COMPARISON OF FENTANYL AND BUPRENORPHINE AS AN ADJUVANT TO ROPIVACAINE IN SINGLE SHOT EPIDURAL
ANAESTHESIA FOR HERNIA SURGERIES
Dissertation submitted to
THE TAMIL NADU DR. M.G.R. MEDICAL UNIVERSITY In partial fulfilment for the award of the degree of
DOCTOR OF MEDICINE IN
ANAESTHESIOLOGY BRANCH X
ESIC MEDICAL COLLEGE & PGIMSR , K.K. NAGAR CHENNAI
MAY 2020
UNIVERSITY REGISTRATION NO: 201720502
ENDORSEMENT BY THE DEAN/
THE HEAD OF THE INSTITUTION
This is to certify that the dissertation titled, “COMPARISON OF FENTANYL AND BUPRENORPHINE AS AN ADJUVANT TO ROPIVACAINE IN SINGLE SHOT EPIDURAL ANAESTHESIA FOR HERNIA SURGERIES” is submitted by DR. JOHN PETER. D 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 work done by him in ESIC MEDICAL COLLEGE & PGIMSR , K.K. NAGAR, CHENNAI, during the academic year 2017 -2020.
DR.SOWMYASAMPATH, M.D., DNB (Paed)., DEAN,
ESIC MEDICAL COLLEGE &PGIMSR, KK NAGAR, CHENNAI – 78.
CERTIFICATE BY THE HEAD OF DEPARTMENT
This is to certify that the dissertation titled, “COMPARISON OF FENTANYL AND BUPRENORPHINE AS AN ADJUVANT TO ROPIVACAINE IN SINGLE SHOT EPIDURAL ANAESTHESIA FOR HERNIA SURGERIES” submitted by DR. JOHN PETER. D 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 research work done by him in ESIC MEDICAL COLLEGE & PGIMSR, K.K. NAGAR, CHENNAI, during the academic year 2017 -2020.
DR.SHIRISHKUMAR CHAVAN, M.D.
PROFESSOR& HEAD OF DEPARTMENT, DEPT. OF ANAESTHESIOLOGY,
ESIC MEDICAL COLLEGE &PGIMSR, KK NAGAR, CHENNAI – 78.
BONAFIDE CERTIFICATE
This is to certify that the dissertation titled, “COMPARISON OF FENTANYL AND BUPRENORPHINE AS AN ADJUVANT TO ROPIVACAINE IN SINGLE SHOT EPIDURAL ANAESTHESIA FOR HERNIA SURGERIES” is a bonafide research work done by Dr. JOHN PETER. D, in partial fulfilment for the award of the degree of Doctor of Medicine in Anaesthesiology by the Tamil Nadu Dr. M.G.R. Medical University, Chennai, done by him in ESIC MEDICAL COLLEGE &
PGIMSR, K.K. NAGAR, CHENNAI, during the academic year 2017 -2020 under my guidance and supervision.
GUIDE
DR.SHIRISHKUMAR CHAVAN, M.D.
PROFESSOR& HEAD OF DEPARTMENT, DEPT. OF ANAESTHESIOLOGY,
ESIC MEDICAL COLLEGE &PGIMSR, KK NAGAR, CHENNAI - 78.
CO-GUIDE
DR. UMA, M.D.,
ASSOCIATE PROFESSOR, DEPT. OF ANAESTHESIOLOGY, ESIC MEDICAL COLLEGE &PGIMSR, KK NAGAR, CHENNAI - 78.
Place:
Date:
DECLARATION
I hereby declare that the dissertation titled, “COMPARISON OF FENTANYL AND BUPRENORPHINE AS AN ADJUVANT TO ROPIVACAINE IN SINGLE SHOT EPIDURAL ANAESTHESIA FOR HERNIA SURGERIES” was done by me in ESIC MEDICAL COLLEGE
&PGIMSR , K.K. NAGAR, CHENNAI, during the period 2017 – 2020 under the guidance of DR.SHIRISHKUMAR CHAVAN, M.D., Professor, Department Of Anaesthesiology, ESIC Medical College & PGIMSR, K.K.
Nagar, Chennai – 78 and submitted to The Tamil Nadu Dr. M.G.R. Medical University, Guindy, Chennai – 32, in partial fulfilment of the requirements for the award of the degree of M.D. Anaesthesiology (Branch X), examinations to be held on May 2020. I have not submitted this dissertation previously to any journal or any university for the award of any degree or diploma.
Date:
Place: Chennai Dr. JOHN PETER. D
UNIVERSITY REGISTRATION NO: 201720502
ACKNOWLEDGEMENT
I am extremely thankful to DR. SOWMYA SAMPATH, M.D., Dean, ESIC Medical College & PGIMSR, K.K. Nagar, Chennai, for her permission to carry out this study.
I am immensely thankful and grateful to my Professor and guide DR.SHIRISHKUMAR CHAVAN, M.D., Head of Department, Dept. Of Anaesthesiology, ESIC Medical College &PGIMSR, K.K. Nagar, Chennai, for his concern, guidance and support in conducting this study.
I am extremely grateful and indebted to my Coguide DR.UMA.R, M.D., Associate Professor, Dept. Of Anaesthesiology, ESIC Medical College
&PGIMSR, K.K. Nagar, Chennai, for her concern, inspiration, meticulous guidance, expert advice and constant encouragement while doing this study.
I am very grateful to express my sincere gratitude to my Associate Professors DR. ILANGO GANESAN, M.D., DR. RADHIKA,M.D,Dept. Of Anaesthesiology, ESIC Medical College & PGIMSR, K.K. Nagar, Chennai, for their constant motivation and valuable suggestions.
I am extremely thankful to all my Assistant Professors and Senior Residentsfor their guidance and expert advice in carrying out this study.
My sincere thanks to the statistician DR. ARUNA PATIL, M.Sc.,PhD., who has been involved in designing the study, and who has helped with the data analysis and interpretation of results.
I would also like to thank, DR. SHANMUGASUNDARAM, HOD of The Department of General Surgery who had permitted to do the study on his patients.
I am thankful to institutional ethical committee for the approval and guidance for this study.
I am thankful to all my colleagues and junior post graduates for their help and advice in carrying out this study.
I am thankful to the theatre staff, anaesthesia technicians, and theatre assistants for their help during the study.
I am grateful to my family members and friends for their moral support and encouragement.
Last but not the least; I thank all the patients for willingly submitting themselves for this study.
CERTIFICATE OF APPROVAL
PLAGIARISM CERTIFICATE
This is to certify that this dissertation work titled “COMPARISON OF FENTANYL AND BUPRENORPHINE AS AN ADJUVANT TO ROPIVACAINE IN SINGLE SHOT EPIDURAL ANAESTHESIA FOR HERNIA SURGERIES” of the candidate DR. JOHN PETER. D with University registration Number 201720502 for the award of Doctor of Medicine in the branch of Anaesthesiology. I personally verified the urkund.com website for the purpose of plagiarism Check. I found that the uploaded thesis file contains from introduction to conclusion pages and result shows twenty two percentage of plagiarism in the dissertation.
Guide & Supervisor sign with Seal.
DR.SHIRISHKUMAR CHAVAN, M.D.
PROFESSOR& HEAD OF DEPARTMENT, DEPT. OF ANAESTHESIOLOGY,
ESIC MEDICAL COLLEGE & PGIMSR, KK NAGAR, CHENNAI - 78.
PLAGIARISM REPORT
LIST OF ABBREVIATIONS
ASA - American Society of Anaesthesiologists DBP - Diastolic Blood Pressure
ECG - Electrocardiogram
HR - Heart rate
Hrs - Hours
IV - Intravenous
Kg - Kilograms
MAP - Mean Arterial Pressure mcg(µg) - microgram
ml - millilitre
mg - Milligrams
min - Minutes
mmHg - Millimeter of Mercury SBP - Systolic Blood pressure
% - Percentage
CONTENTS
Sl.
No TITLE PAGE
NO
1 INTRODUCTION 1
2 AIM & OBJECTIVES 2
3 APPLIED ANATOMY 3
4 PHYSIOLOGICAL EFFECTS OF EPIDURAL BLOCKADE
16
5 PHARMACOLOGY OF ROPIVACAINE 23
6 PHARMACOLOGY OF FENTANYL 27
7 PHARMACOLOGY OF BUPRENORPHINE 32
8 REVIEW OF LITERATURE 37
9 METHODOLOGY 52
10 OBSERVATION AND RESULTS 58
11 DISCUSSION 91
12 SUMMARY 95
13 CONCLUSION 98
14 BIBLIOGRAPHY 99
15 ANNEXURES 106
LIST OF FIGURES
S.NO PAGE
NO 1 Vertebral column, in lateral view (left) and posterior
view (right), illustrating curvatures, lumbar interlaminar spaces and sacral hiatus
4
2 Components of a lumbar vertebra 5
3 Boundaries of the epidural space 8
4 Epidural injection 9
5 Structural formula of Ropivacaine 23
6 Structural formula of Fentanyl 27
7 Structural formula of Buprenorphine 32
8 Mean age comparison between two groups 59
9 ASA Physical status classification 60
10 Comparison of Maximal motor block attained between two groups
61
11 Comparison of Maximal sensory block attained between two groups
62
12 Comparison of Mean time to onset of sensory block at T10 between two groups
63
13 Comparison of Mean time to onset of maximal sensory block between two groups
65
14 Comparison of Mean time to onset of Motor Block (Bromage I) between two groups
67
15 Comparison of Mean time to onset of Maximal Motor Block between two groups
69
S.NO PAGE NO 16 Comparison of Mean Duration Of Analgesia between
two groups
71
17 Comparison of Mean Duration Of Motor Blockade (Bromage I) between two groups
72
18 Heart rate comparison between two groups-Mean plot 77 19 Systolic blood pressure comparison between two groups-
Mean plot
81
20 Diastolic blood pressure comparison between two groups-Mean plot
85
21 Mean arterial pressure comparison between two groups- Mean plot
89
LIST OF TABLES
S.
NO
PAGE NO
1 Dosage of fentanyl 30
2 Age Group Statistics (a) Age Group Statistics (b)
58 59 3 Frequency Distribution for ASA physical status 60 4 Frequency Distribution for maximal motor block attained 61 5 Frequency Distribution for maximal sensory block
attained
62
6 Time to onset of sensory block at T10 –statistics (a) Time to onset of sensory block at T10 –statistics (b)
63
7 Time to onset of maximal sensory block –statistics (a) Time to onset of maximal sensory block –statistics (b)
65
8 Time to onset of Motor Block(Bromage I)–statistics (a) Time to onset of Motor Block(Bromage I)–statistics (b)
67
9 Time to onset of Maximal Motor Block -statistics (a) Time to onset of Maximal Motor Block -statistics (b)
69
10 Duration Of Analgesia -statistics (a) Duration Of Analgesia -statistics (b)
71
11 Duration Of Motor Blockade (Bromage I)-statistics (a) Duration Of Motor Blockade (Bromage I)-statistics (b)
72
12 Comparison of Heart rate (beats per minute) between two groups.(a)
Comparison of Heart rate (beats per minute) between two groups.(b)
74 76
S.
NO
PAGE NO 13 Comparison of Systolic blood pressure between two
groups (a)
Comparison of Systolic blood pressure between two groups (b)
78 80
14 Comparison of Diastolic blood pressure between two groups (a)
Comparison of Diastolic blood pressure between two groups (b)
82 84
15 Comparison of Mean arterial pressure between two groups (a)
Comparison of Mean arterial pressure between two groups (b)
86 88
16 Side effects seen in both groups 90
INTRODUCTION
For lower abdominal and lower limb surgeries, Regional anaesthesia is preferred over General anaesthesia. Regional anaesthesia gives intense pain relief, reduction of sympathetic response, abolishes airway trauma,avoids polypharmacy, early ambulation and so on, compared to general anaesthesia.
Intrathecal anaesthesia and epidural anaesthesia are the two most popular regionalanaesthesia techniques used for lower abdominal and lower limb surgeries. Though Intrathecal anaesthesia also called as subarachnoid block provides complete block, complications like hemodynamic swings due to intense sympathetic blockade and postdural puncture headache (PDPH), whereas in epidural anaesthesia these complications are relatively less.Hence epidural anaesthesia is the most preferred anaesthetic technique for lower abdominal and lower limb surgeries these days.
Different local anaesthetics are used for epidural anaesthesia, most popular inIndia being Lidocaine and Bupivacaine. The drawback of lidocaine is its intermediate duration of action and the drawback of bupivacaine though long acting, is increased incidence of fatal cardiac and neuro toxicity because of narrow cardiovascular/central nervous system toxicity (cc/cns) Ropivacaine and levobupivacaine are the newer long acting amide local anaesthetics which have a wide margin of safety compared to bupivacaine, with all its advantages.
Hence a study was undertaken to compare 0.75% ropivacaine with fentanyl and 0.75% ropivacaine with buprenorphine in singleshot epidural anaesthesia for hernia surgeries.To increase the duration of analgesia fentanyl and buprenorphine were added as additives in this study.
AIM
To study the synergistic effect of adding fentanyl to ropivacaine 0.75%
and buprenorphine to 0.75% ropivacaine in epidural anaesthesia for hernia surgeries, with
OBJECTIVES
Primary
1. Onset and duration of sensory blockade 2. Onset and duration of motor blockade
Secondary
1. Haemodynamic changes
2. Maximum dermatomal level of analgesia 3. Intensity of motor blockade
4. Adverse effects
APPLIED ANATOMY
Epidural blockade is unique in that, it can be placed at virtually any levelof the spine, allowing more flexibility in its application to clinical practice.
Anatomy
The key to safe and effective administration of an epidural blockade beginswith a thorough understanding of the anatomy of the vertebral column, ligaments andblood supply, the epidural space, spinal canal and associated structures.The vertebral column consists of 7 cervical, 12 thoracic and 5 lumbarvertebrae. At the caudal end, the 5 sacral vertebrae are fused to form the sacrum, andthe 4 coccygeal vertebrae are fused to form the coccyx.
The normal spinal column is straight when viewed dorsally or ventrally.
Whenviewed from the side, there are two ventrally convex curvatures in the cervical andlumbar regions, giving the spinal column the appearance of double C.
Figure 1: Vertebral column, in lateral view (left) and posterior view (right),illustrating curvatures, lumbar interlaminar
spaces and sacral hiatus Structure of the vertebrae
Each vertebra is composed of a vertebral body and a bony arch.
Body:It is the mass of the bone through which the weight of the subject is transmitted.
Figure 2: Components of a lumbar vertebra
Vertebral arch
surrounds and protects the spinal cord lying in the vertebral foramen.The arch comprises of pedicles, lamina and spinous process.Pedicles are notched. The notches of the adjacent vertebrae pair together toform an intervertebral foramen through which the spinal nerves emerge on each side.Lamina carries a transverse process, superior and inferior articular processes whichbear the articular facets on each side.Spinous process project backwards from the centre of the neural arch andforms an important palpable land mark for the anaesthesiologist.
Spinous process of the cervical vertebrae
The spinous process of the cervical vertebrae is short and bifid [with exceptionof C1 and C7] and is directed almost horizontally to the body of the vertebra.
Spinous process of the thoracic vertebra
The spinous process of the thoracic vertebra is long and is inclined at an angleof 45 to 60 degree to the body of the vertebra and the skin. So the needle should bedirected at an angle of 45-60 degree cranially, to follow the upper border of the spine to enter the ligamentum flavum.
Spinous process of lumbar vertebra
The spinous process of the lumbar vertebra is directed horizontally backwardsvirtually 90oto the body of the vertebra and the skin. So the needle is to be directedperpendicular to the skin.
Intervertebral disc
These are the connecting links between the vertebral bodies and they account25% of the length of spine.
Joints of the vertebral column
The vertebrae articulate at the intervertebral and facet joints.
Theintervertebral joints are located between adjacent vertebral bodies. They maintain thestrength of attachment between vertebrae. The facet joints are formed betweenthearticular processes.
Ligaments
The vertebral column is bound together by severalligaments such as supraspinous, interspinous, ligamentum flavumand longitudinal ligaments, which give it stability and elasticity.
Ligamentum flavum comprises of yellow elastic fibers and connects adjacent laminae that runfrom the caudal edge of vertebra above to the cephalad edge of the lamina below.Because of its elasticity and its thickness of several millimeters inthe lumbar region, the ligaments impart a characteristic
‘springy’ resistance,particularly to large bore needle with an upturned end [Tuohy needle]
Figure 3: Boundaries of the epidural space
It is the space that lies between the duramater and ligamentum flavum. It extends from the foramen magnum where the dura is fused to thebase of the skull, to the sacral hiatus, which is covered by sacrococcygeal ligament. Itis bounded anteriorly by the posterior longitudinal ligament, laterally the pedicles andthe intervertebral foramina and posteriorly by the ligamentum flavum and anteriorsurface of lamina. The anterior epidural space is very narrow because of the proximityof the dura and the anterior surface of the vertebral canal. It is a space filled with fat, areolar tissue, lymphatics, veins and nerve rootsthat traverse it but no free fluid. Thus it is a potential space.The epidural space is richin blood vessels, including Batsons venous plexus. Batsons plexus is
continuous withthe iliac vessels in the pelvis and the azygous system in the abdominal and thoracicbody walls. Because this plexus has no valves, blood from any of the connectedsystem can flow into the epidural vessels and connect with intracranial veins. This is apotential direct route to brain for drugs, air or other material inadvertently injectedinto an epidural vein. Within the cranium, there is no epidural space as the meningeal dura and the endosteal dura are closely adherent, except where they separate to formthe venous sinuses.
Distension of epidural veins, owing to direct inferior vena cava obstruction [eg.by the gravid uterus] or owing to increased thoracic and abdominal pressure, will alsodiminish the effective volume of the epidural space, with the result that injected localanaesthetic spread more widely up and down the epidural space.
Figure:4 Epidural injection.
Spinal arteries
It is of significance to epidural block that the spinal branches of thesubclavian, aortic and iliac arteries cross the epidural space and enters the epiduralspace in the region of the dural cuffs. The anterior spinal artery territory supplying theanterior horn or motor area of the spinal cord is most vulnerable.
Duralsac
Containing dura, arachnoid, spinal fluid, pia, spinal nerves and spinal cord iscontained with in the annular epidural space.
Dura
Duramater is the outermost meningeal tissue. The spinal duramater begins at the foramen magnum where it fuses with the periosteum of the skull.Caudally dura mater ends at approximately S2, fusing with the filum terminale. The duramater extendslaterally along the spinal nerve roots and becomes, into the intervertebral foramina. The inner edge of the duramater is highly vascularwhich likely results in the duramater being an important route of drug clearance fromboth the epidural space and the sub arachnoid space.The inner surface of the dura mater abuts the arachnoid mater. There is apotential space between these two membranes called subdural space. Occasionally itis possible to inadvertently insert an epidural catheter into the subdural space.
Arachnoid mater
The arachnoid mater is a delicate, avascular membrane. The arachnoidmater herniates through the dura mater into the epidural space to form arachnoidgranulations whichserve as sites for material in the subarachnoid space toexit the central nervous system.
Epidural pressure
In the lumbar region, the major cause of generation of a negative pressure liesin coning of the dura by the advancing needle point. Negative pressure increases asthe needle advances across the epidural space towards the dura..Greatest negative pressure can be obtained if the dura is not distended [eg. By gravityin sitting position or by high abdominal or thoracic pressure]. In pregnancy, theepidural space may well have a positive pressure. Hence hanging drop technique maynot be reliable in pregnant women to identify the epidural space.
Detection of epidural space
The methods for identification of the epidural space take the advantage ofeither the potential negative pressure or the sudden loss of resistance when the needletip penetrates the tough ligamentum flavum.
Negative pressure techniques
1. Hanging drop technique of Gutierrez
2. Odom capillary tube method 3. Manometer method
Loss of resistance technique [described by Sicard, Forester and Dogliotti]
1. Syringe technique [using either normal saline or air]
2. Spring loaded syringe
3. Macintosh balloon technique 4. Brookes device
5. Vertical tube of dawkins
Factors affecting epidural blockade
Many factors affect the efficacy, spread of blockade, fiber types blocked andother aspects of epidural blockade.
Site of injection and nerve root size
Blockade tends to be most intense and has the most rapid onset close to thesite of injection. After lumbar epidural injection, there is a somewhat greater cranialthan caudal spread and there may be a delay in the L5 and S1 segments.
The delay inonset at these segments appears to be due to the large size of these nerve roots.
Age
In youngindividual, the areolar tissue around the intervertebral foramina is soft and loose. Inelderly areolar tissue becomes dense and firm, partially sealing the intervertebralforamina. With aging, the dura becomes more permeable to local anaesthetics becauseof significant increase in the size of the arachnoid villi.The techniqueis technically difficult and hence there is always a chance of failure in elderly.
Height and weight
The correlation between patient height or weight and spread of epidural blockis weak and of little clinical significance.
Position
Comparison of sitting and lateral positions for epidural block reveals nosignificant difference in cephalad spread. Caudal spread of block in seated patients isslightly favoured by the sitting position.
Speed of injection
Increasing the speed of injection has no effect on spread of analgesia is only minimally influenced. However,rapid injection of large volumes of solution may increase CSF pressure, decreasespinal cord blood flow, increase intracranial pressure and pose a risk of spinal orcerebral complications. Local
anaesthetics should be injected into the epidural spaceslowly and preferably in incremental doses.
Volume, concentration and doses of local anaesthetics
Within the range typically used for surgical anaesthesia, drug concentration isrelatively unimportant in determining block spread. However, drug dose and volumeare important variables determining both spread and quality of epidural block.Increasing the volume of local anaesthetics will result in significantly greater averagespread and greater block density, with regard to motor blockade, dosage becomes lessimportant when dilute solutions are used.
Increasing the dosages results in a linearincrease in degree of sensory block and duration of epidural block, where asincreasing concentration results in a reduction in onset time and intensity of motorblockade.
Local anaesthetics
Choice of local anaesthetics is the most important determinant of the durationof epidural block. Chloroprocaine is the shortest duration drug, Lidocaine andMepivacaine provides intermediate duration, and Bupivacaine, Ropivacaine andEtidocaine provide the longest lasting epidural block. The differential capabilities oflocal anaesthetics to block sensory and motor fibers have been referred to as ‘sensorymotor dissociation’.
Epinephrine
Epinephrine in a concentration of 5μg/ml [1:200000] is the most commonadrenergic agonist added to epidural local anaesthetics. It has been shown to prolongthe duration of lidocaine and mepivacaine epidural block by as much as 80%.Vasoconstrictors have been assumed to prolong block by producing localvasoconstriction and thus decreased local anesthetic clearance from the epiduralspace. Epinephrine does notsignificantly prolong the duration of anaesthesia when added to concentrated solutionsof bupivacaine or ropivacaine.
Number and frequency of local anaesthetics injections
Whether augmentation or diminution of neural blockade occurs after repeatedepidural injection of local anaesthetics depends on the local anaesthetic agent, thenumber of injection and timing between injections.Tachyphylaxis has been most clearly demonstrated in association withcontinuous epidural block in patients in whom repeated injections of the short actingamides – lidocaine, prilocaine or mepivacaine are used. The mechanism oftachyphylaxis is not known. It may be partly explained by pH changes in spinal fluidwith repeated injections.
PHYSIOLOGICAL EFFECTS OF EPIDURAL BLOCKADE
With currently available local anaesthetic agents, spinal epidural neuralblockade implies sympathetic blockade accompanied by somatic blockade, whichmay involve sensory and motor blockade alone or in combination. Some of the mostimportant (but not all) of physiological effects of epidural blockade can be discussedin relation to either sympathetic blockade only of vasoconstrictor fibers (below T4)and or of cardiac sympathetic fibers.
Zone of differential blockade
Sensory
In intradural block sympathetic fibers are blockade two or three segmentshigher than sensory fibers. In extradural block, the relationship is complex. Level ofsympathetic block is the same as (or lower than) sensory with epidural blockade.Sympathetic block will be greater when more concentrated solutions are used or whenadrenaline added, as this has similar effect.
Motor
In intradural block, the difference between sensory and motor block is slight(two segments). In extradural block, the difference in levels is greater, depending verymuch on nature of local analgesic solution.All types of nerve
fibers are affected by local anaesthetics, but with in any onefiber type, there is tendency for small, slower conducting fibers to be more readilyblocked than large, fast conducting fibers. Between fiber types however, these rulesdo not hold good. Myelinated preganglionic B fibers which have a faster conductiontime are about three times more sensitive to local anaesthetics than the slower nonmyelinatedpost ganglionic C fibers.Sensory Aαfibers appear to be more sensitive to blockade than motor Aαfibers, although of the same conduction velocity. This may be because sensory fibersconduct at a higher frequency. It has been suggested that this selectivity for sensoryfibers exhibited by Bupivacaine and Ropivacaine is a function of frequency dependentblock, a property not shared by Etidocaine and Amethocaine.
Cardiovascular System
There are different ways in which intra and extradural spinal block can influence the cardiovascular system.
1. Vasodilatation of resistance and capacitance vessels. Block of cardiac efferentsympathetic fibers from T1 and T4 resulting in loss of chronotropic and Inotropicdrive and fall in cardiac output.
2. The arterial or Bainbridge reflex causing-bradycardia.
3. The operation of Marey’s law causing tachycardia.
4. Depression of vascular smooth muscle and â adrenergic blockade of myocardiumwith fall in cardiac output.
5. Adrenaline effect (if used) following absorption, resulting in â stimulation andassociated rise in cardiac output and reduction in peripheral resistance.The overall effect is likely to be greater fall in mean arterial pressure than ifadrenaline had not been used. Block not extending above T4 is not always associatedwith fall of blood pressure in fit young adults although the elderly many suffersignificant hypotension when moderate volumes are injected into the epidural space.Corrective measures may be considered if arterial pressure falls more than 1/3 belowits pre-operative level.Slowing of heart rate is caused if any of the anterior roots carryingsympathetic cardiac accelerator fibers are blocked, as may happen in higher spinalblockade above T4, T5. A further cause of slow pulse rate is the lowering of blood pressure in the right atrium consequent on diminished venous return [Bainbridge(1874-1921) effect]. On the other hand, Tachycardia during spinal analgesia mayresult from the operation of Marey’s Law (a pulse of low tension is fast). Bradycardiais the more frequent effect.
Theories of causation of fall in blood pressure
1. Diminished cardiac output consequent on reduction of venous return to heart, andlack of muscular propulsive force on veins.
2. Dilatation of post arteriolar capillaries and small venules due to paralysis ofvasoconstrictors, compensatory vasoconstriction takes place in areas notanaesthetized via carotid sinus reflexes. In high spinal blocks, majority ofvasoconstrictor fibers including those to arm [T2- T10], are paralyzed, hence lowblood pressure. Total peripheral resistance decreases by only 18% followingcomplete sympathetic block in healthy young adults.
3. Paralysis of sympathetic nerve supply to heart T1-T4. Bradycardia may give riseto fall in cardiac output.
4. Paralysis of sympathetic nerve supply to adrenal glands splanchnic nerves, withconsequent catecholamine depletion
5. Absorption of drug into circulation. This is more likely to be a cause ofhypotension after extradural than after intradural analgesia because of the largeamount of analgesic drug injected.
6. Ischemia and hypoxia of vital centers
7. Hypovolemia, if present, may give rise to fall in blood pressure if central neuralblockade is employed.
8. Compression of great vessels within abdomen, by the pregnant uterus, abdominaltumours or abdominal packs may cause severe hypotension in presence of centralneural blockade.
Respiratory system
Apnoea may be due to medullary ischemia or to a toxic effect of the drug inextradural blocks. The effect of block is largely on cardiovascular system. Vital capacity andforce expiratory volume may be reduced, especially in cigarette smokers. Intercostal muscle paralysis is compensated for by descent of diaphragm, which is made easierthe by the lax abdominal walls.
This not accompanied by hypoxia and hypercapniaalthough the ability to cough forcibly to expel secretion is impaired.The patient may stop breathing so that respiratory support by IPPV and, ifnecessary the tracheal intubation required.
Causes may be:
Inadequate medullary blood flow due to inadequate cardiac output-a serioussituation demanding immediate cardiorespiratory support.
Total spinal analgesia with denervation of all respiratory muscles. True phrenic nerve paralysis is uncommon because all motor roots are large and analgesic solution is likely to be weak when it reaches the cervical region.
Massive epidural spread.
Accidental subdural injection
Toxic effects of local anaesthetic drug.
Injecting narcotic analgesic drugs
Gastrointestinal system
The small gut iscontracted as the sympathetic inhibitory impulses are removed, the vagus being all powerful. Sphincters are relaxed and peristalsis is active although not more frequent.Nausea and vomiting due to the hypotension may occur. Infiltration of local anesthetic solutions may prevent this by blocking vagal afferents.Colonic blood supply and oxygen availability are increased, perhaps an importantfactor in the prevention of anastomotic breakdown following gut resection.
Liver
There are no specific effects of significance.
Endocrine system
The usual increase of ADH during surgery is suppressed. In any case, either regional or general, there is no difference in thepostoperative period once the effects of the block are discontinued. Spinal blocksuppresses the hyperglycemic response to surgery and stress and so is useful indiabetic patients but this does not extend into postoperative period.
Genitor urinary system
Sympathetic supply of kidney is from T11 to L1 via the lowest splanchnicnerves. Any effects on renal function are due to hypotension. Auto regulation of renal blood flow is impaired if mean arterial pressure falls below 50 mmHg. These changes are transient and disappear when blood pressure rises again. Sphincters of bladder are not relaxed, so soiling of table by urine is not seen and tone of ureters is not greatly altered. The penis is often engorged and flaccid due to paralysis of the Nervi erigentes [S2 and S3]. This is a useful positive sign of successful block. Post spinal retention of urine may be moderately prolonged as L2 and L3 contain small autonomic fibers and their paralysis lasts longer than of the larger sensory and motor fibers.
Body temperature
Vasodilatation favors heat loss. Absence of sweating favors hyperpyrexia inhot environments. Catecholamine secretion is depressed, hence less heat is produced by metabolism.
PHARMACOLOGY OF ROPIVACAINE
Ropivacaine is a long acting local anaesthetic that is structurally related tobupivacaine, unlike bupivacaine which is racemic mixture. Ropivacaine is a pure S (-)enantiomer developed for the purpose of reducing the potential toxicity andimproving the relative sensory and motor block profiles.
Chemical structure
It is a monohydrate of hydrochloride salt of 1-propyl-2’, 6’- pipecoloxylidide.Ropivacaine is a long acting amide local anaesthetic agent belonging to thepipecoloxylidine group.
Physiochemical properties
Molecular weight – 328.89 274 (base)
Pka – 8.1
Plasma protein binding – 94%
Lipid solubility – 2.9
Structural formula
Figure: 5 Structural formula of Ropivacaine
Mechanism of action
Like other local anaesthetics, ropivacaine elicits nerve block via reversibleinhibition of sodium ion influx in nerve fibers. This action is potentiated by dosedependent inhibition of potassium channels. Ropivacaine is less lipophilic thanbupivacaine and is less likely to penetrate large myelinated motor fibers, therefore ithas selective action on the pain transmitting Adelta and C nerves rather than Aâ fibers,which are involved in motor function.
Pharmacodynamics
CNS and cardiovascular effects
Ropivacaine is less lipophilic than bupivacaine and that, together with itsstereo selective properties, contributes to ropivacaine having a significantly higherthreshold for cardiovascular and CNS toxicity than bupivacaine in animals andhealthy volunteers. The CNS effects occurred earlier than cardiotoxic symptoms during anintravenous infusion of local anaesthetic (10 mg of Ropivacaine and bupivacaine) inhuman volunteers and the infusion was stopped at this point. Significant changes incardiac function involving the contractility, conduction time and QRS width wasfound to be significantly smaller with Ropivacaine than with bupivacaine.
Other effects
Ropivacaine has been shown to inhibit platelet aggregation at concentrationsof 3.75 and 1.88 mg/ml,
Pharmacokinetic properties
Absorption and distribution
When Ropivacaine is administered intravenously, its pharmacokinetics werelinear and dose proportional upto 80 mg. Ropivacaine from epidural space showscomplete and biphasic absorption. The half life of the initial phase is approximately14 min followed by a slower phase with a mean absorption t1/2 of approximately 4.2hrs.Ropivacaine is bound to plasma proteins to an extent of 94%, mainly to α1–acid glycoprotein. Ropivacainereadily crosses the placenta during epidural administration for cesarean section.After intravascular administration, volume of distribution of Ropivacaine atsteady state was 41L.
The administration of epinephrine with Ropivacaine mayimprove analgesia by reducing vascular uptake of local anaesthetics and by a directagonist effect on spinal α2 receptors.
Metabolism and elimination
Ropivacaine is metabolized extensively in the liver, predominantly byaromatic hydroxylation to 3’-hydroxy Ropivacaine by cytochrome P450
(CYP)1A2and N-dealkylation to 2’6’-pipecoloxylidide by CYP3A4. The kidney is the mainexcretory organ for Ropivacaine, accounting for 86% of the excretion of the drug inthe urine after a single intravenous dose administration.
It has a mean ± SD terminalhalf life of 1.8 ± 0.7 hrs and 4.2 ± 1.0 hrs after intravenous and epiduraladministration respectively.
Relative potency
Ropivacaineis less potent than bupivacaine at lower doses such as those used for epidural orIntrathecal analgesia.
Drug interaction
Cytochrome P4501A2 metabolizes ropivacaine to 3-hydroxy Ropivacaine, themajor metabolite. Thus strong inhibitors of cytochrome P4501A2, such asfluvoxamine given concomitantly during administration of ropivacaine can interactwith ropivacaine and thus lead to increased Ropivacaine plasma levels. Possibleinteractions with drugs known to be metabolized by CYP1A2 via competitiveinhibition such as theophylline and imipramine may also occur.
PHARMACOLOGY OF FENTANYL
Fentanyl citrate is synthetic opioid agonist. It is 75 to 125 times more potent than morphine as an analgesic. It is phenylpiperidine derivative.Fentanyl is a µ-opioid receptor agonist, produces dose-dependent analgesia, ventilatory depression, and sedation, and at very high doses it can produce unconsciousness.
Structural formula
Figure: 6 Structural formula of Fentanyl
PHYSIOCHEMICAL PROFILE
Molecular weight - 528.29
pKa - 8.4
% unionized at pH 7.4 - 8.5%
% bound to plasma proteins - 84%
Potency - 100 > than morphine
MECHANISM OF ACTION
Opioids act as agonists at specific opioid receptors at presynaptic and postsynaptic sites in the central nervous system (mainly the brainstem and spinal cord) as well as in the periphery. These opioid receptors normally are activated by three endogenous peptide opioid receptor ligands known as enkephalins, endorphins, and dynorphins.
1. The principal effect of opioid receptor activation is a decrease in neurotransmission that occurs largely by presynaptic inhibition of neurotransmitter release (acetylcholine, norepinephrine, substance P ,dopamine ).
2. The intracellular biochemical events initiated by opioid receptors with an opioid agonist are characterized by increased potassium conductance, calcium channel inactivation, or both, which produce an immediate decrease in neurotransmitter release.
PHARMACOKINETIC PROFILE
It is highly lipid soluble drug and rapid onset of action and short duration of action. Its short duration of action reflects rapid redistribution to inactive tissues such as fat and skeletal muscles.
Volume of distribution at steady state - 335 litres
Clearance - 1530 ml / minutes
Effect site equilibration time - 6.8 minutes
Hepatic extraction ratio - 0.8 – 0.1
Context sensitive half time - 260 minutes
Elimination half time - 3.1 – 6.6 hours
First pass pulmonary uptake - 75%
METABOLISM
Fentanyl is extensively metabolized by N-demethylation and the pharmacologic activity of fentanyl metabolites is believed to be minimal.
ELIMINATION HALF LIFE
Despite fentanyl has a short duration of action, its elimination half-time is longer than that for morphine . This longer elimination half-time reflects a larger volume of distribution (Vd) of fentanyl due to its greater lipid solubility and thus more rapid passage into highly vascular tissues compared with the less lipid-soluble morphine more than 80% of injected dose leaves the plasma in 5 min.
EFFECTS
High doses of fentanyl s blunt the “stress response”—hemodynamic and hormonal responses to the surgical stimuli—producing only minimal cardiovascular depression. Opioids does not produce muscle relaxation, at high-dose fentanyl may produce muscle rigidity, muscle relaxant is required to achieve adequate surgical conditions. This may increase the difficulty in finding signs of intra -operative awareness.
Clinical Uses
Analgesia (1–2 mcg/kg IV) Adjuvant to inhaled anesthetics to blunt the response to direct laryngoscopy (2–20 mcg/kg IV). Decrease doses of inhaled anesthetics to blunt sympathetic nervous system responses to surgical stimulation (1.5–3 mcg/kg IV, 5 min before induction of anesthesia) Produce surgical anesthesia (50–150mcg/kg IV) Analgesia for early labor (25mcg intrathecal) Postoperative analgesia (transdermal patch)
Table 1: Dosage of fentanyl
Fentanyl Dose
As Analgesic 2 – 6 μg / kg
As infusion 0.5 – 5 μg / kg / hr
For induction 4 – 20 μg / kg
SIDE EFFECTS
Cardiovascular Effects: Fentanyl, even in large doses (50mcg/kg IV), do not release of histamine. Bradycardia is more with fentanyl than morphine and it decreases the blood pressure and cardiac output.
Seizure Activity: In the absence of EEG evidence of seizure activity, it is difficult to distinguish opioid-induced skeletal muscle rigidity or myoclonus from seizure activity.
Respiratory effects: Respiratory depressants action.Magnitude of respiratory depression can be increased while fentanyl is given in combination with other respiratory depressant such as midazolam.
Fentanyl-induced pruritus presents as facial itching ,but it is generalized.
Fentanyl has also reported to have a tussive effect. Patients may be coughed within 1 minute after receiving a bolus dose of fentanyl (1.5 µg/kg).
This is unclear mechanism and it is not attenuated by pretreatment with midazolam or atropine.
PHARMACOLOGY OF BUPRENORPHINE
Buprenorphine is a semi synthetic highly lipophilic opioid derived from the baine, an opium alkaloid related to morphine, and is a long acting analgesic with narcotic agonist and antagonist action. It is a white powder, weakly acidic and with limited solubility in water.
Structural formula
Figure 7: Structural formula of Buprenorphine
Buprenorphine hydrochloride chemically is 17(cycloprophylmethyl)α (1,1 dimethylethyl) -4-5 epoxy -18-19 dihydro-3 hydroxy 6 methoxy, αmethyl- 6, 14 –ethano –morphinan -7-methanol,hydrochloride(5,7(s)).
Molecular formula- C29H41NO4 HCl.
Molecular weight =504.09
Mechanism of Action
Buprenorphine appears to have a high affinity for both μ and ĸreceptors and low to moderate intrinsic activity at μ and ĸ receptors.It binds slowly with and dissociates slowly from the μ receptors.(this mayaccount for the prolonged duration of analgesia
CLINICAL PHARMACOLOGY
It is similar in structure to morphine but approximately 33 timesmore potent. Whereas fentanyl dissociates rapidly from μ receptors (t½ of6.8 minutes), buprenorphine has a higher affinity and takes much longer(t½ of 166 minutes). The onset of action ofbuprenorphine is slow, its peakeffect may not occur until 3hours, and the duration of effect is prolonged(<10 hours). The volume of distribution of buprenorphine is 2.8 L/kg, andits clearance is 20 mL/kg/minute. Plasma concentrations of the metabolitesof buprenorphine (norbuprenorphine,buprenorphine-3-glucuronide, andnorbuprenorphine-3- glucuronide) may approximate or exceed those oftheparent drug. Glucuronide metabolites are biologicallyactive and maycontribute to the overall pharmacology of buprenorphine.
Effect on the CNS
Buprenorphine produces analgesia, sedation, miosis and to a lesserdegree, nausea and vomiting .It may also produce side effects likedizziness , sweating and headache.
Effect on respiratory system
Buprenorphine depresses the respiratory centre and decreases boththe tidal volume and rate of respiration. It decreases minute ventilation atdoses higher than 3μg/kg but maximal respiratory depression is observedonly 3hours later. Respiratory depression can be prevented by prioradministraton of naloxone,but it is not readily reversed once the effectshave been produced.
Pharmacokinetics:
Absorption:
Buprenorphine is relatively well absorbed by most routes includingthe sublingual route. It is a highly lipophilic substance and is well absorbedacross biological membranes.
Protein binding:
It is highly protein bound, primarily to α and β globulinfraction(96%).
Volume of distribution is 2.8L/Kg.
METABOLISM:
Buprenorphine is metabolised in liver by N-dealkylation andglucuronide conjugation and the metabolites are – Buprenorphine 3glucuronide and Norbuprenorphine which have have lower affinity for theμ receptors.
Metabolites are excreted through bile in the faeces and asmaller amount appears in the urine. Clearance rate -20ml/Kg/min.
Preparation, Routes of administration and Doses :
It is available as clear, sterile solution for IV and IM administrationand each ml contains 0.324mg (equivalent to 0.3mg Buprenorphine) 50mganhydrous dextrose, water and HCl to adjust pH.Preservative free Buprenorphine is available as 0.3mg/ml. It is alsoavailable as sublingual tablets.
Therapeutic uses :
1. As premedication 2. As an analgesic
3. Post-operative analgesia
4. Acute pain of moderate to severe degree 5. Chronic pain
6. Asan adjuvant in Neuraxial blockade for intra and post-operative painrelief.
Precautions:
1. It is to be used with caution in patients with COPD, corpulmonale,hypoxia, hypercapnia.
2. It is to be used with caution in head injury, intracranial lesions and incircumstances where CSF pressure may be increased.
3. Patients receiving other narcotics, phenothiazines, sedatives, hypnoticsor other CNS depressants with Buprenorphine can exhibit an additive CNSdepression.
4. It should be cautiously used in elderly/ debilitated patients and thosewith severe renal, hepatic and pulmonary impairment.
5. It should be used with caution in myxoedema or hypothyroidism,adrenocortical suppression,CNS depression, coma, acute alcoholism anddelirium tremens
REVIEW OF LITERATURE
Sigmund Freud (1856-1939), noticed cocaine’s ability to produce numbness ofthe tongue and provided a small sample to his junior colleague, Carl Koller (1858-1944), an intern who was interested in producing local anaesthesia for operations on the eye.
In 1884 Koller reported that the topical application of cocaine to the eye produced anaesthesia of the cornea and conjuctiva.1 Within months of publication of Koller’s paper, cocaine started being injected to produce regional anaesthesia and not just topical anaesthesia.
In 1885, Halsted used cocaine to block the brachial plexus, and J Leonard Corning, a neurologist in New York, injected cocaine intervertebrally in dogs and in patients to relieve chronic pain and not to provide operative anaesthesia.1
Spinal anaesthesia with cocaine was initially produced inadvertently by J Leonard Corning, in 1885 and first used deliberately by August Bier in 1898.
On August 15 1898, August Bier and his assistant August Hildebrandt used the Quinckes method of entering the Intrathecal space and injected between 5 and 15 mg of cocaine to produce spinal anaesthesia in six cases for operations on the lower part of the body. They also reported the result of spinal anaesthesia given to each other.1
Jean Enthuse Sicard and Fernand Cathelin independently introduced cocainethrough the sacral hiatus in 1901, becoming the first practitioners of caudal epidural anaesthesia.
19 years later, a Spanish military surgeon Archile Mario Dogliotti performed abdominal surgery using single shot lumbar epidural anaesthesia. He correctly identified the epidural space describing the sudden loss of resistance notedafter the needle had crossed the ligamentum flavum.
Aburel, Higson and Edwards all devised methods for continuous but cumbersome epidural blockade. However Cuba anaesthesiologist, Manual Martinez Curbelo, is credited with making the technique more practical. On his visit to Mayo Clinic in 1947, he watched Tuohy perform continuous spinal block. Curbelo used the Tuohy needle with a silk ureteral catheter to provide continuous segmental lumbar peridural anaesthesia. Several modifications of the Tuohy-Huber epidural needle have been developed in the more recent past and are being utilized in modern anaesthesia practice.13
Although identified as a local anaesthetic in 1957, Ropivacaine testing did notbegin until 1988.11 Ropivacaine was introduced into clinical practice in 1990.
Grace Maria George, Shaloo Ipe et al[2]in 2014 conducted a prospective, randomized, controlled, double blind study in primi parturients
undergoing elective cesarean section with singleton fetus. A total of 102 parturients in the age group of 20-35 years, American Society of Anesthesiologists (ASA) I or II scheduled for elective cesarean under continuous epidural anesthesia were divided into three groups using a computer-generated random number list. The test dose (3 ml 2% lignocaine with 15 mg adrenaline) and 0.75% ropivacaine 12 ml were given to all parturients. In addition, normal saline 1 ml, fentanyl 50 mg, and buprenorphine 300 mg were given to Group I, II, and III respectively. Sensory block,motor block, analgesia, maternal effects, fetal outcome, and surgeons’ and parturients’ satisfaction were evaluated.
Results of the study showed onset of sensory block was faster in the fentanyland buprenorphine groups compared to ropivacaine group (9.94 ± 0.48, 10.72 ± 0.26 versus 14.59 ± 0.34). Duration of sensory block was prolonged in buprenorphine group as compared to fentanyl and ropivacaine groups (120.41
± 4.31) versus (95.68 ± 3.28, 98.28 ± 3.42). Duration of analgesia was prolonged in buprenorphine group compared to fentanyl and ropivacaine groups (516.38 ± 29.14 versus 327.06 ± 12.41, 285.78 ± 10.10). It proved to be safe for mother and fetus. The surgeon and the parturients were satisfied with the mode of anesthesia.
S. Kiran, Kavita Jinjil, Urvashi Tandon[1] et al conducted a prospective randomized study in patients undergoing infraumbilical surgeries,
who were divided randomly into three groups ‑ Group R (n = 25): received 18 ml of 0.5% ropivacaine for epidural anesthesia and 10 ml of 0.1% ropivacaine boluses for postoperative analgesia; Group RF (n = 25): received 18 ml of 0.5%
ropivacaine with 20 μg fentanyl for epidural anesthesia and 10 ml of 0.1%
ropivacaine with 10μg fentanyl boluses for postoperative analgesia; and Group RD (n = 25): received 18 ml of 0.5% ropivacaine with 10 μg dexmedetomidine for epidural anesthesia and 10 ml of 0.1% ropivacaine with 5 μg dexmedetomidine boluses for postoperative analgesia.Results of the study showed that the mean time for onset of sensory block, in minutes, was 18.6 ± 4.4 in R Group, 12.8 ± 1.8 in RF Group and 10.8 ± 2.7 in RD Group (P <
0.001). There was a statistically significant difference with regard to degree of motor block, with RD Group faring better than RF Group and R Group. The mean time to rescue analgesia, in minutes, was 139.8 ± 21.4 in Group R, 243 ± 29.7 in Group RF, and 312.4 ± 30.2 in Group RD (P < 0.001). Incidence of hypotension at 10 min was 4% and 48% in RF and RD Groups, respectively (P
< 0.001).
Authors concluded that epidural anesthesia achieved with 10 μg dexmedetomidine as an additive to 0.5% ropivacaine is more effective with respect to duration and intensity of analgesia when compared to 0.5%
ropivacaine alone or addition of 20 μg fentanyl to 0.5% ropivacaine.
Anita Kulkarni[25]et al conducted a prospective, randomized, interventional, parallel group, active control study on 60 patients with American Society of Anesthesiologists physical status I–III. Random allocation was carried out into two groups of 30 patients each. Intraoperatively, after administering a loading dose (10 mL of 0.5% bupivacaine) in both the groups, continuous infusions of 0.1% bupivacaine plus fentanyl (2 μg/mL) (Group BF) or 0.1% ropivacaine plus fentanyl (2 μg/mL) (Group RF) were started at the rate of5 mL/h. Postoperatively, same drug concentrations were administered via PCEA pump at 4 mL/h as a baseline infusion (bolus dose, 3 mL; lockout interval, 15 min). Visual analog scale (VAS) score at rest and on coughing was recorded at specific time points. Rescue analgesia was administered as per protocol.
Results of the study showed VAS scores at rest and on coughing were higher in Group BF as compared to Group RF. Group RF had less drug consumption, required fewer PCEA boluses, and had minimal motor blockade as compared toGroup BF.
Authors concluded that good analgesic efficacy with lower drug consumption makes Group RF well suited for postoperative PCEAwith hemodynamic stability and minimal motor blockade.
Dr Santosh Kumar [24]et al conducted a prospective randomised study to compare effects of epidural bupivacaine with buprenorphine over epidural
bupivacaine with fentanyl for lower limb surgeries.60 patients in the age group 20-60 years belonging to ASA I-II posted for elective lower limb surgeries were divided into two groups of 30 each and studied. Group A received 0.5%
Bupivacaine 15ml with 150 mcg Buprenorphine.Group B received 0.5%
Bupivacaine 15ml with 50mcg Fentanyl. Intraoperatively, sensory and motor blockade, quality and duration of Postoperative analgesia, hemodynamic and respiratory parameters, side effects like nausea, vomiting, respiratory depression, pruritus were studied.Results showed both groups had faster onset of sensory and motor blockade. Duration of analgesia was significantly longer in Group Athan Group B (766.6 vs 471 mins). The incidence of Nausea and vomiting was more in group A (40 %) compared to group B (10 %) and pruritus was more in group B (10%) compared to none in group A.It was concluded that epidural buprenorphine was better in providing prolonged satisfactory postoperative analgesia as compared to epidural Fentanyl.
Bajwa SJ, Arora V, Kaur J et al 83 2011conducteda randomized controlled study on100 patients to evaluate the effect of epidural dexmedetomidine and fentanylin lower limb orthopaedic surgeries.A total of 100 patients of both gender aged 21-56 years belonging to ASA 1 and 2whounderwent lower limb orthopaedic surgery were enrolled into the study.Patients wererandomly divided into two groups: Ropivacaine + Dexmedetomidine (RD) andRopivacaine + Fentanyl(RF), comprising 50 patients each.Inj.Ropivacaine 15ml of0.75% was administered epidurally in
both the groups with addition of 1ìg/kg ofdexmedetomidine in RD group and 1ìg/kg of fentanyl in RF group at the rate of1ml/second.Results showed onset of sensory analgesia at T10 (7.12± 2.44 VS 9.14 ± 2.94) andestablishment of complete motor blockade (18.16 ± 4.52 vs 22.98 ± 4.78) wassignificantly earlier in the RD group. Postoperative analgesia was prolongedsignificantly in the RD group (366.62 ± 24.42) and consequently low doseconsumption of local anesthetic LA (76.82 ± 14.28 VS 104.35 ± 18.96) duringepidural top-ups postoperatively. Sedation scores were much better in the RD groupand highly significant (p<0.001). Incidence of nausea and vomiting was significantlyhigher in the RF group, while incidence of dry mouth was higher in the RD group (14%) (p<0.05).
Authors concluded that dexmedetomidine is a better alternative to fentanyl as anepidural adjuvant as it provides comparable stable hemodynamics, early onset andestablishment of sensory anesthesia, prolonged post operative analgesia, lowerconsumption of post-op LA for epidural analgesia; and much better sedation levels.
Griffin RP et al [3] studied in Seventy-three parturients for elective Caesarean section who were allocated randomly to receive extradural block with 20 ml of either 0.5% ropivacaine or 0.5% bupivacaine. If the block did not reach T6 within 30 min, another 5 ml of solution was given. If needed, a further 5 ml was given 45 min after the main dose. The mean total dose of bupivacaine was 23.1 ml (n = 35) and of ropivacaine 23.7 ml (n = 37). There was no
significant difference between the groups in the profile of sensory block produced. There was no significant difference in the time of onset, or intensity of motor block between the groups but the duration of motor block was significantly shorter in the ropivacaine group. There was no significant difference in neonatal outcome, as assessed by Apgar score, umbilical cord blood-gas tensions at delivery or the neurological and adaptive capacity score 2 and 24 h after delivery.
Brown DL [7]et al compared the clinical effectiveness of ropivacaine and bupivacaine in patients undergoing lower-extremity surgery. Forty-five patients were randomized to receive 20 ml of 0.5% ropivacaine or bupivacaine.
Intermittent sensory (pinprick) and motor (Bromage score) measurements were made while the block was in effect, and changes in heart rate, blood pressure and amounts of additional analgesics, sedatives and other medications were also recorded. Presence of tourniquet pain and the quality of anesthesia were also assessed. No differences were found in patient or perioperative characteristics between the groups. The quality and extent of sensory and motor blockade between groups were comparable, although bupivacaine was slightly longer acting. The authors found 0.5% ropivacaine and bupivacaine to be clinically similar in both sensory- and motor-blocking characteristics, with the exception that bupivacaine produced a blockade of slightly longer duration.
Because ropivacaine is reported to be less cardiotoxic than bupivacaine in
animal studies, the similarity of clinical epidural anesthesia may make ropivacaine the preferred agent.
Fuller JG [8] et al assessed the efficacy and safety of epidural morphine in providing analgesia following Caesarean section under epidural anaesthesia.
The morphine was administered as a single bolus, following delivery, in doses ranging from 2 to 5 mg. The duration of analgesia was 22.9 +/- 10.1 . Eleven percent of the patients required no supplemental analgesia during the first 48 hr. Epidural morphine is thus confirmed as an effective analgesic technique post-Caesarean section with 3 mg being the optimal dose. Respiratory depression occurs so respiratory monitoring is indicated.
K.S. Nagesh [26]Et al studied in 60 patients undergoing lower abdominal and lower limb surgeries Group – A: Patients received 8ml of 0.25%
bupivacaine + 0.15mg of buprenorphine. Group – B: patients received 0.25%
of bupivacaine alone. In the post-operative period the following parameters were studied, 1. Onset of analgesia, 2. Duration of analgesia, 3. Vital parameters such as heart beat, blood pressure, respiratory rate, sedation score and visual analogue score were recorded, 4. Side effects like nausea, vomiting, hypotension, respiratory depression, and pruritus allergic reaction were looked for. It was observed that onset of analgesia in Group A (0.25% bupivacaine + 0.15mg buprenorphine) was 7.35 min. When compared to Group B which 15.5 min, which is statically significant (P<0.05). Duration of analgesia in Group A is 17.23 hrs compared to Group B, which is 5.2 hrs, this is statically significant
(P<0.05). Visual analogue scale was reduced in Group A compared to Group B .Thus they concluded that addition of buprenorphine to bupivacaine by epidural injection for post-operative analgesia improves the onset, the duration and the quality of analgesia.
Bajwa SJ[27] et al concluded thatthe addition of 75 µg clonidine to isobaric epidural ropivacaine results in longer, complete and effective analgesia with similar block properties and helped to reduce the effective dose of ropivacaine when compared with plain ropivacaine for cesarean delivery.
Salgado PF[28] et al evaluated the clinical characteristics of epidural anesthesia performed with 0.75% ropivacaine associated with dexmedetomidine. Epidural dexmedetomidine did not affect onset time however it prolonged sensory and motor block duration time (p < 0.05) and postoperative analgesia (p < 0.05), and also resulted in a more intense motor block (p < 0.05). Values of bispectral index were lower in Dexmedetomidine Group (p < 0.05). There was no difference in incidence of hypotension and bradycardia (p > 0.05). Occurrence of side-effects (shivering, vomiting and SpO2 < 90%) was low and similar between groups (p > 0.05). Thus proving that there is clear synergism between epidural dexmedetomidine and ropivacaine, further this drug association does not bring about additional morbidity.
Sukhminder Jit Singh Bajwa[29] and his colleagues in the year 2011 conducted a study in 100 patients comparing the effects of fentanyl and dexmeditomidine as adjuvants to ropivacaine in epidural anaesthesia. Patients were randomly divided into two groups: Ropivacaine + Dexmedetomidine (RD) and Ropivacaine + Fentanyl (RF), comprising 50 patie nts each. Inj.
Ropivacaine, 15 ml of 0.75%, was administered epidurally in both the groups with addition of 1 μg/kg of dexmedetomidine in RD group and 1 μg/kg of fentanyl in RF group. They concluded that Dexmedetomidine seems to be a better alternative to fentanyl as an epidural adjuvant as it provides comparable stable hemodynamics, early onset, and establishment of sensory anesthesia, prolonged post-op analgesia, lower consumption of post-op LA for epidural analgesia, and much better sedation levels.
Sarbjit singh[30] and his colleagues in the year 2014 conducted a study in 100 patients undergoing lower limb orthopaedic surgeries comparing the effects of ropivacaine versus ropivacaine and dexmeditomidine in epidural anaesthesia. Epidural anesthesia was given with 150 mg of 0.75% ropivacaine in Group A and 150 mg of 0.75% ropivacaine with dexmedetomidine (1 µg/kg) in Group B. They concluded that Epidural Dexmedetomidine as an adjuvant to Ropivacaine is associated with prolonged sensory and motor block, hemodynamic stability, prolonged postoperative analgesia and reduced demand for rescue analgesics when compared to plain Ropivacaine.
