“Comparison of Nalbuphine with 0.125% Bupivacaine and Plain 0.125% Bupivacaine in Thoracic Epidural for Post Operative Analge

“COMPARISON OF NALBUPHINE WITH 0.125% BUPIVACAINE AND

PLAIN 0.125% BUPIVACAINE

IN THORACIC EPIDURAL FOR POST OPERATIVE ANALGESIA IN

UPPER ABDOMINAL SURGERY”

Dissertation Submitted in

Partial fulfilment of the University regulations for

M.D. DEGREE EXAMINATION -MAY 2019

MD DEGREE IN ANAESTHESIOLOGY (BRANCH X)

GOVERNMENT THENI MEDICAL COLLEGE, THENI

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

CHENNAI, TAMILNADU

CERTIFICATE

This is to certify that the dissertation titled “Comparison Of Nalbuphine With 0.125% Bupivacaine And Plain 0.125% Bupivacaine In Thoracic Epidural For Post Operative Analgesia In Upper Abdominal Surgery” is a Bonafide original work done by DR.M.SUBHASHINI during May 2016-May 2019 in partial fulfilment of the requirements for M.D. (Anaesthesiology) Branch X- Examination of the Tamilnadu Dr.M.G.R. Medical University to be held in May 2019.

Prof. DR.S.VIJAYA, Prof. DR.S.VIJAYARAGAVAN, M.D., M.D., D.A., Professor and Guide, Professor and HOD, Department of Anaesthesiology, Department of Anaesthesiology, Govt. Theni Medical College, Govt. Theni Medical College, Theni. Theni.

Prof. DR.K.RAJENDRAN, M.S.,D.Ortho., Dean, Govt. Theni Medical College, Theni.

DECLARATION

I DR.M.SUBHASHINI solemnly declare that this dissertation, titled “Comparison Of Nalbuphine With 0.125% Bupivacaine And Plain 0.125% Bupivacaine In Thoracic Epidural For Post Operative Analgesia In Upper Abdominal Surgery” is a Bonafide record of work done by me in the Department of Anaesthesiology, Govt. Theni Medical College and Hospital, Theni under the guidance of Prof. DR.S.VIJAYA, M.D., Professor of Anaesthesiology, Govt. Theni Medical College & Hospital, Theni. This dissertation is submitted to the Tamilnadu Dr.M.G.R. Medical University, Chennai in partial fulfilment of the University regulations for the award of degree of M.D. (Anaesthesiology), Branch X- examination to be held in MAY- 2019.

Place: Theni

Date: DR.M.SUBHASHINI

ACKNOWLEDGEMENTS

I wish to express my sincere thanks to The Dean, Govt. Theni Medical College, Theni for having kindly permitted me to do my study in this institution.

I take great pleasure in expressing my deep sense of gratitude to Prof. DR.S.VIJAYARAGAVAN, M.D., D.A., Professor and Head of the Department of Anaesthesiology, Govt. Theni Medical College, Theni for his motivation, constant supervision and for providing all necessary arrangements for the conduct of the study, without which this dissertation would not have been materialized.

I would like to place on record my indebtedness to my guide Prof. DR.S.VIJAYA, M.D., Professor of Anaesthesiology, Govt. Theni Medical College, Theni for her constant encouragement, constructive criticism and suggestions throughout the period of the study.

I express my profound thanks to Prof. DR. KANNAN BOJARAAJ, M.D., D.A., and Prof. DR.M. BALASUBRAMANI, M.D., D.A., Associate Professors of Anaesthesiology, Govt. Theni Medical College, Theni for their whole hearted help and support in doing this study.

I am extremely thankful to DR.M.SAKUNTALA, M.D., Assistant Professor of Anaesthesiology, Govt. Theni Medical College, Theni for her valuable advice and appropriate guidance to complete this study.

I thank all the Assistant Professors and Senior Residents of Department of Anaesthesiology for their keen interest and encouragement during this study.

I thank all the Professors, Assistant professors and Senior Residents in the Department of Surgery, Govt. Theni Medical College, Theni for their help and support during the course of the study.

I thank the members of the Ethical Committee for permitting me to do the study.

I also wish to thank all my colleagues for their constant help during this study. My thanks are due to all the theatre personnel for their willing cooperation and assistance.

I am deeply grateful to all the patients included in the study, for their whole hearted co-operation in spite of their illness which made this study possible.

CONTENTS

SERIAL NO. CHAPTERS PAGE NO.

1. INTRODUCTION 1

2. HISTORY 2

3. EPIDURAL SPACE – ANATOMICAL 5 CONSIDERATION/TECHNIQUES

4. PHARMACOLOGY 38

5. REVIEW OF LITERATURE 47

6. AIM OF THE STUDY 56

7. MATERIALS AND METHODS 56

8. OBSERVATION AND RESULTS 61

9. DISCUSSION 90

10. CONCLUSION 97

11. ANNEXURES:

BIBLIOGRAPHY I

PLAGIARISM /ETHICAL COMMITTEE II/III CERTIFICATE IV PROFORMA V MASTER CHART

INTRODUCTION:

Acute uncontrolled post-operative pain and the pathophysiological response to surgery by stimulation of autonomic nervous system leads to stress responses causing significant adverse effects and complications to multi organ systems.

The important goal is to reduce the postoperative pain and discomfort

.Controlling pain is a multimodal approach with the use of various pharmacological agents (opioids and non-opioids), by different routes

(intravenous vs regional techniques) with minimal incidence of adverse effects.

In the above setting, Thoracic Epidural Analgesia (TEA) remains the mainstay of treatment in the management of perioperative pain in upper abdominal surgeries.

Advantages of epidural analgesia being the ability to provide prolonged duration of analgesia, minimal adverse effects than with systemic opioids, less haemodynamic changes, improved lung function, minimal gastrointestinal complications (paralytic ileus), early mobilisation and better patient satisfaction.

Nalbuphine is an agonist antagonist opioid related chemically to oxymorphone and naloxone. Acts as µ(mu) antagonist and kappa agonist with analgesic potency equal to that of morphine. Its rapid onset and longer duration of action and less cardiovascular and respiratory side effects makes it a better choice in postoperative analgesia. 2

In this study, we attempted to define the haemodynamic, analgesic profile and efficacy of Nalbuphine as an additive to Bupivacaine in thoracic epidural for postoperative analgesia in upper abdominal surgeries.

HISTORY:

The term extradural, peridural and epidural are synonymous, with a greek and latin origin. The epidural space, consisting of fat and blood vessels lies between the dural envelope of the spinal cord and bony walls of spinal canal and is approached either between the two lamina of adjacent vertebral arches - the

“spinal” epidural route, or through sacral hiatus – the “caudal” approach.

CORNING1 in 1885 was the first to use epidural analgesia. He hypothesised that, “medications injected within the spinal canal will be taken up by the rich plexus of blood vessels around the spinal cord and carried into the substance of spinal cord, allowing direct medication of the cord, that is used for treatment of neurological disease and provide surgical analgesia”. However, from the descriptions of his two experiments, it is evident that he did not achieve a genuine epidural injection.

In 1901, JEAN ATHANASE SICARD2-3 and FERNAND CATHELIN of France popularised caudal/ peridural approach.

MARIN THÉODORE TUFFIER4in the same year, attempted Epidural analgesia by use of Lumbar approach but lacked success. 3

In 1911, LAWEN5, emphasised caudal route to be the only safe approach to the epidural space, which limited the spread of drug to the area supplied by cauda equina.

Only in 1912, FILDES PAGES6 renewed the mid lumbar approach, because of its easy access and wide applicability. He invented the “PAGES method” of identifying epidural space – a “tactile feel” of the needle obtained on piercing ligamentum flavum.

In 1913 HEILE7, revived the idea of epidural block by entering the spinal canal laterally through the intervertebral foramina instead of midline puncture.

In 1930’s, ARCHILE MARIO DOGLIOTTI8-10, with the evidence from Jansen’s, “discovery of negative pressure in the epidural space”, described a practical technique for administering lumbar segmental anaesthesia.

With Dogliotti’s work as foundation, in 1932,GUTIERREZ11 described the “hanging drop technique” to identify the epidural space.

All these works were poorly understood and with the advent of neuromuscular blocking agents in 1946, and much satisfactory muscle relaxation with general anaesthesia alone, there was a rapid decline in use of regional techniques for anaesthesia and analgesia.

Epidural analgesia managed to escape this crisis by the introduction of Tuohy needles and indwelling epidural catheters. With technical refinements it was 4

made possible to maintain analgesia intermittently or continuously for long periods of time.

EUGENE ABUREL12 placed a silk ureteral catheter in the epidural space and used for analgesia for women in labor.

During World War II in America in 1941, ROBERT HINGSON13 was assigned to care for the pregnant wives of United States Coast Guard seamen.

Hingson used Lemmon’s malleable needle and placed it sacrally, deep to the peridural ligament and administered drugs continuously. This safe and effective method of producing painless childbirth became popularly known as

“continuous caudal anaesthesia”.

In 1949, MANUEL MARTINEZ CURBELLO14-15, modified a silk catheter for continuous spinal anaesthesia and inserted it into the lumbar epidural space, producing the first continuous epidural block.

By 1962, the first polyvinyl catheter16 with a closed tip was introduced, making the continuous epidural block much more accurate and easier to perform.

The First use of epidural morphine for analgesia was reported by BEHAR17 in

1979.This technique had given advantage over muscle relaxants in producing analgesia and maintaining voluntary function of the patient.

And then the debate between DE-EFFERENTATION (endotracheal intubation with muscle relaxants - artificial ventilation - awakening the patient to a period of post operative pain , with return of patients protective reflexes , 5

normal movement and respiratory function) and DE-AFFERENTATION

(normal respiratory function that could be preserved even during surgery - pain free ambulation soon after leaving the operating room) was complete.

The ideas from clinical observations had brought epidural analgesia out of its, “former state of empirism to a new level of versatility and clinical safety”.

However certain complications were encountered and reported as in Woolley and Roe18 case explaining paraplegia after spinal anaesthesia in 1954.In 1980’s with spinal chloroprocaine, there was incidence of neurologic deficits and adhesive arachnoiditis and with continuous spinal lidocaine anaesthesia in 1990, patients had developed cauda equina syndrome.

Currently, epidural analgesia has been combined with subarachnoid narcotics to ease the pain of labor. Combined spinal-epidural anaesthesia is one of the leading techniques in obstetric anaesthesia and analgesia.

With recent advances, epidural has widely and safely been used in areas of surgery, obstetrics (walking epidurals, pain free labour), and in areas of chronic pain relief.

ANATOMY OF EPIDURAL SPACE:

The spinal cord is continuous with the brainstem proximally and distally it terminates in the conus medullaris as the “filum terminale” which are fibrous extensions and the “cauda equina” which are the neural extensions. The spinal cord ends at L3 in infants and lower border of L1 in adults. This difference is because of the “differential growth rate” between the bony vertebral canal and the central nervous system.

The spinal cord is covered by three membranes (from innermost to outermost): the pia mater, the arachnoid mater, the dura mater.

The cerebrospinal fluid (CSF) occupies the space between pia mater and arachnoid mater, which is termed the subarachnoid (intrathecal) space.

The Piamater is a highly vascular membrane which closely covers the spinal cord and brain. CSF production per day is 500 ml formed by the choroid plexuses of the cerebral ventricles, with 30 to 80 ml occupying the subarachnoid space.

The Arachnoid mater19-20 is a delicate, nonvascular membrane that acts as the principal barrier to the drugs crossing into and out of the CSF and accounts for

90% of the resistance to drug migration.

Dura, the outermost layer that extends from the foramen magnum to the sacral hiatus and surrounding the dura is the epidural space.

The epidural space is bound21 by;

Anteriorly - Posterior Longitudinal ligaments.

Laterally - Pedicles of vertebrae and Intervertebral foramina.

Posteriorly - Anterior surface of Vertebral body and Ligamentum Flavum.

Above - Foramen Magnum, periosteal and spinal layers of dura fuse together.

Below - Sacrococcygeal Membrane.

CONTENTS OF THE EPIDURAL SPACE:

 Nerve roots

 Fat 8

 Areolar tissue

 Lymphatics,

 Blood vessels including the well-organized Batson’s plexus of veins.

Posterior to the epidural space is the Ligamentum Flavum also known as “yellow ligament”, which extends from the foramen magnum to the sacral hiatus. It is thinnest in cervical region and thickest in lumbar region.

It comprises of two ligamenta flava22-23—the right and the left—which joins in the middle and forms an acute angle with a ventral opening.

The ligamentum flavum is not uniform from skull to sacrum. Hogan’s24-25 study of frozen cryo microtome in cadaver sections also suggested that the epidural 9

space is more segmented and less uniform. He also demonstrated the spread of solution after epidural injection into the tissues of the epidural space was not uniform and this accounts for the unpredictability and patchy distribution of epidural drug spread.

VERTEBRAL ANATOMY:

There are 33 vertebrae - 7 cervical,12 thoracic vertebrae, 5 lumbar vertebrae, 5 sacral and 4 coccygeal fused to form coccyx and 31pair of spinal nerves. The posterior elements of the vertebra is formed by the vertebral arch, spinous process, pedicles, laminae, and the anterior element is formed by the vertebral body.

The vertebrae are joined anteriorly by fibrocartilaginous joints with central disks having the nucleus pulposus, and posteriorly by the zygapophyseal facet joints.

The thoracic spinous process26 is angulated steeply and caudad than the horizontal angulation of lumbar spinous process. This is important clinically for direction of needle insertion and advancement in the thoracic and lumbar levels.

The sacral canal consists of the terminal portion of the dural sac. Dural sac ends at S2. The termination of the dural sac is lower in children. The sacral canal contains a venous plexus which is a part of the valveless internal vertebral venous plexus.

The volume of caudal canal in adults is 10 to 27 ml. This variability in volume accounts for the variation in block height with caudal anaesthesia. 10

BLOOD SUPPLY:

Blood supply to the spinal cord is from;

 One Anterior Spinal artery (originating from the vertebral artery),

 Two Posterior Spinal arteries (originating from the inferior cerebellar

artery), and

 Segmental spinal arteries (originating from the intercostal and lumbar

arteries).

The spinal arteries enter the spinal canal at each intervertebral foramen and give branches to the nerve roots and medullary branches to the spinal cord.

One major branch is the artery of Adamkiewicz, entering variably between T7 and L4 on the left, and it supplies the lower thoracic and upper lumbar regions.

 Anterior two thirds of the spinal cord - Anterior Arterial branches

 Posterior one third - Posterior Arterial branches.

The anterior and deep portion of the cord, and the gray matter is most prone to ischemia leading to “Anterior horn motor neuron injury/ANTERIOR SPINAL

SYNDROME”, as there are few anterior medullary feeder vessels than posterior medullary feeder vessels.

The mid -thoracic part of the spinal cord from T3 to T9 is most prone where segmental medullary feeder vessels are rare.

VENOUS DRAINAGE:

 Three longitudinal Anterior Spinal veins

 Three Posterior Spinal veins

Finally communicating with the segmental anterior and posterior

radicular veins and then into the internal vertebral venous plexus in the

medial and lateral components of the epidural space.

No veins are present in the posterior epidural space except for those

present caudal to the L5-S1disk.

THORACIC VERTEBRAE:

The typical thoracic27 vertebral body is heart shaped, the upper two thoracic vertebra show a transition from cervical type and the lower thoracic vertebrae are similar to the lumbar bodies. The vertebral bodies of T5–8 are flattened on their left side due to the pressure of the descending aorta on these vertebral bodies and they are more prone to erosion by an aneurysm of that aortic segment.

The typical vertebrae T2–8 have upper and lower demi-facets for articulation of the rib-heads. 12

The vertebral foramen is circular with a small diameter. The pedicles are directed backwards, the superior vertebral and inferior notches are deep. Lamina are broad and overlap each other from above down.

The transverse processes is large, directed backwards and laterally, and bears a facet on the tip for articulation with tubercle of corresponding rib. The spines are long and readily palpable.

The spines are angled caudally, and therefore while performing a thoracic epidural in midline approach, a cephalad angulation of the needle is needed to pass between the spines.

The spines of T11 and 12 are more similar to lumbar vertebrae nearly horizontal, short, square type.

FEATURES OF THE ATYPICAL THORACIC VERTEBRAE:

The 1st thoracic vertebra with a body similar to cervical vertebra, a marked upper notch, a complete upper facet for the 1st rib and a small demi-facet and horizontal spine.

The 9th thoracic vertebra is typical and does not articulate with the 10th rib-head and it possess only a superior demi-facet.

The 10th thoracic vertebra articulates with the head of the 10th rib and has only a superior demi-facet and no facets on its transverse process.

The 11th thoracic vertebra articulates only with its rib-head, the transverse process is small and facet-free.

The 12th thoracic vertebra has a lumbar-shaped body with a complete facet, with a small transverse process, without an articular facet but has superior, inferior and lateral tubercles as in a lumbar vertebra.

The inferior articular facet faces outwards and the horizontal spine resembles lumbar vertebrae.

EPIDURAL ANAESTHESIA:

MECHANISM OF ACTION:

Local anaesthetic binds to the nerve tissue disrupting nerve transmission and resulting in neural blockade. The target sites are located within the spinal cord, the superficial and deep portions on the spinal nerve roots in the subarachnoid and epidural spaces. “Spinal nerve roots and dorsal root ganglia” are the most important target binding sites of action.

Nerves in the subarachnoid space are easily accessible and anesthetized, even with a small dose of local anaesthetic, than with the extradural nerves, which are often ensheathed by dura mater, the “dural sleeve”.

The rate of speed of neural blockade depends

 Size.

 Surface area.

 Degree of Nerve fibre myelination.

Anatomical studies have shown that the S1 and L5 posterior roots are larger and most resistant to blockade in epidural anaesthesia.

Smaller nerves are more sensitive to local anaesthetics because of their relatively

“high membrane surface area to axon unit volume ratio”.

Order of blockade29-30:

 Small preganglionic sympathetic fibers (B fibers, 1 to 3 μm, minimally

myelinated) - most sensitive to local anaesthetic blockade.

 Sensory C fibers(0.3 to 1 µ, unmyelinated), which conduct cold

temperature sensation.

 A-delta fibers (1 to 4 µ, myelinated), which conduct pinprick sensation.

 A-beta fibers (5 to 12 µ, myelinated), A-gamma fibers (4-8 µ,

myelinated)which conduct Joint afferents, pressure and touch sensation -

last sensory fibers to be blocked.

 Larger A-alphamotor fibers (12 to 20 μm, myelinated) are more

resistant than any fibres.

ANATOMICAL DETERMINANTS IN BLOCKADE OF MYELINATED

FIBERS:

 Minimum effective concentration “Cm”.

 Time required for anaesthetic molecules to reach target sites on axonal

membranes31.

“Atleast three adjacent nodes of ranvier must be blocked – for complete

blockade32-33”.

 “Anaesthetic solution must bathe a sufficient length of the nerve34.”

So, with increasing dilution more is the time required for the anaesthetic solution to reach greater length of axons and more is the time required for blockade. 17

Regression of blockade:

“RECOVERY” follows in the reverse order35:

 Motor function – Touch – Pinprick - Cold sensation.

The differences between the peak block height, highest or most cephalad level of anaesthesia in relation to each sensory modality, is termed DIFFERENTIAL

SENSORY BLOCK36.”The level of anaesthesia to cold sensation, also an approximate level of sympathetic blockade is most cephalad and is on average one to two spinal segments higher than the level of pinprick (sensory) anaesthesia, which in turn is one to two segments higher than the level of touch

(motor) anaesthesia.”

DRUG UPTAKE, DISTRIBUTION AND ELIMINATION:

When local anaesthetic is injected directly into the subarachnoid and epidural space, it diffuses

 Pia mater - penetrates through the spaces of Virchow –Robin - extensions

of the subarachnoid space along the blood vessels that invaginate the

spinal cord from the pia mater- and reaches deeper dorsal root37 ganglia.

 Arachnoid and Dura mater38 - to enter epidural space.

 Blood vessels of the pia39 and dura maters.

Drug penetration and uptake is, directly proportional to the drug mass, CSF drug concentration, contact surface area, lipid content and local tissue vascular supply and Inversely proportional to the Nerve root size.

 Vascular absorption into the capillary vessels and systemic circulation.

 Uptake into epidural fat (serves as “depot” for injected drugs and LA).

The bioavailability of local anaesthetic in CSF after epidural administration is low <20%.

DRUG DISTRIBUTION:

Diffusion from areas of high concentration - the site of injection to areas of low drug concentration, the other segments of spinal cord. Rostral spread of drug occurs within 10 to 20 minutes and is related to CSF circulation time.

Longitudinal oscillations generated by pulsations of the arteries in the skull are responsible for CSF bulk flow and cephalad distribution of local anaesthetic.

Drug distribution in the epidural space occurs via;

 Crossing the dura mater into the subarachnoid space.

 Rostral and caudal - longitudinal spread within the epidural space.

 Circumferential spread within the epidural space.

 Exit of the epidural space through the intervertebral foramina.

 Binding to epidural fat.

 Vascular absorption into the epidural vessels.

Longitudinal spread of drug by bulk flow within the epidural space occurs only after larger dose (i.e., volume) of drug administration.

Factors affecting distribution of drug in epidural space40;

 Small caliber (greater spread in thoracic space).

 Increased epidural space compliance.

 Decreased epidural fat content.

 Decreased leakage through the intervertebral foramina (elderly and spinal

stenosis).

 Increased epidural pressure (pregnancy).

Drug is distributed from areas of high to low concentration. The direction of drug spread varies with the vertebral level.

 Cephalad in the lumbar region.

 Caudal spread after a high thoracic injection.

 Cephalad spread after a low thoracic injection.

DRUG ELIMINATION:

Regression of neural blockade occurs from a decline in the CSF drug concentration, which is caused by

 Non neural tissue uptake and vascular absorption.

Drug is absorbed by the vessels in the pia mater or the epidural vessels through diffusion before entering the systemic circulation. 20

No drug metabolised occurs in the CSF.

 Time for block regression41 inversely correlates with CSF volume.

 The rate of elimination is dependent on the distribution of local

anaesthetic.

 Greater spread exposes the drug to a larger area for vascular absorption

and thus a shorter duration of action.

 Lipid-soluble local anaesthetics (bupivacaine) bind to epidural fat and

forms a depot that has slow vascular absorption.

PHYSIOLOGY:

“Neuraxial anaesthesia involves blockade of the sympathetic and somatic

(sensory and motor) nervous systems, with compensatory reflexes and unopposed parasympathetic activity. In epidural anaesthesia all effects are similar to spinal anaesthesia except for possibility of large concentrations of LA producing systemic side effects.”

CARDIOVASCULAR SYSTEM:

1. Decreased stroke volume (SV), heart rate (HR):

 Blockade of the peripheral (T1-L2), cardiac (T1-T4)

sympathetic fibers and adrenal medullary secretion. 21

 Sympathectomy - Venous and arterial vasodilation reduces

preload (venous return) and afterload (systemic vascular

resistance).

 Heart rate decreases - high neuraxial block - blockade of cardio

accelerator fibers from T1-T4 (unopposed parasympathetic

activity) – can lead to severe bradycardia and asystole.

 Hypotension causes a compensatory baroreceptor sympathetic

response (vasoconstriction and increased heart rate) above the

level of blockade and reduction in venous return and right

atrial filling - decrease in signal output from intrinsic

chronotropic stretch receptors (increase in parasympathetic

Activity) - nullifying the effect/ maintaining HR.

2. Maintained/ Decreased Cardiac output(CO):

 Biphasic response42 - early transient increase then decrease

in CO.

 Especially in elderly patients with preexisting hypertension

and high baseline systemic vascular resistance.

 Vasodilatory change depends on the baseline sympathetic

tone and extent of sympathectomy.

 Systemic vascular resistance decreases only 15% to 18%

after neuraxial blockade in healthy normovolemic patients. 22

 In elderly patients with cardiac disease, systemic vascular

resistance decrease by 25%, cardiac output decreases by

10%.

3. Decrease in Arterial blood pressure is more gradual and of less

magnitude with epidural than with spinal anaesthesia.

4. Decrease in Coronary blood flow paralleled the decrease in

mean arterial blood pressure but percent extraction of myocardial

oxygen43 remained unchanged.

CENTRAL NERVOUS SYSTEM:

 Hypotension decreases cerebral blood flow (CBF) in elderly patients44,

those with preexisting hypertension.

 CBF and velocity decline as a result of changes in the cerebral

vasculature, impaired cerebral autoregulation especially in the elderly.

 No change in cognitive function.

RESPIRATORY SYSTEM:

 Decrease in vital capacity and expiratory reserve volume45 – paralysis of

the abdominal muscles necessary for forced exhalation.

 Blockade of the intercostal and abdominal muscles is adequately

compensated by unaltered function of the diaphragm and accessory

respiratory muscles. 23

 Respiratory arrest –hypo-perfusion of the respiratory centers in the

brainstem.

GASTROINTESTINAL SYSTEM:

 Neuraxial blockade(T6 to L1) - disrupts splanchnic sympathetic

innervation to GIT resulting in contracted gut and hyperperistalsis.

 Nausea and vomiting due to gastrointestinal hyperperistalsis46 caused by

unopposed parasympathetic (vagal) activity - Atropine is effective in high

blocks (T5).

 Thoracic epidural anaesthesia (TEA) has a direct blood pressure–

dependent effect on intestinal perfusion.

 TEA improves hepatic, gastric and anastomotic mucosal blood flow and

prevents anastamotic leak47after colorectal surgeries.

 RENAL:

 Decrease in renal perfusion and urine output with considerable decrease

in mean arterial pressures.

 Neuraxial blocks is a frequent cause of urinary retention, which

necessitates bladder catheterization in patients.

PREGNANCY:

 Pulmonary function affected minimally (reduction of 3% to 6% for forced

vital capacity[FVC]48 and6% to 13% for peak expiratory flow rate

[PEFR]), irrespective of the peak sensory block level.

 In overweight pregnant women - vital capacity declines by 24%. 24

OBESITY:

 The impact of neuraxial blockade on lung volume variables is

significantly reduced compared with general anaesthesia but is

significantly more in overweight patients.

 Decline in vital capacity is proportional to the BMI value49 (33% decrease

for BMI> 40 Kg/m2.

 Thoracic epidural anaesthesia lessens the decline in postoperative vital

capacity and hastens recovery compared to intravenous opioids.

INDICATIONS:

 Surgical anaesthesia for procedures that involve the lower

extremities, perineum, pelvic girdle, or lower abdomen.

 In providing, intraoperative analgesia, acute postsurgical pain, and

severe chronic pain associated with malignancy.

 In labor and delivery – labor analgesia/ walking epidurals.

 Postoperative analgesia after hip, knee replacement, laparotomy,

Thoracotomy and even in cardiac surgery.

 In patients with preexisting respiratory disease undergoing

abdominal surgery.

CONTRAINDICATIONS:

ABSOLUTE:

 Patient refusal. 25

 Localized sepsis.

 Allergy to any of the drugs planned for administration.

 A patient’s inability to maintain stillness during needle puncture, which

can expose the neural structures to traumatic injury.

 Raised intracranial pressure – Brain stem herniation.

RELATIVE:

Neurological:

 Myelopathy or Peripheral Neuropathy.

 Spinal Stenosis.

 Spine Surgery.

 Multiple Sclerosis – Increased sensitivity to LA – prolonged sensory and

motor blockade.

 Spina Bifida.

Cardiac conditions:

 Aortic Stenosis or Fixed Cardiac Output.

 Hypovolemia

Hematological:

 Thrombo prophylaxis.

 Inherited Coagulopathy - Hemophilia, Von Willebrand disease, or

Idiopathic Thrombocytopenic Purpura.

Infection:

 Systemic infection and Meningitis.

 Patients with profound bacteremia or Septic shock.

FACTORS AFFECTING EPIDURAL BLOCK HEIGHT:

Drug Factors:

. Volume and total mass of injectate - the most important factor.

. 1 to 2 mL of solution per segment to be blocked.

. Additives (bicarbonate, epinephrine, and opioids) - influence onset,

quality, duration of analgesia and anaesthesia, but do not affect spread.

Patient Factors:

. Age - less volume required in the elderly50due to,

 Decreased leakage of LA through intervertebral foramina.

 Decreased compliance of epidural space - greater spread.

 Increased sensitivity of the nerves.

. Less LA is needed to produce the same epidural spread in pregnant

patients,

 Engorgement of epidural veins secondary to increased abdominal

pressure.

. Continuous positive airway pressure51 - increases the height of a thoracic

epidural block.

Procedure Factors:

. Level of injection.

. Patient position - spread/ faster onset on dependent side in decubitus

positions.

. Needle bevel direction/ speed of injection – does not influence spread of

drug.

EPIDURAL TECHNIQUE:

Preparation:

“Written informed consent, monitoring, and resuscitation equipment, intravenous access, and choosing the patient and drugs appropriately depending on comorbidities and the nature of surgery.

Sterility is very important because a catheter is often left in situ.

The extent of the surgical field must be known for placement of epidural catheter at appropriate level.”

Epidural needles/ Catheters:

“A wide variety of epidural needles are used for epidural anaesthesia.

Tuohy needles are most common, needles are 16 to 18 g in size and have a 15- to

30-degree curved, blunt “Huber” tip - to both reduce the risk of accidental dural puncture and guide the catheter cephalad. The needle shaft is marked in 1-cm intervals so depth of insertion can be identified. 28

The catheter are flexible, calibrated, durable, radiopaque plastic with either a single end hole or multiple side orifices near the tip.

Use of multiorifice catheters are superior but in pregnant women often resulted in epidural venous cannulation52. “

IDENTIFICATION OF EPIDURAL SPACE:

1. The Hanging Drop Sign Of Gutierrez: -

53  Negative pressure are found in the thoracic region (C7 – T3) when

patients are sitting. 29

 In the midline and upper thoracic regions - negative pressure

persists even after the drop has been sucked in. When a fine stream

of fluid is squirted in to the hub - disappears rapidly in to the

epidural space, giving a confirmatory sign.

 False Hanging Drop Sign: Due to muscular movements with

inspiration when a small pocket of negative pressure appears as the

muscle groups slide one upon the other.

Ancillary Signs To Differentiate The False (Superficial) Hanging Drop Sign

From True Identification Of Epidural Space:

SIGN FALSE TRUE

Initial aspiration of drop Feeble Authoritative

Persistent negative Absent Usually present pressure

Cardiac pulsations Absent Present

EPIDURAL INDICATORS FOR NEGATIVE PRESSURE:

Visual Aids: U-Tube manometers54-56, Aneroid manometer57, Zorraquin’s bulb indicator58,Odom’s Indicator59, Zelenka balloon indicator60, Brooks’ indicator61,Dawkins’ gravity Indicator.62

Auditory devices:63 - Negative pressure in epidural space - “sounds like bursting bubbles” 30

2. Loss Of Resistance Test Of Sicard And Forestier And Of Dogliotti:

 Recognition of a sudden release of resistance to injection - as

needle emerges from ligamentum flavum into epidural space.

 Readily felt with large bore needle of low internal resistance than

with fine bore needle of high internal resistance.

 False loss of resistance (30%) – defects in interspinous ligament64.

Epidural Indicators For Loss Of Resistance Test:

o Calibrated Needles, Mechanical stylets, Zelenka’s U -tube and

balloon indicator.

o “Macintosh’s balloon indicators65” - Small air filled balloon

mounted on a male adaptor. The needle is placed in spinal ligaments

and balloon is attached and inflated – On entering the epidural space

the balloon deflates.

CONFIRMATORY TESTS FOR EPIDURAL PUNCTURE:

 Aspiration Test.

 Sterile Water Injection: Fluids without iso-tonicity are painful in

epidural space. Lund in 1966, recommended this test in conscious

patients as an alternative safety measure if the test dose is omitted.

 Rapid Injection Of Saline Or Local Anaesthetic:

o Conscious subjects - Rise of CSF pressure - Feelings of

discomfort and anxiety without any change of respiratory

pattern. 31

o Unconscious/ anaesthetised subjects – Increase in rate and depth

of respiration66-67.

 DRIP-BACK TEST: To decide the origin of the dripping liquid.

o Temperature test of Gutierrez: CSF is warm, LA is cold.

o Chemical Test For CSF - CSF has 45 to 65 mg % of glucose.

Glucose oxidase test – positive blue colour change with CSF.

o Chemical Test For LA - Thiopentone Precipitation Test68 -CSF

has a pH >7.0, LA has pH of 3.5 to 5.0. With 2.5% Thiopental

(pH – 10.6) precipitates with acidic LA.

o Dye Test - dangerous as sterile methylene blue is neurotoxic.

Position:

 Sitting and Lateral decubitus positions.

 Shorter insertion times occur in sitting position than with lateral

decubitus position.

Projection and Puncture:

 Level of needle insertion - depending on the location of surgery.

LEVEL OF

NATURE OF EPIDURAL REMARKS

SURGERY INSERTION

Hip surgery,

lower extremity, Lumbar epidural More cephalad spread

obstetric analgesia L2 – L5 of drug.

Colectomy

Anterior resection Lower Thoracic More cranial spread

Upper abdominal surgery Epidural than caudal.

T6 – T8

Thoracic surgeries Upper thoracic More caudad spread of

Mastectomy Epidural drug.

T2 - T6

 Important surface landmark;

 Intercristal line (corresponding to L4-L5 interspace),

 Inferior angle of the scapula ( T7 vertebral body),

 Root of scapular spine (T3),

 Vertebra prominens (C7). 33

Approach:

 Midline.

 Paramedian.

 Modified Paramedian (Taylor approach).

 Caudal.

Midline approach:

“Used for lumbar and low thoracic epidurals. After LA infiltration of the skin, the non dominant hand rested on the back of the patient, with the thumb and index finger of the dominant hand holding the needle hub or wing.

The angle of approach should be,

 Only slightly cephalad - lumbar and low-thoracic regions.

 More cephalad – Mid thoracic regions.

In a controlled fashion, the Tuohy needle should be advanced with the stylet in place through the supraspinous ligament and into the interspinous ligament, at this point the stylet is removed and syringe attached and the needle rests firmly in the tissues. Further advancement of needle into the ligamentum flavum for both loss of resistance to air or saline and hanging-drop methods.

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 non dominant hand. Ligamentum flavum is a tougher structure with increased resistance, so when the epidural space is subsequently 34

entered, the pressure applied to the syringe plunger allows the solution to flow without resistance into the epidural space.

Loss of resistance to air is less reliable in identifying the epidural space, results higher chance of incomplete block, and both pneumocephalus and venous air embolism.”

The depth from skin to the ligamentum flavum is 4 cm (3.5 and 6 cm). In the lumbar region, the ligamentum flavum is 5 to 6 mm thick in the midline. Angle 35

of insertion, perpendicular(90°) in lumbar vertebra and cephalad (40°) in thoracic spines.

When the epidural space is identified, the depth of the needle at the skin should be noted. The syringe is then removed and a catheter gently threaded to the 15- to 18-cm mark so that sufficient length of catheter is in the epidural space. The needle can then be carefully withdrawn, and the catheter is withdrawn to allow 4 to 6 cm in the epidural space.

Catheter space less than 4 cm in length in the epidural space69-72;

 Risk of catheter dislodgement.

 Inadequate analgesia.

Threading more of the catheter in the epidural space - catheter malposition or complications.

The Tsui test:“To confirm the epidural catheter position. This test73 stimulates the spinal nerve roots with a low electrical current conducted through normal saline in the epidural space and an electrically conducting catheter. At currents of 1 to 10 mA, corresponding muscle twitches (i.e., intercostal or abdominal wall muscles for thoracic epidural catheters) can be used to identify catheter tip location. “Subarachnoid and subdurally positioned epidural catheters elicit motor” responses at a much lower threshold current74,75 (<1 mA)”.

Paramedian Approach:

Used in mid- to high thoracic region, where the angulation of the spine is cephlad and the spaces are narrow. The needle is inserted 1 to 2 cm lateral to the 37

inferior tip of the spinous process of corresponding vertebra. The needle is advanced horizontally until the lamina is reached and then redirected medially and cephalad to enter the epidural space.

Taylor approach:

Modified paramedian approach via the L5-S1 interspace, which is useful in trauma patients who cannot tolerate or able to maintain a sitting position. The needle is inserted 1 cm medial and 1 cm inferior to the posterior superior iliac spine and is angled medially and cephalad 45° to 55° angle.

Epidural test dose:

Before initiating an epidural local anaesthetic infusion, a test dose may be administered. The purpose is to rule out intrathecal or intravascular catheter placement.

A small volume 3 ml of lignocaine 1.5% with epinephrine( 1 in 2 lakhs dilution)of 5µg/ ml of Adrenaline in per ml of LA. Another specific method was with 10 to 15 μg of epinephrine alone in non pregnant adult patients, an increase in systolic blood pressure more than 15 mm Hg or an increase in heart rate more than 10 beats/min ascertained intravascular placement of epidural catheter.

COMPLICATIONS:

1. Neurologic:

 Paraplegia

 Cauda Equina Syndrome 38

 Epidural Haematoma

 Nerve Injury

 Post Dural Puncture Headache(PDPH)

 Transient Neurological Symptoms

2. Cardiovascular:

 Hypotension

 Bradycardia

 Cardiac arrest

3. Respiratory:

 Respiratory depression – Neuraxial opiods – dose dependent.

Early – occurs in first 30 min – with lipophilic drugs.

Late - > 2 hrs after drug administration – Fentanyl, Sufentanil.

4. Infections:

 Bacterial meningitis – Streptococcus viridans.

 Epidural abscess.

5. Backache.

6. Nausea and Vomiting.

7. Urinary Retention.

8. Pruritis.

9. Shivering.

Complications specific to epidural anaesthesia:

 Intravascular injection.

 Subdural injection. 39

BUPIVACAINE – PHARMACOLOGY:

“It is a widely used amide local anaesthetic and brought into clinical use in 1963 first introduced by Emblem in 1966. Structure is similar to lignocaine except that the amine containing group is butyl piperidine.

Levobupivacaine the s-enantiomer of bupivacaine is also available with less cardio toxicity. For clinical use it is supplied as hydrochloride salt.

Local anaesthetics consist of a lipophilic and a hydrophilic portion separated by a connecting hydrocarbon chain. The hydrophilic group is usually a tertiary amine, as diethyl amine, the lipophilic portion is usually an unsaturated aromatic ring, as para amino benzoic acid.

The lipophilic portion is essential for anaesthetic activity.

An ester(–CO–) or an amide (–NHC–) bond links the hydrocarbon chain to the lipophilic aromatic ring. The nature of this bond forms the basis for classifying drugs as ester local anaesthetics or amide local anaesthetics.

Chemical structure:

Bupivacaine HCL (1-butyl-2', 6' pipecoloxylidide hydrochloride) is a long acting amide local anaesthetic. First synthesized in 1957 by Ekernstam at A. B. Bafors

Laboratories in Molndel, Sweden.

Pharmacokinetics:

 Molecular weight (base) – 288 daltons.

 Pka - 8.1.

 Bound in plasma - 95%.

 Volume of distribution - 0.9 - 0.4 litres/kg.

 Clearance - 7.1-2.8 ml/min/kg.

 Lipid solubility - 2.4-1.2 hours.

 Peak time - 0.17-0.5 hour.

 Peak concentration - 0.8microgram/ml.

 Toxic plasma concentration - >1.5microgram /ml.

 Plasma protein binding site - alpha1 acid glycoprotein. 41

Mechanism of action76:

 “Binds to the intracellular portion of sodium channels - blocks sodium

influx into nerve cells - prevents depolarization.

 Pain transmitting nerve fibres - thinner, unmyelinated/lightly myelinated -

diffuse more readily than into thicker, myelinated nerve fibres like touch,

proprioception.

 Penetration of the nervesheath by the remaining free drug molecules.

 Permeate the nerve’saxon membranes and accumulate within the

axoplasm - the speed and extent dependon a particular drug’s pKa and on

lipophilicity

 Binding of local anaesthetic to sites on voltage-gatedNa+ channels -

prevents opening of the channels byinhibiting the conformational changes

and occlude the pore path for Na+ions.

Metabolism:

 Metabolised77-78 by enzymes in the liver by aromatic

hydroxylation, N-dealkylation, amide hydrolysis and conjugation.

 Metabolite is N-dealkylated desbutyl bupivacaine.

DOSE : 2 -3mg/kg.

Clinical Uses:

 Central neuraxial blockade (intrathecal, epidural, caudal)

 For peripheral nerve blocks and infiltration analgesia.” 42

TOXICITY:

“ACCIDENTAL INTRAVASCULAR INJECTION / SYSTEMIC

ABSORPTION:

 Depends on dose administered, Vascularity of tissues, Presence of

adrenaline in solution, Properties of drug.

 5 mcg of adrenaline/ ml of la solution (1:2 lakhs dilution) – decreases

systemic absorption by 1/3 rd.

 Local anaesthetic systemic toxicity79-80 (LAST)

 Mild systemic symptoms: Auditory changes, Circumoral numbness,

Metallic taste, Agitation.

 Central nervous system - seizure, CNS depression, coma, respiratory

arrest.

 Cardiovascular events - hypertension, hypotension, tachycardia,

bradycardia, ventricular arrhythmias, cardiac arrest.

 At a plasma concentration of 4.5 – 5 mcg/ml – seizures.

TREATMENT – RECENT RECOMMENDATIONS:

From American society of regional anaesthesia and pain medicine81-82.

 Airway management.

 Seizure suppression – Thiopentone/ Benzodiazepines /neuromuscular

blocking agents.

 Cardiac arrest – ACLS, 43

Use small initial doses of epinephrine (10–100 mg boluses),

Vasopressin is not recommended. Avoid calcium channel blockers, beta-

adrenergic blockers, and Local anaesthetics (lidocaine, procaine).

 Ventricular arrhythmias – Amiodarone.

 Lipid emulsion therapy - at first signs of LAST, 1.5 ml/ kg bolus of 20%

lipid emulsion. Infusion at 0.25 ml/kg/min for at least 10 min after return

of circulatory stability second bolus increasing infusion to 0.50 ml/ kg if

circulatory stability not attained. Upper limit of lipid emulsion for first 30

min is 10 ml /kg.

 CARDIOPULMONARY BYPASS if lipid emulsion treatment fails.”

NALBUPHINE:

“Nalbuphine hydrochloride (Nubain) is classified as a synthetic opioid agonist- antagonist. Chemically, it is related to the opioid antagonist, naloxone and the potent opioid agonist oxymorphone. The chemical name for nalbuphine is 17-

(cyclobutylmethyl)-4,5-α epoxymorphinan-3,6α, 14-triol hydrochloride.

Agonist-antagonist opioids are usually produced by alkylation of the piperidine nitrogen and the addition of a three-carbon side chain such as a propyl, allyl, or methyl allyl to morphine.

CHEMICAL STRUCTURE:

PROPERTIES:

Nalbuphine hydrochloride molecular weight is 393.91 and is soluble in H2O and ethanol; insoluble in CHCl3 and ether. Nalbuphine hydrochloride has pKa values of 8.71 and 9.96.

MECHANISM OF ACTION:

Nalbuphine is a μ-receptor antagonists and full or partial agonists at the κ receptors. It has agonistic potency of 1/10 th of that of oxymorphine, analgesic potency similar to that of morphine in equipotent doses, antagonistic activity

¼ th of that of Nalorphine.

Activation of supraspinal and spinal kappa receptors results in limited analgesia.

Agonist-antagonist opioids are less prone to abuse because they cause less euphoria and are associated with less drug-seeking behavior and physical dependence.

The agonist-antagonist compounds depress respiration in a manner similar to that of morphine, but ceiling effects83-85 exists( 30 mg for adults).

Nalbuphine decreases cardiac workload, with little or no changes in heart rate, blood pressure and pulmonary arterial pressure.

It has rapid onset of action occurs within 5 to 10 minutes after administration.

The plasma half-life is 5 hours and the duration of analgesic activity has been reported to range from 3 to 6 hours. Dose of 0.2 mg /kg. Nalbuphine is metabolized by the liver and excreted by the kidneys.

Many studies have shown that, Nalbuphine is effective in controlling,

 Prevention of intrathecal morphine induced pruritis86.

 Potent antishivering agent similar to meperidine87. 46

 Nalbuphine 10 to 20 mg IV, reverses postoperative depression of

ventilation caused by fentanyl but maintains analgesia88.

Adverse effects:

 Sedation is the most common side effect, occurring in about one-third of

patients treated with nalbuphine.

 The incidence of dysphoria is less than that with pentazocine or

butorphanol but is qualitatively similar and increases in frequency as the

dose of nalbuphine increases.

 Abrupt withdrawal of nalbuphine after chronic administration produces

withdrawal symptoms that are milder than those of morphine and more

severe than those of pentazocine – low abuse potential.

INTERACTIONS:

Subsequent use of morphine-like drugs for anaesthesia or postoperative analgesia after preoperative medication with nalbuphine may not provide adequate analgesia.

Conversely, the antagonist effects of nalbuphine at mu receptors could be an advantage in the postoperative period to reverse ventilatory depressant effects of opioid agonists while still maintaining analgesia.”

REVIEW OF LITERATURE:

1. COMPARISON OF NALBUPHINE WITH 0.5% BUPIVACAINE

AND NORMAL SALINE WITH 0.5% BUPIVACAINE FOR POST

OPERATIVE EPIDURAL ANALGESIA89.

Journal of evolution of medical and dental sciences 2015;

vol.4, issue 48, june 15; page: 8382 – 8389.DOI:

10.14260/jemds/2015/1215.

Evaluation of role of Nalbuphine as an additive to Bupivacaine in

increasing the duration of analgesia postoperatively by epidural

anaesthesia in lower abdominal surgeries. Epidural Nalbuphine 0.2 mg/kg

with 0.5% Bupivacaine produces early onset of sensory blockade

(3.23±0.97 min vs 15.30±2.97 min) and prolongs the duration of

analgesia (449±67 min vs 185.93±32.43 min) in comparison to 0.5%

Bupivacaine with normal saline.

2. EPIDURAL NALBUPHINE FOR POST-OPERATIVE ANALGESIA

IN ORTHOPAEDIC SURGERY90.

www.aeroline.org / DOI: 10. 4103/0259 -1162.158004.

Veena chatrath, joginder pal attri et al, used combined spinal epidural

technique for comparative evaluation of post-operative pain relief with

Bupivacaine hydrochloride 0.25% and Nalbuphine (10 mg) vs 0.25%

Bupivacaine hydrochloride with Tramadol(100mg). 48

The mean duration (380±11.49 min vs 380±9.8 min), quality of analgesia

and patient satisfaction (4.40±0.871 vs 3.90±1.150) was effective

compared to Tramadol in the Nalbuphine group.

3. A COMPARATIVE STUDY BETWEEN EPIDURAL

BUTARPHANOL, NALBUPHINE, AND FENTANYL FOR POST-

OPERATIVE ANALGESIA IN LOWER ABDOMINAL

SURGERIES91.

Asian journal of pharmaceutical and clinical research. Vol.10, issue 5,

2017.

DOI: http://dx.doi.org/10.22159/ajpcr.2017.v10i5.16802.

Swarna baneerjee et al, studied the post-operative analgesic benefits in

patients administered with Butorphanol (2mg), Nalbuphine (10 mg),

Fentanyl (100mcg) in 0.125% Bupivacaine in lumbar epidural for lower

abdominal surgeries.

The mean time of onset of analgesia was early in Fentanyl group (6.32

min) when compared to other groups (Nalbuphine – 14.64

min/Butorphanol - 11.24 min) and the duration of analgesia much longer

in Butorphanol group ( 481.68 min) when compared to other groups

(Nalbuphine – 294.68 min/ Fentanyl – 178.60 min).

4. COMPARATIVE STUDY OF CAUDAL EPIDURAL

BUPIVACAINE AND BUPIVACAINE PLUS NALBUPHINE IN

POST-OPERATIVE ANALGESIA IN CHILDREN92.

Ain – Shams journal of anaesthesiology 2015, 08:628 – 633 49

Mohamed et al, studied the comparative effect of Bupivacaine alone and

with Nalbuphine in caudal epidural analgesia in children.

There was no significant haemodynamic changes, motor block and

urinary retention between Bupivacaine 0.125% alone and 0.125%

Bupivcaine with Nalbuphine (0.1 mg/kg), however there was significant

difference in

Post-operative pain and sedation scores and prolonged duration of

analgesia and sedation and time to first rescue analgesia (6.2±1.4 hrs vs

10.1±1.5 hrs).

5. PRELIMINARY STUDY OF EPIDURAL NALBUPHINE IN

TREATMENT OF POST-OPERATIVE PAIN: A COMPARISON

WITH EQUIPOTENT DOSE OF EPIDURAL MORPHINE93.

J Anesth 3:54 – 57, 1989

Weksler N, Ovadia L et al, compared the use of Nalbuphine (0.15 mg/kg)

and an equipotent dose of Morphine (0.1 mg/kg) in epidural analgesia in

45 patients undergoing upper abdominal surgery. Analgesic efficacy was

found to be excellent in both groups with longer duration of analgesia in

Morphine group (6.30±2.15 hrs vs 16.40±5.50 hrs), besides drowsiness,

other significant side effects as respiratory depression were less in

Nalbuphine group than with Morphine.

Thus epidurally administered Nalbuphine is better choice than Morphine

providing good analgesia and minor side effects.

6. EPIDURAL NALBUPHINE FOR ANALGESIA FOLLOWING

CAESAREAN DELIVERY:DOSE – RESPONSE AND EFFECT OF

LOCAL ANAESTHETIC CHOICE94.

CAN J ANAESTH 1991/38:6/pp – 728-732.

Camman R. William et al, studied the analgesic profile of Nalbuphine

epidurally for post-operative pain relief was investigated in 58 patients

undergoing elective caesarean delivery under epidural anaesthesia.

Nalbuphine was administered in doses of 10mg, 20mg, 30 mg along with

2% lignocaine or 2 – chlorprocaine 3%. 20 – 30 mg of epidural

Nalbuphine provided analgesia for 2-4 hrs with minor side effects of

somnolence but with 2- chlorprocaine 3% there was minimal or no

analgesia post-operatively.

7. A COMPARISON OF ANALGESIC AND SIDE EFFECTS OF

CONTINUOUS EPIDURAL MORPHINE AND NALBUPHINE

AFTER A CAESREAN SECTION95.

Korean J Anesthesiol 2001; 41:59 -65.

Sang mook lee et at, evaluated the analgesic efficacy and side effects of

Epidural Morphine and Epidural Nalbuphine in 59 patients undergoing

caesarean section.

Analgesia effects were good in two groups with a VAS of < 3, and no

significant haemodynamic changes in both groups. Patients in group M

had lower pain scores which were significant at 6, 12, 24 hrs when 51

compared to Nalbuphine group. However Morphine group had more

incidence of side effects.

8. COMPARISON BETWEEN CAUDAL DEXMEDETOMIDINE AND

NALBUPHINE IN CHILDREN UNDERGOING HYPOSPADIAS

SURGERY: A PROSPECTIVE RANDOMISED DOUBLE BLIND

CONTROLLED STUDY96.

Pediatric Anesthesia and Critical care journal 2016; 4(1): 48 -54.

DOI: 10.14587/paccj.2016.10

Salama et al, investigated the efficacy of adding Dexmedetomidine or

Nalbuphine to local anaesthetic in 60 children undergoing hypospadias

surgery.

Post-operative pain scores were significantly decreased in

Dexmedetomidine group with a longer duration of analgesia (16±0.74

hrs) compared to Nalbuphine (6.7±0.38 hrs) group. Sedation scores were

comparable in both groups and not statistically significant.

9. A RANDOMISED DOUBLE BLIND CONTROL STUDY OF

EFFECTS OF ADDING NALBUPHINE TO SPINAL

BUPIVACAINE FOR LOWER ABDOMINAL SURGERIES IN

ELDERLY PATIENTS97.

Anaesth Pain & Intensive care 2013; 17(2): 145-148

Manisha sapate sahu et al, evaluated the onset, duration of sensory and

motor blockade with plain hyperbaric Bupivacaine and hyperbaric

Bupivacaine with Nalbuphine administered intrathecally in 40 patients 52

posted for lower abdominal surgeries, and also assessed the analgesic

efficacy and incidence of side effects with Nalbuphine.

There was no significant difference in mean onset of sensory (60 sec vs

58 sec) and motor block(110 sec in both group), and peak sensory block(

380 sec in both group) and peak motor block( 220sec vs 210 sec) in

Bupivacaine and Nalbuphine groups respectively.

Duration of post-operative analgesia was prolonged in Nalbuphine group

(566±15.5 min) compared to Bupivacaine group (159.5±18.42 min) is

statistical significant with no incidence of complications and side effects.

10. A COMPARATIVE STUDY OF EPIDURAL NALBUPHINE WITH

BUPIVACAINE VS.BUPIVACAINE ALONE IN INFRA

UMBILICAL SURGERIES98.

J. Evolution Med.Dent.Sci. 2016; 5(77):5710-5715,

DOI:10.14260/jemds/2016/1288.

Ramakrishna CD et al, studied in 100 patients with lumbar epidural

undergoing elective infraumblical surgery, the onset of sensory and motor

blockade, duration of analgesia, quality of post-operative analgesia.

The mean onset of sensory blockade (5.22 min vs 9.52 min) and mean

onset of motor blockade (7.8 min vs 12.84 min) and duration of analgesia

(287.40±29 min) was significant in Nalbuphine group compared to plain

Bupivacaine group. Better quality of analgesia and no incidence of side

effects occurred in Nalbuphine group. And thus concluded, Nalbuphine 53

hastens the onset of sensory and motor block, prolongs duration of

analgesia with stable haemodynamics.

11. EFFICACY OF EPIDURAL NALBUPINE IN POST OPERATIVE

PAIN CONTROL99.

Anesthesiology V.61, no 3A September 1984

M.S.Mok et al. studied the efficacy of Epidural Nalbuphine in post-

operative pain control in 30 post-surgical patient posted for elective

abdominal surgery.

The onset of pain relief appeared at 15minutes, peak action at 30-

60minutes and lasted for 13.6±4.2 hours. No incidence of adverse effects,

respiratory depression, motor or autonomic blockade in any patients.

12. COMPARATIVE STUDY OF DEXMEDETOMIDINE AND

NALBUPHINE AS AN ADJUVANT TO BUPIVACAINE IN

LOWER LIMB SURGERY DONE UNDER EPIDURAL

ANESTHESIA100.

Med pulse International Journal of Anesthesiology, July 2017:3(1):34-42

Sonali et al. studied the clinical profile of Nalbuphine and

Dexmedetomidine as an adjuvant to Bupivacaine in Epidural anesthesia

in 70 patients undergoing infraumblical and lower abdominal surgeries.

The onset of sensory blockade was earlier in Dexmedetomidine group

compared to Nalbuphine group (10.06±4.42min vs 13.88±7.83min) mean

onset of motor blockade (9.22±3.87 vs 11±6.28min), and duration of

analgesia is longer in Dexmedetomidine group (353.86±51.36min vs 54

295.28±65.95min) with no significant hemodynamic changes and no

adverse effect in Nalbuphine group.

13. COMPARISON OF NALBUPHINE VERSUS EPIDURAL

BUPRENORPHINE FOR IMMEDIATE POST OPERATIVE

ANALGESIA IN PATIENT UNDERGOING KNEE

ARTHROSCOPY101.

Anestesiologia pediatrica 2013; 67(5), Sep - Oct 190-197.

Delgado et al. compared the analgesia provided by Nalbuphine with

Buprenorphine in Epidural for immediate postoperative pain in 52 patients

undergoing arthroscopic knee surgery.

A statistically significant difference in systolic pressure was found in

Nalbuphine group however diastolic pressure showed no significance.

Pain scores were equivocal in both groups and statistically significant with

much incidence of itching, nausea in Buprenorphine group than in

Nalbuphine.

14. A COMPARISON OF EQUIPOTENT DOSES OF TRAMADOL

AND NALBUPHINE IN GYNECOLGICAL LAPAROTOMIES

POST-OPERATIVELY102.

Pak armed forces med j 2016:66(5) 738-741.

Thanveer Hussein et al. compared the mean consumption of equipotent

doses of Tramadol and Nalbuphine for first 12 hours of post-operative

analgesia in 100 patients undergoing gynaecological laparotomies 55

The mean VAS score remained equivocal in both groups with a significant

difference in time to first demand of analgesia (0.57±0.48 vs 1.06±1.46

hours)

15. EFFECT OF NALBUPHINE AS AN ADJUVANT ON

LEVOBUPIVACINE INDUCED CAUDAL ANALGESIA IN

CHILDREN UNDERGOING SURGICAL PROCEDURES,

CONTROLLED RANDOMISED DOUBLE BLINDED STUDY103.

Egyptian journal of anaesthesia (2016), 32, 97-102.

R.H.SALEH et al. studied the reduction in intraoperative use of volatile

anaesthetic, compared the effects of plain Levobupivacaine 0.25% and

Nalbuphine 0.1mg/kg with 0.25% Levobupivacaine in single shot caudal

epidural in post-operative analgesia in 40 children undergoing lower

abdominal surgeries.

The time to first analgesia was prolonged in Nalbuphine group ( 11.2±1.6

vs 5.9±1 hour) with significant higher sedation score at 30minutes, 1hour,

2 hours in Nalbuphine group. No incidence of motor block , urinary

retention in both groups.

16. A COMPARATIVE STUDY OF POSTOPERATIVE ANALGESIA

AFTER SPINAL NALBUPHINE WITH BUPIVACAINE AND

SPINAL BUPIVACAINE FOR LOWER LIMB SURGERIES.104

Journal of evidence based medicine and healthcare vol2, issue 38 , sep 21

2015 pg; 6105-6109 56

T.Padma et al. studied to establish the effectiveness of Nalbuphine as an

intrathecal adjuvant and for post-operative analgesia in 50 patients

undergoing lower abdominal surgeries.

The mean onset of sensory blockade in Nalbuphine and Control group

(56sec vs 58sec) and mean onset of motor blockade (105± 2.2sec vs

205±2.4sec) and peak onset of motor block (370±2.3 sec vs 215±2.1 sec)

and duration of postoperative analgesia (464±20.02 min vs 158.5±19.03

min) was statistically significant in Nalbuphine group.

17. A COMPARATIVE STUDY OF NALBUPHINE (0.3 mg/kg) + 0.5%

BUPIVACAINE WITH 0.5% BUPIVACAINE ALONE IN

EPIDURAL ANESTHESIA INVOLVING INFRAUMBILICAL

SURGERIES105.

Indian Journal of Applied Research,

Vol-7, issue-11, Nov-2017/ ISSN – 2249-555X.

Sanjay P Gadre et al, designed this study to compare the haemodynamic

and analgesic effects of Nalbuphine with Bupivacaine and Bupivacaine

alone in Epidural anaesthesia.

The mean onset of sensory block (6.8±1.13 min vs 11.03±1.33min), motor

block (9.87±1.22min vs 15.3±0.88min), duration of analgesia

(414.6±37.7min vs 255.67±26.6 min) was statistically significant in

Nalbuphine with Bupivacaine group providing mild sedation and minimal

side effects.

AIM OF THE STUDY:

To compare the Onset of analgesia,

Duration of analgesia.

Level of consciousness (sedation).

Pain scoring by VAS(Visual Analogue Scale).

Haemodynamic changes.

Need for rescue analgesia.

Incidence of complications and other side effects.

MATERIAL AND METHODS:

The study was designed to be a prospective, double blind, randomised controlled trial.

A total of 60 patients undergoing elective and emergency upper abdominal surgery were randomly allocated by Systematic random sampling into two groups of 30 each.

GROUP A – Nalbuphine 10 mg with 0.125% Bupivacaine.

GROUP B – Normal Saline with 0.125% Bupivacaine.

After obtaining approval by the instituitional ethical committee and written informed consent from the patient, this study was conducted on 60 patients.

INCLUSION CRITERIA:

 Age between 18 – 55yrs.

 Both sex.

 Patients ASA grade I, II, III physical status.

 Posted for elective and emergency upper abdominal surgery in GTMCH.

EXCLUSION CRITERIA:

• Patients who were pregnant, known alcoholic, drug abusers, allergy to

drug involved in the study, bradycardia, any type of AV block, heart

failure,

• Significant neurological, hepatic, renal, pulmonary diseases.

• Pt. with ASA – grade IV, V.

• Infection at site of injection.

• Contraindications like thrombocytopenia, coagulopathy.

• Uncooperative patients.

• Failed Epidural in patients will also be excluded from the study.

METHODOLOGY:

Patient’s detailed history, general physical and systemic examination during preoperative visit.

Basic demographic data like age, sex, height, weight were noted. 59

Linear Visual Analogue scale(VAS) was explained to all patients. IV cannulation through 18 gauge iv cannula and patient preloaded with 15 ml/kg of

Ringer Lactate. Premedication with Inj.Midazolam 0.1 – 0.5mg/kg IM, 45min-

1hr before procedure. Monitors connected to record Pulse Rate, Mean Arterial

Pressure, SPO2, ECG.

Before induction of either general or regional anaesthesia, 17 – 18 gauge

Epidural TUOHY needle was inserted at T9 – T11 level, 18 - 19 gauge epidural catheter was threaded through the epidural space for 4-5cm and placed at T7-

T9level. Epidural test dose of 3ml of lignocaine with adrenaline (1 in 2,00,000 dilution, 5 mcg/ml) administered to rule out intrathecal and intravascular misplacement of catheter.

` Surgery was proceeded and intraoperative fluid management was done according to haemodynamic parameters and blood loss of the patient. After surgery, these patients were shifted to postoperative care unit and monitored.

GROUP A received 1ml of Nalbuphine (10mg) with 2.5ml of 0.5%

Bupivacaine, diluted in NS to 10ml.

GROUP B received 1ml of Normal Saline with 2.5ml of 0.5% Bupivacaine, diluted in NS to 10ml.

The following parameters were observed;

 Level of consciousness (sedation) by Wilson’s sedation scoring.

WILSON’S SEDATION SCORING:

1 – Awake And Alert.

2 – Awake But Drowsy.

3 – Eyes Closed But Arousable To Command.

4 – Eyes Closed But Arousable To Mild Physical Stimulation.

5 – Eyes Closed And Unarousable To Mild Physical Stimulation.

 Pain scoring by visual analogue scale:

Using a 10cm VAS with 0 and 10 labelled as “no pain” and “worst pain

imaginable respectively. Scores were to be obtained at 2 hourly interval.

 Duration of analgesia - calculated when the visual analogue scale

reached 5 or more, or when the patient complained of moderate to

severe pain.

 SPO2 monitored continuously. 61

 Pulse Rate, Blood Pressure, Mean Arterial Pressure, Respiratory

Rate were recorded every 5 min.

 Need for rescue analgesia was noted.

 Side effects like nausea, vomiting, pruritis, respiratory depression,

urinary retention and degree of sedation are also noted in both groups.

RESULTS:

Table 1: Age distribution of the study groups (n=60)

Group A Group B Total Age group n (%) n (%) n (%)

<25 years 3 (10) 1 (3.3) 4 (6.7)

26 - 40 years 9 (30) 4 (13.3) 13 (21.7)

41 - 55 years 18 (60) 25 (83.3) 43 (71.7)

Total 30 (100) 30 (100) 60 (100)

Mean (± S.D) Age: 44.88 ± 9.80. Age distribution of subjects in both the groups was comparable with minor difference.

30 Group A Group B 25

20 18

10 9 3 4 1 0 <25 years 26 to 40 years 40-55 years

Fig 1: Age distribution of the study groups (n=60) 63

Table 2: Distribution of the study groups according to mean age (n=60)

Mean Student Std. Mean Group N Age ‘t’test Deviation difference (years) p value

A 30 42.43 10.852 -4.90 0.052 B 30 47.33 8.083

The difference in mean age between subjects in the two groups was not statistically significant and hence the groups were comparable.

Table 3: Gender distribution of the study groups (n=60)

Female Male Total Group n (%) n (%) n (%)

Group A 11 (55) 19 (47.5) 30 (50)

Group B 9 (45) 21 (52.5) 30 (50)

60 Total 20 (100) 40 (100) (100)

Chi-square value: 0.300 p value:0.584

The difference in gender distribution of subjects between the 2 groups

was not statistically significant. 64

Fig 2: Gender distribution of the study groups (n=60)

25 Group A Group B 21 20 19 15 11 10 9 5 0 Female Male

Table 4: Distribution of the study groups according to body weight (n=60)

Mean Student Std. Mean Group N weight ‘t’test Deviation difference (Kg) p value

A 30 55.80 9.901 -0.200 0.939 B 30 56.00 10.222

The difference in mean weight between subjects in the two groups was not

statistically significant and hence the groups were comparable. 65

Fig 3: Distribution of the study groups according to body weight (n=60)

Table 5: Distribution of the study groups according to body height (n=60)

Student Mean height Mean Group N Std. Deviation ‘t’test (cms) difference p value

A 30 158.73 5.330 -0.367 0.781 B 30 159.10 4.816

The difference in mean height between subjects in the two groups was not

statistically significant and hence the groups were comparable. 66

Fig 4: Distribution of the study groups according to body body mass index

(n=60)

Table 6: Distribution of the subjects according to indication of surgery

(n=60)

Group A GroupB Total Surgery indication n (%) n (%) n (%)

Elective 22 (73.3) 21 (70) 43 (71.7)

Emergency 8 (26.7) 9 (30) 17 (28.3)

Total 30 (100) 30 (100) 60 (100)

Chi-square value: 0.082 p value:0.774

The difference in distribution of elective and emergency surgeries done between the groups was not statistically significant. 67

30 Group A 22 21 Group B 20

10 8 9

0 Elective Emergency Fig 5: Distribution of the subjects according to indication of surgery (n=60)

1 Group B Renal surgery 1 Group A 9 Emergency laparotomies 8

6 Hepatobilary surgery 8

9 Gastrointestinal surgeries 7

5 Hernia surgery 6

0 2 4 6 8 10

Fig 6: Distribution of the subjects according to type of surgery (n=60) 68

Table 7: Distribution of the subjects according to type of surgery (n=60)

GroupA Group B Total Surgery type n (%) n (%) n (%)

Supraumbilical hernia surgery 6 (20) 5 (16.7) 11 (18.3) (umbilical, paraumbilical, epigastric)

Gastrointestinal surgeries (gastric outlet obstruction, duodenal ulcers, 7 (23.3) 9 (30) 16 (26.7) growth - stomach, small bowel)

Hepatobiliary surgery (obstructive 8 (26.7) 6 (20) 14 (23.3) jaundice, cholecystitis)

Emergency laparotomies (perforative 8 (26.7) 9 (30) 17 (28.3) peritonitis, hollow viscous perforation)

Renal surgery (nephrectomy) 1 (3.3) 1 (3.3) 2 (3.3)

Total 30 (100) 30 (100) 60 (100)

Chi-square value: 0.685 p value:0.953

The difference in distribution of type of surgeries done between the

groups was not statistically significant.

Table 8: Distribution of the study groups according to time of onset of sensory blockade (n=60)

Mean onset Student Std. Mean Group N time ‘t’test Deviation difference (mins) p value

A 30 7.07 1.081 -10.767 <0.001 B 30 17.83 2.984

The difference in mean time of onset of sensory blockade between

subjects in the two groups was statistically significant with group A

having shorter and quicker onset of action (sensory blockade) by

approximately 10 mins than group B.

Fig 7; showing time of onset of sensory blockade between the 2 groups

(n=60)

Table 9: Distribution of the study groups according to duration of

analgesia (n=60)

Mean Student analgesia Mean Group N Std. Deviation ‘t’test duration difference p value (hrs)

A 30 8.4033 0.61503 4.73 <0.001 B 30 3.6733 0.52780

Comments: The difference in mean duration of analgesia between

subjects in the two groups was statistically significant with group A

having higher duration of analgesia by approximately 4 hours and 45

mins than group B.

Fig 8 showing duration of analgesia between the 2 groups (n=60) 71

Table 10: Group-wise comparison of heart rate at various time

periods (n=60)

Group Mean PR Std. Deviation N

A 99.67 15.196 30 Heart rate B 95.70 14.346 30 Baseline Total 97.68 14.787 60

A 87.53 10.670 30 Heart rate B 90.47 13.148 30 15 min Total 89.00 11.963 60

A 86.17 10.498 30 Heart rate B 82.83 11.489 30 30 min Total 84.50 11.040 60

A 85.57 9.797 30 Heart rate B 79.43 10.285 30 60 min Total 82.50 10.427 60

A 86.00 9.385 30 Heart rate B 80.37 9.084 30 2 hours Total 83.18 9.587 60 72

Factorial-Repeated measures ANOVA was applied to test the difference

in mean heart rate at various time intervals between the two groups.

mean heart rate * Model mean heart rate Group

Wilks’s Lambda F 58.60 17.217

Df 4,55 4,55 p value <0.001 <0.001

There was statistically significant difference in the heart rate over time as

suggested above but as there was statistically significant interaction

between heart rate and the Group variable, heart rate at various time

periods was analysed in each group individually to report the simple

effects.

Fig 9 showing HR at various time periods in both groups 73

Table 11: Comparison of heart rate at various time periods in Group

A (n=30)

Group A Time N Mean Std. Deviation

Baseline 99.67 15.196 30

15 min 87.53 10.670 30

30 min 86.17 10.498 30

60 min 85.57 9.797 30

2 hour 86.00 9.385 30

Group A

Wilks’s Lambda F 24.156

p value <0.001

Partial Eta square 0.788

Comparison Group (1 vs 2) Mean difference p

(1 - 2) value

Baseline vs 15 min 12.133 <0.001

Baseline vs 30 min 13.500 <0.001

Baseline vs 60 min 14.100 <0.001

Baseline vs 120 min 13.667 <0.001

Post-Hoc Test for heart rate (n=30)*

There was statistically significant drop in heart rate from baseline till

15 mins and then it stabilises at the lower rate after 15 mins as

observed in post-hoc tests.

Table 12: Comparison of heart rate at various time periods in Group

B (n=30)

Group B

Time Std. N Mean Deviation

Baseline 95.70 14.346 30

15 min 90.47 13.148 30

30 min 82.83 11.489 30

60 min 79.43 10.285 30

2 hour 80.37 9.084 30

Group B

Wilks’s Lambda F 40.793

p value <0.001

Partial Eta square 0.863

Post-Hoc Test for heart rate in Group B (n=30)*

Comparison Group (1 vs 2) Mean difference p

(1 - 2) value

Baseline vs 15 min 5.233 <0.001

Baseline vs 30 min 12.867 <0.001

Baseline vs 60 min 16.267 <0.001

Baseline vs 120 min 15.333 <0.001

15 min vs 30 min 7.633 <0.001

15 min vs 60 min 11.033 <0.001

15 min vs 120 min 10.100 <0.001

30 min vs 60 min 3.40 <0.001

There was statistically significant drop in heart rate from baseline till

60 mins (as against 15 mins in Group A) and then it stabilises at the

lower rate at 2 hours as observed in post-hoc tests.

Fig 10 showing group-wise comparison of mean oxygen saturation at various time periods (n=60)

There was no statistically significant difference in the mean oxygen saturation over time as suggested above and also there was no statistically significant difference in changes of oxygen saturation over time between the two groups.

Table 13: Group-wise comparison of mean arterial pressure at

various time periods (n=60)

Group Mean MAP Std. Deviation N

A 95.20 7.058 30 MAP B 96.83 10.296 30 Baseline Total 96.02 8.790 60

A 82.40 6.941 30 MAP B 84.90 9.125 30 15 min Total 83.65 8.136 60

A 80.20 6.419 30 MAP B 79.27 8.366 30 30 min Total 79.73 7.408 60

A 83.17 6.534 30 MAP B 80.47 6.720 30 60 min Total 81.82 6.711 60

A 89.10 6.082 30 MAP B 88.17 5.615 30 2 hours Total 88.63 5.822 60 79

Factorial-Repeated measures ANOVA was applied to test the difference

in mean arterial pressure at various time intervals between the two

groups.

Model mean MAP Mean MAP * Group

Wilks’s Lambda F 54.12 3.248

Df 4,55 4,55 p value <0.001 0.018

There was statistically significant difference in mean arterial pressure

over time as suggested above but as there was statistically significant

interaction between mean arterial pressure and the Group variable, mean

arterial pressure at various time periods was analysed in each group

individually to report the simple effects.

Fig 11 showing Group-wise comparison of mean arterial pressure at various time periods (n=60)

Table 14: Comparison of mean arterial pressure at various time periods in Group A (n=30)

Group A Time N Mean Std. Deviation

Baseline 95.20 7.058 30

15 min 82.40 6.941 30

30 min 80.20 6.419 30

60 min 83.17 6.534 30

2 hour 89.10 6.082 30

81 Group A

Wilks’s Lambda F 29.926

p value <0.001

Partial Eta square 0.822

Post-Hoc Test for mean arterial pressure Group A (n=30)*

Mean difference Comparison Group (1 vs 2) p value (1 - 2)

Baseline vs 15 min 12.800 <0.001

Baseline vs 30 min 15.000 <0.001

Baseline vs 60 min 12.033 <0.001

Baseline vs 120 min 6.100 0.008

15 min vs 30 min 2.200 0.042

15 min vs 120 min -6.70 <0.001

30 min vs 60 min -2.967 0.001

30 min vs 120 min -8.900 <0.001

60 min vs 120 min -5.933 <0.001

There was statistically significant drop in MAP from baseline till 30

mins, it raises again to baseline levels by 120 minutes. 82

Table 12: Comparison of mean arterial pressure at various time periods in Group B (n=30)

Group B

Time Std. N Mean Deviation

Baseline 96.83 10.296 30

15 min 84.90 9.125 30

30 min 79.27 8.366 30

60 min 80.47 6.720 30

2 hour 88.17 5.615 30

Group B

Wilks’s Lambda F 28.95

p value <0.001

Partial Eta square 0.817

Post-Hoc Test for mean arterial pressure in Group B (n=30)*

Comparison Group (1 vs 2) Mean difference p

(1 - 2) value

Baseline vs 15 min 11.933 <0.001

Baseline vs 30 min 17.567 <0.001

Baseline vs 60 min 16.367 <0.001

Baseline vs 120 min 8.667 <0.001

15 min vs 30 min 5.633 <0.001

15 min vs 60 min 4.433 0.017

30 min vs 120 min -8.900 <0.001

60 min vs 120 min -7.700 <0.001

*Only statistically significant pair-wise comparisons mentioned. All other comparisons not significant. There was statistically significant drop in mean arterial pressure from baseline till 30 mins and then it raises again marginally by 60 mins and then raises significantly by 120 minutes and both the drop and rise in MAP was statistically significant in the Group B as observed in post-hoc tests.

Table 13: Group-wise comparison of sedation score at various time

periods (n=60)

Chi- Group Sedation score Group B square p A value

Baseline 1 30 30 NA n=60 2 0 0

1 0 30 15 min 2 22 0 <0.001* n=60 3 8 0

1 0 30 30 min 2 15 0 <0.001* n=60 3 15 0

1 0 30 60 min 2 13 0 <0.001* n=60 3 17 0

1 0 30

2 hours 2 8 0 <0.001* 85

n=60 3 21 0

4 1 0

2 8 0 4 hours 3 20 0 NA n=30 4 2 0

6 hours 2 20 0 NA n=30 3 10 0

8 hours 1 17 0 NA n=30 2 13 0

10 hours 1 17 0 NA n=17

There was no statistically significant difference in the sedation score

in baseline. No subject in Group B attained sedation whereas all the

subjects in Group A had a sedation score of 2 and above at 15 min, 30

mins, 60 mins, 2 hours, 4 hours and 6 hours.

Fig 12 showing mean sedation score over time between 2 groups.

Table 15: Group-wise comparison of Visual analog score for pain

(VAS) at various time periods (n=60)

Chi-

VAS pain score Group A Group B square

p value

6 4 1

Baseline 7 8 10 0.470 n=60 8 9 8

9 8 11 87

10 1 0

1 15 7

15 min 2 12 10 0.020* n=60 3 3 10

4 0 3

1 15 7

30 min 2 15 12 0.003* n=60 3 0 10

4 0 1

1 15 7

60 min 2 15 13 0.005* n=60 3 0 9

4 0 1

1 14 4

2 16 12 2 hours 3 0 10 <0.001* n=60 4 0 3 88

6 0 1

1 12 0

2 17 0

3 1 0 4 hours 5 0 4 <0.001* n=60 6 0 11

7 0 9

8 0 6

1 6 0

6 hours 2 18 0 n=30 3 3 0 NA

4 3 0

2 3 0

3 4 0 8 hours 4 4 0 NA n=30 5 4 0

6 9 0 89

7 5 0

8 1 0

5 2 0

10 hours 6 4 0 NA n=14 7 3 0

8 5 0

There was no statistically significant difference in the VAS pain score

in baseline. The subjects in Group A had lower VAS score than Group

B at 15 min, 30 mins, 60 mins, 2 hours, and 4 hours and this

difference was statistically significant.

Fig 13 showing mean VAS score over time between 2 groups. 90

Table 16: Group-wise comparison of side effects and rescue analgesia

(n=60)

Parameter Group A Group B

Side-effects 0 0

Rescue analgesia 0 2

There was no side-effects reported in both groups. Two subjects in

Group B needed rescue analgesia while no subject in group A needed

it.

DISCUSSION

This study is a prospective, randomised double blind controlled comparative study done to assess the hemodynamic, analgesic profile and efficacy of Nalbuphine as an adjuvant in providing postoperative analgesia in thoracic epidural for upper abdominal surgeries.

The discovery of opioid receptors in brain and spinal cord, action of narcotics through opioid receptor have become an eye opener in achieving satisfactory postoperative analgesia with narcotic administration in regional techniques. The use of wide variety of additives along with local anaesthetics with epidural has increased patient comfort and satisfaction and has become a popular technique for management of acute postoperative pain. However there are some disadvantages associated with narcotics like nausea, vomiting, pruritus, sedation, respiratory depression and urinary retention. Opioids have anti nociceptive effects on central or spinal cord levels. Stimulation of opioid receptors on the central nervous system leads to inhibition of neuronal serotonin uptake which leads to augmentation of spinal inhibitory pain pathways. The role of opioids in spinal inhibition of nociceptive transmission is evident. The dorsal horn nociceptive neuron exhibit

“windup” phenomenon - a frequency dependent potentiation of response to repeated C fibre stimulation. Opioids reduce the release of primary afferent transmitters via inhibitory presynaptic opioid receptor terminals 92

thus reducing or blocking C fibre stimulation of the dorsal horn nociceptive neurons and delaying the onset of windup.

Nalbuphine is a synthetic opioid with mixed kappa agonist and mu antagonist activity. Because of its affinity to kappa receptors it results in analgesia, sedation, cardiovascular stability and minimal respiratory depression and low abuse potential. Because of its mu receptor antagonism it is devoid of pruritus, nausea vomiting and respiratory depression and also antagonises the respiratory depression activity of other narcotics. Nalbuphine exhibits the ceiling effects for respiratory depression and is a safety feature of this drug.

Demographic data comparing Age, Gender, Weight, Height and

BMI distribution were comparable in both groups and not statistically significant by students “t” test.

ASA grading and Type of surgeries done under elective and emergency of subjects in both the groups were comparable with minor differences and are not statistically significant by “chi square test”.

The difference in mean time of onset of analgesia between subjects in the two groups was statistically significant( p < 0.001) by chi square test with group A having shorter and quicker onset of action by approximately 10 mins than group B (7.07min Vs 17.83min). This faster onset of action of Nalbuphine may be attributed to its lipophilicity.

The difference in mean duration of analgesia between subjects in the two groups was statistically significant( p< 0.001) by student “t “test 93

with group A having longer duration of analgesia by approximately 4 hours and 45 mins than group B (8.4 hrs Vs 3.6 hrs).The synergistic action of nalbuphine on bupivacaine may have prolonged the duration of analgesia.

There was statistically significant difference in the heart rate and mean arterial pressure over time in both groups but as there was statistically significant interaction between heart rate and the Group variable, heart rate at various time periods was analysed in each group individually.

In group A, a statistically significant drop in heart rate from baseline till 15 mins and then it stabilises at the lower rate after 15 mins as observed in post-hoc tests. And in group B statistically significant drop in heart rate from baseline till 60 mins (as against 15 mins in Group A) and then it stabilises at the lower rate at 2 hours as observed in post-hoc tests.

In group A, drop in mean arterial pressure from baseline till 30 mins and then it raises again significantly to reach near-baseline levels by

120 minutes and both the drop and rise in MAP was statistically significant as observed in post-hoc tests. In group B, drop in mean arterial pressure from baseline till 30 mins and then it raises again marginally by

60 mins and then raises significantly by 120 minutes and both the drop and rise in MAP was statistically significant in the Group B as observed in post-hoc tests. These haemodynamic changes may be attributed to the 94

peak plasma concentration and action of the two drugs involved in the study.

The respiratory rate and saturation showed no significant differences over the period of time and are not statistically significant.

With Wilsons sedation scores, no subject in Group B attained sedation whereas all the subjects in Group A had a sedation score of 2 and above at 15 min, 30 mins, 60 mins, 2 hours, 4 hours and 6 hours.

As for the level of analgesia, there was no statistically significant difference in the VAS pain score in baseline. The subjects in Group A had lower VAS score than Group B at 15 min, 30 mins, 60 mins, 2 hours, and

4 hours and this difference was statistically significant.

There was no incidence of side-effects reported in both groups. No patient had respiratory depression, pruritis, nausea, vomiting. The ceiling effects of nalbuphine may have prevented increasing sedation and respiratory depression in these patients.

Only two subjects in Group B needed rescue analgesia while there was no need for rescue analgesia in Group A .

Some of the studies similar to this study are briefed below,

Sanjay P Gadre et al studied that the mean onset of sensory block

(6.8±1.13 min vs 11.03±1.33min), motor block (9.87±1.22min vs

15.3±0.88min), duration of analgesia (414.6±37.7min vs 255.67±26.6 min) was statistically significant in Nalbuphine with Bupivacaine group. 95

Sateesh et al,suggested that epidural Nalbuphine 0.2 mg/kg with

0.5% Bupivacaine produces early onset of sensory blockade (3.23±0.97 min vs 15.30±2.97 min) and prolongs the duration of analgesia(449±67 min vs 185.93±32.43 min) in comparison to 0.5% Bupivacaine with normal saline.

Ramakrishna CD et al, suggesting the mean onset of sensory blockade (5.22 min vs 9.52 min) and mean onset of motor blockade( 7.8 min vs 12.84 min) and duration of analgesia (287.40±29 min) was significant in Nalbuphine group compared to plain Bupivacaine group.

Mohamed et al, suggested that with Nalbuphine (0.1 mg/kg), there was significant difference in postoperative pain and sedation scores and prolonged duration of analgesia and sedation and time to first rescue analgesia (10.1±1.5 hrs).

M.S.Mok et al studied that with nalbuphine onset of pain relief appeared at 15minutes, peak action at 30-60minutes and lasted for

13.6±4.2 hours and no incidence of adverse effects.

SUMMARY:

A prospective double blind comparative study of nalbuphine with 0.125% bupivacaine and plain 0.125% bupivacaine in thoracic epidural for post operative analgesia in upper abdominal surgery was carried out in a population of 60 patients of ASA I – III undergoing elective and emergency surgeries. They were randomised and allocated into two groups with group A, patients receiving

Nalbuphine with 0.125% Bupivacaine and group B receiving Normal Saline with 0.125% Bupivacaine.

The aim of the study was to compare the onset and duration of analgesia, level of consciousness(sedation), pain scoring by VAS (Visual analogue scoring), haemodynamic changes and incidence of complications and other side effects.

Before induction of anaesthesia, Epidural Tuohy needle was inserted at

T9 – T11 level. Using 18 gauge epidural catheter was threaded through the epidural space for 4-5cm and placed at T7-T9level. After epidural test dose of

3ml of lignocaine with adrenaline given to rule out intrathecal and intravascular misplacement of catheter. Patients in Group A received 1ml of

Nalbuphine(10mg) with 2.5ml of 0.5% Bupivacaine, diluted in NS to 10ml and

Group B received 1ml of Normal Saline with 2.5ml of 0.5% Bupivacaine, diluted in NS to 10ml and the patient was observed for the study parameters over time.

The data were collected, compiles and statistical analysed.

The mean time of onset of analgesia was short and quick onset of action in group A than group B (7.07min Vs 17.83min). The mean duration of analgesia was longer in group A than group B (8.4 hrs Vs 3.6 hrs). In group A, drop in heart rate and mean arterial pressure from baseline till 30 mins and reach near-baseline levels by 120 minutes, and in group B, drop in heart rate and mean arterial pressure from baseline till 30 mins and reaches baseline by 120 minutes was observed. No subject in Group B attained sedation whereas all the subjects in Group A had a sedation score of 2 and above at 15 min, 30 mins, 60 mins, 2 hours, 4 hours and 6 hours. The subjects in Group A had lower VAS score than Group B at 15 min, 30 mins, 60 mins, 2 hours, and 4 hours and this difference was statistically significant. There was no incidence of side-effects like respiratory depression, pruritis, nausea, vomiting in both groups. Only two subjects in Group B needed rescue analgesia.

The study concludes that epidural nalbuphine in a dose of 0.2 mg /kg with

0.125% bupivacaine, provides faster onset and longer duration of analgesia with better quality and patient satisfaction.

CONCLUSION:

The study concludes that epidural nalbuphine in a dose of 0.2 mg /kg with

0.125% bupivacaine, provides faster onset and longer duration of analgesia with better quality and patient satisfaction. Although there were significant haemodynamic changes over time which correlated with peak plasma action of the two drugs involved in the study, there was no incidence of any adverse effects and complications reported in both groups.

ANNEXURE - I

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ANNEXURE - II

ANNEXURE - III

GOVERNMENT THENI MEDICAL COLLEGE

THENI, TAMILNADU, INDIA-635531.

(Affiliated to THE TAMILNADU DR.M.G.R MEDICAL UNIVERSITY)

ETHICAL COMMITTEE CERTIFICATE

Name of the Candidate: Dr. M.SUBHASHINI

Course : M.D., Anaesthesiology

Period of Study : MAY 2017 – SEPTEMBER 2018

College : GOVERNMENT THENI MEDICAL COLLEGE

Dissertation Topic : COMPARISON OF NALBUPHINE WITH 0.125%

BUPIVACAINE AND PLAIN 0.125% BUPIVACAINE INTHORACIC EPIDURAL

FOR POST OPERATIVEANALGESIA IN UPPER ABDOMINAL SURGERY.

The Ethical Committee, Government Theni Medical College has decided to inform that your Dissertation Topic is accepted and you are permitted to proceed with the above study.

Place: Theni Secretary,

Date: Ethical Committee

ANNEXURE - IV

PROFORMA Date:

Name:IP.No:

Age/sex: Ward/Unit:

Diagnosis/procedure: Height/weight:

Thoracic epidural -  Needle/ gauge size:  Level/tip: ASA risk: Co-morbidities:

Group: A B

1. Onset of action:

2. Sedation score: 1 2 3 4 5

3. Pain scoring: initial vas 10 9 8 7 6 5 4 3 2 1 After drug: 10 9 8 7 6 5 4 3 2 1

4. Vitals:

TIME PULSE BP MAP RR SPO2 RATE 0 min 5 min 10 min 15 min 30 min 1 hr 1.5 hrs 2 hrs

5. Vas score/sedation score: @ 2 hr 4 hr 6hr 8 hr 10hrs 6. Duration of analgesia: 7. Need for rescue analgesia:yes/ no 8. Side effects: Nausea//Vomiting Pruritis Respiratory depression Urinary retention Sedation score – Wilson Sedation Scoring: 1 – Awake and alert. 2 – Awake but drowsy. 3 – Eyes closed but arousable to command. 4 – Eyes closed but arousable to mild physical stimulation. 5 – Eyes closed and unarousable to mild physicalstimulation.

Pain scoring:

Duration of analgesia: Duration of analgesia was calculated when the visual analogue scale reached 5 or more, or when the patient complained of moderateto severe pain.

ANNEXURE V: MASTER SHEET

S.No. Age Sex Height Weight ASARisk Group Type of Name Diagnosis surgery 1. Moorthi 37 M 160 60 II A 1 INCISIONAL HERNIA 2. Vaiyadurai 55 M 164 44 II A 1 FATTY HERNIA OF LINEA ALBA 3. Vijaya 55 F 150 35 III A 1 CARCINOMA OESOPHAGUS 4. Dalina beevi 50 F 148 70 II A 1 INCISIONAL HERNIA 5. Veeraetchi 42 F 152 65 I A 1 SUPRAUMBILICAL HERNIA 6. Subbaiah 47 M 160 47 II A 1 PYLORIC MASS 7. Raja 55 M 156 50 III A 1 CARCINOMA STOMACH 8. Kannan 40 M 162 46 II A 1 GOO/ PREPYLORIC ULCER 9. Minnalkodi 40 F 154 56 II A 1 CBD/GB CALCULUS 10. Parvathy 53 F 155 52 II A 1 OBSRTUCTIVE JAUNDICE 11. Muniyandi 50 M 156 50 II A 1 OBSTRUCTIVE JAUNDICE 12. Suseela 50 F 158 76 II A 1 CHOLELITHIASIS/OBESITY 13. Dhinesh kumar 28 M 170 54 II A 1 CHRONIC CALCULUS PANCREATITIS 14. Muthupandi 27 M 162 56 I A 2 HOLLOW VISCOUS PERFORATION 15. Aandikaalai 50 M 158 53 I A 1 HEPATIC FLEXURE OF COLON GROWTH 16. Jeyapandian 40 M 165 42 I A 2 SIGMOID VOLVULUS/INTESTINAL OBSTRUCTION 17. Ayyadurai 49 M 158 54 I A 1 OBSTRUCTED EPIGASTRIC HERNIA 18. Jeyanthi 25 F 148 52 I A 2 INTESTINAL PERFORATION 19. Ponraj 19 M 165 65 II A 2 BLINT INJURY ABDOMEN 20. Jegan pandian 57 M 162 72 II A 2 PERFORATIVE PERITONITIS 21. Sekar 35 M 160 60 II A 2 BLUNT INJURY ABDOMEN LIVER LACERATION 22. Shahul hameed 48 M 160 70 II A 1 UMBILICAL HERNIA/ SUBACUTE INTESTINAL OBSTRUCTION 23. Amirtham 48 M 164 65 II A 2 INTESTINAL PERFORATION 24. Palthai 50 F 158 46 II A 1 GOO/ PREPYLORIC ULCER 25. Pandiyarajan 27 M 166 60 I A 1 RIGHTB PUJ OBSTRUCTION 26. Kalavathi 29 F 155 55 I A 1 OBSTRUCTIVE JAUNDICE 27. Maariyammal 48 F 158 60 II A 1 HYDATID CYST LIVER 28. Kanimozhi 25 F 154 40 II A 1 GOO/ PREPYLORIC ULCER 29. Ramu 49 M 160 56 II A 1 PSEUDOCYST OF PANCREAS 30. Mithran 45 M 164 63 I A 2 PERFORATIVE PERITONITIS 31. Chinnathai 54 F 152 48 II B 2 INTESTINAL PERFORATION 32. Aandikaalai 50 M 166 53 I B 1 GROWTH HEPATIC FLEXURE OF COLON 33. Bharathi 50 F 150 65 II B 1 LEFT RENAL CELL CARCINOMA 34. Muniyandi 55 M 162 45 II B 1 OBSTRUCTIVE JAUNDICE 35. Selvaraj 50 M 158 54 II B 1 OBSTRUCTIVE JAUNDICE 36. Mookan 46 M 162 60 II B 1 DUODENAL ULCER/GOO 37. Selvam 53 M 164 55 II B 2 INTESTINAL PERFORATION 38. Velusamy 53 M 160 70 II B 2 DU PERFORATION 39. Lakshmanan 50 M 158 58 II B 2 PERFORATIVE PYLORIC MASS 40. Arulmani 38 F 154 62 I B 1 SUBACUTE INTESTINAL OBSTRUCTION/ ADHESIVE COLITIS 41. Prabhu deva 21 M 160 48 I B 2 DU PERFORATION 42. Chinnaponnu 50 F 154 55 II B 1 PERIAMPULLARY CARCINOMA 43. Thangavel 50 M 166 47 III B 1 CARCINOMA STOMACH 44. Chandran 45 M 158 50 I B 1 PSEUDOCYST OF PANCREAS 45. Maarimuthu 50 M 156 42 III B 1 CARCINOMA STOMACH 46. Kanniyammal 50 F 154 42 II B 1 ANTRAL MASS 47. Chinnasamy 47 M 162 60 I B 1 UMBILICAL HERNIA 48. Mohammed fathima 30 F 152 58 I B 1 PARAUMBILICAL HERNIA 49. Malar 40 F 154 45 I B 2 INTESTINAL PERFORATION 50. Bhagavathyraj 50 M 165 45 II B 2 DU PERFORATION 51. Ganesan 56 M 160 42 II B 1 CARCINOMA ASCENDING COLON 52. Gurusamy 44 M 158 54 II B 2 PERFORATIVE PERITONITIS 53. Salaith Pitchai 50 M 164 65 II B 1 SUBACUTE INTESTINAL OBSTRUCTION 54. Santhanam 45 M 156 50 II B 2 ADHESIVE COLITIS 55. Veeramani 56 M 160 54 I B 1 CHRONIC CHOLECYSTITIS 56. Muthaiyah 55 M 164 80 II B 1 EPIGASRIC HERNIA 57. Kannan 43 M 160 67 I B 1 PARAUMBILICAL HERNIA 58. Annapadham 53 F 156 60 I B 1 ILEO COLIC INTESSUSCEPTION 59. Pitchaiammal 33 F 158 68 II B 1 SPLEENOMEGALY 60. Jeganathan 53 M 170 78 I B 1 EPIGASTRIC WITH UMBILICAL HERNIA

Onset Duration HR HR HR HR HR S.No. Name Surgery done time time 0 15 m 30 m 1 hr 2 hr 1. Moorthi MESH REPAIR 8 MIN 8 HRS 88 86 88 86 80 2. Vaiyadurai ANATOMICAL REPAIR 6 MIN 9 HRS 108 96 90 95 90 3. Vijaya OESOPHAGECTOMY WITH PULL THROUGH PROCEDURE 5 MIN 9 HRS 94 85 79 79 77 4. Dalina beevi MESH REPAIR 6 MIN 8 HRS 100 85 84 80 89 5. Veeraetchi HERNIOPLASTY 7 MIN 8.30 HRS 98 84 80 87 90 6. Subbaiah PARTIAL GASTRECTOMY WITH GASTROJEJUNOSTOMY 8 MIN 8.30 HRS 76 72 71 72 70 7. Raja GASTRECTOMY WITH GJ 8 MIN 7.45 HRS 106 92 90 91 96 8. Kannan TRUNCAL VAGOTOMY WITH GJ 7 MIN 8.30 HRS 118 98 96 99 102 9. Minnalkodi OPEN CHOLECYSTECTOMY 6 MIN 9HRS 98 80 78 84 82 10. Parvathy CBD EXPLORATION 6 MIN 9 HRS 96 80 84 86 85 11. Muniyandi OPEN CHOLEDOCHOJEJUNOSTOMY 9 MIN 8.45 HRS 122 96 94 98 96 12. Suseela OPEN CHOLECYSTECTOMY WITH SLEEVE GASTRECTOMY 8 MIN 8 HRS 102 90 86 84 89 13. Dhinesh kumar MODIFIED PRISTOWS PROCEDURE 6 MIN 9 HRS 110 98 92 84 88 14. Muthupandi LAPAROTOMY AND PROCEED 8 MIN 8.40 HRS 118 106 96 94 88 15. Aandikaalai LAPAROTOMY AND PROCEED 6MIN 7 HRS 80 78 80 83 80 16. Jeyapandian SIGMOID RESECTION AND ANASTAMOSIS 6 MIN 8 HRS 104 90 92 87 81 17. Ayyadurai LAPAROTOMY AND PROCEED 8 MIN 9 HRS 88 76 72 74 78 18. Jeyanthi LAPARPTOMY AND PROCEED 7 MIN 9 HRS 140 110 114 108 108 19. Ponraj LAPAROTOMY AND PROCEED 6 MIN 8 HRS 94 80 78 76 74 20. Jegan pandian LAPAROTOMY AND PROCEED 8 MIN 9.5HRS 116 98 96 94 96 21. Sekar EXPLORATIVE LAPAROTOMY 8 MIN 8 HRS 98 88 84 80 78 22. Shahul hameed LAPAROTOMY AND PROCEED 8 MIN 9.5 HRS 120 109 107 106 98 23. Amirtham LAPAROTOMY AND PROCEED 6 MIN 9 HRS 98 78 96 74 84 24. Palthai LAPAROTOMY AND PROCEED 9 MIN 8 HRS 88 74 70 78 82 25. Pandiyarajan SIMPLE NEPHRECTOMY 6 MIN 7.45 HRS 94 84 80 82 86 26. Kalavathi CBD EXPLORATION 7MIN 8 HRS 82 83 80 79 80 27. Maariyammal EXCISION 8 MIN 8.30 HRS 76 70 71 72 70 28. Kanimozhi VAGOTOMY WITH GJ 6 MIN 9 HRS 88 84 82 80 86 29. Ramu CYSTOGASTROSTOMY 7 MIN 8. 15 HRS 110 98 96 99 100 30. Mithran LAPAROTOMY AND PROCEED 8 MIN 8 HRS 80 78 79 76 77 31. Chinnathai LAPAROTOMY AND PROCEED 20 MIN 4 HRS 118 103 98 90 80 32. Aandikaalai RESECTION ANASTAMOSIS 15 MIN 4 HRS 86 82 78 70 74 33. Bharathi RADICAL NEPNRECTOMY 16 MIN 4 HRS 92 80 76 74 82 34. Muniyandi CHOLECYSTECTOMY / CHOLEDOCHODUODENOSTOMY 14 MIN 3.30 HRS 82 78 78 73 76 35. Selvaraj CHOLECYSTECTOMY / CHOLEDOCHODUODENOSTOMY 16MIN 3.40 HRS 67 61 62 60 63 36. Mookan TRUNCAL VAGOTOMY/GASTRECTOMY WITH ANASTAMOSIS 22 MIN 4 HRS 88 79 72 76 82 37. Selvam LAPAROTOMY AND PROCEED 15 MIN 3 HRS 88 89 80 78 76 38. Velusamy LAPAROTOMY AND PROCEED 20 MIN 4.15 HRS 118 112 102 96 92 39. Lakshmanan LAPAROTOMY AND PROCEED 17 MIN 4 HRS 104 90 80 82 88 40. Arulmani LAPAROTOMY/RESECTION ANASTAMOSIS 18 MIN 3.45 HRS 88 76 70 72 80 41. Prabhu deva LAPAROTOMY AND PROCEED 16 MIN 2.30 HRS 76 68 62 64 70 42. Chinnaponnu TRIPLE BYPASS 15 MIN 4 HRS 106 98 80 76 74 43. Thangavel DISTAL GASTRECTOMY WITH GJ 17 MIN 4 HRS 88 85 76 74 82 44. Chandran CYSTOGASTROSTOMY 15 MIN 2.30HRS 78 80 74 68 70 45. Maarimuthu DISTAL GASTRECTOMY WITH GJ 25 MIN 3.30 HRS 112 102 92 86 88 46. Kanniyammal GASTRECTOMY WITH GJ 2O MIN 3.45 HRS 80 74 68 66 72 47. Chinnasamy MESH REPAIR 22MIN 3.30 HRS 118 108 96 94 98 48. Mohammed fathima MESH REPAIR 16MIN 3.15HRS 94 98 94 88 82 49. Malar LAPAROTOMY AND PROCEED 18 MIN 4 HRS 112 106 100 102 103 50. Bhagavathyraj LAPAROTOMY AND PROCEED 24 MIN 4 HRS 102 90 78 76 78 51. Ganesan RESECTION ANASTAMOSIS 20 MIN 4 HRS 108 105 98 90 94 52. Gurusamy LAPAROTOMY AND PROCEED 22 MIN 4.30 HRS 110 108 98 92 84 53. Salaith Pitchai LAPAROTOMY AND PROCEED 15 MIN 3.45 HRS 98 100 86 78 78 54. Santhanam RESECTION ANASTAMOSIS 16 MIN 3.30 HRS 117 106 90 86 88 55. Veeramani OPEN CHOLECYSTECTOMY 15 MIN 4.15 HRS 90 92 82 78 70 56. Muthaiyah MESH REPAIR 18 MIN 4 HRS 94 93 88 86 84 57. Kannan MESH REPAIR 16 MIN 3.45HRS 86 82 76 70 75 58. Annapadham LAPAROTOMY 20 MIN 4.30HRS 86 89 79 76 73 59. Pitchaiammal SPLEENECTOMY 17 MIN 4 HRS 106 100 98 90 85 60. Jeganathan MESH REPAIR 15 MIN 4.15 HRS 79 80 74 72 70

Spo2 Spo2 Spo2 Spo2 Spo2 MAP MAP MAP MAP MAP RR RR RR RR RR S.No. Name 0 15 m 30 m 1 hr 2 hr 0 15 m 30 m 1 hr 2 hr 0 15 m 30 m 1 hr 2 hr 1. Moorthi 100 100 100 100 100 110 80 82 84 76 12 13 14 14 14 2. Vaiyadurai 98 98 98 98 99 93 84 78 80 90 14 14 13 14 14 3. Vijaya 100 100 100 100 100 107 75 80 84 89 14 15 14 14 14 4. Dalina beevi 100 100 100 100 100 98 83 78 84 96 16 14 14 14 13 5. Veeraetchi 100 100 100 100 100 98 84 74 81 86 14 12 13 12 13 6. Subbaiah 100 100 100 100 100 95 94 94 95 97 14 13 12 13 15 7. Raja 100 100 100 100 100 90 81 79 82 92 13 14 14 13 14 8. Kannan 100 100 100 100 100 90 79 78 82 86 15 14 14 15 16 9. Minnalkodi 100 100 100 100 100 96 78 73 82 91 14 15 14 16 17 10. Parvathy 100 100 100 100 100 90 79 82 86 85 16 15 4 15 16 11. Muniyandi 100 100 100 100 100 103 83 76 81 96 15 14 14 15 14 12. Suseela 100 100 100 100 100 93 81 79 81 96 15 14 14 15 16 13. Dhinesh kumar 100 100 100 100 100 100 83 79 86 86 15 16 14 15 14 14. Muthupandi 100 100 100 100 100 83 69 72 74 87 14 15 16 15 15 15. Aandikaalai 100 100 99 99 100 88 86 82 84 92 15 14 14 15 13 16. Jeyapandian 97 97 98 98 97 90 87 85 93 95 15 14 14 13 14 17. Ayyadurai 100 100 100 100 100 90 79 81 82 88 14 12 12 13 13 18. Jeyanthi 100 98 98 99 99 90 73 73 73 83 12 14 14 14 13 19. Ponraj 100 100 100 100 100 100 88 82 84 83 16 16 16 15 16 20. Jegan pandian 100 100 100 100 100 106 88 83 81 94 14 15 15 14 14 21. Sekar 100 100 100 100 100 90 76 82 78 85 12 13 12 13 14 22. Shahul hameed 99 100 100 100 100 103 96 96 105 100 16 14 13 15 14 23. Amirtham 100 100 100 100 100 88 74 72 80 90 14 14 13 13 12 24. Palthai 100 100 100 100 100 91 74 73 76 89 14 14 15 12 13 25. Pandiyarajan 100 100 100 100 100 92 76 72 78 90 15 14 15 16 17 26. Kalavathi 100 100 100 100 100 90 77 75 80 84 16 15 14 14 15 27. Maariyammal 100 100 100 100 100 100 94 94 95 97 15 14 16 14 14 28. Kanimozhi 100 100 100 100 100 110 93 85 83 87 14 15 13 14 15 29. Ramu 100 100 100 100 100 90 88 81 79 73 15 16 14 15 14 30. Mithran 100 100 100 100 100 92 90 86 82 90 16 17 15 14 15 31. Chinnathai 100 100 100 100 100 106 73 63 68 82 17 16 18 15 16 32. Aandikaalai 100 100 100 100 100 110 98 90 92 98 15 16 14 15 16 33. Bharathi 100 100 100 100 100 88 78 77 80 93 15 14 14 15 16 34. Muniyandi 100 100 100 100 100 96 83 82 83 84 16 14 16 16 14 35. Selvaraj 100 100 100 100 100 106 90 88 93 93 17 16 15 14 15 36. Mookan 100 100 100 100 100 110 103 90 83 90 15 14 13 14 15 37. Selvam 100 100 100 100 100 83 86 73 76 78 13 14 15 16 15 38. Velusamy 100 100 100 100 100 106 75 70 72 82 17 16 15 16 16 39. Lakshmanan 100 100 100 100 100 103 86 87 79 96 15 16 15 16 17 40. Arulmani 100 100 100 100 100 90 78 79 81 88 14 15 13 12 15 41. Prabhu deva 100 100 100 100 100 100 82 74 78 93 15 14 14 16 17 42. Chinnaponnu 100 100 100 100 100 90 78 72 80 90 15 16 17 15 16 43. Thangavel 100 100 100 100 100 85 79 75 84 93 16 17 15 14 15 44. Chandran 100 100 100 100 100 90 78 74 86 90 15 14 13 15 16 45. Maarimuthu 100 100 100 100 100 107 85 83 83 90 14 15 16 14 15 46. Kanniyammal 100 100 100 100 100 90 86 82 84 92 15 16 18 17 16 47. Chinnasamy 100 100 100 100 100 106 90 82 86 96 14 13 12 13 14 48. Mohammed fathima 100 100 100 100 100 96 90 79 78 86 16 16 16 17 15 49. Malar 100 100 100 100 100 83 74 68 63 83 14 15 13 15 16 50. Bhagavathyraj 100 100 100 100 100 93 80 73 80 86 14 15 12 13 14 51. Ganesan 100 100 100 100 100 96 84 77 85 94 15 14 13 15 14 52. Gurusamy 100 100 100 100 100 116 86 73 77 86 16 15 16 17 15 53. Salaith Pitchai 100 100 100 100 100 98 74 68 73 87 14 15 14 15 16 54. Santhanam 100 100 100 100 100 74 72 76 78 83 15 16 14 17 15 55. Veeramani 100 100 100 100 100 112 108 98 90 92 16 15 14 15 16 56. Muthaiyah 100 100 100 100 100 86 80 77 74 79 14 15 13 16 14 57. Kannan 100 100 100 100 100 98 96 83 80 84 15 16 17 15 16 58. Annapadham 100 99 98 99 99 107 100 98 91 95 14 13 15 15 16 59. Pitchaiammal 100 100 99 100 100 90 86 83 78 79 17 15 14 15 16 60. Jeganathan 99 98 97 98 99 90 89 84 79 83 14 14 15 16 15

SS SS SS SS SS SS SS SS SS VAS VAS VAS VAS VAS VAS VAS VAS VAS S.No. Name 0 15 m 30 m 1 hr 2 hr 4 hr 6 hr 8 hr 10 hr 0 15 m 30 m 1 hr 2 hr 4 hr 6 hr 8 hr 10 hr 1. Moorthi 1 2 3 3 3 4 3 1 7 3 2 2 2 2 2 6 2. Vaiyadurai 1 2 2 2 2 2 2 2 1 6 1 1 1 1 1 2 5 3. Vijaya 1 2 2 2 3 3 3 2 1 6 2 2 2 2 2 2 3 4. Dalina beevi 1 2 2 3 3 3 3 2 7 1 1 1 1 1 2 7 5. Veeraetchi 1 3 3 3 3 3 3 2 1 7 2 2 2 2 2 2 4 6 6. Subbaiah 1 2 3 3 3 3 2 2 1 8 1 1 1 1 1 1 3 6 7. Raja 1 3 3 3 3 3 2 1 9 1 1 1 1 2 4 7 8. Kannan 1 2 2 2 2 2 2 1 1 9 1 1 1 1 1 2 4 8 9. Minnalkodi 1 2 2 2 2 2 2 2 1 9 2 2 2 2 2 2 2 5 10. Parvathy 1 2 2 2 2 3 3 2 1 9 2 2 2 2 2 2 4 7 11. Muniyandi 1 2 2 2 2 2 2 1 1 9 1 1 1 1 1 1 5 8 12. Suseela 1 3 3 3 3 3 2 1 8 1 1 1 1 1 1 6 13. Dhinesh kumar 1 2 3 3 3 3 2 1 1 9 2 2 2 2 2 2 4 8 14. Muthupandi 1 2 2 3 3 3 3 2 1 8 1 1 1 1 1 1 5 7 15. Aandikaalai 1 3 3 3 3 3 2 1 7 3 2 2 2 3 3 6 16. Jeyapandian 1 3 3 3 4 4 3 1 7 1 1 1 1 1 1 6 17. Ayyadurai 1 2 2 2 3 3 2 1 1 7 1 1 1 2 2 2 6 8 18. Jeyanthi 1 2 3 3 3 3 2 2 1 6 2 2 2 2 2 2 2 8 19. Ponraj 1 2 2 2 2 2 2 1 8 2 2 2 2 2 3 8 20. Jegan pandian 1 3 3 3 3 3 3 2 1 7 1 1 1 1 1 1 3 6 21. Sekar 1 3 3 3 3 3 2 1 9 1 1 1 1 1 2 7 22. Shahul hameed 1 2 2 2 2 2 2 2 1 10 2 2 2 2 2 2 3 5 23. Amirtham 1 3 3 3 3 3 2 1 1 8 2 2 2 2 2 2 2 6 24. Palthai 1 2 2 2 3 3 2 1 8 1 1 1 1 2 2 6 25. Pandiyarajan 1 2 2 2 3 3 2 1 8 2 2 2 2 2 2 6 26. Kalavathi 1 2 2 2 3 3 3 2 6 1 1 1 1 1 3 6 27. Maariyammal 1 2 3 3 3 2 2 1 1 8 2 2 2 2 2 4 5 7 28. Kanimozhi 1 2 3 3 3 3 3 2 1 7 3 2 2 2 2 2 6 29. Ramu 1 2 2 2 2 2 2 1 9 1 1 1 1 1 2 7 30. Mithran 1 2 3 3 3 3 2 1 8 2 2 2 2 2 4 7 31. Chinnathai 1 1 1 1 1 8 3 3 3 3 6 32. Aandikaalai 1 1 1 1 1 7 4 4 4 4 6 33. Bharathi 1 1 1 1 1 7 2 2 2 2 6 34. Muniyandi 1 1 1 1 1 7 2 2 2 3 8 35. Selvaraj 1 1 1 1 1 7 1 1 1 1 6 36. Mookan 1 1 1 1 1 9 1 1 37. Selvam 1 1 1 1 1 9 3 3 3 4 8 38. Velusamy 1 1 1 1 1 9 1 1 1 3 8 39. Lakshmanan 1 1 1 1 1 8 2 2 2 2 6 40. Arulmani 1 1 1 1 1 7 2 2 2 2 5 41. Prabhu deva 1 1 1 1 1 7 3 3 3 3 7 42. Chinnaponnu 1 1 1 1 1 9 3 3 3 3 8 43. Thangavel 1 1 1 1 1 8 3 3 3 3 7 44. Chandran 1 1 1 1 1 7 3 3 3 6 6 45. Maarimuthu 1 1 1 1 1 7 1 1 1 4 7 46. Kanniyammal 1 1 1 1 1 8 3 3 3 3 6 47. Chinnasamy 1 1 1 1 1 8 2 2 2 2 6 48. Mohammed fathima 1 1 1 1 1 9 2 2 2 2 7 49. Malar 1 1 1 1 1 9 1 1 1 1 5 50. Bhagavathyraj 1 1 1 1 1 8 1 1 1 1 5 51. Ganesan 1 1 1 1 1 9 2 2 2 2 8 52. Gurusamy 1 1 1 1 1 9 3 3 3 3 8 53. Salaith Pitchai 1 1 1 1 1 6 2 2 2 2 5 54. Santhanam 1 1 1 1 1 7 2 2 2 2 7 55. Veeramani 1 1 1 1 1 7 4 3 2 2 6 56. Muthaiyah 1 1 1 1 1 9 3 2 2 2 7 57. Kannan 1 1 1 1 1 8 4 3 3 3 6 58. Annapadham 1 1 1 1 1 9 1 1 1 3 7 59. Pitchaiammal 1 1 1 1 1 9 3 2 2 2 6 60. Jeganathan 1 1 1 1 1 8 2 2 2 2 7

KEY FOR MASTER SHEET

No. COLUMNS 1 Name of the patient 2 Age of the patient (in years) 3 Sex M - male F - female 4 Height (in cms) 5 Weight (in kgs) 6 ASA Risk (I, II & III) 7 Group (A & B) 8 Type of surgery 1- Elective 2- Emergency 9 Diagnosis 10 Surgery done 11 Onset time 12 Duration time 13-17 HR – Heart Rate 18-22 SP02 23-27 MAP – Mean Arterial Pressure 28-32 RR – Respiratory Rate 33-41 SS – Sedation score 42-50 VAS – Visual Analogue Scale