperative administration of gabapentin and pregabalin are

effective in reducing the incidence of chronic postsurgical pain.34

Literature Review



S.Y. Kim et al., (2011) conducted Pregabalin reduces post-operative pain after

mastectomy: a double-blind, randomized, placebo-controlled study says Pregabalin is

used for the treatment of neuropathic pain and has shown analgesic efficacy in post-

operative pain and concluded that Perioperative administration of pregabalin for a single

day (75 mg twice daily) was easy, safe and effective in reducing post-operative pain in

patients undergoing mastectomy. 31

Dalim Kumar Baidya et al., (2011) studied pregabalin in acute and chronic pain

as concluded the pregabalin exhibits a significant opioid sparing effect in the first 24

hour and a significant reduction in opioid – related adverse effects (vomiting). The

incidence of visual disturbance is significant with pregabalin other side effects like

sedation and dizziness are also increased. However, pregabalin 150 – 600 mg / day

has a proven efficacy under chronic neuropathic pain conditions like painful diabetic

neuropathy, post therapeutic neuralgia, central neuropathic pain and fibromyalgia. It

may be more cost- effective than high dose gabapentin and may be effective in patients

who have previously failed to respond to gabapentin.38

SS Harsoor et al., (2011) studied Emergency concepts in postoperative pain

management as informed from this study pregabalin is known to produce analgesic,

sedative and anti-anxiety properties. The reports about its role in acute pain

management are equivocal, but its use in chronic pain is well established. The

properties such as the absence of respiratory depression, gastric-sparing effects and

anxiolysis make pregabalin a useful adjuvant even in the management of post-surgical

pain, but probably larger studies may be needed before the drug is advocated for

routine use.37

Literature Review



Spreng UJ et al., (2011) conducted a study on Effect of a single dose of

pregabalin on post-operative pain and pre-operative anxiety in patients undergoing

discectomy. A randomized, placebo-controlled study of 150 mg pregabalin administered

before lumbar discectomy in general anesthesia and concluded A single dose of

pregabalin (150 mg) reduced post-operative pain at rest and morphine consumption

during the post-anesthetic care unit period after lumbar discectomy. Pre-operative

anxiety was lower, without increased incidence of side effects. 35

J. Zhang et al., (2011) studied Efficacy of pregabalin in acute postoperative pain:

a meta-analysis and concluded that the perioperative administration of pregabalin has a

significant opioid-sparing effect in the first 24 hr after surgery. Postoperative vomiting

was reduced, whereas visual disturbance was more common with pregabalin

administration. The efficacy of perioperative pregabalin in more painful procedures and

on the prevention of chronic pain should be investigated in future studies.39

Asokumar Buvanendran et al., (2010) conducted a study on Perioperative oral

pregabalin reduces chronic pain after total knee arthroplasty: a prospective,

randomized, controlled trial. A randomized, placebo controlled , double blind trial was

conducted 240 patients randomly assigned to the two groups were obtained from 113

pregabalin patients an 115 placebo patients was concluded that perioperative

pregabalin administration reduces the incidence of chronic neuropathic pain after total

knee replacement, with less opioid consumption and better range of motion during the

first 30 days of rehabilitation. In the doses tested it is associated with a higher risk of

early postoperative sedation and confusion.40

https://www.ncbi.nlm.nih.gov/pubmed/?term=Spreng%20UJ%5BAuthor%5D&cauthor=true&cauthor_uid=21385158

Literature Review



Nalini Vadivelu et al., (2010) studied Recent advances inn postoperative pain

management says that recent years also have witnessed a heightened research interest

in the analgesic, sedative, anxiolytic and opioid sparing effects of pregabalin, a

structural analogue of GABA and derivative of gabapentin in various pain settings,

including postoperative pain. Pregabalin has a e4stablished efficacy of varying degree

in neuropathic pain conditions such as post therapeutic neuralgia, painful diabetic

neuropathy, central neuropathic pain and fibromyalgia. While some studies do not

demonstrate a significant analgesic effect in the acute, including postoperative pain

scenario other studies suggest pregabalin to have effective sedative and opioid sparing

effects useful characteristics for the control of acute pain.9

Carlo Luca Romano et al., (2009) conducted a study on pregabalin, celecoxib

and their combination for treatment of chronic low back pain a double blind, prospective

study concluded that the combination of celecoxib and pregabalin is more effective than

monotherapy for chronic low back pain, with similar adverse effects.43

R Andrew Moore et al., (2009) conducted a study on Pregabalin for acute and

chronic pain in adults. A Randomized, double blind trials reporting on the analgesic

effect of pregabalin, with subjective pain assessment by the patient as either the

primary or a secondary outcome and concluded that Pregabalin has proven efficacy in

neuropathic pain conditions and fibromyalgia. A minority of patients will have substantial

benefit with pregabalin, and more will have moderate benefit. Many will have no or trivial

benefit, or will discontinue because of adverse events. Individualization of treatment is

needed to maximize pain relief and minimize adverse events. There is no evidence to

support the use of pregabalin in acute pain scenarios. 49

Literature Review



Kishor Gandhi et al., (2009) studied multimodal pain management techniques in

hip and knee arthroplasty. He says that multimodal approach to pain control involves

administration of combination and often multiple analgesics or modalities at various time

points during the course of surgery that includes preoperative period. Pain control after

knee and hip arthroplasty can be achieved with the combination of drugs used during

the preoperative , intra operative and the post-operative periods (NSAIDs, COX 2

Inhibitors, α 2 agonist, NMDA antagonists, anti convulsants and centrally acting

analgesics as acetaminophen) was concluded multi model analgesia offers many

benefits to patients undergoing total joint arthroplasty. Opioids remain an integral part of

most analgesic plans but techniques that reduce opioid requirements typically improve

pain control both at rest and motion, reduce opioid relate3d side effects, provide better

patient satisfaction and according to a recent study, may reduce the incidence of long

term pain following surgery.17

Ittichaikulthol W et al., (2009) studied Effects of pregabalin on post-operative

morphine consumption and pain after abdominal hysterectomy with/without salphingo-

oophorectomy: a randomized, double-blind trial and to evaluate the effect of

premedication with pregabalin 300 mg compared with lorazepam 0.5 mg on post-

operative morphine consumption in women undergoing abdominal hysterectomy

with/without salphingo-oophorectomy and concluded A 300 mg pregabalin

administered 1 hr preoperatively before abdominal hysterectomy with/without salphingo-

oophorectomy significantly reduced morphine consumption, VNRS pain score and

improved satisfaction score at 24 hr post operatively without any significant differences

https://www.ncbi.nlm.nih.gov/pubmed/?term=Ittichaikulthol%20W%5BAuthor%5D&cauthor=true&cauthor_uid=19845240

Literature Review



in side effects. Pregabalin is an alternative combination to opioids as multimodal

analgesia.52

Aditya V Maheshwari et al., (2009) conducted a study on Multimodal pain

management after total hip and knee arthroplasty at the Ranawat Orthopedic Center as

concluded Multimodal protocols after THA and TKA have been a substantial advance;

they provide better pain control and patient satisfaction, lower overall narcotic

consumption, reduce hospital stay and improve function while minimizing complications.

Although no pain protocol is ideal, it is clear that patients should have optimum pain

control after THA and TKA for enhanced satisfaction and function.42

O. Mathiesen et al., (2008) conducted a study on Pregabalin and

dexamethasone for postoperative pain control: a randomized controlled study in hip

arthroplasty. In this study total one hundred and twenty patients were randomly divided

in to three groups in Group A (placebo) and Group B (pregabalin 300 mg) and Group C

(pregabalin + dexamethasone 8 mg). the medication and acetaminophen 1 g were

given before operation and the results are 24 hr morphine consumption was significantly

reduced in Group B and C compared with Group A. vomiting was reduced in Group C

compared with Group B. sedation was significantly increased in Group B compared with

the other groups and concluded from the study was Pregabalin resulted in a 50%

reduction in 24 h postoperative morphine requirements. This was not associated with a

reduced incidence of nausea or vomiting. Pregabalin resulted in increased levels of

sedation. Combining pregabalin and dexamethasone provided no additional effects on

pain or opioid requirements.44

Literature Review



Stefan Bergman et al., (2006) conducted Knee complaints vary with age and

gender in the adult population. Population based reference data for the knee injury and

Osteoarthritis Outcome Score (KOOS). The population based cohort study with Knee

specific KOOS was done in 840 subjects aged 18 to 84 yr patients. Result was 68%

response rate. Women in the age group 55 – 74 reported more knee related complaints

in all the KOOS subscales than age matched men. The differences were significant for

the subscales pain, symptoms and ADL function. In men, worse ADL and sport and

Recreation function was seen in the oldest age group 75 – 84 yrs compared to the

younger age groups. In Women, worse pain, ADL, sport and recreation and QOL were

seen already in the age group 55 – 74 compared to the younger age groups. The

concluded pain and other symptoms, physical function and knee related quality of life to

vary with age and gender implying the use of age and gender matched reference values

for improved understanding of the outcome after interventions due to knee injury and

knee OA.46

Ewa M Roos et al., (2003) studied the knee injury and Osteoarthritis outcome

score (KOOS): from joint injury to osteoarthritis was concluded KOOS was developed

as an extension of the WOMAC Osteoarthritis index with the purpose of evaluating short

and long term symptoms and function in young and physically active subjects with knee

injury and OA. The questions of the WOMAC LK 3.0 were retained so that a WOMAC

score might be calculated separately and compared with the KOOS score. As expected,

larger effects sizes for KOOS as compared with WOMAC were shown for young

subjects with knee injury.48

Literature Review



Asokumar Buvanendran et al., (2003) conducted a study on Effects of

Perioperative Administration of a Selective Cyclooxygenase 2 Inhibitor on Pain

Management and Recovery of Function after Knee Replacement a Randomized

Controlled Trial and concluded Perioperative use of an inhibitor of cyclooxygenase 2 is

an effective component of multimodal analgesia that reduces opioid consumption, pain,

vomiting, and sleep disturbance, with improved knee range of motion after TKA.49

M. Hyllested et al., (2002) conducted a study on Comparative effect of

paracetamol, NSAIDs or their combination in postoperative pain management: a

qualitative review was perform a systematic, qualitative review of postoperative pain

studies comparing paracetamol (min 1000 mg) with NSAID in a double- blind,

randomized manner as concluded Paracetamol is a viable alternative to the NSAIDs,

especially because of the low incidence of adverse effects, and should be the preferred

choice in the high risk patients. It may be appropriate to combine paracetamol with

NSAIDs, but future studies are required, especially after major surgery, with specific

focus on a potential increase in side effects from their combined use. 54

C.M.Hill et al., (2001) conducted a study on Pregabalin in patients with

postoperative dental pain A randomized, double-blind, placebo-controlled, parallel-

group trial was undertaken to compare pregabalin to placebo and 400 mg of ibuprofen

using a dental pain model administered postoperatively to patients and concluded

pregabalin group had a significantly longer duration of analgesia than the ibuprofen

group and had the highest score on the patient global impression of study medication.

Adverse events were reported more frequently in the pregabalin 300-mg group.62

Literature Review



John D. Bradley et al., (1991) conducted a study on Comparison of an Anti-

inflammatory dose of ibuprofen, an analgesic dose of ibuprofen and acetaminophen in

the treatment of patients with osteoarthritis of the knee. A randomized double blind trial,

184 patients with chronic knee pain due to osteoarthritis were given either 2400 or 1200

mg of ibuprofen per day or 4000 mg of acetaminophen per day and concluded

symptomatic treatment of osteoarthritis of the knee, the efficacy of acetaminophen was

similar to that of ibuprofen, whether the latter was administered in an analgesic or an

anti-inflammatory dose.59

Aim & Objectives



3. AIM AND OBJECTIVES

3.1 Aim:-

To assess the management of postoperative pain and the Quality of Life of

osteoarthritis patients after total knee arthroplasty.

3.2 Objectives:-

To assess the effect of NSAID’s Vs Pregabalin with NSAIDs after total knee

arthroplasty

To compare the Quality of Life of osteoarthritis patients after total knee

arthroplasty

Plan of Study

A Clinical Study On Management Of Postoperative Pain And Quality Of Life Of


4. PLAN OF STUDY

This study was carried out a period from the month of November 2016 to October 2017.

The proposed study has been designed below.

PHASE I

PHASE II

PHASE III

Identification of target area

for possible research

Literature review

Preparation of study

protocol

Designing of Data entry

form & Selection of

Questionnaire

Obtaining approval from

ethical committee

Obtaining consent from the

Patient

Data collection

Analysis of Data

Interpretation and

Reporting the Results

Methodology

A Clinical Study on Management of Postoperative Pain And Quality of Life of


5. METHODOLOGY

5.1 STUDY DESIGN:

The study was a Prospective Observational study.

5.2 STUDY SITE:

The study was carried out in the Department of Orthopedics at Vivekanandha

Medical Care Hospital, Tiruchengode.

5.3 DURATION OF THE STUDY:

The study was conducted from Nov 2016 to Oct 2017 in the Department of

Orthopedics.

5.4 INCLUSION CRITERIA:

Patient’s with 40 to 75 years of age

Both male and female patients

Patients with treatment of NSAID’s or Pregabalin with NSAID’s

Patients who underwent Total Knee Arthroplasty.

5.5 EXCLUSION CRITERIA:

Allergy or intolerance to any of the study drugs

Severe liver failure and heart or renal failure patients.

Patient with history of opioid medication usage.

Patient with bleeding disorder

Methodology



5.6 ETHICAL CLEARANCE:

The study was approved (Ref.No:SVCP/IEC/JAN/2016/12) by Institutional Ethical

Committee of Vivekanandha Medical Care Hospital (Annexure - 1).

5.7 STUDY POPULATION:

Total 245 patients medical and medication history were reviewed. From that 110

patients were included in the study as per the inclusion and exclusion criteria. Out of

which 14 patients were withdrawn from this study due to poor compliance and missed

follow up. Totally 96 patients were completed the study.

Total no of patients screened

(n = 245)

Total no of patients included Total no of patients excluded

(n = 110) (n = 135)

Total no of patients Completed the study Total no of patients withdrawn from the study

(n = 96) (n=14)

Group A (NSAID’s) Group B (Pregabalin with NSAID’s)

(n = 50) (n = 46)

Methodology



5.8 SOURCES OF DATA:

Patient case records.

Designed data entry form and pain questionnaire.

Medication charts and Lab reports and patient / patient care taker’s

interview.

Visual analogue pain Scale and Knee injury and Osteoarthritis Outcome

Score Pain questionnaire.

5.9 METHOD OF STUDY:

Patients were selected randomly to the study as per the inclusion and exclusion

criteria. Selected patients were divided in to two groups.

Group A consist 50 patients with the treatment of NSAIDs (Paracetamol 325 mg+

Aceclofenac 100 mg) and Group B consist 46 patients with the treatment of Pregabalin

75 mg + NSAIDs (Paracetamol 325 mg + Aceclofenac 100 mg)

The patient demographics data was collected by using data entry form. The

baseline score of pain, symptoms, Activities of daily living, Sport and recreation function

and quality of life assessed by using KNEE INJURY AND OSTEOARTHRITIS

OUTCOME SCORE (KOOS) questionnaire, to enrolled subjects were asked to answer

KOOS questionnaire and VISUAL ANALOGUE SCALE (VAS).

Methodology



The initial score was considered as a baseline. The study subjects were followed

once in 60 days for 6 months and they were asked to answer the same questionnaire.

The effect of the treatment was assessed by comparing the baseline score with follow

up score.

The Quality of Life of the patient before and after the treatment was assessed by

KOOS.

5.10 STATISTICAL ANALYSIS:

All results were analyzed using computerized statistical package of graph Pad

instat Version 3.10. Values are represented as Mean ± SD (standard Deviation). Scores

of KOOS Questionnaire and Visual Analogue Scale (VAS) were compared by using the

Student’s t-test. P<0.05 was considered as statistically significant.

Results



6. RESULTS

A total of 96 Osteoarthritis patients after Total Knee Arthroplasty were selected

as per inclusion and exclusion criteria. The demographic details, Visual Analogue pain

scale score and pain scores (KOOS) were collected at baseline. The study subjects

were followed once in 60 days for 6 months.

6.1 AGE WISE DISTRIBUTION AMONG THE STUDY POPULATION

Among 96 patients, 9.40% (9) were in the age group of 40 – 49 years, 24 % (23)

were in the age group of 50 – 59 years, 48 % (46) were in the age group of 60 – 69

years, 18.75 % (18) were in the age group of 70 – 79 years. The mean age of the study

population was 61.66 ± 7.56 years (range 40 - 79). (Table 1, Figure 4)

Table 1: AGE WISE DISTRIBUTION AMONG STUDY POPULATION (n = 96)

S. No AGE (YEARS) NO OF PATIENT PERCENTAGE

1. 40 – 49 09 09.40%

2. 50 – 59 23 24.00%

3. 60 – 69 46 48.00%

4. 70 – 79 18 18.75%

5. Mean Age 61.66 ± 7.56

Figure 4: AGE WISE DISTRIBUTION AMONG STUDY POPULATION (n = 96)

9.4

24

48

18.75

0

20

40

60

80

100

40-49 50-59 60-69 70-79

Pe

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ge

Age in Years

Results



6.2 GENDER WISE DISTRIBUTION AMONG STUDY POPULATION (n = 96)

A total of 96 osteoarthritis patients, males were 41.66% (40) and Females were

58.34 % (56). (Table 2, Figure 5)

Table 2: GENDER WISE DISTRIBUTION AMONG THE STUDY POPULATION

(n = 96)

S. No GENDER NUMBER OF PATIENT PERCENTAGE

1. MALE 40 41.66%

2. FEMALE 56 58.34%

Figure 5: GENDER WISE DISTRIBUTION AMONG THE STUDY POPULATION

Results



6.3 BODY MASS INDEX (BMI) AMONG THE STUDY POPULATION

A total of 96 osteoarthritis patients, 65.62% (63) were in normal body weight,

34.38% (33) were in over body weight. (Table 3, Figure 6)

Table 3: BMI AMONG THE STUDY POPULATION (n = 96)

S. No BMI NUMBER OF PATIENT PERCENTAGE

1. NORMAL WEIGHT 63 65.62%

2. OVER WEIGHT 33 34.38%

BMI - Body Mass Index

Figure 6: BMI AMONG THE STUDY POPULATION (n = 96)

65.62

34.38

0

10

20

30

40

50

60

70

80

90

100

Normal Weight Overweight

Pe

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BMI

Results



6.4 COMPARISON OF EFFECT OF NSAIDs AND PREGABALIN WITH NSAIDs FOR

OSTEOARTHRITIS AFTER TKA ON VAS

On VAS score, there were significant differences between baseline 5.7 ±

0.58 and 2nd follow up was 4.42 ± 0.86 of NSAIDs alone and Pregabalin with NSAIDs

baseline 5.6 ± 0.93 and follow up 2 2.56 ± 0.34. P< 0.01 (Table 4, figure 7)

Table 4: COMPARISON OF NSAIDs Vs PREGABALIN WITH NSAIDs ON VAS

S. No VAS SCORE BASELINE FOLLOW UP-1 FOLLOW UP-2

1. NSAIDs

5.7 ± 0.58

5.18 ± 0.59

4.42 ± 0.86 **

2. PREGABALIN WITH

NSAIDS

5.6 ± 0.93

3.97 ± 0.46

2.56 ± 0.34 **

NSAIDs- Non Steroidal Anti-inflammatory Drugs, VAS – Visual Analogue Scale ** p < 0.01

Figure 7: COMPARISON OF NSAIDs Vs PREGABALIN WITH NSAIDs ON VAS

5.7

5.18

4.42

5.6

3.19

2.56

0

1

2

3

4

5

6

Baseline Follow Up 1 Follow Up 2

VA

S S

CO

RE

NSAIDS Vs Pregabalin with NSAIDs

NSAIDs

Preg with NSAIDs

Results



6.5 EFFECT OF NSAIDs DRUG FOR OSTEOARTHRITS PATIENTS AFTER TKA

USING KOOS QUESTIONNAAIRE

The mean score of overall KOOS score at baseline of pain was 62.78 ± 7.92 and

2nd follow up was 79.06 ± 6.68 which shows the significant difference among the

participants (p˂ 0.01) (Table 5, Figure 8)

Table 5: EFFECT OF NSAIDs FOR OSTEOARTHRITS PATIENTS AFTER TKA

S. No PARAMETERS BASELINE FOLLOW UP-1 FOLLOW UP-2

1. Pain 62.78 ± 7.92 70.84 ± 6.70 79.06 ±6.68 **

2. Symptoms 61.28 ± 11.72 68.36 ± 11.84 78.56 ± 9.80 **

3. Activities of Daily Living 76.42 ± 6.46 82.42 ± 5.41 88.14 ± 3.55 **

4. SRF 91.3 ± 2.82 92.7 ± 3.61 93.8 ± 3.28 **

5. QOL 57.7 ± 9.63 59.38 ± 8.80 64.92 ± 6.00 **

SRF – Sports and Recreation Function, QOL – Quality of Life **P<0.01

Figure 8: EFFECT OF NSAIDs FOR OSTEOARTHRITS PATIENTS AFTER TKA

62.78 61.28

76.42

91.3

57.7

70.84 68.36

82.42

92.7

59.38

79.06 78.56

88.14 93.8

64.92

0

10

20

30

40

50

60

70

80

90

100

Pain Symptoms ADL SRF QOL

Pe

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ge

NSAIDs DRUG FOR OA PATTIENTS AFTER TKA

Baseline

Follow Up 1

Follow Up 2

Results



6.6 EFFECT OF PREGABALIN WITH NSAIDs FOR OSTEOARTHRITIS PATIENTS

AFTER TKA USING KOOS QUESTIONNAIRE

The mean score of overall KOOS pain score at baseline of pain was 67.19 ± 5.73

and 2nd follow up was 92.73 ± 3.45 which shows the significant difference among the

participants (p ˂ 0.01) (Table 6, Figure 9)

Table 6: EFFECT OF PREGABALIN WITH NSAIDs FOR OSTEOARTHRITIS

PATIENTS AFTER TKA USING KOOS QUESTIONNAIRE

S. No PARAMETERS BASELINE FOLLOW UP-1 FOLLOW UP-2

1. Pain 67.19 ± 5.73 84.96 ± 4.02 92.73 ± 3.45**

2. Symptoms 67.87 ± 8.35 83.56 ± 6.23 89.23 ± 3.59**

3. Activity of Daily Living 80.21 ± 5.40 89.52 ± 2.14 94.97 ± 2.71**

4. SRF 92.39 ± 5.55 93.58 ± 4.03 92.60 ± 2.52**

5. QOL 57.5 ± 8.18 71.60 ± 3.49 81.56 ± 5.29**

SRF – Sports and Recreation Function, QOL – Quality of Life **P<0.01

Figure 9: EFFECT OF PREGABALIN WITH NSAIDS FOR OA PATIENTS AFTER

TKA

67.19 67.87

80.21

92.39

57.5

84.96 84.96 89.52

93.58

71.6

92.73 89.23 94.97

92.6

81.56

0

10

20

30

40

50

60

70

80

90

100


Pe

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PREG WITH NSAIDs FOR OA PATIENTS AFTER TKA

Baseline

Follow Up 1

Follow Up 2

Results




OSTEOARTHRITIS AFTER TKA ON PAIN

On pain, there were significant differences between baseline 62.78 ± 7.92 and 2nd follow

up 79.06 ± 6.68 of NSAIDs alone and Pregabalin with NSAIDs baseline 67.19 ± 5.73

and 2nd follow up 92.73 ± 3.45 (p< 0.01)

Table 7: COMPARISON OF NSAIDs Vs PREGABALIN WITH NSAIDs ON PAIN

S. No GROUP BASELINE FOLLOW UP-1 FOLLOW UP-2

1. NSAIDs 62.78 ± 7.92

70.84 ± 6.70

79.06 ± 6.68**

2. PREGABALIN WITH NSAIDS

67.19 ± 5.73

84.96 ± 4.02

92.73 ± 3.45**


Figure 10: COMPARISON OF NSAIDs Vs PREGABALIN WITH NSAIDs ON PAIN

62.78

70.84

79.06

67.19

84.96

92.73

0

10

20

30

40

50

60

70

80

90

100


Pe

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ge

NSAIDS Vs Pregabalin with NSAIDs on Pain

NSAIDs

Preg with NSAIDs

Results




OSTEOARTHRITIS AFTER TKA ON SYMPTOMS

On Symptoms, there were significant differences between baseline 61.28 ± 11.72

and 2nd follow up 78.56 ± 9.80 of NSAIDs alone and Pregabalin with NSAIDs baseline

67.87 ± 8.35 and 2nd follow up 89.23 ± 3.59. P< 0.01

Table 8: COMPARISON OF NSAIDs Vs PREGABALIN WITH NSAIDs ON

SYMPTOMS


1. NSAIDs 61.28 ± 11.72

68.36 ± 11.84

78.56 ± 9.80 **


67.87 ± 8.35

83.56 ± 6.23

89.23 ± 3.59 **


Figure 11: COMPARISON OF NSAIDs Vs PREGABALIN WITH NSAIDs ON

SYMPTOMS

61.28 68.36

78.56

67.87

83.56 89.23

0

20

40

60

80

100


Pe

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nta

ge

NSAIDS Vs Pregabalin with NSAIDs on Symptoms

NSAIDs

Preg with NSAIDs

Results




OSTEOARTHRITIS AFTER TKA ON ACTIVITY OF DAILY LIVING

On Activity of Daily Living, there were significant differences between baseline

76.42 ± 6.46 and 2nd follow up 88.14 ± 3.55 of NSAIDs alone and Pregabalin with

NSAIDs baseline 80.21 ± 5.40 and 2nd follow up 94.97 ± 2.71. P< 0.01

Table 9: COMPARISON OF NSAIDs Vs PREGABALIN WITH NSAIDs ON ADL


1. NSAIDs 76.42 ± 6.46

82.42 ± 5.41

88.14 ± 3.55 **


80.21 ± 5.40

89.52 ± 2.14

94.97 ± 2.71 **

NSAIDs- Non Steroidal Anti-inflammatory Drugs, ADL – Activities of Daily Living ** P < 0.01

Figure 12: COMPARISON OF NSAIDs Vs PREGABALIN WITH NSAIDs ON ADL

76.42 82.42

88.14

80.21

89.52 94.97

0

10

20

30

40

50

60

70

80

90

100


Pe

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ntg

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Pregabalin with NSAIDs on ADL

NSAIDs

Preg with NSAIDs

Results



6.10 COMPARISON OF EFFECT OF NSAIDs AND PREGABALIN WITH NSAIDs

FOR OSTEOARTHRITIS AFTER TKA ON SPORT AND RECREATION FUNCTION

On Sport and Recreation Function, there were significant differences

between baseline 91.3 ± 2.82 and 2nd follow up 93.8 ± 3.28 of NSAIDs alone and

Pregabalin with NSAIDs baseline 92.39 ± 5.55 and 2nd follow up 92.60 ± 2.52. P< 0.01

Table 10: COMPARISON OF NSAIDs Vs PREGABALIN WITH NSAIDs ON SRF


1. NSAIDs 91.3 ± 2.82

92.7 ± 3.61

93.8 ± 3.28 **


92.39 ± 5.55

93.58 ± 4.03

92.60 ± 2.52 *

SRF – Sport and Recreation Function ** P < 0.01

Figure 13: COMPARISON OF NSAIDs Vs PREGABALIN WITH NSAIDs ON SRF

91.3 92.7 93.8 92.39 93.58 92.6

0

10

20

30

40

50

60

70

80

90

100


Pe

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NSAIDS Vs Pregabalin with NSAIDs on SRF

NSAIDs

Preg with NSAIDs

Results



6.11 COMPARISON QUALITY OF LIFE OF NSAIDs Vs NSAIDs AND PREGABALIN

GROUP

On Quality of Life, there were significant differences between baseline 57. 7 ±

9.63 and 2nd follow up 64.92 ± 6.00 of NSAIDs s alone and Pregabalin with NSAIDs

baseline 57.5 ± 8.18 and 2nd follow up 81.56 ± 5.29. (P< 0.01)

Table 11: COMPARISON OF NSAIDs Vs PREGABALIN WITH NSAIDs ON QOL


1. NSAIDs 57. 7 ± 9.63

59.38 ± 8.80

64.92 ± 6.00 **


57.5 ± 8.18

71.60 ± 3.49

81.56 ± 5.29 **

QOL – Quality Of Life ** P < 0.01

Figure 14: COMPARISON OF NSAIDs Vs PREGABALIN WITH NSAIDs ON QOL

76.42

82.42 88.14

80.21

89.52 94.97

0

10

20

30

40

50

60

70

80

90

100


Pe

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ntg

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Pregabalin with NSAIDs on QOL

NSAIDs

Preg with NSAIDs

Results



6.12 COMPARISON OF EFFECTIVENESS OF GROUP A & B BY KOOS

QUESTTIONNAIRE

On KOOS score, there were significant differences between Group A & Group B

on Pain, Symptoms, ADL and QOL but Sport and Recreation Function was not

significant. (p < 0.01)

Table 12: COMPARISON OF EFFECTIVENESS OF GROUP A & GROUP B

S. No PARAMETERS GROUP A GROUP B

1. Pain 79.06 ±6.68 92.73 ± 3.45 **

2. Symptoms 78.56 ± 9.80 89.23 ± 3.59 **

3. Activities of Daily Living 88.14 ± 3.55 94.97 ± 2.71 **

4. SRF 93.8 ± 3.28 92.60 ± 2.52

5. QOL 64.92 ± 6.00 81.56 ± 5.29 **

SRF – Sport & Recreation Function, QOL – Quality of Life. ** p < 0.01

FIGURE 15: COMPARISON OF EFFECTIVENESS OF GROUP A & GROUP B

0

10

20

30

40

50

60

70

80

90

100


79.06 78.56

88.14 93.8

64.92

92.73 89.23

94.97 92.6

81.56

Pe

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COMPARISON OF EFFECTIVENESS OF GROUP A & B

Group A

Group B

Discussion



7. DISCUSSION

The study comprised 96 patients, out of which 46 patients were in the age

group of 60 - 69 years. In this study, the female patients (58.34%) were more

suffered by Osteoarthritis than male patients (41.66%). Seiji Ohtori et al 12 showed

that mean age of 70.0±8.0 years while that of this study was 61.65 ± 7.55 years.

In this study majority of patients were normal weights (65.62%). As per the

study Asokumar Buvanendran et al36 the majority of the patients were having over

body weight.

Comparison of Effect of NSAIDs Vs Pregabalin with NSAIDs on VAS

In this study totally 96 patients divided in to two different groups evaluated

pain at movement after total knee arthroplasty.

Analysis of NSAIDs group showed that the mean difference VAS score was

5.7 ± 0.58 on Baseline, 5.18 ± 0.59 on first review and 4.42 ± 0.86 on final review.

The mean difference was statistically significant and the result was clearly indicates

the mean decrease the pain score. (p< 0.01).

Analysis of Pregabalin with NSAIDs group showed that the mean difference

VAS score was 5.6 ± 0.93 on baseline, 3.97 ± 0.46 on First review and 2.56 ± 0.34

on second review. The mean difference was statistically significant and the result

indicates the mean decrease the pain score. (p< 0.01).

Discussion



NSAIDs Vs Pregabalin with NSAIDs group compared and analysed, that the

mean difference of VAS on Baseline after TKA was not statistically significant and

the p value was < 0.88 but on the first review the mean difference was statistically

significant. The result indicates the mean difference of Group B was decrease the

pain score than NSAIDs alone.

Fei Li et al 21 resulted to indicate that the pregabalin played an important role

in the VAS with rest at 24 hr and 48 hr, No statistically significant differences were

found in the VAS score with rest at 72 hr and VAS on movement at 24 hr between

the pregabalin group and the control group.

Jokela et al 55 found that premedication with 75 or 150 mg pregabalin

significantly reduced the VAS score for postoperative pain at 24 hr after laparoscopic

gynaecologic surgery (p < 0.05) when compared with diazepam 5 mg.

O. Mathiesen et al 40 have reported that pregabalin administration could

reduce the VAS score at 24 hr compared with placebo postoperatively.

Gianesello et al 56 showed that perioperative administration of pregabalin at a

dose of 300 mg everyday resulted in a significant reduction in VAS scores at 48 hr

postoperatively for patients undergoing major spinal surgery. These outcomes

demonstrate that administration of pregabalin could reduce VAS score at 24 and 48

h with rest after surgery. The VAS at 72 h with rest postoperatively was not

significant in our pooled data. The decreased benefits of pregabalin on pain during

movement could be explained by the short mean elimination half-life of pregabalin.

No significant difference was found in VAS on movement at 24 h, and the result was

similar to another meta-analysis of pregabalin for tonsillectomy.

Discussion



Compared with our studies these outcomes are not significant of VAS score.

The score of the pregabalin group was lower than that of the control group. In

summary, preoperative administration of pregabalin could improve acute pain control

after TKA.

Comparison of Effect of NSAIDs Vs Pregabalin with NSAIDs on KOOS

The perioperative administration of pregabalin to patients undergoing TKA

was a significant decrease in the incidence of chronic neuropathic pain 3 month after

surgery. Neuropathic pain of the operated knee can result in substantial discomfort

and limit activities of daily living. This is the first large prospective clinical trial

examining the incidence of chronic neuropathic pain after TKA and defining a

strategy to prevent the development of this distressing chronic pain syndrome.

Fassoulaki A et al 57, the administration of gabapentin to woman undergoing

total abdominal hysterectomy did not reduce acute postoperative pain, but there was

a decrease in pain at I month postoperatively.

In our study, perioperative administration of pregabalin with NSAIDs

pregabalin with NSAIDs group was more effective in reducing pain compared with

NSAIDs alone group.

Asokumar Buvanendran et al 36 resulted that the efficacy of the perioperative

use of pregabalin to reduce chronic neuropathic after TKA.

The pregabalin with NSAIDs was also effective in improved active and

passive ROM after TKA in our study compared with NSAIDs alone group patients.

The mean difference KOOS Score of symptoms was statically significant (p<0.01)

and result indicates the symptoms was decreased and the knee flexion was

improved compared with NSAIDs alone.

Discussion



Chiu KY et al 58 resulted that oral perioperative administration of Pregabalin

improved knee flexion and ROM after TKA. This study is statistically significant of our

study. It has been demonstrated that knee flexion was performed and questioned at

every reviews to patients of stiffness after wakening in the morning, stiffness after

sitting or lying or resting later in the day, swelling in the knee, feeling of grinding,

hear clicking sound from the knees and straighten and bending knee fully and

walking. The patients was performed well in straighten and bending knee fully.

It is likely that this beneficial effect on knee function after total knee

arthroplasty was attainment of nearly full functionality in the Pregabalin with NSAIDs

group compared with NSAIDs alone.

Analysis of Activities and daily living after TKA in NSAIDs Vs Pregabalin with

NSAIDs group patients the mean difference was statistically significant (p < 0.01) in

final review. The result indicates the ADL was improved in Pregabalin with NSAIDs

group compared with NSAIDs alone group.

The comparison and analysed of SRF of NSAIDs Vs Pregabalin with NSAIDs

group was not statistically significant (p < 0.03) on second review. The result

indicated the Pregabalin with NSAIDs group was not significant compared with

NSAIDs group.

Discussion



QUALITY OF LIFE

In our study that the QOL was significantly improved in Pregabalin with

NSAIDs compared as NSAIDs plain group.

Compared and analysed of NSAIDs and Pregabalin with NSAIDs group was

the mean difference of NSAIDs group the quality of life was statistically not

significant on first Review (p < 0.0.3). but comparison of first review and second

review the quality of life was statically significant. The result indicated the QOL was

improved. The mean difference of Pregabalin with NSAIDs group was statistically

significant on every review. The result indicates mean difference of QOL was

improved. The comparison of NSAIDs group and Pregabalin with NSAIDs group the

mean difference was statistically significant on first and second reviews.

Based on these findings, Pregabalin with NSAIDs group patients had less

pain and more QOL of OA patients after total knee arthroplasty compared with

NSAIDs group patients.

Conclusion



8. CONCLUSION

The present study showed that pregabalin with NSAIDs group was more

effective in reducing pain after total knee arthroplasty as compared with NSAIDs

group.

As per the study, pregabalin with NSAIDs group results revealed that a better

improvement in osteoarthritis symptoms, activities of daily living and quality of life

within short duration as compared to NSAIDS used patients. Regular patient

counselling, maintenance of diet and exercise with good patient compliance may

improve the quality of life of patients in day to day activities.

However, long term treatment of pregabalin may reduce the dependence of

analgesics and decrease the OA related neuropathic pain incidence. There by we

can reduce the NSAIDs related side effects and improve the overall quality of life of

OA patient after arthroplasty.

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Vivekanandha Medical Care Hospital, Elayampalayam

Institutional Ethics Committee

INFORMED CONSENT FORMAT FOR RESEARCH PROJECTS

(Strike off items that are not applicable)

I / We (write name of the investigator(s) here), am / are carrying

out a study on the topic: as part of my / our research

project being carried out under the aegis of the Department of:

(Applicable to students only): My / our research guide is:

The justification for this study is:

The objectives of this study are:

Primary Objective:

Secondary Objective:

Sample size:

Study volunteers / participants are (specify population group & age group):

Location:

We request you to kindly cooperate with us in this study. We propose collect background information

and other relevant details related to this study. We will be carrying out:

Initial interview (specify approximate duration):

Data collected will be stored for a period of years. We will / will not use the data as part of another

study.

Health education sessions: Number of sessions: 1.Approximate duration of each session:

Clinical examination (Specify details and purpose):

Blood sample collection: Specify quantity of blood being drawn: No. of times it will be collected:

Whether blood sample collection is part of routine procedure or for research (study) purpose:

1. Routine procedure 2. Research purpose

Specify purpose, discomfort likely to be felt and side effects, if any:

Whether blood sample collected will be stored after study period: Yes / No, it will be destroyed

Whether blood sample collected will be sold: Yes / No

Whether blood sample collected will be shared with persons from another institution: Yes / No

Medication given, if any, duration, side effects, purpose, benefits:

Whether medication given is part of routine procedure: Yes / No (If not, state reasons for giving this

medication)

Whether alternatives are available for medication given: Yes / No (If not, state reasons for giving this

particular medication)

Final interview (specify approximate duration): NA If photograph is taken, purpose:

Benefits from this study:

Risks involved by participating in this study:

How the results will be used:

If you are uncomfortable in answering any of our questions during the course of the interview /

biological sample collection, you have the right to withdraw from the interview / study at anytime.

You have the freedom to withdraw from the study at any point of time. Kindly be assured that your

refusal to participate or withdrawal at any stage, if you so decide, will not result in any form of

compromise or discrimination in the services offered nor would it attract any penalty. You will continue

to have access to the regular services offered to a patient. You will NOT be paid any remuneration for

the time you spend with us for this interview / study. The information provided by you will be kept in

strict confidence. Under no circumstances shall we reveal the identity of the respondent or their families

to anyone. The information that we collect shall be used for approved research purposes only. You will

be informed about any significant new findings - including adverse events, if any, – whether directly

related to you or to other participants of this study, developed during the course of this research which

may relate to your willingness to continue participation.

Consent: The above information regarding the study, has been read by me/ read to me, and has been

explained to me by the investigator/s. Having understood the same, I hereby give my consent to them

to interview me. I am affixing my signature / left thumb impression to indicate my consent and

willingness to participate in this study (i.e., willingly abide by the project requirements).

Signature / Left thumb impression of the Study Volunteer / Legal Representative:

Signature of the Interviewer with date: Witness:

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SSWWAAMMYY VVIIVVEEKKAANNAANNDDHHAA CCOOLLLLEEGGEE OOFF PPHHAARRMMAACCYY

Elayampalayam – 637205

Department of Pharmacy Practice

1 of 2 SVCP/DPP/F-02/16/01

CASE ANALYSIS FORM

Case No: Department DOA DOD

Patient Name Age Sex Height

Family History Occupation

Weight

Complaints on Admission

Medical History Medication History

Social History (Smoker, Alcoholic, Tea, Coffee,

Tobacco, Betel Nuts, Pan etc..)

Allergies ( Drugs, Foods and Others)

Physical Examination

Temp BP PR RR

Lab Investigation

S. No Lab Parameter Value Normal

Range S. No Lab Parameter Value

Normal

Range

Urine Analysis

Imaging Study Report

SSWWAAMMYY VVIIVVEEKKAANNAANNDDHHAA CCOOLLLLEEGGEE OOFF PPHHAARRMMAACCYY

Elayampalayam – 637205

Department of Pharmacy Practice

2 of 2 SVCP/DPP/F-02/16/01

Medication Chart

S.No Brand Name

(Generic Name) Dose Frequency

Date of Administration

Discharge Medication

S.No Brand Name (Generic Name) Dose Frequency / Duration

Prepared by: Verified by:

Final Diagnosis

Progress Chart

S. No Date BP Temp PR RR Others

ANNEXURE V - Visual Analogue Scale


Source: Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee Injury and Osteoarthritis

Outcome Score (KOOS)--development of a self-administered outcome measure. J Orthop Sports Phys Ther.

1998 Aug;28(2):88-96.

The Knee Injury and Osteoarthritis Outcome Score (KOOS) is a questionnaire designed to assess short and

long-term patient-relevant outcomes following knee injury. The KOOS is self-administered and assesses five

outcomes: pain, symptoms, activities of daily living, sport and recreation function, and knee-related quality of

life. The KOOS meets basic criteria of outcome measures and can be used to evaluate the course of knee

injury and treatment outcome. KOOS is patient-administered, the format is user-friendly and it takes about 10

minutes to fill out.

Scoring instructions

The KOOS's five patient-relevant dimensions are scored separately: Pain (nine items); Symptoms (seven

items); ADL Function (17 items); Sport and Recreation Function (five items); Quality of Life (four items). A

Likert scale is used and all items have five possible answer options scored from 0 (No problems) to 4

(Extreme problems) and each of the five scores is calculated as the sum of the items included.

Interpretation of scores

Scores are transformed to a 0–100 scale, with zero representing extreme knee problems and 100

representing no knee problems as common in orthopaedic scales and generic measures. Scores between 0

and 100 represent the percentage of total possible score achieved.

Page 1


Page 2


Pain

P1 How often is your knee painful? Never Monthly Weekly Daily Always

What degree of pain have you experienced the last week when…?

P2 Twisting/pivoting on your knee None Mild Moderate Severe Extreme

P3 Straightening knee fully None Mild Moderate Severe Extreme

P4 Bending knee fully None Mild Moderate Severe Extreme

P5 Walking on flat surface None Mild Moderate Severe Extreme

P6 Going up or down stairs None Mild Moderate Severe Extreme

P7 At night while in bed None Mild Moderate Severe Extreme

P8 Sitting or lying None Mild Moderate Severe Extreme

P9 Standing upright None Mild Moderate Severe Extreme

Symptoms

Sy1 How severe is your knee stiffness after first wakening in the morning?

None Mild Moderate Severe Extreme

Sy2 How severe is your knee stiffness after sitting, lying, or resting later in the day?


Sy3 Do you have swelling in your knee?

Never Rarely Sometimes Often Always

Sy4 Do you feel grinding, hear clicking or any other type of noise when your knee moves?


Sy5 Does your knee catch or hang

up when moving?


Sy6 Can you straighten your knee fully?

Always Often Sometimes Rarely Never

Sy7 Can you bend your knee fully? Always Often Sometimes Rarely Never


Page 3

Activities of daily living

What difficulty have you experienced the last week…?

A1 Descending None Mild Moderate Severe Extreme

A2 Ascending stairs None Mild Moderate Severe Extreme

A3 Rising from sitting None Mild Moderate Severe Extreme

A4 Standing None Mild Moderate Severe Extreme

A5 Bending to floor/picking up an object


A6 Walking on flat surface None Mild Moderate Severe Extreme

A7 Getting in/out of car None Mild Moderate Severe Extreme

A8 Going shopping None Mild Moderate Severe Extreme

A9 Putting on socks/stockings None Mild Moderate Severe Extreme

A10 Rising from bed None Mild Moderate Severe Extreme

A11 Taking off socks/stockings None Mild Moderate Severe Extreme

A12 Lying in bed (turning over,

maintaining knee position)


A13 Getting in/out of bath None Mild Moderate Severe Extreme

A14 Sitting None Mild Moderate Severe Extreme

A15 Getting on/off toilet None Mild Moderate Severe Extreme

A16 Heavy domestic duties (shovelling, scrubbing floors, etc)


A17 Light domestic duties (cooking, dusting, etc)


Sport and recreation function

What difficulty have you experienced the last week…?

Sp1 Squatting None Mild Moderate Severe Extreme

Sp2 Running None Mild Moderate Severe Extreme

Sp3 Jumping None Mild Moderate Severe Extreme

Sp4 Turning/twisting on your injured

knee


Sp5 Kneeling None Mild Moderate Severe Extreme


Page 4

Knee-related quality of life

Q1 How often are you aware of your

knee problems?

Never Monthly Weekly Daily Always

Q2 Have you modified your lifestyle to avoid potentially damaging activities to your knee?

Not at all Mildly Moderately Severely Totally

Q3 How troubled are you with lack of confidence in your knee?

Not at all Mildly Moderately Severely Totally

Q4 In general, how much difficulty

do you have with your knee?


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a clinical study on management of postoperative pain …

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