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A RANDOMISED CONTROLLED STUDY COMPARING INTRATHECAL HYPERBARIC BUPIVACAINE‑‑‑‑FENTANYL MIXTURE AND ISOBARIC BUPIVACAINE‑‑‑‑FENTANYL MIXTURE IN

COMMON UROLOGICAL PROCEDURES

Dissertation submitted to

THE TAMILNADU DR.M.G.R MEDICAL UNIVERSITY In partial fulfilment for the award of the degree of

DOCTOR OF MEDICINE IN

ANAESTHESIOLOGY BRANCH X

DEPARTMENT OF ANAESTHESIOLOGY, THANJAVUR MEDICAL COLLEGE,

THANJAVUR – 613004.

MAY 2018

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CERTIFICATE

This is to certify that the dissertation entitled “ A RANDOMISED CONTROLLED STUDY COMPARING INTRATHECAL HYPERBARIC BUPIVACAINE‑‑‑‑FENTANYL MIXTURE AND ISOBARIC BUPIVACAINE‑‑‑‑FENTANYL MIXTURE IN COMMON UROLOGICAL PROCEDURES” submitted by Dr.S.U.SHAM KUMAR in partial fulfilment for the award of the degree of Doctor of Medicine in Anaesthesiology by the Tamilnadu Dr.M.G.R Medical University,Chennai is a bonafide record of the work done by him in the Department of Anaesthesiology, Government Thanjavur Medical College, during the academic year 2015 – 2018.

Prof.Dr.Shanthi Paulraj M.D(Anaes), Head of the Department,

Department of Anaesthesiology, Thanjavur Medical College,

Thanjavur

Prof.Dr.S.Jeyakumar,M.S.,M.Ch.,Vascular surgery

Dean

Thanjavur Medical College, Thanjavur.

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DECLARATION

I,Dr.S.U.SHAM KUMAR solemnly declare that the dissertation titled“ A RANDOMISED CONTROLLED STUDY COMPARING INTRATHECAL HYPERBARIC BUPIVACAINE

‑‑‑‑ FENTANYL MIXTURE AND ISOBARIC BUPIVACAINE ‑‑‑‑

FENTANYL MIXTURE IN COMMON UROLOGICAL PROCEDURES ” is a bonafide work done by me at Thanjavur Medical College Hospital,Thanjavur,during 2015 – 2018.

The dissertation is submitted to “The TamilnaduDr.M.G.R Medical University,Chennai” Tamilnadu as a partial fulfilment for the requirement of M.D Degree examinations–Branch–X (Anaesthesiology) to be held in May 2018.

Place:Thanjavur

Date: Dr.S.U.SHAMKUMAR

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ACKNOWLEDGEMENT

I am extremely thankful to Prof.Dr.S.Jeyakumar, M.S., M.Ch., Vascular Surgery, Dean , Thanjavur Medical College , for his kind permission to carry out this study.

I am immensely grateful to my guide Prof.Dr.Shanti Paulraj, M.D., Anaesthesiology, Head of the Department of Anaesthesiology, for her concern and support in conducting the study.

I express my gratitude to Prof.Dr.C.Kumaran, M.D.,Anaesthesiology, Associate Professor, Department of Anaesthesiology for his concern and support in conducting the study.

I am greatly indebted to my co-guide Dr.B.Mohamed Sameer M.D., Anaesthesiology, Assistant Professor, Department of Anaesthesiology, for his inspiration ,guidance and comments at all stages of this study.

I am thankful to all Assistant Professors of the Department of Anaesthesiology , for their guidance and help . I am thankful to all my colleagues for the help rendered in carrying out this dissertation.

I thank all the patients for willingly submitting themselves for this study.

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INDEX

SI.NO TITLE PAGE NO.

1 INTRODUCTION 1

2 AIM OF THE STUDY 3

3 ANATOMY AND PHYSIOLOGY 4 4 PHARMACOLOGY OF BUPIVACAINE 20 5 PHARMACOLOGY OF FENTANYL 29

6 MATERIALS AND METHODS 39

7 REVIEW OF LITERATURE 43

8 OBSERVATION AND RESULTS 54

9 DISCUSSION 75

10 SUMMARY 86

11 CONCLUSION 89

12 BIBLIOGRAPHY 90

13 PROFORMA 94

14 MASTER CHART 96

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INTRODUCTION

In 1898, August Bier was the first person to demonstrate spinal anaesthesia using Cocaine as the local anaesthetic solution .Since then, it is one technique which is being widely used for both elective and emergency surgeries .Subarachnoid block provides effective sensory and motor blockade with faster onset .The baricity and the dose of drug administered are the most important determinants of block achieved.[1]

Many drugs are used as adjuncts to local anaesthetic solution .They are opioids,alpha 2 agonists,vasoconstrictors ,Neostigmine,Ketamine, Magnesium, NSAIDS and others.This addition of adjuvant has further expanded the advantage of regional anaesthesia like rapid onset of action, reduction of the local anaesthetic requirements, reduction of the risk of local anaesthetic toxicity ,prolongation of the sensory block, improvement of the analgesic quality, improvement of the hemodynamic stability and prolongation of duration of postoperative analgesia[1] .

In the year 1901, intrathecal Morphine was first used by Racoviceanu- Pisteti .The dose administered and lipid solubility of opioids are major determinants of its effects when administered intrathecally . Fentanyl which is highly lipid soluble, has a rapid onset and shorter duration of action when compared to hydrophilic opioids such as Morphine.

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Addition of Fentanyl to Bupivacaine will reduce its dose requirement and prolong its duration of analgesia.[1]

This research is designed to study the effect of baricity of local anaesthetic solution on the characteristics of subarachnoid blockade.

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AIM OF THE STUDY

The aim of the study is to compare the efficacy and haemodynamic effects of intrathecal isobaric Bupivacaine – Fentany mixture and hyperbaric Bupivacaine – Fentanyl mixture in common urological procedures.

The following factors were compared :

1.Characteristics of sensory and motor blockade such as the time of onset, duration of block and maximum height of sensory block achieved.

2.Haemodynamic changes such as variations in heart rate and blood pressure.

3.The need for supplementation with intravenous sedation or general anaesthesia.

4.Adverse effects such as giddiness, nausea, vomiting, shivering, pruritis and respiratory depression.

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ANATOMY AND PHYSIOLOGY

The sympathetic blockade, sensory analgesia and motor blockade produced by spinal anaesthesia depends on the dose, volume and concentration of local anaesthetic injected into the intrathecal space.

The vertebral canal extends from the foramen Magnum to the sacral hiatus. The number of vertebrae are divided in to 7 in cervical , 12 in thoracic level, 5 in lumbar region , sacrum and coccyx consists of 5 and 4 each which are fused segments. The adult spine presents four curvatures:

1.The cervical and lumbar curvatures are convex forwards (lordosis).

2.The thoracic and sacral curvatures are concave forwards (kyphosis).

The lordosis are postural, while kyphosis are produced by arrangement of the bones themselves. The vertebrae are held together by a series of overlapping ligaments namely[2,3]

• Anterior longitudinal ligament

• Posterior longitudinal ligament

• Ligamentum flavum

• Interspinous ligament

• Supraspinous ligament

• Intervertebral discs.

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There are certain common palpable landmarks that corresponds to particular level, including the most prominent spinous process which usually corresponds to the seventh cervical vertebra. The inferior angle of scapula usually corresponds to the seventh thoracic vertebra. Tuffier line is defined as

“The line joining the highest point of two iliac crests and crosses the vertebral column approximately at the level of L4 -L5 intervertebral space”.

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The intervertebral canal consists of:

1. Roots of spinal nerves

2. Spinal membrane with the spinal cord and cerebrospinal fluid 3. Vessels, fat and areolar tissue.

The spinal cord is the continuation of medulla oblongata and it ends below in conus medullaris from which filum terminale descends vertically as cauda equina. In adults spinal cord extends from the upper border of first cervical vertebrae to the lower border of first lumbar vertebrae. The spinal cord extends till the upper border of second lumbar vertebra and still lower in infants.

The coverings of spinal cord from outside to inside are

• duramater

• arachnoidmater

• piamater.

The duramater is attached to the margins of foramen Magnum above and ends below at the lower border of the second sacral vertebra. The anterior and posterior nerve roots from the spinal cord pierce the investing layer of duramater and carry the prolongation (dural cuff) which blends with the perineurium of the mixed spinal nerve.

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The arachnoid mater is a thin transparent sheath closely applied to duramater. The subdural space is a potential space which contains only small amount of serous fluid to allow the dura and arachnoid to move over each other.

The piamater closely invests the cord and sends delicate septa into its substances. From each lateral surface of the piamater, a fibrous band, the denticulate ligament projects into the subarachnoid space. Inferiorly the piamater ends as a prolongation termed as filum terminale.The filum terminale is attached to periosteum of the coccyx by penetrating the distal end of the dural sac.

The subarachnoid space is filled with the cerebrospinal fluid and it contains the spinal nerve roots and the denticulate ligament. Lumbar puncture is routinely done below the second lumbar vertebra to L5-S1 interspace to avoid damage to the spinal cord that ends at the lower border of first lumbar vertebra.

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VASCULAR ANATOMY OF SPINAL CORD[4]

Blood supply of spinal cord is mainly from three longitudinal arterial channels namely

• One anterior spinal artery

• Two posterior spinal arteries

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The main source of blood supply to the spinal arteries is from the vertebral arteries. However it reaches only up to the cervical segment of the cord. The spinal arteries also receive blood through radicular arteries that reaches the cord along the roots of spinal nerves. These radicular arteries are formed by the vertebral, ascending cervical, deep cervical, intercostal, lumbar and sacral arteries.

Only few of these radicular arteries are larger in size. The arteria radicularis magna or artery of Adamkiewicz, the largest of the radicular arteries supplies blood to the lower two-thirds of the spinal cord. Its position is variable.

There is no anastamosis between the anterior spinal artery and the posterior spinal artery, so the occurrence of thrombosis in any of these arteries will cause spinal cord infarction. Venous drainage of the spinal cord is mainly through six longitudinal venous channels. They are anteromedian and posteromedian venous channels which lie in the midline and two paired anterolateral and posterolateral channels. These channels join together to form a venous plexus, from here the venous blood drains through the radicular vein into segmental and vertebral veins of the neck, the azygos veins of the thorax, lumbar veins of the abdomen and lateral sacral veins of the pelvis.

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CEREBROSPINAL FLUID[4]

The cerebrospinal fluid is an ultrafiltrate of plasma secreted by choroid plexus of third, fourth and lateral ventricles at a rate of 0.3 to 0.5ml/min. The average volume ranges from 120 to 150 ml, of which 25 ml is in the cerebral subarachnoid space, 35 ml in the ventricles and about 75 ml is in the spinal subarachnoid space . It is a colourless liquid with slight opalescence due to globulin.

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PHYSICAL CHARACTERISTICS OF CEREBROSPINAL FLUID

CIRCULATION OF CEREBROSPINAL FLUID

From the lateral ventricles it enters the 3rd ventricles through the interventricular foramina. Then it flows through the cerebral aqueduct and it reaches the 4th ventricle. It enters the subarachnoid space through foramen of Magendie and Luschka in the roof of 4th ventricle, and it finally circulates around the spinal cord and over the cerebral hemispheres.

ABSORPTION

The main site of cerebrospinal fluid absorption is into the venous system through the arachnoid villi and arachnoid granulations. These are most numerous in superior saggital sinus and its lateral lacunae. Approximately 300-380 ml of cerebrospinal fluid enters venous circulation each day.

pH 7.4

Specific gravity at body

temperature 1.003 to 1.067

Density 1.0003gm/ml

Baricity 1.0000

Pressure in sitting positon 3-12 mmHg

Cells 3-5/cumm

Proteins 20mg/dl

Glucose 45-80 mg/dl

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It plays an important role in spinal anaesthesia as a media for dispersion of the local anaesthetic drug to the spinal nerve. The spread of the local anaesthetics in the intrathecal space is determined mainly by the specific gravity of the injected drug.

SITE OF ACTION OF LOCAL ANAESTHETIC DRUGS[5]

Local anaesthetic solution injected into the subarachnoid space mixes with the cerebrospinal fluid and comes in contact with the spinal cord and the peripheral nerve roots. The nerve roots leaving the spinal canal are readily exposed to the local anaesthetic solution as they are not covered with epithelium.

ZONE OF DIFFERENTIAL BLOCKADE

In subarachnoid block, sympathetic fibres are blocked two to six segments higher than the sensory fibres. Sympathetic block will be greater when more concentrated solutions are used or when adrenaline is added.

Motor block will be two segments below the sensory block.

ORDER OF BLOCKADE OF NERVE FIBRES[4]

1. Autonomic preganglionic B fibres

2. Temperature fibres- cold fibres first followed by warm fibres 3. Pinprick fibres

4. Fibres conveying pain greater than pin prick

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5. Touch fibres

6. Deep pressure fibres 7. Somatic motor fibres

8. Fibres conveying vibratory sense and proprioceptive impulses.

During recovery, sensations return in the reverse order, but it has been suggested that sympathetic activity returns before sensation.

MINIMUM EFFECTIVE CONCENTRATION

Cm is the minimum concentration of the drug required to produce conduction blockade of nerve impulses.

Factors influencing Cm are:

1.Diameter of nerve fibres 2.Degree of myelination 3.Tissue pH.

SPREAD OF LOCAL ANAESTHETICS IN SUBARACHNOID SPACE The local anaesthetic solution is diluted by CSF and therefore its original concentration is less than the actual mass of drug injected. Spread is also determined by the baricity of the injected solution. Baricity is a ratio comparing the density of a local anaesthetic solution at a specific temperature to the density of CSF at the same temperature.

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The baricity of the hypobaric solution is less than 1.0000 or has a specific gravity less than 1.0069. The baricity of hyperbaric solution is greater than 1.0000 or has a specific gravity greater than 1.0069. Hypobaric and hyperbaric solutions are prepared from isobaric solutions by the addition of various amounts of sterile distilled water and dextrose respectively.

Isobaric solutions do not move under the influence of gravity in the CSF. The position of the patient will determine the most dependent part of the subarachnoid space to which the hyperbaric solutions will settle as it is being heavier than CSF. In supine patient, hyperbaric solutions gravitate to the thoracic kyphosis.

FATE OF LOCAL ANAESTHETICS IN SUBARACHNOID SPACE After injection of local anaesthetic solution into subarachnoid space, its concentration falls rapidly. The initial steep fall is due to mixing with CSF and subsequent absorption is into nerve roots and spinal cord. The removal of local anaesthetic solution following subarachnoid injection is primarily by vascular absorption. Depending on the type of the drug used, it is metabolized in plasma by pseudocholinesterase or in the liver. The duration of anaesthesia is increased by addition of a vasoconstrictor to the local anaesthetics which will delay the absorption of the drugs.

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PHYSIOLOGICAL EFFECTS OF SUBARACHNOID BLOCK CARDIOVASCULAR EFFECTS

The tone of the vascular smooth muscles is dependant on the innervation by the sympathetic fibres from the 5th thoracic to the first lumbar levels of the spinal cord. The blockade of these sympathetic fibres will cause a drop in the blood pressure along with a reduction in the heart rate. The cardiac contractility is brought down with the blockade of T1 to T4 fibres , which are associated with acceleration of sympathetic system of the heart. A central neuraxial blockade can cause hypotension , decreased heart rate and collapse of the cardiovascular system which is due to Bezold-Jarisch reflex.

RESPIRATORY EFFECTS

Even with high thoracic levels, the tidal volume remains unchanged.

Minimal decrease in the lung vital capacity can be caused by the paralysis of the abdominal muscles which are responsible for forced expiration and this decrease cannot be attributed either to phrenic nerve or diaphragmatic function impairment. Higher levels of block may unfavourably affect the ability to cough effectively and clear the respiratory secretions. Hypoperfusion of the centers of respiration in the brain can cause respiratory arrest during spinal anaesthesia , which is a rare occurrence.

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GASTROINTESTINAL FUNCTION

An unopposed parasympathetic activity can lead to increased peristaltic activity of the GIT causing nausea and vomiting in about 20% of the cases receiving spinal anaesthesia. Favourable operating conditions can be provided by a vagal tone dominance leading to small contracted gut with active peristalsis. Blood flow to the liver can decrease when there is fall in mean arterial pressure.

RENAL FUNCTION

Reduction in blood flow to the kidneys is of minor importance due to the wide margins of physiological reserve. Catheterizing the bladder is often mandated in neuraxial blocks which causes retention of urine and in turn leading to delay in patient leaving the hospital earlier.

INDICATIONS FOR SUBARACHNOID BLOCK

Spinal anaesthesia can be administered for surgeries below umbilicus such as

• Lower abdominal surgeries

• Lower limb surgeries

• Urological procedures

• Obstetric procedures

• Gynaecological surgeries

• Perineal and rectal surgeries

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CONTRAINDICATIONS FOR SUBARACHNOID BLOCK The absolute contraindication for subarachnoid block are

• Patient refusal

• Local sepsis

The relative contraindications include

• Raised intracranial pressure

• Coagulopathy

• Neurological disease

• Fixed cardiac output states

• Documented allergy to local anaesthetics

• Major spine deformities or previous surgery on the spine

• Haemodynamic instability

FACTORS INFLUENCING THE HEIGHT OF BLOCKADE IN SUBARACHNOID BLOCK

• Dose of the drug injected

• Volume of fluid injected

• Specific gravity of the solution

• Position of the patient during injection

• Posture of patient after injection

• Choice of interspace

• Patient factors- Age, Height and Pregnancy

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FACTORS NOT INFLUENCING THE HEIGHT OF BLOCKADE IN SUBARACHNOID BLOCK

• Patient factors- Weight, Sex.

• Barbotage.

• Rate of injection.

• Composition and circulation of cerebrospinal fluid.

• Direction of bevel of the standard needle (although not of the Whitacre needle).

COMPLICATIONS OF SUBARACHNOID BLOCK The immediate complications include

• Hypotension

• Bradycardia

• Toxicity due to intravascular injection

• Allergic reaction to local Anaesthetic

• Hypoventilation ( brain stem hypoxia )

The late complications include

• Postdural puncture headache

• Retention of urine

• Backache

• Meningitis

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• Transient neurological symptoms

• Cauda equina syndrome

• Anterior spinal artery syndrome

• Horner’s syndrome

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PHARMACOLOGY OF BUPIVACAINE[6,7,8]

Bupivacaine, an amino amide local anaesthetic was first synthesized in Sweden by A.F Ekenstam and his colleagues in 1957. First report of its use was in 1963 by L.J Teluvio. It is one of the long acting local anaesthetic agents available, which is extensively used for intrathecal, extradural and peripheral nerve blocks.

CHEMICAL STRUCTURE OF BUPIVACAINE

Bupivacaine has an IUPAC nomenclature of 1-butyl-n-(2,6- dimethylphenyl) piperidine-2-carboxamide.

PHYSIOCHEMICAL PROPERTIES[9]

Molecular formula C18H28N20Hcl

Molecular weight 288.43gm/mol

Solubility in water 25mg/ml pH of saturated solution 5.2

pka 8.1

Specific gravity 1.021 at 37C

Melting point 247 to 258 C

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MECHANISM OF ACTION[10,11]

Bupivacaine has a action same as that of other local anaesthetics. The primary action of local anaesthetics is on the cell membrane axon, on which it produces electrical stabilization. Bupivacaine acts by blocking the conduction of nerve impulses. This blockade of conduction is done by inhibiting passage of sodium ions through ion-selective sodium channels which is an specific receptor for molecules of local anaesthetic in nerve membranes. The propagation of action potential is not achieved because the threshold potential needed for propagation of action potential is not reached due to decreased rate of depolarization, which is due to failure in increase of permeability of the sodium ion channel.The resting transmembrane potential or threshold potential is not altered by the local anaesthetics.

The mechanism by which local anaesthetics block sodium conductance is as follows

1. Local anaesthetics in the cationic form act on the receptors within the sodium channels on cell membrane and block it. The local anaesthetics can reach the sodium channel either via the lipophilic pathway directly across the lipid membrane or via the axoplasmic opening. This mechanism accounts for 90% of the nerve blocking effects of amide local anaesthetics.

2. The second mechanism of action is by membrane expansion. This is a nonspecific drug receptor interaction.

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Other site of action targets

• Voltage dependent potassium ion channels

• Calcium ion currents (L-type most sensitive)

• G protein coupled receptors Dosage depends on

• Area to be anaesthetized

• Number of nerve segments to be blocked

• Individual tolerance

• Technique of local anaesthesia

• Vascularity of area

AVAILABILITY

Ampules – 0.5% Bupivacaine hydrochloride 4cc

- 0.5% Bupivacaine with dextrose (heavy) 4cc Vials - 0.25% and 0.5% Bupivacaine hydrochloride 30 cc Dosage - Maximum dosage 3mg/kg body weight.

ANAESTHETIC POTENCY

Hydrophobicity appears to be a primary determinant of intrinsic anesthetic potency and Bupivacaine is highly hydrophobic, hence it is very potent.

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ONSET OF ACTION

The onset of conduction blockade is dependent on the dose or concentration of the local anesthetic. The onset of action of Bupivacaine is between 4 – 6 mins and maximum anaesthesia is obtained between 15 – 20 minutes.

DURATION OF BLOCK

The duration of anaesthesia varies according to the type of block. The average duration of peridural block is about 3.5 – 5 hours, for nerve block 5 – 6 hours and for intrathecal block it is about 1.5 to 2 hours.

PHARMACOKINETICS

The concentration of Bupivacaine in blood is determined by the amount injected, the rate of absorption from the site of injection, the rate of tissue distribution and the rate of biotransformation and excretion of Bupivacaine. It can be detected in the blood within 5 minutes of infiltration or following epidural or intercostal nerve blocks. Plasma levels are related to the total dose administered. Peak levels of 0.14 to 1.18 µg/ml were found within 5 mins to 2 hrs, and they gradually declined to 0.1 to 0.34 µg/ml by 4 hrs.

PLASMA BINDING

In plasma, drug binds avidly with protein to the extent of 70 -90%. The rank order of protein binding is Bupivacaine, Mepivacaine and Lidocaine.

Conversely, the unbound active fraction is one seventh of Lidocaine and one fifth of Mepivacaine.

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ABSORPTION

The absorption of Bupivacaine in the body is determined by the injection site, amount of drug injected and inclusion of vasoconstrictor to the drug injected.The highest level of Bupivacaine in the blood is determined by total amount of drug injected at any particular site. Absorption is faster in areas of high vascularity.

TOXICITY

The toxic plasma concentration is set at 4 - 5 µg/ml. Maximum plasma concentration rarely approach toxic levels.

DISTRIBUTION

Rapid distribution phase: (α)

In this phase the drug is distributed to highly vascular region.

Half life of α- being 2.7 minutes.

Slow disappearance phase: (β)

In this phase the drug distributes to slowly equilibrating tissues.

Half life of (β)- being 28 minutes.

Biotransformation and excretion phase: (δ)

Half life of δ is 3.5 hours and clearance is 0.47litre/minute.

Organs with high blood flow show increased concentration of the drug.After rapid entry into the venous circulation , the pulmonary extraction limits the concentration of the drug reaching systemic circulation .This first pass pulmonary extraction of Bupivacaine is dose dependant.

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The skeletal muscle is the largest reservoir of the drug despite having the least affinity for Bupivacaine.

BIOTRANSFORMATION AND ELIMINATION:

The liver is the primary site in which Bupivacaine undergoes biotransformation by enzymatic degradation.The primary route of excretion is through kidneys.

The factors determining the elimination of Bupivacaine are:

a) Renal perfusion

b)Factors affecting urinary pH BUPIVACAINE

N-DEALKYLATION

2,6 PIPECOLYOXYLIDINE (IN URINE)

The rate at which the drug is cleared from the renal system is inversely proportional to its protein binding and pH of the urine.

PHARMACODYNAMICS

CENTRAL NERVOUS SYSTEM

The depression of the central nervous system is attributed to Bupivacaine’s ability to cross the blood brain barrier readily at higher doses.Initially the patient feels light headedness and dizziness followed by

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visual and auditory disturbances. Finally the patient may became drowsy and disoriented. The excitatory signs such as tremors involving the muscles of face in addition to the muscle twitching and tremors are objective by nature. When the dose is further increased cardiovascular or respiratory arrest may occur.The central nervous system toxicity is increased by factors that increase the delivery of Bupivacaine to the central nervous system such as acidosis and elevation of PaCO2

AUTONOMIC NERVOUS SYSTEM

Bupivacaine does not inhibit the Noradrenaline uptake and hence has no sympathetic potentiating effect. The sensory nerve fibres are more suspectiable to blockade by Bupivcaine than the motor fibres. The sensitivity of Bupivacaine is maximum towards the myelinated preganglionic B fibers which have faster conduction speed.

CARDIOVASCULAR SYSTEM

The primary cardiac electrophysiological effect of a local anaesthetic is a decrease in the maximum rate of depolarization in Purkinje fibers and ventricular muscle. This action by Bupivacaine is far greater compared to Lignocaine and also, the rate of recovery of block is slower with Bupivacaine.

Therefore there is complete restoration of Vmax between action potential particularly at higher rates. Therefore Bupivacaine is highly arrythmogenic.

Bupivacaine reduces the cardiac contractility by blocking the calcium

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transport. Low concentration of Bupivacaine produces vasoconstriction whereas high doses cause vasodilatation.

RESPIRATORY SYSTEM

When the maximum amount of the drug reaches the plasma the medullary centres which are concerned with respiration are inhibited leading to respiratory depression. The paralysis of respiratory muscles of diaphragm as occurring during high spinal or total spinal may also cause respiratory depression.

ADVERSE EFFECTS

Adverse effects are encountered in clinical practice mostly due to overdose, inadvertent intravascular injection or slow metabolic degradation.

CENTRAL NERVOUS SYSTEM

The effect on central nervous system can be either excitation or depression. The initial manifestations include nervousness,dizziness, blurring of vision and later the patients may develop drowsiness,convulsions and unconsciousness.

CARDIOVASCULAR SYSTEM

Myocardial depression, hypotension, arrhythmia, ventricular type conduction defect, SA node depression and cardiac arrest.

ALLERGIC REACTIONS

Urticaria, bronchospasm and hypotension.

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OTHERS

Ringing sensation in ears, miosis, shivering and regurgitation

TREATMENT OF ADVERSE EFFECTS

Treatment is mainly symptomatic which includes

1.Methods to maintain circulation and ventilation using oxygen.

2.Intravenous fluids

3.Convulsions: injection Diazepam (0.1-0.2mg) or Thiopentone sodium (2-3mg/kg) or a muscle relaxant with oxygen.

4.Allergic reactions: steroids

5.Ventricular fibrillation :Amiodarone (5mg/kg iv) or defibrillation.

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PHARMACOLOGY OF FENTANYL[12,13]

Fentanyl is a synthetic phenylpiperidine opioid of the 4-anilopiperidine series which is structurally related to pethidine. Commercially, Fentanyl is formulated as a citrate available as an aqueous solution without preservatives.

Each ml contains a base of 50mcg of fentanyl.

PHYSIOCHEMICAL PROFILE

Molecular weight 528.29

pKa 8.4

% Unionized at pH 7.4 8.5%

Octanol/water partition coefficient 816

% bound to plasma proteins 84%

Potency 80 times more potent than

morphine

PHARMACODYNAMICS:

ANALGESIA:

Analgesia results from action of Fentanyl on opiod mu receptor both supraspinally in the brain and in the spinal cord.Intravenous Fentanyl produces effective analgesia at plasma concentrations between 0.6-3.0ng/ml.

CARDIOVASCULAR SYSTEM

Arterial blood pressure, cardiac output and pulmonary vascular

(38)

Fentanyl like other opioid agonists (except Pethidine) causes bradycardia,that responds to intravenous Atropine.Peripheral vasodilation is much less than Morphine due to absence of histamine release.

RESPIRATORY SYSTEM

Fentanyl causes a direct dose related respiratory depression by its depressant effect on the medullary respiratory centre, manifested as a decreased sensitivity to carbon dioxide and reduced respiratory rate. It is reversed by intravenous Naloxone administration. Plasma Fentanyl concentrations greater than 2ng/ml is associated with clinical respiratory depression. The degree of respiratory depression is affected by various factors like type of surgery, age and individual pharmacodynamic response.

CENTRAL NERVOUS SYSTEM:

Fentanyl causes less sedation than equianalgesic doses of Morphine .In dose of 10mcg/kg,Fentanyl causes dose related reduction in cerebral blood flow and CMRO2 . Muscle rigidity probably reflects a manifestation of a catatonic state,a basic pharmacological property of opioids, related to enhancement of Dopamine biosynthesis in the caudate nucleus.

(39)

GASTROINTESTINAL TRACT

Fentanyl decreases gastrointestinal tract motility ,increases intrabiliary pressure and causes a varying incidence of nausea and vomiting.The vomiting is mediated via stimulation of the chemoreceptor trigger zone in the area postrema.

GENITO-URINARY SYSTEM

Fentanyl like other opioids causes relaxation of the detrussor muscle and increase in the urethral sphincter tone leading to urinary retention.This is probably not dose related and is more common with central neuraxial administration.

PHARMACOKINETICS

Fentanyl is a highly potent lipophilic opioid ,producing a rapid onset of action of relatively shorter duration. After intravenous administration,Fentanyl is rapidly distributed to brain,heart and other highly perfused tissues. It also crosses the placental barrier easily. Peak effect occurs in 5 minutes. Within short time the drug redistributes to the inactive tissues sites like skeletal muscle and fat leading to the decrease in plasma concentration of drug ,thus terminating its effect. About 75% of initial dose undergos first pass pulmonary uptake when low doses(1-2mcg/kg) are administered, redistribution terminates the effect and the drug appears short acting.

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With administration of large intravenous doses or continous infusion, progressive saturation of inactive tissues sites occur.

PHARMACOKINETIC PROFILE:

Volume of distribution at steady

state(vdss) 335litres

Clearance 1530ml/min

Effect-site equilibrium time 6.8min Hepatic extraction ratio 0.8-0.1 Context-sensitive half time(4hrs

infusion) 260 mins

Elimination half time 3.1 – 6.6 hrs

METABOLISM

Fentanyl is biotransformed in the liver to inactive metabolites,primarily Norfentanyl and several hydroxylation products.Only 4-7% of drug is excreted unchanged in the urine.Elimination half time of Fentanyl is longer than that of morphine because of the high lipid solubility of Fentanyl. Elimination half time is prolonged in elderly patients. A high hepatic extraction ratio means that the clearance of Fentanyl is limited by hepatic blood flow.

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ROUTES OF ADMINISTRATION AND DOSAGE INTRAMUSCULAR

50-100mcg may be administered as premedication 30-60 minutes prior to surgery.

INTRAVENOUS

Can be given for intraoperative and post operative analgesia.

Postoperative analgesia is achieved by intravenous loading dose of 1-2mcg/kg followed by continuous or variable infusion at the rate of 1-2mcg/kg/hr. It can be used for patient-controlled analgesia(PCA) as a bolus dose of 20-50 mcg with lockout intervals.

TRANSDERMAL

Transdermal Fentanyl patch is available in four sizes, providing sustained release of Fentanyl at rates of 25,50,75 and 100 mcg/hr for periods of 48-72 hrs. Skin acts as a secondary reservoir contributing to prolonged residual Fentanyl concentrations.

TRANSMUCOSAL

Oral transmucosal Fentanyl citrate (OTFC) incorporates Fentanyl citrate in candy mixture shaped into a lozenges or stick. The median time to onset of analgesia is 4 minutes and the duration of analgesia lasts for about 150 minutes.

(42)

INTRANASAL

Fentanyl is administered with a metered dose device with each spray delivering 4 to 5mcg Fentanyl. Time of onset of analgesia is about 15 minutes.

TRANSPULMONARY

Inhalational administration of Fentanyl produces rapid and effective drug delivery. A dose of 300mcg of Fentanyl administered via oxygen driven nebuliser produces effective postoperative analgesia in 5 minutes and lasts for about 2 hours.

NEURAXIAL ADMINISTRATION

Epidural and intrathecal administration of Fentanyl are long established routes for intraoperative and postoperative analgesia .Epidural dose as a single bolus administration varies from 1-3mcg/kg .Analgesia begins in 15 minutes lasting for 2-4 hours. Epidural infusion rate range from 0.5- 2.5mcg/kg/hr .In addition, Fentanyl has been used in patient controlled epidural analgesia(PCEA) in doses of 20-25mcg with lockout interval of 6-10 mins and background infusion in the rate 0.5-1mcg/kg/hr. The minimum intrathecal bolus requirement for post operative analgesia is 20mcg while dose of 10mcg is effective in obstetric patients .Onset of analgesia is usually within 5-15 minutes and duration is variable ,ranging from 1-5 hours. Other modes of administration include continuous/bolus administration via an intrathecal catheter.

(43)

CLINICAL APPLICATIONS PREMEDICATION

Fentanyl in doses of 50-100mcg may be administered intramuscularly 30-60 minutes prior to surgery.Oral transmucosal Fentanyl citrate in doses between 15-20mcg/kg administered 45 mins before surgery produces reliable preoperative sedation and facilitates induction of anaesthesia in children.

ADJUVANT TO GENERAL ANAESTHESIA

Fentanyl in doses of 1-2mcg/kg given intravenously provides analgesia.

It can be used as an adjuvant to blunt circulatory responses that occur during direct laryngoscopy for endotracheal intubation and sudden changes in the level of surgical stimulation. Large doses of Fentanyl, 50-150mcg/kg intravenously has been used especially in cardiothoracic procedures, principally because of its stable hemodynamic effects.

ADJUVANT IN CENTRAL NEURAXIAL BLOCK

Fentanyl added to local anaesthetic either intrathecally or epidurally, improves the quality of intraoperative analgesia and also provides good post operative analgesia.

POSTOPERATIVE ANALGESIA

Fentanyl administration by intravenous, epidural, intrathecal and transdermal routes provides effective postoperative analgesia. Newer routes like intranasal and inhalational administration are being evaluated as less invasive means of postoperative analgesia.

(44)

SIDE EFFECTS

Commonly occurring side effects include dose dependant respiratory depression, muscle rigidity, nausea, vomiting, pruritis, urinary retention and bradycardia .These effects are reversed by administration of Naloxone intravenously.

INTRATHECAL FENTANYL

Intrathecal Fentanyl administration is an established route for intraoperative and postoperative analgesia.

PHARMACOKINETICS

Fentanyl has the same baricity as cerebrospinal fluid at room temperature and its addition to hyperbaric Lignocaine or Bupivacaine makes the solution hyperbaric. On injection into subarachnoid space , Fentanyl mixes with cerebrospinal fluid and attaches itself to spinal opioid receptors.Opioids in the cerebrospinal fluid is present as free drug because protein binding of drug in the cerebrospinal fluid is negligible.

Cerebrospinal fluid dynamics do not provide any means of drug removal. Diffusion into the spinal cord and absorption into the blood flowing through spinal cord removes all the Fentanyl. The rate determining step of drug removal is likely to be the rate constant of Fentanyl transfer from cerebrospinal fluid to spinal cord and this rate constant is directly related to lipophilicity.Fentanyl can also migrate from the cerebrospinal fluid into the epidural vascular compartment via the duramater.

(45)

However details of systemic pharmacokinetics of Fentanyl are not known. Once in the cerebrospinal fluid Fentanyl like other opiods, spread rostrally. The high affinity of Fentanyl with binding sites in the lipid – rich spinal cord leads to only 10% of the administered dose to migrate to the cervical region.

APPLICATION

Intrathecal Fentanyl is usually combined with local anaesthetics for perioperative anaesthesia and analgesia particularly in obstetrics. Fentanyl administration intrathecally provides more intense and complete analgesia at rest at a lower dose requirement when compared to the epidural or intravenous routes.

MODES OF ADMINISTRATION AND DOSAGES

Fentanyl is administered either intrathecally as single bolus injection, repeated patient administered controlled analgesia boluses or continuous infusion via an intrathecal catheter .Effective postoperative analgesia can be achieved with bolus dose of 20mcg. Infusions of 0.8mcg/kg/hr produces satisfactory analgesia in patients undergoing thoracotomy.

(46)

SIDE EFFECTS OF INTRATHECAL FENTANYL

Side effects are relatively minor with intrathecal Fentanyl. The incidence of significant respiratory depression is relatively low , as intrathecal administration of Fentanyl results in lower systemic absorption than epidural route. A 30% increased incidence of urinary retention ,varying incidence of pruritis and occasional episodes of nausea have been observed.

(47)

MATERIALS AND METHODS:

This study was carried out in the Urology theatre in Thanjavur Medical College Hospital, Thanjavur. After obtaining approval from the institutional ethical committee and informed written consent, 80 ASA 1 and 2 patients scheduled for common elective urological procedures such as TURP,URSL and TURBT performed under subarachnoid block were prospectively enrolled.

GROUP A: Patients received 3ml of preservative free 0.5% isobaric Bupivacaine with 25 mcg of Fentanyl.

GROUP B: Patients received 3ml of preservative free 0.5% hyperbaric Bupivacaine with 25 mcg of Fentanyl.

INCLUSION CRITERIA:

The inclusion criteria for the study were 1.18-60 years of age

2.Both gender 3.ASA 1 and 2

EXCLUSION CRITERIA:

The exclusion criteria for the study were 1.Refusal by patient

2.Hypovolemia 3.Spinal deformity

4.Pre-existing neurological deficit.

(48)

PREOPERATIVE PREPARATION:

Preoperative evaluation was performed. Patients were premedicated with T.Diazepam 5mg the night before surgery and on the morning of surgery. In the operating room, appropriate equipment for airway management and emergency drugs were kept ready.

The horizontal position of the operating table was checked. Patients were shifted to the operating room and positioned.

Following arrival in operation theatre ,intravenous access was established with 18 G cannula.The patients were preloaded with crystalloids at 10ml/kg.Pulse oxymeter, electrocardiogram and noninvasive blood pressure monitors were connected.The patients were placed in sitting position and lumbar puncture was performed under strict aseptic precautions at L3 –L4 space using 25 G Quincke’s spinal needle.

The anaesthesiologist performing the procedure was blinded to the drug injected. According to the allocated group, the patients received either hyperbaric Bupivacaine or isobaric Bupivacaine 3ml with 25 mcg of Fentanyl The patients were then placed in supine position. After 10 minutes ,the patients were put in lithotomy position.

An anaesthesiologist blinded to patient allocation and study group performed the intraoperative and postoperative assessment. Systolic and diastolic blood pressure,heart rate and respiratory rate were recorded at 1st

(49)

min,5th minute and thereafter every 5 minutes upto 30 minutes and then every 10 minutes till 60 minutes.

Hypotension was said to have occurred if the systolic blood pressure and diastolic blood pressure had fallen below 20% from the base line and was treated with supplemental oxygen , increasing the infusion rate of intravenous fluids and Injection Ephedrine in incremental doses of 6mg.Bradycardia was defined as heart rate less than 50/min and was managed with intravenous Atropine in incremental doses. On completion of surgery, patients were transfered to postoperative ward after complete resolution of motor blockade and stabilization of blood pressure.

ASSESSMENT OF MOTOR BLOCKADE:

Motor block was assessed by using Modified Bromage Scale.The time of onset of motor block was defined as the time interval between the local anaesthetic solution injected and the establishment of grade 4 on Bromage scale.

Grade Criteria Degree of block 1 Free movement of legs and feet 0% (nil) 2 Just able to flex knees with free

movement of feet 33% (partial)

3 Unable to flex knees but with

free movement of feet 66%(almost complete) 4 Unable to move legs or feet 100%(complete)

(50)

The duration of motor block was assessed as the time interval between local anaesthetic injection to the patient’s ability to flex feet.

ASSESSMENT OF SENSORY BLOCKADE:

The time of onset of sensory block was assessed as the time interval between local anaesthetic injection to the onset of complete loss of pinprick sensation in anterior axillary line bilaterally at T10 level.

The level of sensory block achieved after 20 mins of local anesthetic injection was taken as the maximum level of sensory block achieved .Two segment regression time from the maximum level of sensory block achieved was taken as the duration of sensory block. Adverse effects such as giddiness, nausea, vomiting, shivering, pruritis and respiratory depression were noted.

Respiratory rate less than 10 per minute was considered as respiratory depression. The patients were supplemented with intravenous sedation with Injection Midazolam 0.05mg/kg or general anaesthesia when the subarachnoid block was inadequate or when the duration of block did not last longer than the duration of surgery.

(51)

REVIEW OF LITERATURE

Magdy et al [14] in 2015 conducted a prospective randomized blind study on 99 patients undergoing TURP under spinal anesthesia. The patients were divided into 3 groups .

Group 1 received intrathecal 10mg hyperbaric Bupivacaine 0.5%

Group 2 received 5mg isobaric Bupivacine added to 5mg hyperbaric Bupivacaine resulting in slightly hyperbaric solution.

Group 3 received 10mg of isobaric Bupivacaine 0.5%

The sensory and motor blockade was assessed . The first request for analgesia and the incidence of side effects were recorded.Onset of sensory block was compared in 3 groups. Motor block had set earlier in hyperbaric group and slightly hyperbaric group.

Higher level of sensory block were observed in isobaric group.Recovery from sensory and motor block was earlier in hyperbaric group. The need for analgesia was earlier in hyperbaric group than other groups.

Hence they concluded that use of slightly hyperbaric Bupivacine (density1.013) than the traditional hyperbaric Bupivacaine (density1.028) and the isobaric one (density =1.007) results in good quality spinal block with fewer side effects.

Rashmi et al[15] in 2015,performed a prospective randomized double blind study involving parturients who were allocated in two groups.

(52)

Group L received 2ml of 0.5% isobaric Levobupivaciane Group B reveived 2ml of 0.5% hyperbaric Bupivacine

The characteristic of sensory and motor blockade were assessed.Adverse effects such as hypotension , bradycardia ,nausea and vomiting were recorded.

The duration of both sensory and motor block were shorter in group L when compared to group B,the difference being highly significant(p <

0.001).The maximum sensory block height achieved in group L was significantly lower than the group B (p=0.003).

The incidence of side effects was lower in group L as compared to group B with p value less than 0.05. Hence they concluded adequate surgical anaesthetia was achieved in both groups but isobaric Levobupivacaine can result in fewer incidence of side effects when compared to hyperbaric Bupivacaine.

Luiz eduardo imbelloni et al [16] in 2014 conducted a prospective study to evaluate parameters of thoracic spinal anesthesia (latency,motor block and paresthesia) ,the cardiovascular changes comparing low dose of isobaric and hyperbaric Bupivacaine in 200 orthopaedic patients of ASA 1 and 2 physical status. Patient remained in head down position 10-20 degrees for 10 mins.It was found that the baricity of the solution did not affect the onset of blockade.

The duration of motor block was greater than the sensory block with isobaric

(53)

solution, whereas the duration of sensory block was greater than the motor block with hyperbaric solution. The incidence of paresthesia was 4%.The incidence of hypotension was 12.5% with no difference between the solutions.

Hence,it was concluded that by providing a sensory block of longer duration hyperbaric Bupivacaine is better when compared to isobaric solution for thoracic spinal anaesthesia. Thoracic spinal anaesthesia provides excellent anaesthesia for lower limb orthopaedic surgery.

Kumkum et al[17] in 2013 conducted a prospective randomized clinical study on 54 male patients, ASA 1and 2 scheduled for Transurethral resection of prostate under subarachnoid block. The patients were divided into two groups.

Group R received 4ml of 0.75% isobaric Ropivacaine

Group RF received 3.5ml of 0.75% isobaric Ropivacaine with 0.5ml (25microgram) of Fentanyl.

The characteristics of sensory and motor blockade,intraoperative haemodynamic changes were evaluated between the two groups.The median time to achieve sensory blockade at T10 dermatome was longer in group RF when compared to group R. The median duration of sensory blockade at T10 dermatome was longer in group RF when compared to group R .The median duration of motor block was significantly shorter than the duration of sensory blockade,with p less than 0.001. An initial hypotension was observed in both

(54)

groups but hypotension requiring treatment with vasopressors occurred in 5 patients of group R and 11(40%)patients of group RF. In this study they observed that subarachnoid administration of Ropivacaine alone or with intrathecal Fentanyl has provided effective surgical anaesthesia for Transurethral resection of prostate surgery with cardiovascular stability.

Intrathecal Ropivacaine with Fentanyl has no effect on onset of sensory analgesia but has improved the quality and duration of sensory blockade.

Hence, they concluded that intrathecal 0.75% isobaric Ropivacaine alone or with Fentanyl has provided effective surgical anaesthesia for transurethral resection of prostate with haemodynamic stability.

Hallworth et al[18] in 2005 conducted a double blinded prospective study involving 150 patients undergoing elective lower segment caesarean section under subarachnoid block. They were randomized into 3 groups to receive hyperbaric , hypobaric and isobaric solutions of 10mg of Bupivacaine in either sitting or right lateral position. The level of sensory block,motor block, hypotensive episodes and use of ephedrine were evaluated. In lateral position, the baricity had no effect on spread of sensory level for Bupivacaine compared to sitting position. There was a statistically significant difference in spread with hypobaric solution producing higher levels of sensory block than the hyperbaric solution (p=0.002). Median maximum sensory level block with hyperbaric solution were T3 compared to T2 for isobaric and hypobaric

(55)

solution. Motor block was significantly reduced (p=0.029) with increasing baricity and this trend was significant (p=0.033) for lateral position only Incidence of hypotension and ephedrine usage was increased with decreasing baricity,with hypobaric sitting group having the most incidence of hypotension (76%).

Mochamat et al[19] in 2014 conducted a prospective study in 60 patients to compare the onset of anaesthesia and duration of action of isobaric and hyperbaric solution undergoing lower abdominal, hip and lower extremity surgeries.

Group I received 20mg of 0.5% isobaric Bupivacaine whereas group H received 20mg of 0.5% hyperbaric Bupivacaine .

Subarachnoid block was administered at L3-L4 space in sitting position.

The onset of analgesia and motor block was faster with isobaric solution. The duration of sensory and motor block was longer in isobaric group.

Haemodynamic changes were not relevant in both the groups.

Hence, it was concluded that isobaric solution produced more rapid onset and longer duration of sensory and motor blockade when compared to hyperbaric Bupivacaine.

Hussain et al[20] in 2011 conducted a prospective randomised study in 60 male patients of ASA 1 and 2 physical status to evaluate the effects of isobaric

(56)

Bupivacine with low dose of Fentanyl in endoscopic urologic surgeries .One group received 0.5% hyperbaric Bupivacaine and other group received 0.5.%

isobaric Bupivacaine. In both group Bupivacaine were mixed with low dose of Fentany 10microgram. Non invasive blood pressure,heart rate,Spo2 ,levels of sensory and motor blockade were recorded.

The mean operation time was 49.9±9.55 and 50.10± 7.98 minutes in HBF and IBF groups respectively and the difference was not statiscally significant (p>0.05). The mean time for request for first analgesic was 402.50

± 37.21 and 288.90 ± 25.22 min in HBF and IBF groups respectively and the difference was statistically significant (p<0.001). There was no difference in the level of sensory block and the total amount of fluid infused (p>0.05).

Baseline heart rate and blood pressure of the two studied groups were similar.

After the intrathecal injection blood pressure reduced significantly in both the groups (p<0.001) but remained in the acceptable level. No significant difference in the adverse effects were observed in the two groups.

Hence,they concluded that intrathecal isobaric Bupivacaine with low dose Fentanyl can be used as alternate to hyperbaric Bupivacaine for endoscopic urological procedure with fewer side effects related to intrathecal opiods.

Nedim et al[21] in 2010 conducted a prospective study involving 60 patients of ASA 1 and 2 physical status posted for elective orthopaedic,

(57)

urological and gynaecological surgery under spinal anesthesia. One group received 3ml of 0.5% hyperbaric Bupivacaine whereas other group received 3ml of 0.5% isobaric Bupivacaine. After 20 minutes, the height of sensory block was determined. In hyperbaric group highest level of block was T1 (3.33%) and lowest level was T7 (6.66%) with a mean of T5. In isobaric group highest level was T5 (3.33%)and lowest level (3.33%) was L2 with a mean of T10 .Mode as the most frequent value in the series of the hyperbaric group was T5,and in the isobaric group T10 (p<0.01) .

Hence, they concluded that isobaric Bupivacine gives a comfortable anaesthesia for surgeries in which sensory block of T10 is sufficient rather than higher block producing significant changes in blood pressure and heart rate achieved with hyperbaric Bupivacaine .

Yurtlu et al[22] in 2012 conducted a randomised prospective study involving 144 patients of ASA 1 and 2 status undergoing elective or emergency lower segment caesarean section subarachnoid block. The patients were divided into 4 groups. First group received 10mg of hyperbaric Bupivacaine (H10), second group received sequential 5mg administration of hyperbaric and isobaric Bupivacaine (H5P5), third group received sequential administration of 5mg isobaric and hyperbaric Bupivacaine (P5H5) and fourth group received 10mg of isobaric Bupivacaine (P10). The incidence of

(58)

hypotension, bradycardia and ephedrine required to treat hypotension were recorded. Fetal apgar scores, pH of umbilical cord blood were also recorded.

The incidence of hypotension in various groups were as follows:

H10 – 69.4%

H5P5-66.7%

P10-75%

P5H5-83.3%

The incidence of hypotension, bradycardia and ephedrine consumption , pH of cord blood and side effects were not significantly different among the groups.

Hence,they concluded that when the dose of local anaesthetics is the same , the incidence of spinal induced hypotension cannot be lowered using hyperbaric, isobaric or sequential injection of a half dose of Bupivacaine for spinal anesthesia during lower segment caesarean section.

Toptas et al[23] in 2014 conducted a prospective randomised control study including 60 patients between 18 to 65 years with ASA 1 and 2 status undergoing lower abdominal, urological and lower extremity surgeries done under spinal anaesthesia.

The patients were randomly allotted into 2 groups. First group received 15mg of hyperbaric Bupivacaine and second group received 15mg of isobaric Bupivacaine.

(59)

Haemodynamics were recorded for 30 mins after subarachnoid block.

Analysis of heart rate variability were recorded on the day of surgery, after volume load and 20 mins after subarachnoid block. Low frequency(LF) and high frequency(HF) values and LF/HF ratios were recorded. The incidence of hypotension was 26.6% in group 1 and 23.3% in group 2. There were no significant difference in LF, HF values and LF/HF ratio between two groups.

In group 1, LF/HF ratio were significantly lower and HF values were significantly high at 20 mins after spinal anaesthesia when compared to base line value (p less than 0.05)

Hence, they concluded that the group which received hyperbaric Bupivacaine caused a significantly greater decrease in LF/HF ratio and significantly greater increase in HF values when compared to the other group.

Gurmukh das et al[24] in 2012 conducted a prospective randomised double blinded study in 60 patients of ASA 1 and 2 status undergoing lower segment caesarean section under subarachnoid block. They were divided into 2 groups.One group received 10mg plain Bupivacaine with 25microgram Fentanyl and the other group received 10mg hyperbaric Bupivacaine with 25 microgram Fentanyl. Characteristics of sensory and motor block and hypotensive episodes were evaluated among the groups. There was no difference in onset, time to achieve maximum level of blockade and haemodynamic parameters between the groups. However plain (isobaric)

(60)

Bupivacaine took more time for 2 dermatome sensory level regression below T4 and resulted in prolonged block duration. No statistically significant difference was found in haemodynamic parameters between the two groups or the use of Atropine and ephedrine.

Hence,they concluded both groups had adequate anaesthesia for caesarean section without any difference in time of onset, extent of block and haemodynamic parameters. However two segment regression time was delayed in the group receiving isobaric Bupivacaine and Fentanyl which may have caused prolonged duration of block.

Madhusudan et al[25] in 2016 conducted a prospective randomised control study in one hundred ASA 1 and 2 patients undergoing Urological procedures.The patients were divided into two groups randomly.Group 1 received 3.5ml of 0.5% isobaric Bupivacaine - Fentanyl and group 2 received 3.5ml of 0.5% hyperbaric Bupivacaine-Fentanyl mixture intrathecally. The heart rate, blood pressure , respiratory rate, onset and duration of sensory and blockade were compared.

The haemodynamic stability was better in isobaric Bupivacaine-Fentanyl group than the other group. The mean onset time in group 1 for both sensory block (4 min) and motor block (5min) was longer when compared to group 2 and the difference was statistically significant with p<0.05 .The mean duration of sensory block (185.4 ± 16.08 min) and motor block (201.6 ± 14.28 min)

(61)

was longer in hyperbaric Bupivacaine – Fentanyl group than the other group and the difference was statistically significant with p<0.05 .The incidence of adverse effects were greater in hyperbaric Bupivacaine –Fentanyl group .The need for supplementation with intravenous sedation was greater for patients in isobaric Bupivacaine-Fentanyl group when compared to the patients in hyperbaric Bupivacaine - Fentanyl group. Hence they concluded that isobaric Bupivacaine - Fentanyl mixture provides adequate anaesthesia with better haemodynamic stability.

Nedim et al[26] in 2010 conducted a prospective randomised control study in 60 patients of ASA 1 and 2 physical status to compare the haemodynamic effects of hyperbaric and isobaric Bupivacaine in spinal anaesthesia undergoing gynaecology ,urology, orthopaedics and vascular surgery. The pulse frequency,systolic blood pressure , diastolic blood pressure and mean arterial pressure were recorded in the two groups.

It was observed that the above parameters had significantly decreased in hyperbaric Bupivacaine group when compared to the isobaric Bupivacaine group.

Hence they concluded that by choosing the appropriate baricity of local anaesthetic solution, we can significantly affect the haemodynamic status of the patient.

(62)

OBSERVATION AND RESULTS

TABLE 1: AGE DISTRIBUTION BETWEEN THE TWO GROUPS.

Age group in years

Group A Group B

Number % Number %

18 - 32 4 10 4 10

33 - 46 8 20 13 32.5

47 - 60 28 70 23 57.5

Total 40 100 40 100

Mean 50.53 48.95

S.D ± 10.735 ± 11.24

p value 0.52

Not significant

The age distribution between the two groups were comparable and the difference was not significant with a p value of 0.52 (Table 1).

(63)

TABLE 2 : TYPE OF SURGERY.

Surgery

Group A Group B TOTAL Number % Number % Number %

Cystoscopy 1 2.5 - - 1 1.3

Flap cover 1 2.5 - - 1 1.3

Meatoplasty - - 1 2.5 1 1.3

Teflon dilation 1 2.5 - - 1 1.3

TURBT - - 3 7.5 3 3.8

TURP 13 32.5 11 27.5 24 30

Urethroplasty 1 2.5 - - 1 1.3

URSL 19 47.5 25 62.5 44 55

Vesicolithotripsy 4 10 - - 4 5

Total 40 100 40 100 80 100

(64)

TABLE 3: COMPARISON OF TIME OF ONSET OF SENSORY BLOCKADE BETWEEN THE TWO GROUPS.

Group Range(min) Mean(min) S.D p value

A 3 – 6 4.25 ±.59

0.000 Significant

B 1 - 2 1.13 ±.34

The mean time of onset of sensory block was rapid in Group B (1.13 min) than in Group A (4.25 min) and the difference was significant with a p value of 0.000 (Table 3 , Fig. 1) .

(65)

FIG 1. COMPARISON OF TIME OF ONSET OF SENSORY BLOCKADE BETWEEN THE TWO GROUPS.

Onset of action

ISOBARIC 4.25

HYPERBARIC 1.13

0.00 1.00 2.00 3.00 4.00 5.00

Mean value in Minutes

TIME OF ONSET OF SENSORY BLOCK

(66)

TABLE 4: COMPARISON OF TIME OF ONSET OF MOTOR BLOCKADE BETWEEN THE TWO GROUPS

Group Range(min) Mean(min) S.D p value

A 5– 6 5.25 ±.44

0.000 Significant

B 1 - 2 1.25 ±.44

In our study, the time of onset of motor block was rapid in Group B (1.25min) than in Group A (5.25 min) and the difference was significant with a p value of 0.000 (Table 4, Fig. 2).

(67)

FIG 2. COMPARISON OF TIME OF ONSET OF MOTOR BLOCKADE BETWEEN THE TWO GROUPS

TIME OF ONSET

ISOBARIC 5.25

HYPERBARIC 1.25

0.00 1.00 2.00 3.00 4.00 5.00 6.00

Mean Value in Miutes

TIME OF ONSET OF MOTOR BLOCKADE

(68)

TABLE 5: COMPARISON OF MAXIMUM BLOCK HEIGHT ACHIEVED BETWEEN THE TWO GROUPS.

Maximum sensory block height after 20

minutes

Group A Group B

Number % Number %

T 4 - - 6 15

T 6 1 2.5 34 85

T 8 7 17.5 - -

T 10 32 80 - -

Total 40 100 40 100

p value 0.000

Significant

The maximum sensory block height achieved after 20 minutes was higher in Group B when compared to Group A and the difference was highly significant with a p value of 0.000 (Table 5).

References

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