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:
SWAMY VIVEKANANDHA COLLEGE OF PHARMACY
Elayampalayam, Tiruchengode-637205
Namakkal (Dt.), Tamilnadu.
Phone: 04288-234417
Fax: 04288-234417
Dr. T. TAMILSELVAN, M. Pharm., Ph.D.,
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.
Dr. T. TAMILSELVAN, M. Pharm., Ph.D.,
Place:
Date:
SWAMY VIVEKANANDHA COLLEGE OF PHARMACY
Elayampalayam, Tiruchengode-637205
Namakkal (Dt.), Tamilnadu.
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:
SWAMY VIVEKANANDHA COLLEGE OF PHARMACY
Elayampalayam, Tiruchengode-637205
Namakkal (Dt.), Tamilnadu.
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
9. Comparison of NSAIDs Vs Pregabalin with NSAIDs on
Activities and Daily Living 55
10. Comparison of NSAIDs Vs Pregabalin with NSAIDs on
Sport and Recreation Function 56
11. Comparison of NSAIDs Vs Pregabalin with NSAIDs on
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
11. Comparison of NSAIDs Vs Pregabalin with NSAIDs on
Symptoms 54
12. Comparison of NSAIDs Vs Pregabalin with NSAIDs on
Activities and Daily Living 55
13. Comparison of NSAIDs Vs Pregabalin with NSAIDs on
Sport and Recreation Function 56
14. Comparison of NSAIDs Vs Pregabalin with NSAIDs on
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
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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
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Osteoarthritis Patients After Total Knee Arthroplasty Page 2
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
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Osteoarthritis Patients After Total Knee Arthroplasty Page 3
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
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Osteoarthritis Patients After Total Knee Arthroplasty Page 4
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
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Osteoarthritis Patients After Total Knee Arthroplasty Page 5
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.
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Osteoarthritis Patients After Total Knee Arthroplasty Page 6
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
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Osteoarthritis Patients After Total Knee Arthroplasty Page 7
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
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Osteoarthritis Patients After Total Knee Arthroplasty Page 8
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
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Osteoarthritis Patients After Total Knee Arthroplasty Page 9
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
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Osteoarthritis Patients After Total Knee Arthroplasty Page 10
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
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Osteoarthritis Patients After Total Knee Arthroplasty Page 11
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
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Osteoarthritis Patients After Total Knee Arthroplasty Page 12
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
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Osteoarthritis Patients After Total Knee Arthroplasty Page 13
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
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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
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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
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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
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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
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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
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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
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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.
Mechanism of Action:
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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.
Adverse drug Reaction:
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.
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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).
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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.
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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.
Mechanism of Action:
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.
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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.
Adverse drug Reaction:
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.
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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.
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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)
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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)
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 39
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
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 40
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
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 41
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
Osteoarthritis Patients After Total Knee Arthroplasty Page 42
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
Osteoarthritis Patients After Total Knee Arthroplasty Page 43
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
A Clinical Study on Management of Postoperative Pain And Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 44
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
A Clinical Study on Management of Postoperative Pain And Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 45
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
A Clinical Study on Management of Postoperative Pain And Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 46
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
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 47
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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nta
ge
Age in Years
Results
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 48
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
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 49
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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nta
ge
BMI
Results
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 50
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
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 51
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
rce
nta
ge
NSAIDs DRUG FOR OA PATTIENTS AFTER TKA
Baseline
Follow Up 1
Follow Up 2
Results
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 52
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
Pain Symptoms ADL SRF QOL
Pe
rce
nta
ge
PREG WITH NSAIDs FOR OA PATIENTS AFTER TKA
Baseline
Follow Up 1
Follow Up 2
Results
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 53
6.7 COMPARISON OF EFFECT OF NSAIDs AND PREGABALIN WITH NSAIDs FOR
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**
NSAIDs- Non Steroidal Anti-inflammatory Drugs, VAS – Visual Analogue Scale ** p < 0.01
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
Baseline Follow Up 1 Follow Up 2
Pe
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nta
ge
NSAIDS Vs Pregabalin with NSAIDs on Pain
NSAIDs
Preg with NSAIDs
Results
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 54
6.8 COMPARISON OF EFFECT OF NSAIDs AND PREGABALIN WITH NSAIDs FOR
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
S. No GROUP BASELINE FOLLOW UP-1 FOLLOW UP-2
1. NSAIDs 61.28 ± 11.72
68.36 ± 11.84
78.56 ± 9.80 **
2. PREGABALIN WITH NSAIDS
67.87 ± 8.35
83.56 ± 6.23
89.23 ± 3.59 **
NSAIDs- Non Steroidal Anti-inflammatory Drugs, VAS – Visual Analogue Scale ** p < 0.01
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
Baseline Follow Up 1 Follow Up 2
Pe
rce
nta
ge
NSAIDS Vs Pregabalin with NSAIDs on Symptoms
NSAIDs
Preg with NSAIDs
Results
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 55
6.9 COMPARISON OF EFFECT OF NSAIDs AND PREGABALIN WITH NSAIDs FOR
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
S. No GROUP BASELINE FOLLOW UP-1 FOLLOW UP-2
1. NSAIDs 76.42 ± 6.46
82.42 ± 5.41
88.14 ± 3.55 **
2. PREGABALIN WITH NSAIDS
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
Baseline Follow Up 1 Follow Up 2
Pe
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ntg
e
Pregabalin with NSAIDs on ADL
NSAIDs
Preg with NSAIDs
Results
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 56
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
S. No GROUP BASELINE FOLLOW UP-1 FOLLOW UP-2
1. NSAIDs 91.3 ± 2.82
92.7 ± 3.61
93.8 ± 3.28 **
2. PREGABALIN WITH NSAIDS
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
Baseline Follow Up 1 Follow Up 2
Pe
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nta
ge
NSAIDS Vs Pregabalin with NSAIDs on SRF
NSAIDs
Preg with NSAIDs
Results
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 57
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
S. No GROUP BASELINE FOLLOW UP-1 FOLLOW UP-2
1. NSAIDs 57. 7 ± 9.63
59.38 ± 8.80
64.92 ± 6.00 **
2. PREGABALIN WITH NSAIDS
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
Baseline Follow Up 1 Follow Up 2
Pe
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Pregabalin with NSAIDs on QOL
NSAIDs
Preg with NSAIDs
Results
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Osteoarthritis Patients After Total Knee Arthroplasty Page 58
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
Pain Symptoms ADL SRF QOL
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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nta
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COMPARISON OF EFFECTIVENESS OF GROUP A & B
Group A
Group B
Discussion
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 59
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
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 60
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
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 61
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
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 62
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
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 63
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
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 64
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.
References
A Clinical Study on Management of Postoperative Pain and Quality of Life of
Osteoarthritis Patients After Total Knee Arthroplasty Page 65
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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
Knee Injury and Osteoarthritis Outcome Score (KOOS)
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
Knee Injury and Osteoarthritis Outcome Score (KOOS)
Page 2
Knee Injury and Osteoarthritis Outcome Score (KOOS)
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?
None Mild Moderate Severe Extreme
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?
Never Rarely Sometimes Often Always
Sy5 Does your knee catch or hang
up when moving?
Never Rarely Sometimes Often Always
Sy6 Can you straighten your knee fully?
Always Often Sometimes Rarely Never
Sy7 Can you bend your knee fully? Always Often Sometimes Rarely Never
Knee Injury and Osteoarthritis Outcome Score (KOOS)
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
None Mild Moderate Severe Extreme
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)
None Mild Moderate Severe Extreme
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)
None Mild Moderate Severe Extreme
A17 Light domestic duties (cooking, dusting, etc)
None Mild Moderate Severe Extreme
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
None Mild Moderate Severe Extreme
Sp5 Kneeling None Mild Moderate Severe Extreme
Knee Injury and Osteoarthritis Outcome Score (KOOS)
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?
None Mild Moderate Severe Extreme
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