Urkund Analysis Result

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COMPARISION OF EPIDURAL 0.2% ROPIVACAINE WITH FENTANYL VERSUS 0.2% LEVOBUPIVACAINE WITH

FENTANYL FOR POSTOPERATIVE ANALGESIA FOR MODIFIED RADICAL MASTECTOMY

DISSERTATION SUBMITTED FOR M. D. ANAESTHESIOLOGY

THE TAMILNADU DR. M.G.R. MEDICAL UNIVERSITY

DEPARTMENT OF ANAESTHESIOLOGY COIMBATORE MEDICAL COLLEGE AND HOSPITAL GOPALAPURAM, COIMBATORE –

641018 TAMILNADU, INDIA MAY 2020

REGISTRATION NUMBER: 201620652

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CERTIFICATES

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COIMBATORE MEDICAL COLLEGE & HOSPITAL CERTIFICATE

This is to certify that this dissertation entitled“ Comparision of epidural 0.2% ropivacaine with fentanyl versus 0.2% levobupivacaine with fentanyl for postoperative analgesia for modified radical mastectomy”

by Dr.P.Kiruthiga, is a work done by her during the period of study in the department of Anaesthesiology from January 2017 to January 2018 under the guidance of Dr.K.Santha Arulmozhi, Professor & HOD, Department of Anaesthesiology, CMCH.

Dr.K.Santha Arulmozhi D.A.,M.D., Professor & HOD,

Department of Anaesthesiology, CMCH,

Coimbatore – 18.

Dr.B.ASOKAN M.S.,M.Ch.

DEAN, CMCH,

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CERTIFICATE-II

This is to certify that this dissertation entitled“ Comparision of epidural 0.2% ropivacaine with fentanyl versus 0.2% levobupivacaine with fentanyl for postoperative analgesia for modified radical mastectomy”

of the candidate Dr.P.Kiruthiga with registration number 201620652 for the award of M.D. Degree in the branch of Anaesthesiology.

I personally verified the urkund.com website for the purpose of plagiarism check. I found that the uploaded thesis file contains from introduction to conclusion pages and result shows4 percentage of plagiarisim in the dissertation.

Dr.K.Santha Arulmozhi D.A.,M.D., Professor & HOD,

Department of Anaesthesiology, CMCH,

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Urkund Analysis Result

Analysed Document:DISSERTATION UNIVERSITY.doc (D56683265) Submitted:10/8/2019 6:00:00 PM

Submitted By:kir990@gmail.com Significance:4 %

Sources included in the report:

https://www.researchgate.net/publication/324500359A-comparative-study of-low-concentration-of-levobupivacaine-versus-ropivacaine-with-fentanyl- for-patient-controlled-epidural-labour-analgesia.

https://www.researchgate.net/figure/Side-effects-with-ropivacaine-Group- R-and-ropivacaine fentanyl-Group-RF-tbl2-9021175.

https://www.ijss-sn.com/uploads/2/0/1/5/20153321/15-ijss-feb-oa15 - 2019. pdf.

https://www.researchgate.net/publication/327243746-A-study-on-evaluati onof-epidural-levobupivacaine-0125-and-ropivacaine-0125-with-and-witho ut-fentanyl-for-postoperative-pain-relief-in-abdominal-surgeries

Instances where selected sources appear:

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DECLARATION

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DECLARATION BY THE CANDIDATE

I hereby declare that this dissertation entitled,“ Comparision of epidural 0.2% ropivacaine with fentanyl versus 0.2% levobupivacaine with fentanyl for postoperative analgesia for modified radical mastectomy”

is a bonafide work done by me under the guidance and supervision of

Dr.K.Santha Arulmozhi, HOD & Professor, Department of Anaesthesiology, Coimbatore medical college and hospital. This study was conducted at the Coimbatore medical college and hospital, Coimbatore under the aegis of The Tamilnadu Dr.MGR Medical university, Chennai, as part of the requirement for the award of M.D.Degree in Anaesthesiology.

DR.P.Kiruthiga, BI year postgraduate,

Department of Anaesthesiology, CMCH,

Coimbatore- 641018.

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ACKNOWLEDGEMENT

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ACKNOWLEDGEMENT

I express my sincere gratitude and thanks to Dr.K.Santha Arulmozhi D.A.,M.D., Professor & HOD, Department of Anaesthesiology of Coimbatore medical college and hospital for being my guide. It was her valuable suggestions, guidance and constant encouragement in every step that has helped me to complete my research work.

I express my sincere gratitude and thanks to Dr.K.Asokan M.S.,M.Ch., Professor of Department of plastic surgery & Dean, Coimbatore

medical college and hospital for his valuable support and guidance.

I am obliged to thank Dr.G.ANITHA D.A.,M.D., Assistant professor in anaesthesiology for her extensive support during the whole period.

I extend my thanks to Dr.ELANGO M.S.,Department of General surgery, Anaesthesia technicians and theatre technicians for their immense help during my study period.

Also I thank other staff members for their constant support during the research.

Dr.P.Kiruthiga

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INTRODUCTION

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INTRODUCTION

Pain is a predominant complaint of most of the patients following surgical interventions.Failure to relieve pain is morally and ethically

unacceptable.Effective postoperative pain management has a humanitarian role and reduces morbidity,patient suffering,duration of hospital stay,and also promotes wound healing,rapid recovery and discharge.In oncological surgeries,postoperative pain relief reduces the risk of cancer recurrence and metastasis.

Pain activates Hypothalamic-pituitary-adrenal axis,which has been implicated in immunosuppression,leading to reduction of NK cell

activity,thereby promoting tumor cell proliferation.Pain and inflammation also leads to acute release of cytokines,prostaglandins,cyclo-oxygenases,all these mediators leads to inhibition of apoptosis,promotion of angiogenesis and immunosuppression, there by causing cancer progression.Hence effective postoperative analgesia results in decreased stress response via reduction of pain and found to reduce the risk of recurrence and metastasis.

Epidural anaesthesia is the most commonly used technique

for providing postoperative analgesia in major surgeries.Thoracic epidural analgesia is particularly effective in reducing pain after thoracic and upper abdominal surgery.

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In my study,thoracic epidural technique is chosen for postoperative pain management for patients undergoing modified radical mastectomy procedure.Lower concentration of local anaesthetic agent either alone or in combination with opioids or alpha-2 agonists are used in epidural for postoperative analgesia.Bupivacaine,Lignocaine with adrenaline are most commonly used local anaesthetic in epidural technique.As compared with Bupivacaine,Levobupivacaine and ropivacaine are associated with less risk of cardiac and central nervous system toxicity and are less likely to result in unwanted postoperative motor blockade.Addition of opioid like fentanyl helps in improving the analgesic efficacy.

This study was designed to compare the efficacy of

0.2% Ropivacaine with fentanyl and 0.2% Levobupivacaine with fentanyl in thoracic epidural infusion for postoperative pain relief in modified radical mastectomy surgery.

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AIMS AND OBJECTIVES

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AIMS AND OBJECTIVES

The aim of the study is to compare the analgesic efficacy and adverse effects of 0.2% Ropivacaine versus 0.2% Levobupivacaine with fentanyl when administered postoperatively in thoracic epidural infusion for postoperative pain relief in patients undergoing modified radical

mastectomy surgery.

The following parameters are studied:

1. Analgesic efficacy by measuring pain intensity using visual analogue scale.

2. Hemodynamic changes by measurement of blood pressure,pulse rate,and oxygen saturation.

3. Adverse effects like

nausea,vomiting,bradycardia ,hypotension

pruritus,shivering,and bradypnea(Respiratory rate<12).

4. Assessment of sensory blockade by loss of temperature sensation.

5. Assessment of motor blockade by modified bromage scale.

6. Sedation level among both groups.

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DEFINITION OF PAIN

The International Association for the Study of Pain (IASP) defines pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage."^[1]

PHYSIOLOGY OF PAIN PERCEPTION:-

The four elements of pain processing include:

(1) transduction, (2) transmission, (3) modulation, and (4) perception.

TRANSDUCTION:

Noxious thermal, chemical, or mechanical stimuli are converted into an action potential.[17]

TRANSMISSION:

When the action potential is conducted through the nervous system via the first-, second-, and third-order neurons, which have cell bodies located in the dorsal root ganglion, dorsal horn, and thalamus, respectively.[17]

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MODULATION:

It involves altering afferent neural transmission along the pain pathway. The dorsal horn of the spinal cord is the most common site for modulation of the pain pathway, and modulation can involve either inhibition or augmentation of the pain signals.[17] Inhibitory spinal modulation includes:

(1) Release of inhibitory neurotransmitters such as γ-amino butyric acid (GABA) and glycine by intrinsic spinal neurons, and

(2) Release of norepinephrine, serotonin, and endorphins in the dorsal horn from the motor cortex. ^[17]

Spinal modulation, which results in augmentation of pain pathways:

(1) Central sensitization,which is a consequence of neuronal

plasticity due to repetitive C-fiber stimulation of dorsal horn neurons.

[17]

PERCEPTION:

Results from the integration of painful input into the somato-sensory and limbic cortices.

Traditional analgesic therapies have only targeted pain perception.

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PHYSIOLOGY OF PAIN PERCEPTION

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PHYSIOLOGICAL AND PSYCHOLOGICAL EFFECTS OF ACUTE POSTOPERATIVE PAIN^[2]:-

Tachycardia, Cardiovascular Hypertension,

Increase in cardiac work load,

Increase inmyocardial oxygen consumption,

Myocardial ischemia and infarction in coronary artery disease patients.

Respiratory muscle spasm (splinting), Decrease in vital capacity,

Respiratory Atelectasis, Hypoxia,

Increased risk of pulmonary infection

Gastrointestinal Postoperative ileus

Increased risk of oliguria and

Renal Urinary retention due to increased sphincter tone by sympathetic activity.

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Coagulation Increased risk of thromboembolism

Immunological Impaired immune function

Muscular Muscle weakness and fatigue.

Limited mobility can increase the risk of thromboembolism

Psychological Anxiety, fear, and frustration results in poor patient satisfaction.

Water and Sodium and water retention,

electrolyte Potassium excretion, due to increase in catecholamines, balance: aldosterone, ADH,cortisol.

Endocrine: Increase in adrenal corticotrophic hormone, cortisol,antidiuretic hormone, growth hormone, catecholamines, renin, angiotensin II, aldosterone, glucagon,interleukin 1 (IL-1).

Decrease in insulin and testosterone.

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CLINICAL ASSESSMENT OF ACUTE PAIN Simple pain scoring systems:

1. Categorical rating scales (CRS):

Frequently used to assess postoperative pain,it uses verbal method for pain description.eg:no pain, mild pain, moderate pain, severe pain.^[2]

2. Visual analog scale (VAS):

It employs a 10-cm drawn line with the left point descriptor labeled

"no pain" and the right-sided equivalent labeled "worst possible pain”.It requires patients to mark their current pain severity on the continuum.[2]

3. Verbal numerical rating scale (VNRS):

Patients are asked to estimate their pain severity as a number,

"0" being no pain and "10" being the worst possible pain.^[2]

Minimum assessment intervals^[2]: 5-min intervals following:

• Bolus injections of i.v. opioids or epidural local anesthetics with or without opioid.

• Increasing rates of i.v. or epidural infusions 2-h intervals for the first 24-48 h postoperatively.

4-h intervals as absolute minimum thereafter.

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MANAGEMENT OF ACUTE POSTOPERATIVE PAIN:

NON-PHARMACOLOGICAL METHODS : 1.Relaxation" technique (e.g.aromatherapy), 2.Hypnosis,

3.Cold or heat therapy ,

4.Transcutaneous electrical nerve stimulation.

PHARMACOLOGICAL METHODS:

1. Opioids

Routes of administration:Intravenous ,oral, patient controlled analgesia, epidural,intrathecal route 2.Non-steroidal anti-inflammatory drugs

3.Local anaesthetics

Plexus and individual nerve blocks, Wound infiltration,Interpleural analgesia,

Central neuraxial analgesia (epidural or intrathecal technique).

Paravertebral block.

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EPIDURAL ANAESTHESIA:

DEFINITION:

Epidural anaesthesia is obtained by blocking spinal nerves in the epidural space as the nerves emerge from the dura and then pass into the intervertebral foramina.Anaesthetic solution is deposited outside the dura. A segmental block is produced chiefly of spinal sensory and sympathetic nerve fibres.Motor fibres may be partially blocked.

HISTORICAL PERSPECTIVES:

CORNING Performed first epidural anaesthesia with cocaine for pain relief in extremity in 1885.

CATHELIN Performed First Epidural anaesthesia in sacral region

PAGES Performed First Lumbar epidural anesthesia in 1921.

DOGLIOTTI Described Loss of resistance technique in 1939

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HINGSON Developed continuous caudal technique for obstetrics

CURBELO Performed Lumbar epidural catheterization for surgery

BEHAR First used morphine for epidural analgesia in 1979.

CRAWFORD Performed Thoracic epidural anaesthesia in 1951.

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DISTINCT FEATURES OF THORACIC & LUMBAR VERTEBRAE:

THORACIC LUMBAR

VERTEBRAE VERTEBRAE

Number of vertebrae: Twelve Five

Vertebral Body: Smaller,heart shaped but Larger,kidney shaped larger than cervical

Vertebral foramen: Circular Triangular

Spinous process: Angulated and steeply Horizontal angulation caudad

Transverse process: Articular facets for ribs Articular facets for ribs

present absent

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The thoracic spinous process is angulated and steeply caudad as opposed to almost horizontal angulation of the lumbar spinous process.

This is a clinically important distinction for needle insertion and advancement in the thoracic versus lumbar levels.^[1]

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ANATOMY OF EPIDURAL SPACE:- BOUNDARIES:-

Anteriorly - Posterior longitudinal ligament, Posteriorly - Ligamentum flavum.

Laterally - Pedicles and Intervertebral foramina, Superiorly - Fusion of spinal and peri-osteal layers of

dura mater at the foramenmagnum.

Inferiorly -Sacro-coccygeal membrane

CONTENTS OF THE EPIDURAL SPACE:-

Nerve roots and fat, areolar tissue, lymphatics, and blood vessels including the well-organized Batson venous plexus.^[1]

NEGATIVE PRESSURE IN THE EPIDURAL SPACE:-

Originally, Heldt and Maloney described a negative extradural pressure in1828. It is greatest in the thoracic region since the intra

thoracic pressure is transmitted via paravertebral space, less in the lumbar and least or absent in the sacral region.

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Lower lumbar region - 0.5cm of water

Upper lumbar region -1.0 cm of water

Thoracic region -1.0to -3.9 cm of water.

THEORIES OF NEGATIVE PRESSURE IN EPIDURAL SPACE:

1) THE TRANSMISSION THEORY:

Proposed by BeyerSmith in 1947.Negative pressure in the epidural space is caused by the transmission of the intrapleural

negative pressure through the intervertebral foramina. It varies with the depth of respiration. A rise in negative pressure may favour the spread of local anaesthetic solution in the epidural space.

2) CONE THEORY:

This says that the epidural needle introduced depresses the dura, creating a large space, it is thus an artefact caused by the indentation of dura by the advancing needle .Proposed by Janzen in 1926.

3) FLEXION THEORY:

This theory says that, more the flexion of spine, the greater the negative pressure and it was stated by Oden in 1938.

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MECHANISM OF ACTION^[1]:-

Drug distribution in the epidural space is more complex,with

possible contributions from one, some, or all of the following mechanisms:

1) Crossing the dura mater into the subarachnoid space, 2)Rostral and caudal spread within the epidural space, 3)Circumferential spread within the epidural space,

4)Exit of the epidural space through the intervertebral foramina, 5)Binding to epidural fat, and

6)Vascular absorption into the epidural vessels.^[1]

PHYSIOLOGICAL EFFECTS OF AN EPIDURAL BLOCKADE:-

Differential Blockade Order of blockade:

1)Sympathetic (B fibres)

2) Sensory:C fibres [cold temperature]>A- δ [pin prick] >A-β [Touch] fibres

2) Motor fibres(A -α)last to be blocked.

Central Nervous System Effects Decreases the requirements of other

anaesthetic agents including volatile agents Cardiovascular Effects 1)Decrease in blood pressure

2)Decrease in heart rate

3)Decrease in cardiac contractility

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Pulmonary Effects Thoracic epidural analgesia -Decrease the incidence of pneumonia, respiratory failure,and improve oxygenation.

Gastrointestinal Effects Symphathetic blockade- Gastrointestinal hyperperistalsis caused by unopposedvagal activity.

Renal/Genitourinary Effects S²– S⁴ blockade→Urinary retention

Neuroendocrine Effects Decreases surgical stress response and decreases stress hormones(cortisol,ADH).

EFFECTS OF EPIDURAL ON CARDIOVASCULAR SYSTEM:-

REVERSE BAINBRIDGE REFLEX Decreased Systemic vascular resistance

Results in decreased right atrial filling

Results in decreased stimulation of chronotropic stretch receptors

Results in decreased heart rate

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EFFECTS OF EPIDURAL ON THE RESPIRATORY SYSTEM:

Following thoracic and abdominal surgical procedures:

Decreased diaphragmatic activity

Decreased Functional residual capacity

Atelectasis

Ventilation/perfusion mismatch

Hypoxia

Thoracic epidural analgesia has been found to decrease the incidence of pneumonia, respiratory failure,and improve

oxygenation.The patient ability to cough is not restricted because of adequate analgesia so that the patient can clear out retained secretions.

IDENTIFICATION OF EPIDURAL SPACE:-

There are several methods to identify the epidural space. These methods utilises the potential negative pressure or use of the sudden disappearance of resistance when the ligamentum flavum is penetrated.

Negative pressure technique includes:

1) Hanging drop sign (Guttierez sign) 2) Capillary tube method

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Loss of resistance technique includes:

1) Syringe technique 2) Spring loaded syringe

3) Balloon technique (Macintosh's extradural space indicator) 4) Brooks device

5) Vertical tube of Dawkins Others:

1) Ultrasonic localization

2)Oxford epidural space indicator EPIDURAL TECHNIQUE:- PREPARATION:-

Patient preparation includes consent, monitoring, and resuscitation equipment, intravenous access, and choosing the patient and drugs

appropriately depending on comorbidities and the nature of surgery.^[1]

POSITION:-

Sitting position.

Lateral decubitus position.

Shorter insertion times occur in the sitting position for thoracic epidurals compared with the lateral decubitus position, but success rates are equal.^[1]

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EPIDURAL NEEDLE INSERTION SITE:-

The level of needle insertion depends on the location of surgery.

Epidural insertion site for common surgical procedures^[1]

Nature of the surgery Suggested level of Remarks insertion

Hip surgery, Lower extremity and Lumbar L²-L⁵ obstetrics analgesia

Colectomy, Anterior resection, Lower thoracic Spread more cranial than

Upper abdominal surgery T⁶-T⁸ caudal

Thoracic surgery T²-T⁶ Midpoint of the surgical

incision

Important surface landmarks include:-

TABLE

Vertebra prominens C7 5STED

EPRAL INSERTIO

Spine of scapula T3 SSRGICALN

Inferior angle of scapula T7 PROCEDU

L4-5 RES

Intercristal line interspace

Posterior superior iliac spine S2

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VARIOUS APPROACHES TO EPIDURAL TECHNIQUE^[1]: Midline,

Paramedian,

Modified paramedian (Taylor approach),and Caudal.

TYPES OF EPIDURAL NEEDLES AND CATHETERS:-

Epidural needles with catheter assortment. A: 19-G reusable Crawford epidural needle. B: 19-G disposable Tuohy needle.

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TUOHY NEEDLES:

Tuohy needles are most commonly used. These needles are usually 16 to 18 g in size and have a 15- to 30-degree curved, blunt “Huber” tip designed to both reduce the risk of accidental dural puncture and guide the catheter cephalad. The needle shaft is marked in 1-cm intervals so that depth of insertion can be identified.The catheter is made of a flexible, calibrated, durable, radiopaque plastic with either a single end hole or multiple side orifices near the tip.

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C,SINGLE–END-HOLE EPIDURAL CATHETER. D, CLOSED-TIP, MULTIPLE–SIDE-HOLE CATHETER. E, SPRING WIRE–

REINFORCED,

POLYMERCOATED EPIDURAL CATHETER.

Multiple-orifice catheters are superior, with a reduced incidence of inadequate analgesia.

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APPROACH TO EPIDURAL SPACE:-

A midline approach is commonly chosen for thoracic approaches.

After local anesthetic infiltration of the skin, the nondominant hand can be rested on the back of the patient, with the thumb and index finger holding the needle hub or wing. The angle of approach should be more cephalad in the midthoracic region, because of the significant downward angulation of the spinous processes.^[1]

NEEDLE INSERTION IN

(B)THORACIC EPIDURAL (C) LUMBAR EPIDURAL

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METHOD OF IDENTIFICATION OF EPIDURAL SPACE:- Most commonly used methods are:

1)Loss-of

resistance technique to either air or saline 2) Hanging drop technique.

LOSS-OF-RESISTANCE TECHNIQUE:-

In this technique glass versus low-resistance plastic and Luer- Lok versus friction hub syringes are required.^[1]

In a controlled fashion, the needle should be advanced with the stylet in place through the supraspinous ligament and into the interspinous ligament, at which point the stylet can be removed and the syringe attached.

If it is in the correct location, the needle should rest firmly in the tissues.If the needle is merely inserted into the supraspinous ligament and then loss- of-resistance technique is begun, there is an increased chance of false loss- of-resistance, possibly because of defects in the interspinous ligament .^[1]

Air or saline are the two most common noncompressible media used to detect a loss-of-resistance when identifying the epidural space. Each involves intermittent (for air) or constant (for saline) gentle pressure

applied to the bulb of the syringe with the dominant thumb while the needle is advanced with the nondominant hand. A combination of air and saline may also be used, incorporating 2 mL of saline and a small (0.25 mL) air bubble.

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Usually the ligamentum flavum is identified as a tougher structure with increased resistance, and when the epidural space is subsequently entered, the pressure applied to the syringe plunger allows the solution to flow without resistance into the epidural space.^[1]

Disadvantages of using Air to detect Loss of resistance:- 1)Less reliable in identifying the epidural space, 2)Higher chance of incomplete block,

3)Pneumocephalus causing headaches, 4)Venous air embolism in rare cases.^[1]

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Disadvantage of using saline:-

1)Accidental dural puncture can’t be readily detected.^[1]

The negative intrathoracic pressure may influence the pressure in the epidural space in the thoracic region and should be maximal during

inspiration.When a thoracic approach is chosen, needle control is of equal or greater importance because injury to the spinal cord is possible if the needle is advanced too far.

When the epidural space is identified, the depth of the needle at the skin should be noted. The syringe can then be removed and a catheter gently threaded to approximately the 15- to 18-cm mark to ensure a sufficient length has entered the epidural space. The needle can then be carefully withdrawn, and the catheter is withdrawn to leave 4 to 6 cm in the space. Catheter space less than 4 cm in length in the epidural space may increase the risk of catheter dislodgement and inadequate analgesia, whereas threading more catheter may increase the likelihood of catheter malposition or complications. The Tsui test may be used to confirm the epidural catheter position.^[1]

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EPIDURAL TEST DOSE:-

Before initiating an epidural local anesthetic infusion,a test dose may be administered. The purpose of this is to exclude intrathecal or intravascular catheter placement.3 ml of 1.5%lidocaine with epinephrine 10 to 15 μg (1 in 2,00,000) dilution is used for this purpose. If the catheter is placed intravascular ,there will be an increase in systolic blood pressure more than 15 mm Hg or an increase in heart rate more than 10 beats/min.^[1]

If the catheter is placed intrathecally there will be signs of subarachnoid blockade such as subjective feeling of heaviness,sensory loss to pin prick and hypotension.

CATHETER FIXATION:-

When the catheter is positioned at the desired depth, it must be secured to the skin. Commercial fixation devices exist, and some are superior to tape alone. Tunneling can reduce catheter migration.^[1]

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PARAMEDIAN APPROACH:-

The paramedian approach is particularly useful in the mid thoracic to high thoracic region, where the angulation of the spine and the narrow

spaces render the midline approach difficult. The needle should be inserted 1 to 2 cm lateral to the inferior tip of the spinous process corresponding to the vertebra above the desired interspace. The needle is then advanced horizontally until the lamina is reached and then redirected medially and cephalad to enter the epidural space.^[1]

COMPLICATIONS OF EPIDURAL ANESTHESIA:-

TECHNIQUE RELATED CATHETER EPIDURAL

RELATED RELATED

Post dural puncture headache Retained catheter Hemodynamic changes

Damage to the blood vessel Coiling of Urinary retention catheter

Neurological sequelae Shearing of Local anaesthetic toxicity (physical,chemical,ischemia, catheter

spinal artery syndrome)

Hematoma Inadequate or failure of block

Infection Total spinal anaesthesia

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ROPIVACAINE

Clinically introduced in the year 1992.Ropivacaine is a new

aminoamide local anaesthetic.It is the monohydrate of the hydrochloride salt of propyl-2,6-pipecoloxylidide and is prepared as the pure enantiomer from the parent chiral molecule propivacaine.Mepivacaine and bupivacaine are

members of this group and currently produced for clinical use as racemic mixtures the enantiomers containing equal proportions of the “S” and “R”

forms but ropivacaine is the single S- enantiomer.It has propyl group on the piperidine nitrogen atom compared to bupivacaine which has butyl group.^[4]

PHYSICAL PROPERTY:

Molecular weight 275g/mol

Pk^a (25⁰C) 8.1

Partition coefficient 2.9

Protein binding% 94

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CHEMICAL STRUCTURE^[1]:

(2S)-N-(2,6-dimethylphenyl)-1-propylpiperidine-2-carboxamide

MECHANISM OF ACTION:

Ropivacaine causes reversible blockade of impulse propagation along nerve fibres by preventing the inward movement of sodium ions through the cell membrane .It is less lipophilic than Bupivacaine and it is less likely to penetrate large myelinated motor fibres,thus it has an

selective action on pain transmitting A-delta and C nerve fibres compared to A-beta fibres.When administered epidurally Ropivacaine provides analgesia by blocking impulse transmission at the nerve roots and dorsal root ganglia.^[4]

Anaesthetic uses:-

Infiltration,Peripheral nerve blockade,Intrathecal and epidural.^[1]

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Available preparations^[1]:- 2.5- and 5-mg/mL solutions 5- and 10-mg/mL solutions 5- and 7.5-mg/mL solutions.

PHARMACODYNAMICS:

CARDIOVASCULAR EFFECTS:

Ropivacaine is less lipophilic than bupivacaine and that, together with its stereoselective properties, contributes higher threshold for

cardiotoxicity and CNS toxicity than bupivacaine.^[4]The slow reversal of Na+ channel blockade after a cardiac action potential, which is a hallmark of bupivacaine, is considerably faster with ropivacaine. In addition to these electrical differences, the negative inotropic potency of ropivacaine on isolated cardiac tissue appears to be considerably less than that of bupivacaine.^[1]

Significant changes in cardiac function involving the contractility, conduction time and QRS width occurred,and the increase in QRS width was found to be significantly smaller with ropivacaine than with bupivacaine.^[4]

CENTRAL NERVOUS SYSTEM EFFECTS:-

The CNS effects occurr earlier than cardiotoxic symptoms.It

includes excitation,tingling sensation around the mouth, tremor, dizziness, seizures,loss of consciousness,respiratory depression and apnea.

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OTHER ACTIONS:-

Ropivacaine has been shown to inhibit platelet aggregation in plasma at concentrations of 0.375% and 0.188%. Like other anaesthetics, Ropivacaine has antibacterial activity in vitro, inhibiting the growth of Staphylococcus aureus,Escherichia coli, and Pseudomonas aeruginosa.^[4]

PHARMACOKINETICS:

Ropivacaine LIVER

CYTOCHROME P 450 Aromatic hydroxylation

2,6-pipecoloxylidide 3-hydroxyropivacaine

Both metabolites have significantly less local anaesthetic potency than ropivacaine).^[3]

1. Because only a very small fraction of ropivacaine is excreted unchanged in the urine (about 1%) when the liver is functioning normally, dosage adjustments based on renal function do not seem necessary.^[3]

Overall, clearance of ropivacaine is higher than that determined for bupivacaine (may offer an advantage over bupivacaine in terms of systemic toxicity).^[3]

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2. Ropivacaine is highly bound to alpha 1-acid glycoprotein.^[3]

DRUG INTERACTIONS:

 Ropivacaine should be used with caution in patients

receiving other local anaesthetics or agents structurally related to amide- type local anaesthetics, since the toxic effects of these drugs are

additive.^[4]

 Ropivacaine is metabolised by Cytochrome P4501A2.Inhibitors of cytochrome P4501A2, such as fluvoxamine,verapamil given

concomitantly during administration of Ropivacaine,will result in increased plasma levels.^[4]

 Ropivacaine is compatible with fentanyl citrate,sufentanil citrate,morphine sulphate,and clonidine hydrochloride.

 Precipitation may occur in alkaline solutions because, Ropivacaine has poor solubility at pH>6

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DOSE^[1]:

Drug Concentration Volume Maximum Dose (mg) Onset Duration

(%) (mL) Without/With

(min) (min) Epinephrine

Epidural Ropivacaine 0.2-0.75 15-30 200/250 15-20 180-350

Thoracic Ropivacaine 0.2 6-14ml/hr 12-28mg/hr(without Epidural

(postoperative epinephrine)

continuous

infusion pain)

Major nerve Ropivacaine 0.2-0.5 30-50 200/250 20-30 360-720

block

Spinal Baricity Total dose:

Ropivacaine Isobaric 0.5 3-4 15-20 90-200

Hyperbaric 0.75 2-3 15-20 90-200

Infiltration Ropivacaine 0.2-0.5 200/ 250 120-240/

180-240

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ADVERSE EFFECTS:

Hypersensitivity reactions,Nausea,vomiting,Hypotension, bradycardia, paresthesia,dizziness,headache,Cardiac arrythmia, Cardiac arrest and Symptoms of CNS toxicity.

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LEVOBUPIVACAINE:-

Levobupivacaine is anamino-amidelongactinglocal anaesthetic belonging to the family n-alkylsubstituted

pipecoloxylidide.Levobupivacaine is the (S)-enantiomer ofbupivacaine.

PHYSICAL PROPERTY:

Molecular weight 288g/mol

Pk^a (25⁰C) 8.1

Partition coefficient 3.6

Protein binding% 97

CHEMICAL STRUCTURE^[5]:-

(2S)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide

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MECHANISM OF ACTION:-

Levobupivacaine exerts its local anaesthetic effect by blocking voltage-gated sodium channels in the peripheral neurons.It diffuses across the neuronal plasma membrane in its unionised form.Once inside the cytoplasm, it gets ionised and this ionised form enters and blocks the voltage-gated sodium channel from the cytoplasmic side. For this to occur, the sodium channel must first become active so that gating mechanism is in the open state. Therefore levobupivacaine preferentially inhibits neurons that are in active state.When administered epidurally

levobupivacaine provides analgesia by blocking impulse transmission at the nerve roots and dorsal root ganglia.

METABOLISM :-

Alpha1-glycoprotein is the main binding site for levobupivacaine.

Protein binding of levobupivacaine is more (97%) than that of racemic bupivacaine (95%). Less than 3% of the drug circulates free in plasma. The free proportion of the drug can have an action on the other tissues, causing unwanted side-effects and toxic manifestations. In newborns and in protein- deficient states like under nutrition and nephrotic syndrome, lesser amount of protein is available for binding, causing higher levels of free drug, resulting in toxic effects at lower doses.^[6]

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Levobupivacaine LIVER

CYP1A2 & CYP3A4

Desbutyl levobupivacaine 3-hydroxy levobupivacaine

In vivo, the 3-hydroxy levobupivacaine appears to undergo further transformation to glucuronide and sulfate conjugates. Metabolic inversion of levobupivacaine to R(+) bupivacaine was not evident both in vitro and in vivo.Clearance is reduced when hepatic function is damaged.^[5]

ANAESTHETIC USES^[5]:-

Subarachnoid block,Epidural anaesthesia, Infiltration and Peripheral nerve blockade.

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DOSE^[1]:

Drug Concentr Volume Maximum Dose (mg) Onset Duration

ation (mL) Without/With

(min) (min) Epinephrine

Epidural Levobupivacaine 0.25%- 15-30 200/250 15-20 180-350

0.75 %

Thoracic Levobupivacaine 0.125% 10-15ml/hr 12.5-18.75mg/hr Epidural

5-7.5ml/hr continuous

0.25% 12.5-18.75mg/hr

infusion

Major nerve Levobupivacaine 0.25%- 30-50 200/225 20-30 360-720

block

0.5%

Spinal Baricity Total dose:

Levo- Isobaric 0.5% 3-4 15-20 90-200

bupivacaine Hyperbaric 0.75% 2-3 15-20 90-200

Infiltration Levobupivacaine 0.25% 150 120-480

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ADVERSE EFFECTS:-

Hypersensitivity,Nausea,vomiting,hypotension,bradycardia,paresthesia, dizziness,headache,Cardiac arrythmia,Cardiac arrest and CNS toxicity.The cardiac toxicity and central nervous system toxicity is lower than that of bupivacaine.

FENTANYL

Fentanyl is a phenylpiperidine-derivative, synthetic opioid agonist which acts at µ and κ opioid receptors.As an analgesic, fentanyl is 75 to 125 times more potent than morphine.^[3]

MECHANISM OF ACTION:-

Epidural opioids work by crossing the dura and arachnoid

membrane to reach the CSF and acts on µ-opioid receptor present in spinal cord dorsal horn. Lipophilic opioids, such as fentanyl,partition into epidural fat and therefore are found in lower concentrations in CSF than hydrophilic opioids,such as morphine and hydromorphone.^[1]

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Fentanyl are also readily absorbed into the systemic circulation, and several studies suggest that this is the principal analgesic mechanism.

Opioids synergistically enhance the analgesic effects of epidural local anesthetics, without prolonging motor block.^[1]

A combination of local anesthetic and opioid reduces the dose- related adverse effects of each drug independently. As with intrathecal

opioids,there appears to be a therapeutic ceiling effect above which only side effects increase. Opioids may also be used alone, particularly when there are concerns regarding hemodynamic instability.^[1]

PHARMACOKINETICS:-

Pk 8.4

Partition coefficient 955

Protein binding% 84

Elimination Half-Time(hr) 3.1-6.6

The onset of epidural fentanyl is 5 to 15 minutes and lasts only 2 to 3 hours.^[1]

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METABOLISM:-

Fentanyl is extensively metabolized by N-demethylation and the pharmacologic activity of fentanyl metabolites is minimal.

ELIMINATION HALF-TIME:-

Fentanyl has a short duration of action,but its elimination half- time is longer than that for morphine.This longer elimination half-time reflects a larger volume of distribution (Vd) of fentanyl due to its greater lipid solubility and thus more rapid passage into highly vascular tissues compared with the less lipid-soluble morphine^[3].

The plasma concentrations of fentanyl are maintainedby slow reuptake from inactive tissue sites, which accounts for persistent drug effects that parallel the prolonged elimination half-time.^[3]

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CLINICAL USES^[3]:- 1)Analgesia

2)Adjuvant to inhaled anesthetics to blunt the stress response to direct laryngoscopy

3)Decrease doses of inhaled anesthetics needed to blunt

sympathetic nervous system responses to surgical stimulation 4)Produce surgical anesthesia (50–150 mcg/kg IV)

5)Analgesia for early labor

6)Postoperative analgesia (transdermal patch/intravenous infusion) 7)Postoperative Epidural infusion(2mcg/ml of local anaesthetic)

SIDE EFFECTS:-

1) Respiratory depression.

2) Cardiovascular Effects:Bradycardia is more prominent with fentanyl than morphine.

3)Skeletal muscle rigidity.

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REVIEW OF LITERATURE

1) E.Sitsen et al^[7]compared the efficacy of levobupivacaine 0.125%,ropivacaine 0.125% and ropivacaine 0.2%, all combined with sufentanil 0.5µg/mL, in patient-controlled epidural analgesia after

hysterectomy under combined epidural and general anesthesia.Sixty-three patients were studied,21 patients in each group.They concluded that there was no potency difference between ropivacaine and levobupivacaine in a concentration of 0.125% mixed with sufentanil 0.5 mg/mL. Both

solutions provided adequate pain relief with similar side effects.

Increasing the concentration of ropivacaine to 0.2% did not result in better analgesia or a reduction in sufentanil consumption.

2)Casati, Andrea et al^[8]compared the efficacy of continuous popliteal sciatic nerve block produced with 0.2% ropivacaine ,

0.2% levobupivacaine , or 0.125% levobupivacaine infused with a patient- controlled system on 60 patients of 20 in each group. They concluded that both 0.125% and 0.2% levobupivacaine provide effective adequate

postoperative analgesia without differences from that provided by 0.2%

ropivacaine. If early mobilization of the operated foot is required, the 0.125% concentration of levobupivacaine is preferred rather than 0.2%.

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3)Afaf AA1 et al^[9]conducted a randomized double-blind study to evaluate the effectiveness and safety of two different concentrations of levobupivacaine as epidural infusion for postoperative pain relief. Fifty patients who underwent orthopaedic lower limb surgeries were recruited and randomly allocated to receive either 0.1% (Group A) or 0.2%

levobupivacaine (Group B) with 2 mcg/ml fentanyl as epidural infusion for postoperative pain relief over 24 hours. Pain score, motor blockade,

hemodynamic parameters and the need for rescue analgesia were recorded.

The study concluded 0.2% levobupivacaine with 2 mcg/ml fentanyl provided more superior analgesia compared to 0.1% levobupivacaine with 2 mcg/ ml fentanyl in patients who underwent lower limb orthopaedic surgery, but with a significant higher incidence of hypotension that responded to volume replacement.There was no significant difference in degree of motor blockade and need for rescue analgesia in both groups.

4)Chuttani et al^[10] conducted a comparative study of low

concentration of levobupivacaine versus ropivacaine with fentanyl for patient- controlled epidural labour analgesia.60 labouring parturients were randomly allocated into two equal groups to receive either 0.1% ropivacaine with 2 µg/ml fentanyl or 0.1% levobupivacaine with 2 µg/ml fentanyl as

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epidural solutions via PCEA pump infusions (4 ml/h) after 15 ml loading dose of the respective solutions.

They concluded both drugs were equally efficacious in providing adequate analgesia for all stages of labour, exhibiting comparable reduced hourly and total local anaesthetic drug consumption with consequent negligible motor block, high maternal satisfaction and clinically insignificant adverse maternal or fetal effects.

5)Takashi Egashira et al^[11]carried out a study to evaluate the

comparative efficacy of levobupivacaine and ropivacaine for epidural block in outpatients with degenerative spinal disease and sciatica.They studied 32 patients (19 men and 13 women) with degenerative spinal disease and sciatica^.The epidural block was produced with a caudal approach (0.125%

levobupivacaine or 0.2% ropivacaine, 15 mL). The upper level of analgesia, lumbosacral pain, motor blockade, and hemodynamic changes were evaluated by pin prick, visual analogue scale (VAS), Bromage scale, and arterial blood pressure and heart rate at 15, 30, 60, and 90 minutes after epidural block, respectively. The recovery time to mobilization, ambulation, and spontaneous micturition were measured. They concluded that 0.125% levobupivacaine and 0.2% ropivacaine for epidural block by caudal approach provided similar lumbosacral pain relief, degree and recovery of

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motor blockade, and hemodynamic effects in outpatients with degenerative spinal disease.

6)Saroa, et al^[12] conducted a study on comparative evaluation of ropivacaine and levobupivacaine for postoperative analgesia after

ultrasound-guided paravertebral block in 30 patients undergoing

percutaneous nephrolithotomy.Patients were randomized to receive single shot of 20 ml of either ropivacaine (0.2%) or levobupivacaine (0.2%) in paravertebral block.The results of this trial demonstrated that both the local anesthetics, i.e., ropivacaine and levobupivacaine in the concentration of 0.2% were equally efficacious in providing postoperative pain relief with equivocal cumulative rescue analgesic consumption and no episodes of nausea ,vomiting or hemodynamic instability in the postoperative period.

7)ShenChihWang et al^[13]compared three different concentrations of Ropivacaine(group 1, 0.1% ; group 2, 0.15%; group 3, 0.2%) for postoperative Patient-controlled thoracic epidural analgesia after upper abdominal surgery.33 patients who had received PCEA after upper abdominal surgery were included in the analysis. The number of patients in each ropivacaine/fentanyl group was 11 .The PCEA device was programmed to deliver a patient-controlled bolus of 2mL with a lockout time of 20 minutes and background infusion of 5mL/hr for 72 hours.

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V Visual analog(VAS) pain scores, adverse events and the extent of sensory or

motor block were recorded 12, 36 and 60 hours after surgery.

Conclusions:There were no differences among the three groups regarding total consumption. In group 1, VAS scores during ambulation and cough 12 hours postoperatively were significantly higher than in the other two groups (p < 0.05). There was no motor block. Sensory block as assessed by loss of temperature sensation only occurred in the group with the highest concentration (0.2%) of ropivacaine. The overall incidence of adverse events was less than 40%.Both thoracic epidural 0.15% and 0.2%

ropivacaine provide effective postoperative pain control in combination with fentanyl without motor block. Ropivacaine 0.15% with 1 μg/mL fentanyl solution is preferable considering the lower incidence of adverse events.

8)DeCosmo et al^[14] conducted a study on 2 different

concentration of levobupivacaine (Group A: 0.125% and Group B:

0.0625%) combined

with sufentanil (1 mg/mL) in continuous epidural infusion for

post-thoracotomy patients to investigate quality of analgesia, motor block and side-effects. An intravenous PCA system has been used in the

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vomiting and pruritus probably because of the smaller amount of rescue morphine administered.

At the concentration of 0.125% epidural levobupivacaine in combination with sufentanil allowed to obtain a good pain control with no adverse effects and motor block at all.

9)Patil, et al^[15] compared continuous epidural infusion of 0.125%

ropivacaine with 1 µg/ml fentanyl versus 0.125% bupivacaine with 1 µg/ml fentanyl for postoperative analgesia in 60 patients undergoing major abdominal surgery. Postoperatively, they received 0.125% bupivacaine with 1 ug/ml fentanyl (Group B) or 0.125% ropivacaine with 1 ug/ml fentanyl (Group R) at the rate of 6 ml/h. Hemodynamic parameters, visual analog scale (VAS), level of sensory block, and degree of motor block (based on Bromage scale) were monitored for 24 hours postoperatively.

Hemodynamic parameters and VAS scores were comparable in the two groups. The level of sensory block was higher in bupivacaine group. There were more patients with higher Bromage score in the (23.3%) bupivacaine group than in (6.7%) ropivacaine group though the difference was not statistically significant.

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10)Khan et al^[16] conducted a comparative study on Analgesic and hemodynamic Spectrum of Levobupivacaine versus Ropivacaine.The study was conducted on 90 American Society of Anesthesiologists I and ASA ΙΙ patients appearing for lower limb surgeries.A bolus of 20 ml of 0.5%

levobupivacaine and 0.75% ropivacaine was given via epidural route to both the groups comprising 45 patients each who were randomly selected.

Both the drugs are found to be equally potent in terms of analgesic and hemodynamic parameters. Both the drugs have near equal sensory onset and complete sensory regression taking place nearly 190 min for both the drugs. The duration of analgesia for both the drugs was around 175 min with no statistical difference. Both the drugs exhibited comparable hemodynamic response with heart rate, systolic and diastolic blood pressure being stable and comparable without any statistical difference.

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METHODOLOGY SOURCE OF DATA:-

The study population includes Carcinoma breast patients posted for Modified radical mastectomy in Coimbatore government medical college hospital,Coimbatore, Tamilnadu in the Department of

Anaesthesiology, operation theatre and postoperative ICU.

PLACE OF STUDY:-

Coimbatore government medical college and hospital.

STUDY PERIOD:-

July 2017 to September 2018 STUDY DESIGN:-

A Prospective Randomised clinical study.

STUDY POPULATION:-

Carcinoma breast patients posted for modified radical mastectomy.

STUDY PERIOD:

January 2017 to January 2018

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SAMPLE SIZE:

Total subjects:100,50 patients in each group.

GROUP LF:50 patients receiving 0.2%Levobupivacaine with fentanyl GROUP RF:50 patients receiving 0.2%Ropivacaine with fentanyl

INCLUSION CRITERIA:

1. Female patients aged 35 to 65 years with carcinoma breast posted for modified radical mastectomy

2. ASA III

EXCLUSION CRITERIA:

1. Patients associated with severe Cardiovascular , Respiratory , endocrine and CNS disease.

2. Bleeding disorders(Coagulopathies).

3. Allergy to Local anaesthetics.

4. Kyphoscoliosis.

5. BMI>35.

6. Local site infection.

7. Patient refusal.

8. Psychiatric disease.

METHOD OF RANDOMIZATION:- Sealed envelope method

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PREOPERATIVE ASSESSMENT:-

Informed consent

History

Physical examination

Airway and spine assessment Laboratory investigations:

Complete blood count

Random blood sugar (Fasting and postprandial blood sugar if necessary).

Renal parameters.

Chest X-ray.

Electrocardiogram.

Echocardiogram(if necessary).

METHODOLOGY:

During preoperative visit on day before surgery,patients were thoroughly explained about the procedure to be undertaken and the risks and benefits associated with this procedure.They were made well

conversant with Visual analog scale for postoperative pain assessment.

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After receiving the patient in the theatre, baseline pulse rate, and blood pressure (using NIBP), ECG and SpO2 are measured and

intravenous crystalloids started.After informing the procedure,before induction of general anaesthesia,epidural catheterisation was performed.

EPIDURAL TECHNIQUE:-

Strict aseptic precaution

Patient in Right lateral/sitting position

Skin infiltration with 2ml of 2%Lignocaine at T5-6 or T6-7 space.

Epidural space is identified by loss of resistance technique using 18G Touhy’s needle.

Epidural catheter introduced through Tuohys needle and advanced cephalad for a length of 5cm and fixed.

Test dose of 3ml of 1.5% Lignocaine with adrenaline (1 in 2,00,000 dilution)given.

Intradural/Intravascular placement of the catheter is ruled out.

Baseline vitals recorded.Surgery is proceeded with general anaesthesia. After surgery,in post-operative intensive care unit,patients were randomly assigned into two groups.

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ADMINISTRATION OF POST OPERATIVE ANALGESIA:- DRUGS GIVEN:-

Group RF:-50 patients received 0.1ml/kg/hour of

0.2%Ropivacaine with 1mcg/ml fentanyl in thoracic epidural infusion for 24 hours in postoperative period.

Group LF:-50 patients received 0.1ml/kg/hour of

0.2%Levobupivacaine with 1mcg/ml fentanyl in thoracic epidural infusion for 24hours postoperatively.

Visual analog scale to assess pain sensation, motorblock, sedation, haemodynamics,and adverse events were evaluated during 24hours infusion.

PAIN SCORE:-

Pain is assessed by Visual analog scale.Pain score is assessed every 15 minutes for first hour,every 30 minutes for next six hours,and every one hour thereafter for 24 hours postoperatively.When the patient complained of pain , the pain intensity was assessed based on Visual analog scale & if pain score reaches more than or equal 2,the rate of infusion was increased by 2ml/hour maximum upto 14 ml/hour till VAS score become less than 2.

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ASSESSMENT OF HEMODYNAMIC PARAMETERS:-

Hemodynamic parameters was measured every 15 minutes for first hour,every 30 minutes for next six hours,and every one hour thereafter for 24 hours postoperatively. The following variables are measured:

Pulse rate

Non invasive blood

pressure Electrocardiogram SpO2

If the patient develops symptomatic hypotension(Blood pressure less than 90/60mm Hg),crystalloids 100ml bolus is rushed,if symptomatic hypotension persists vasopressors ephedrine 6mg i.v stat administered and infusion rate is tapered by 0.02 to 0.04ml/kg/hour.

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If the patient develops bradycardia(heart rate less than 60 per minute),infusion rate is tapered by 0.02 to 0.04ml/kg/hour.If

symptomatic bradycardia occurs,intravenous atropine 0.5mg stat given.

ASSESSMENT OF MOTOR BLOCKADE:-

Assessment of motor block is done by modified bromage scale, assessed every 15 minutes for first hour,every 30 minutes for next six hours,and every one hour thereafter for 24 hours postoperatively.

0- No block(Able to raise extended arm to 90 degree for a full 2s) 1- Partial block(Able to flex the elbow and move fingers but unable

to raise the extended arm).

2- Almost complete block(Unable to flex the elbow but able to move finger).

3-Complete block(Unable to move arm,elbow,fingers)

If the patient’s bromage score reaches 1,then the infusion rate was tapered by 0.02 to 0.04ml/kg/hour and extent of motor blockade was reassessed every 15mins, till it reaches 0.

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ASSESSMENT OF SEDATION:-

Assessment of sedation is done by the Sedation score which is assessed every 15 minutes for first hour,every 30 minutes for next six hours,and every one hour thereafter for 24 hours postoperatively.

1- Oriented conversation 2- Confused conversation 3- Inappropriate conversation

4- Severe sedation/No conversation.

ADVERSE EFFECTS:- 1) Nausea 2) Vomiting 3) Bradycardia 4) Hypotension 5) Desaturation 6) Pruritis 7) Dry Mouth 8)Shivering

If the patient develops severe nausea and

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STATISTICAL ANALYSIS:-

The collected data was analysed using IBM,SPSS (Statistical package for social sciences) statistics software 23.0Version. Data descriptive statistics frequency analysis was used to describe descriptive data and percentage analysis was used for categorical variables. For continuous variables, mean and standard deviation was used. Independent t-test was used for finding the significant difference between bivariate samples in independent Groups and to find significant difference in categorical data. A probability value of ≤0.05 was considered to be significant.

In this study patients were randomly allocated into two groups of 50 patients in each group:Group RFreceived 0.1ml/kg/hour of 0.2%Ropivacaine with 1mcg/ml fentanyl in thoracic epidural infusion for 24hours in postoperative period andGroup LF received 0.1ml/kg/hour of 0.2%Levobupivacaine with 1mcg/ml fentanyl in thoracic epidural infusion for 24hours postoperatively.

The Visual analog scale for analgesic efficacy, motor blockade, sedation,hemodynamic changes including systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse rate, respiratory parameters like SpO²were assessed and compared during 24hours infusion.

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Results Table 1: Study distribution

Groups Frequency Percent

Ropivacaine-Fentanyl 50 50.0

Levobupivacaine-Fentanyl 50 50.0

Total 100 100.0

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Ropivacaine-Fentanyl, Levobupivacaine-Fentanyl

Table 2: Age distribution

Groups N Mean SD P value

Age Ropivacaine-Fentanyl 50 52.44 12.120 .835 Levobupivacaine-Fentanyl 50 52.92 10.806

P-Value is >0.05 and it is not statistically significant.

Table 3: Gender distribution

Groups Female

Ropivacaine-Fentanyl 50(100%) Levobupivacaine-Fentanyl 50(100%)

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Table 4: ASA distribution

Groups I II III

Ropivacaine-Fentanyl 0(0%) 0(0%) 50(100%) Levobupivacaine-Fentanyl 0(0%) 0(0%) 50(100%)

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Table 5: BMI distribution

Groups UNDER OVER P value

WEIGHT NORMAL WEIGHT OBESE Ropivacaine-Fen 1(2.0%) 25 20(40.0%) 4(8.0%)

tanyl (50.0%) .158

Levobupivacaine 3(6.0%) 28(56.0%) 19(38.0%) 0(0%) -Fentanyl

P- Value is >0.05 and it is not statistically significant.

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Table 6: Systolic Blood Pressure:-

TIME GROUPS N MEAN S.D P

VALUE Ropivacaine-Fentanyl 50 131.40 16.238 .505 BASELINE Levobupivacaine-Fentanyl 50 133.66 17.484

5 MIN Ropivacaine-Fentanyl 50 128.96 16.748 .945

Levobupivacaine-Fentanyl 50 128.72 18.204

30 MIN Ropivacaine-Fentanyl 50 116.22 15.454 .041*

150 MIN Ropivacaine-Fentanyl 50 120.16 11.129 .185 Levobupivacaine-Fentanyl 50 122.78 8.318

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VII HR Ropivacaine-Fentanyl 50 121.16 8.911 .264

VIII HR Ropivacaine-Fentanyl 50 123.70 6.935 .331 Levobupivacaine-Fentanyl 50 124.96 5.935

IX HR Ropivacaine-Fentanyl 50 119.18 9.382 .705

X HR Ropivacaine-Fentanyl 50 119.68 10.551 .554

XI HR Ropivacaine-Fentanyl 50 120.44 8.420 .351

XII HR Ropivacaine-Fentanyl 50 117.98 17.383 .210 Levobupivacaine-Fentanyl 50 121.38 7.843

XIVHR Ropivacaine-Fentanyl 50 115.86 9.891 .181

XVI HR Ropivacaine-Fentanyl 50 118.18 8.642 .689

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XVIII HR Ropivacaine-Fentanyl 50 118.78 6.908 .830 Levobupivacaine-Fentanyl 50 119.08 7.030

XX HR Ropivacaine-Fentanyl 50 117.54 7.744 .288

XXII HR Ropivacaine-Fentanyl 50 120.62 8.179 .317

XXIV HR Ropivacaine-Fentanyl 50 116.90 8.855 .543

Levobupivacaine-Fentanyl 50 117.92 7.837 P- Value is <0.05 and it is statistically significant.

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Table 7: Diastolic Blood Pressure

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VIII HR Ropivacaine-Fentanyl 50 74.54 6.115 .332

XII HR Ropivacaine-Fentanyl 50 75.84 5.080 .708

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XVI HR Ropivacaine-Fentanyl 50 75.72 5.257 .690 Levobupivacaine-Fentanyl 50 76.14 5.245

XVIII HR Ropivacaine-Fentanyl 50 74.08 5.458 .398

XX HR Ropivacaine-Fentanyl 50 75.08 5.495 .177

XXII HR Ropivacaine-Fentanyl 50 74.56 5.618 .530

XXIV HR Ropivacaine-Fentanyl 50 73.78 7.152 .434

*P- Value is <0.05 and it is statistically significant.

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Table 8: Mean.Arterial.Pressure

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VIII HR Ropivacaine-Fentanyl 50 90.86 5.119 .127

XII HR Ropivacaine-Fentanyl 50 90.42 4.572 .842

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Urkund Analysis Result

CERTIFICATES

Urkund Analysis Result

DECLARATION

ACKNOWLEDGEMENT

TABLE OF CONTENTS

INTRODUCTION

AIMS AND OBJECTIVES