RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA

SYNOPSIS

OF

DISSERTATION

"A COMPARATIVE STUDY OF DEXMEDETOMIDINE WITH CLONIDINE AS ADJUVANTS TO ISOBARIC ROPIVACAINE IN EPIDURAL ANAESTHESIA IN LOWER ABDOMINAL & LOWER LIMB SURGERIES"

Submitted by

Dr. VARSHA

M.B.B.S.

POST GRADUATE STUDENT IN

ANAESTHESIOLOGY (M.D.)

DEPARTMENT OF ANAESTHESIOLOGY

ADICHUNCHANAGIRI INSTITUTE OF MEDICAL SCIENCES,

B.G.NAGARA-571448


RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA

ANNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1 / NAME OF THE CANDIDATE
AND ADDRESS
(in block letters) / Dr. VARSHA
PG IN ANAESTHESIOLOGY,
ADICHUNCHANAGIRI INSTITUTE OF
MEDICAL SCIENCES.B.G NAGARA,
MANDYA DISTRICT -571448
2. / NAME OF THE INSTITUTION /

ADICHUNCHANAGIRI INSTITUTE OF

MEDICAL SCIENCES, B.G.NAGARA.
3. / COURSE OF STUDY AND SUBJECT /

M.D IN ANAESTHESIOLOGY

4. / DATE OF ADMISSION TO COURSE / 12th JUNE 2012
5. / TITLE OF THE TOPIC / A COMPARATIVE STUDY OF DEXMEDETOMIDINE WITH CLONIDINE AS ADJUVANTS TO ISOBARIC ROPIVACAINE IN EPIDURAL ANAESTHESIA IN LOWER ABDOMINAL & LOWER LIMB SURGERIES
6. / BRIEF RESUME OF INTENDED WORK
6.1  NEED FOR THE STUDY
6.2 REVIEW OF LITERATURE
6.3 OBJECTIVES OF THE STUDY / APPENDIX-I
APPENDIX-IA
APPENDIX-IB

APPENDIX-IC

7 / MATERIALS AND METHODS
7.1  SOURCE OF DATA
7.2 METHOD OF COLLECTION OF DATA : (INCLUDING SAMPLING PROCEDURE IF ANY)
7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER ANIMALS, IF SO PLEASE DESCRIBE BRIEFLY.
7.4 HAS ETHICAL CLEARENCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3 / APPENDIX-II
APPENDIX-IIA
APPENDIX-IIB
YES
APPENDIX-IIC

YES

APPENDIX-IID
8. / LIST OF REFERENCES /

APPENDIX – III

9. / SIGNATURE OF THE CANDIDATE /
10. /

REMARKS OF THE GUIDE

/ The following study will help for further research study to know the efficacy of new drugs like ropivacaine and Analgesic and Sedative properties of alpha-2 agonists.
11 / NAME AND DESIGNATION
(in Block Letters)
11.1 GUIDE / Dr. CHETHAN ANANDA T.N. MBBS, DA, DNB
ASSOCIATE PROFESSOR,
DEPARTMENT OF ANAESTHESIOLOGY,
AIMS, B.G. NAGARA-571448
11.2 SIGNATURE OF THE GUIDE
11.3 CO-GUIDE (IF ANY) / -
11.6 SIGNATURE / -
11.5 HEAD OF DEPARTMENT / Dr. RADHA M.K, M.D
PROFESSOR AND HEAD
DEPARTMENT OF ANAESTHESIOLOGY
AIMS, B.G. NAGARA-571448
11.6 SIGNATURE
12 / 12.1 REMARKS OF THE CHAIRMAN
AND PRINCIPAL / The facilities required for the investigation will be made available by the college
Dr. M.G SHIVARAMU M.B.B.S., MD
PRINCIPAL,
AIMS, B.G. NAGARA.
12.2 SIGNATURE

APPENDIX-I

6.0 BRIEF RESUME OF THE INTENDED WORK:

APPENDIX –I A

6.1 NEED FOR THE STUDY:

Epidural anesthesia is a central neuraxial block technique which involves use of local anesthetics injected into the epidural space to produce a reversible loss of sensation and motor function and is one of the most common regional technique used for lower abdominal and lower limb surgeries. Epidural anesthesia provides excellent operating conditions for surgical procedures below the umbilicus.

Advantages of epidural anesthesia over spinal anesthesia is that it is able to provide anesthesia for prolonged surgeries with better hemodynamic stability.

Advantages of epidural anesthesia over general anesthesia is that the intubation and extubation responses are avoided and there will be a choice to provide postoperative analgesia. Epidural anesthesia can reduce the adverse physiologic responses to surgery too.

Different local anesthetics are used for epidural anesthesia, most popular being lignocaine and bupivacaine .The drawback of lignocaine is its intermediate duration of action and drawback of bupivacaine, though long acting is increased incidence of cardiac toxicity.

Ropivacaine is replacing bupivacaine as drug of choice in epidural anesthesia. Ropivacaine is a long-acting amino amide local anesthetic structurally related to bupivacaine.1 Ropivacaine has been shown to have an increased therapeutic index in human volunteer studies. In several studies it was concluded that ropivacaine was less cardiac depressant, less arrhythmogenic and less neurotoxic than bupivacaine.2

However it has some limitations. The onset of sensory and motor blockade may be delayed. The duration of analgesia provided by a dose of epidural ropivacaine is only 4-6 hours, thereby requiring frequent administration of the drug for post op analgesia. There is also no intra operative sedation leading to inadvertent use of sedatives.

Therefore a number of drugs have been tried as adjuvants to epidural ropivacaine to overcome these limitations.alpha-2 adrenergic agonists have both analgesic and sedative properties when used as an adjuvant in regional anaesthesia.

Dexmedetomidineis a relatively selective alpha2-adrenergic agonist, not only decrease sympathetic tone and attenuate the stress response to anesthesia and surgery,but also cause sedation and analgesia. The majority of patient receiving were effectively sedated yet were easily arousable, a unique feature not observed with other sedatives.3 Dexmedetomidine suppresses the activity in the descending noradrenergic pathway, which modulates nociceptive neurotransmission, terminates propagation of pain signals leading to analgesia. The hypnotic and supraspinal analgesic effects are mediated by the hyperpolarization of noradrenergic neurons, which suppresses neuronal firing in the locus ceruleus along with inhibition of norepinephrine release and activity in the descending medullospinal noradrenergic pathway, secondary to activation of central alpha-2 adrenergic receptors.This suppression of inhibitory control triggers neurotransmitters that decrease histamine secretion producing hypnosis similar to normal sleep, without ventilatory depression, making dexmedetomidine a near ideal sedative.4

Clonidine is an established alpha 2 adrenoceptor agonist with antihypertensive properties, when administered epidurally has an analgesic action that is largely mediated by alpha 2 adrenoceptors in dorsal horn of spinal cord clonidine is useful adjuvant to opioid and LA agent for postop analgesia after major abdominal surgeries and orthopedic surgery.5 Clonidine enhances both sensory and motor blockade from epidural injection of local anesthetics.

The present study is being undertaken to evaluate the onset time of sensory and motor blockade, sedation, duration and analgesic efficacy of Dexmedetomidine 1.5μg/kg in comparison to Clonidine 2μg/kg used as adjuvants to 0.75% Ropivacaine in epidural anesthesia in lower abdominal and lower limb surgeries.

APPENDIX –I B

6.2 REVIEW OF LITERATURE

1.  Sharrawy EE and Yagiela JA conducted a study on 72 ASA 1 patient scheduled for extraction of a mandibular third molar after inferior alveolar nerve block using different concentration of ropivacaine. The result concluded that 0.5% and 0.75% concentrations were effective for inferior nerve blockade, with both a rapid onset and prolongs duration of pain control.1

2.  Feldman HS, Arthur GR, Covino BG conducted a study with lidocaine, bupivacaine, ropivacaine to compare their convulsant and supraconvulsant doses in conscious dogs. The results suggests that the convulsive doses for ropivacaine and bupivacaine are similar. However, ropivacaine may possess a greater safety of margin and be less arrhythmogenic than bupivacaine after accidental rapid iv injection. Only lidocaine was devoid of arrythmogenic activity.2

3.  Gertler R, Brown C, Mitchell DH, Silvius EN studied about Dexmedetomidine a novel sedative and analgesic agent. This review aims to give background information to improve understanding of the properties and applications of the novel alpha-2 adrenoceptor agonists, Dexmedetomidine.3

4.  Gerwal A studied about Dexmedetomidine. This editorial aims to provide an overview of its current clinical status and new therapeutic avenues under investigation.4

5.  Patel, Sanjay S, Dunn, Christopher J, Bryson, Harriet M. In conclusion data suggests a role for epidural clonidine as an adjunctive agent for the control of pain. In particular, it may be useful in patient unsatisfied with opioid or local anesthetic agents. However, the place of epidural clonidine as an alternative or adjunctive analgesic agent depend on the acceptability of epidural route of administration and hemodynamic and sedative side effects.5

6.  Bajwa SJ, Bajwa SK, Kaur J, Singh G, Arora V, Gupta S.et al conducted a prospective randomized study which included 50 adult female patients between the ages of 44 and 65 years of ASAI/II grade who underwent vaginal hysterectomies with epidural block with ropivacaine and dexmedtomidine (group RD) and ropivacaine and clonidine (group RC). It is concluded that Dexmedetomidine is a better neuraxial adjuvant compared to clonidine for providing early onset of sensory analgesia, adequate sedation and a prolonged post-operative analgesia.6

7.  Bajwa SJ, Bajwa SK, Kaur J conducted a randomized double blind study among 51 healthy parturients, scheduled for elective cesarean section by epidural block with ropivacaine (group R) and ropivacaine with clonidine(group RC).It is concluded that addition of 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 delivary.7

8.  Vieira AM, Schnaider TB, Brandao AC, Pereira FA, Costa ED, Fonseca CE. et al conducted a randomized double-blind study among 40 patients, aged 18 to 50 years, weighing 50 to 100 kg, physical status ASA I or II, submitted to subcostal cholecystectomy with epidural clonidine and ropivacaine and with dexmedetomidine with ropivacaine. It is concluded that there is an association of clonidine or dexmedetomidine to 0.75% ropivacaine in inducing analgesia and sedation in 2 and 6 hours after anesthetic recovery in patients submitted to subcostal cholecystectomy and that clonidine promotes more prolonged analgesia.8

9.  Salgad PF, Sabbag AT, Silva PC, Brienze SL, Dalto HP, Modolo NS. et al conducted a double-blinded study with 40 patients, ASA physical status 1 and 2, scheduled for hernia repair surgery or varicose vein surgery, who were operated under epidural anesthesia with ropivacaine plus saline and ropivacaine plus dexmedetomidine. It is concluded that there is a clear synergism between epidural dexmedetomidine and ropivacaine. Dexmedetomidine increases sensory and motor block duration during epidural anesthesia with ropivacaine, prolongs postoperative analgesia and does not cause hemodynamic instability. Sedation and no respiratory depression is an advantage of the association between ropivacaine and dexmedetomidine.9

10.  Gupta S, Raval D, Patel M, Patel N, Shah N conducted a randomized double blind study with 60 adult patients of ASA grade 1 and 2 scheduled for post op pain relief in total knee replacement surgeries by epidural clonidine with bupivacaine and with bupivacaine alone. It concluded that addition of clonidine to bupivacaine epiduraly prolongs motor and sensory block and analgesia, without an increased incidence of side effects.10

11.  Bajwa SJ, Arora V, Kaur J, Singh A, Parmar SS conducted a study on 100 patients aged 21-56 years of ASA 1 and 2 who underwent lower limb orthopedic surgery with epidural ropivacaine plus dexmedetomidine and ropivacaine plus fentanyl. It seems that dexmedetomidine to be better alternative to fentanyl as an epidural adjuvant as it provides comparable stable hemodynamic, 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.11

12.  Rockemann MG, Seeling W, Brinkmann A, Goertz AW, Hauber N, Junge J.et al conducted a study on 45 patients scheduled for pancreatectomy in combined general/epidural anesthesia. This study characterizes analgesia and hemodynamics after epidural clonidine 8microg/kg or clonidine 4microg/kg plus morphine 2mg in comparison to epidural morphine 50microg/kg. it concluded that hemodynamic alteration after epidural clonidine under conditions of stable filling pressures is caused mainly by a decrease in HR. It is not an effect of analgesia but of the intrinsic anti hypertensive action of clonidine.12

APPENDIX –IC
6.3 AIMS AND OBJECTIVES OF STUDY
This study will be under taken to evaluate the efficacy of 1.5μg/kg Dexmedetomidinein comparison to 2μg/kg clonidineas adjunct to 17ml of 0.75% Ropivacaine for epidural anaesthesia with special emphasis on their sedative and analgesic properties in lower abdominal and lower limb surgeries in adults aged 30 to 60 years.
APPENDIX-II

7.0 MATERIALS AND METHODS

APPENDIX-II A

7.1 SOURCE OF DATA

The study will be conducted on 60 patients aged between 30 to 60 years undergoing lower abdominal and lower limb surgeries at Adichunchanagiri institute of medical sciences during the academic year from June 2012 to July 2015.

APPENDIX-II B

7.2 METHOD OF COLLECTION OF DATA

60 patients, belonging to ASA grade I and II, aged between 30 to 60 years, undergoing lower abdominal and lower limb surgeries will be randomly selected after obtaining Informed written consent.

Ø  The study population will be randomly divided into 2 groups with 30 patients in each group.

Ø  Study group RD-would receive 17ml of 0.75% Ropivacaine + 1.5μg/kg Dexmedetomidine.

Ø  Study group RC- would receive 17ml of 0.75% Ropivacaine + 2μg/kg clonidine.

Ø  Result values will be recorded using a preset Proforma.

Procedure:

All patients will undergo pre anaesthetic evaluation on the previous day of surgery. Basic lab investigations like CBC, FBS or RBS, blood urea, serum creatinine chest X-ray and ECG will be carried out. The entire procedure will be explained to the patient.

All the patients were visited in the previous night of proposed surgery day and tab alprazolam 0.5mg given at bed time and tab ranitidine 150mg given at bed time and also on the day of surgery with sip of water 2 hours before anesthetic procedure.

Patient is shifted to procedure room on the day of surgery. Drug and equipments necessary for resuscitation and general anesthesia are kept ready .An IV line is secured using 18G cannula and 500ml of RL infusion started which is given for all patients half an hour before anesthetic procedure as pre loading. Base line blood pressure, heart rate and respiratory rate will be noted.

All the equipments necessary to administer epidural anesthesia are checked and kept ready. The patient will be placed in left lateral position and the back is drapped with betadine. With all aseptic measures the skin over L3-L4 interspace is anesthetized with 2ml of 2% Lignocaine. An 18G Touhy needle will be passed through this space and advanced slowly until it enters epidural space which is confirmed by loss of resistance to air technique. Then an 18G epidural catheter is passed through the needle into epidural space and secured with minimum of 3-4cm within the space. 3ml of 2% Lignocaine with adrenaline 1:200000 is given as test dose to confirm the proper placement of catheter.3 min later, 17 ml of the solution containing 0.75% Ropivacaine plus study drug is injected through the epidural catheter intermittently over 3 min. Surgical position is given after 25-30 min after drug administration.

The following parameters will be monitored:

Ø  Onset of sensory block assessed by bilateral pin prick method

Ø  Degree and level of motor blockade - using Modified Bromage scale.