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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1.
NAME OF THE CANDIDATE
AND ADDRESS
2.
NAME OF THE INSTITUTION
3.
COURSE OF STUDY & SUBJECT
4.
DATE OF ADMISSION TO THE
COURSE
5.
Dr. RAJESH.R.NAYAK.
POST GRADUATE STUDENT
DEPARTMENT OF ANAESTHESIOLOGY,
BANGALORE MEDICAL COLLEGE &
RESEARCH INSTITUTE,
BANGALORE - 560002
BANGALORE MEDICAL COLLEGE AND
RESEARCH INSTITUTE
DOCTOR OF MEDICINE IN
ANAESTHESIOLOGY
06 - 06 – 2013
TITLE OF THE TOPIC:
A COMPARATIVE STUDY OF DESFLURANE REQUIREMENT AND RECOVERY
CHARACTERISTICS IN ENTROPY GUIDED GENERAL ANAESTHESIA WITH OR
WITHOUT DEXMEDETOMIDINE INFUSION.
6.
BRIEF RESUME OF THE INTENDED WORK
6.1 NEED FOR THE STUDY:
Desflurane is a new inhalational anaesthetic with lowest blood gas solubility coefficient and
hence associated with faster recovery times. It is also said to be more economical as it reduces
the stay in the operating room. However desflurane is considered to be more expensive than
other volatile anaesthetics1. Hence, studies on reduction in its consumption have gained more
importance.
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Dexmedetomidine is a highly selective alpha 2 adrenoceptor agonist, which possesses
hypnotic , sedative, anxiolytic, sympatholytic and analgesic properties without producing
significant respiratory depression2,3. Sedative and hypnotic drugs have the ability to reduce both
the anaesthetic and opioid requirements.,4,5,6 Although experience with alpha 2 agonists as sole
anaesthetic is limited, these drugs reduce anaesthetic requirement6. Its sympatholytic effect
decreases mean arterial pressure (MAP) and heart rate (HR) by reducing norepinephrine
release,8,9. By using entropy we can measure the adequacy of depth of anaesthesia. The
difference between the response entropy and state entropy should be less than 10.
Studies evaluating the effect of dexmedetomidine infusion on consumption of
desflurane anaesthesia using entropy are sparse. In our study we decided to evaluate the effect
of continuous infusion of dexmedetomidine on the requirement of desflurane and its recovery
characteristics while continuously monitoring entropy.
6.2 REVIEW OF LITERATURE:
Earl M Stry and coworkers studied the emergence and recovery characteristics
of desflurane versus sevoflurane in morbidly obese surgical patients. They studied 50 morbidly
obese patients(BMI >35 and ASA physical status II-III) requiring gastrointestinal bypass surgery
via open laparotomy. Patients were randomized to receive desflurane and sevoflurane for
maintenance of anaesthesia. They concluded that recovery after prolonged anaesthesia with
desflurane is shorter than with sevoflurane anaesthesia10.
Keles and coworkers studied balanced anaesthesia with dexmedetomidine
added to desflurane or sevoflurane in spinal surgery. Sevoflurane and desflurane inhalational
anaesthetics were used for fast track neuroanaesthesia. Dexmedetomidine is used to provide
analgesia, sedation and hemodynamic stability. One hundred patients of ASA I-II aged between
18-65 were randomly divided into two groups. Following the standard anaesthesia induction
group (D+D) (n=50) received 2-4% desflurane + 0.2mcg per kg per hr dexmedetomidine and
group (S+D) (n=50) received 1-3% sevoflurane +0.2 mcg per kg per hr dexmedetomidine in
60% N2O for anaesthesia management. Extubation time and fast track criteria & Aldrete criteria
were evaluated in the operating room, at the 5th and 10th minute and in the postanaesthetic care
unit at the 5th, 15th and 25th minutes. They concluded that balanced anaesthesia with desflurane &
2
dexmedetomidine combination is superior to sevoflurane & dexmedetomidine in extubation and
time to reach fast track criteria and aldrete criteria in spinal surgery.
S.K. Tsai and others studied recovery in 25 adult patients of ASA I undergoing
elective orthopedic procedure after anaesthesia with 0.65 MAC desflurane (n=16) and isoflurane
(n =9) with 60 % nitrous oxide in oxygen. Early emergence from anaesthesia was assessed in the
operating room by measuring time to spontaneous movement, cough, response to painful pinch,
tracheal extubation ,opening of eyes and stating correct name, age and body parts. The return of
cognitive functions in the late recovery phase was assessed in the post-anaesthesia care unit
(PACU) by post-anaesthesia recovery scores (PARS), the Trieger dot test (TDT) and the digit
substitution test (DST). Recovery times were not increased by increased duration of desflurane
anaesthesia. The desflurane patients showed no delirium, minimal sedation and less shivering
during the entire postoperative course. They concluded that desflurane anaesthesia was superior
to isoflurane anaesthesia, not only in emergence, but also in the recovery of cognitive functions.
Aliyeva A and coworkers studied the effect of 2 different doses of
dexmedetomidine on desflurane consumption and hemodynamic parameters. Sixty patients aged
18-60 were divided into 3 groups. Group A received 1mcg /kg of dexmedetomidine infusion,
group B received 0.5 mcg/kg of dexmedetomidine infusion and group C received physiological
saline solution. During operation hemodynamic parameters, desflurane consumption were
recorded. It is concluded that administration of dexmedetomidine as 1mcg/kg and 0.5 mcg/kg
infusion decreased desflurane consumption by 45 % compared to control group11.
Shin HW and coworkers studied the effect of dexmedetomidine infusion at 1
mcg/kg on sevoflurane consumption during general naesthesia. Forty two patients of ASA status
I and II undergoing gynaecological surgery with anticipated operation time of 2 hrs, were
randomly assigned to receive dexmedetomidine 1mcg/kg (Dex group) or saline (Control group)
intravenously over 10 min before anaesthetic induction. After tracheal intubation with propofol
2mg/kg,cisatracurium 0.15 mg/kg intravenous, anaesthesia was maintained with sevoflurane,O2
50 %, N2O 50%. It was concluded that preanaesthetic dexmedetomidine 1mcg/kg single infusion
decreased the sevoflurane consumption without the change of recovery times12.
Robert J Fragen et Al studied the effect of dexmedetomidine on the minimum
alveolar concentration of sevoflurane in adults aged55 to 70 years. Forty five adults aged
between 55-70 years with ASA grade I and II were enrolled in this study. They Concluded that
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Dexmedetomidine 0.7 ng/ml decreased the MAC of sevoflurane by 17%, whereas there was no
difference between the placebo and the dexmedetomidine 0.39 ng/ml group13.
6.3
6.3 AIM AND OBJECTIVES OF THE STUDY:
To study the effect of dexmedetomidine infusion on desflurane consumption, recovery
characteristics and side effects in entropy guided general anaesthesia.
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MATERIAL AND METHODS:
7.1 SOURCE OF DATA:
a) Study Site
Victoria hospital And Bowring and Lady Curzon Hospitals attached to
Bangalore Medical College and Research Institute .
b) Study Duration
The study will be done between November 2013 to May 2015
c) Design Of Study
Prospective, randomized, control trial, double blind study.
.
d) Sample Size
Keeping the power of study as 80% and confidence limit at 95%,to detect a 20%
change in desflurane consumption, the minimum sample size required is 12
in each group. We have included 25 patients in each group. Patients classified as
per American Society of Anesthesiologists (ASA) classes I and II scheduled for
elective surgery under general anaesthesia will be studied. The patients will be
randomly allocated into two groups of 25 each.
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e) Inclusion criteria
1) Patients who give informed written consent.(annexure I)
2) Patients aged between 18 to 45 years.
3) Patients belonging to ASA Grade I and Grade II.
f) exclusion criteria:
1) An allergy to adrenergic agonists.
2) A history of uncontrolled hypertension.
3) Heart block greater than first degree. History of uncontrolled hypertension.
4) A history of alcohol or drug abuse.
5) Clinically significant neurologic, cardiovascular, renal, hepatic, gastrointestinal diseases.
7.2 METHOD OF COLLECTION OF DATA:
1) Sampling method:
After obtaining informed written consent from patients, patients will be randomly divided into 2
groups
Group D : Dexmedetomidine group – patients
Group P: Control group-Patients.
MATERIALS AND METHODS:
With a minimum Fasting state of 6-8 hours before anaesthesia IV access will be obtained and
standard monitoring will consist of Electrocardiography (ECG), pulse Oximetry, Noninvasive
Blood pressure(NIBP), Entropy sensor, Neuromuscular transmission indicator(NMT) and
capnography. The spectral entropy will be measured with a plug in Datex ohmeda entropy S/5
module. All patients will be pre-oxygenated with 100% oxygen for 3 minutes and inj.Midazolam
0.05mg/kg IV, inj.Fentanyl 2micrograms/kg IV will be administered.
Dexmedetomedine group (D) patients will be given a loading dose of inj.Dexmedetomedine
1microgm/kg IV made to 20ml with normal saline, over 10 minutes. Anaesthesia will be induced
with inj. Propofol in successive 30mg doses every 2 minutes until RE drops to 60,and will be
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confirmed with loss of response to verbal commands .Control group(C) patients will receive
similar volume of normal saline 0.9% over 10 minutes, and anesthesia will be induced with
inj.Propofol in the same manner as in group (D). Additional dose of inj.Propofol 20-30 mg bolus
will be given until no increase in entropy values is observed. Both groups will receive
inj.Vecuronium 0.1mg/kg IV to facilitate tracheal intubation. A maintenance dose of inj.
Dexmedetomedine infusion at 0.5microgm/kg/hour made to 20 ml with normal saline, will be
administered till the end of surgery. Anaesthesia will be continued with Desflurane in 60%
nitrous oxide in oxygen and ventilated to maintain end tidal CO2 between 35-40mmHg.
Desflurane concentration will be adjusted according to entropy parameters for adequate depth of
general anaesthesia and also clinical variables like HR, NIBP, Mean arterial pressure(MAP).
Adequate muscle relaxation will be guided by NMT monitor. Entropy values will be recorded atbaseline before induction, after induction, before intubation, 1minute after intubation and every
5minutes thereafter, along with all other vital parameters till the end of surgery. Fresh gas flow
will be at 6L/minute until the difference between inspiratory and expiratory Desflurane
concentration is less than 20% and then the FGF rate will be reduced to 1.5L/minute. Infusion of
Dexmedetomedine will be stopped 30 minutes prior to expected time of completion of surgery.
Desflurane administration will be cut off at the beginning of skin closure and the fresh gas flow
will be increased to 6L/minute oxygen at the end of the skin closure. This would define the
beginning of recovery period. Residual neuromuscular blockade will be reversed with
inj.Neostigmine 0.5mg/kg and inj.Glycopyrrolate 0.005mg/kg and patient will be extubated after
recovery of adequate respiratory effort and muscle power.
Age, sex, body weight, duration of surgery (minutes), duration of anaesthesia (minutes) will be
recorded.
Parameters observed.
1.Total and hourly Desflurane consumption.
2.Entropy parameters, Systolic blood pressure SBP, Diastolic blood pressure DBP, Mean
Arterial Pressure MAP, Heart rate will recorded intra-operatively at baseline before induction,
after induction, before intubation, 1minute after intubation and every 5minutes thereafter
3.Time for extubation
4.Ramsay sedation Score(annexure II) and modified aldrete score (annexure III)after extubation.
Statistical analysis:
Parametric data will be assessed with Independent sample T test and paired T test. Benferroni’s
correction applied as appropriate .Non parametric data will be assessed with Chi square test and
Fischer exact test.
7.3 Does the study require any investigation or intervention to be conducted on patients or
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other humans or animals? If so please describe briefly.
A) It does not require any intervention on animals.
B) Investigations only on patients that are routine for the study with their consent.
7.4 Has ethical clearance has been obtained from your institution in case of 7.3?
YES
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LIST OF REFERENCES:
1. Edmond I-Eger II Inhalational anaesthetics uptake and distribution ; Millers Anaesthes
Lavs I Ericsson. Lee A. Fleischer Jeanine P. Weiner-Kronish. William L. Young. Churchill
Livingstone Elsvier ; Philadelphia. 7th edition 2005. Page 554-558.
2. Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative,amnestic and analgesic
prpperties of small-dose Dex infusion..Anaesth Analg2000;90:699-705
3. Talke P, Richardson CA, Scheinin M, Fisher DM. Postoperative pharmacokinetics and
sympatholytic effects of dexmedetomidine. Anesth Analg 1997;85:1136 – 428.
4.Aantaa R,Taakola ML,Kallio A,Kanto J.Reduction of the minimum alveolar concentration of
isoflurane by dexmedetomidine. Anaesthesiology 1997;86;1055-1060
5. Aho M, Erkola O, Kallio A, Scheinin H, Korttila K. Dexmedetomidine infusion for
maintenance of anesthesia in patients undergoing abdominal hysterectomy. Anaesth Analog
1992
6.tanski DR: Monitoring depth of anesthesia. In: Miller RD (ed): Anesthesia, 4th ed. New York:
Churchill Livingstone, 1994:1127–59.
7.David .B . Glick.The autonomic nervous system.Millers anaesthesia.Editors .Lavs I
Ericsson.Lee A. Fleischer Jeanine P. Weiner-Kronish. William L. Young. Churchill
Livingstone Elsvier ; Philadelphia. 7th edition 2005. Page 285.
8.Talke p. Chen R, Thomas B, Aggarwall A, Gottelib A, Thorborg P, Heard S, Chung A,Son
SI,Kallio A . The hemodynamic and adrenergic effects of perioperative dexmedetomidine
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infusion after vascular surgery. Anaesth Analg 2000;90:834-839.
9.Guler G,Akin Z, Tosun E,Eskiatascoly,Mizrak A,Boyaci A.Single dose dexmedetomidine
attenuates airway and circulatory reflexes during extubation. Acta Anaesthesiol scand
2005;49:1088-1091
10. Earl M Strum and coworkers . Anaes Analg 2004;99:1848-1854.
11. Aliveya A and coworkers. Erciyes Medical Journal 2009 Vol 31 No 2 pages 110-118.
12.Shin HW and coworkers Korean J of Anaesthesiol 2013 Aug ;65(2): 114-120.
13.Robert J Fragen & Paul. C. Fitzgerald. Journal of clinical Anae Vol II Sep 1999 pages 442446.
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9.
SIGNATURE OF THE
CANDIDATE
10.
REMARKS OF THE GUIDE
11.
11.1
11.2
NAME AND DESIGNATION
OF GUIDE
DR. HARSOOR SIDHARAMESHWAR
PROFESSOR & HEAD
DEPARTMENT OF ANAESTHESIOLOGY.
BMC&RI
SIGNATURE
11.3
CO-GUIDE ( IF ANY )
11.4
SIGNATURE
11.5
HEAD OF THE
DEPARTMENT
11.6
SIGNATURE
12.1
REMARKS OF THE
CHAIRMAN AND PRINCIPAL
12.2
SIGNATURE
DR. HARSOOR SIDHARAMESHWAR
PROFESSOR & HEAD
DEPARTMENT OF ANAESTHESIOLOGY.
BMC&RI
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ANNEXURE I
INFORMED WRITTEN CONSENT
A single randomized double-blind trial to study the effect of desflurane consumption and
recovery characteristics in entropy guided general anaesthesia with or without dexmedetomidine
infusion.
You are invited to take part in this research study. The information in this
document is meant to help you decide whether or not to take part. Please feel free to ask if you
have any queries or concerns.You are being asked to participate in this study being conducted in
Department of Anaesthesiology,Victoria hospital/Bowring and Lady Curzon hospital,Bangalore
Medical College and Research Institute because you satisfy our eligibility criteria which are:
(1)Age between 18 to 50 years
(2)No contraindication to the use of the agent to be used in the study, which means absence of
any systemic disease, not on any long term steroids.
You will be one of the 50 patients we plan to recruit in this study. You will be assigned to either
of the two study groups. One group of patients will receive standard medications, which are
injection glycopyrolate,injection midazolam,injection fentanyl,injection thiopentone,injection
succinyl choline,injection vecuronium, desflurane inhalation plus normal saline while other
group of patients will receive standard medications and dexmedetomidine infusion.
What is the purpose of research?
Desflurane is an inhalational anaesthetic commonly used now-a-days. It has many advantages
over other inhalational anaesthetics. It undergoes minimal metabolism. It can be safely used in
liver and kidney disorders. It can be safely used in old age patients. It is beneficial in long
duration surgeries. When desflurane is used as an inhalational anaesthetic extubation time and
eye opening time are shorter. Totally hospital stay is found to be less. But desflurane is said to be
expensive. By using dexmedetomidine infusion we can reduce the consumption of desflurane.
The studies on effect of dexmedetomidine infusion on desflurane consumption and recovery
characteristics in entropy guides general anaesthesia are limited. So in this study we want to
establish that desflurane requirement will be reduced and there will be early recovery when
dexmedetomidine infusion is used.
We have obtained permission from the Institutional Ethics Committee for conducting this study.
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Possible risks to you
The study drug is a well established treatment, and so far, in earlier studies with this dosage
given, has not demonstrated any side effects.
Possible benefits to you
You are not expected to get any benefit from being on this research study, other than the
treatment benefit and free investigations/tests.
Possible benefits to other people
The results of the research may provide benefits to the society in terms of advancement of
medical knowledge and/or therapeutic benefit to future patients.
The alternatives you have
If you do not wish to participate, you have the alternative of getting the standard treatment for
your condition.
Confidentiality of the information obtained from you
You have the right to confidentiality regarding the privacy of your medical information (personal
details, results of physical examinations, investigations, and your medical history). By signing
this document, you will be allowing the research team investigators, other study personnel,
institutional ethics committee, if required. The results of clinical tests and therapy performed as
part of this research may be included in your medical record. The information from this study, if
published in scientific journals or presented at scientific meetings, will not reveal your identity.
How will your decision to not participate in the study affect you?
Your decision not to participate in this research study will not affect your medical care or your
relationship with the investigator or the institution. Your doctor will still take care of you and
you will not lose any benefits to which you are entitled.
Contact persons
For further information/questions,you can contact us at the following address
Dr.Harsoor Sidharameshwar Professor and HOD Department of Anaesthesiology.BMC & RI
Dr.Rajesh. R. Nayak,PG student,Department of Anaesthesiology,BMC&RI
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I, Mr/Mrs/Ms
,exercising my own free willpower of choice,
hereby give consent for myself as an object in the clinical study “A COMPARATIVE STUDY
OF
DESFLURANE
ENTROPY
CONSUMPTION
GUIDED
GENERAL
AND
RECOVERY
ANAESTHESIA
CHARACTERISTICS
WITH
OR
IN
WITHOUT
DEXMEDETOMIDINE INFUSION conducted by Dr.Harsoor Sidharameshwar, Dr.Rajesh.R.
Nayak. Department of Anaesthesiology, Victoria hospital/ Bowring and Lady Curzon hospital,
Bangalore Medical college and Research Institute.
The attending doctors have informed me to my satisfaction and in a language best understood by
me, the purpose of this study, the materials to be used during the course of this study as well as
the side effects/ complications associated with the methods/tools to be used.
I shall not hold the doctors or the staff responsible for any untoward consequences. I am also
aware of my right to opt out of the study without prejudice to further treatment at any time
during the course of the study without having to give any reasons to do so.
Signature of attending doctor :
Date :
Signature/Left thumb
impression of patient
Signature of witness :
Date :
12
ANNEXURE II
VAS (Visual Analogue Scale)

Pain severity will not be at rest ,in supine position and also on exertion using peak flow.

Pain severity will be noted at 2, 6hours and 24 hours post operatively.

It will be noted for Incisional, Visceral and shoulder pain.

Inj Diclofenac 75mg intravenously will be given on demand as rescue analgesic.
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ANNEXURE III
RAMSAY SEDATION SCALE
1- anxious and agitated, restless
2- co-operative, oriented, tranquil
3- responsive to verbal commands, drowsy
4- “asleep”, responsive to light stimulation(loud noise, tapping)
5- asleep, slow response to stimulation
6- no response to stimulation
ANNEXURE IV
MODIFIED ALDRETE SCORE
Level of consciousness Score
Awake and oriented 2
Arousable with minimal stimulation 1
Responsive only to tactile stimulation 0
Physical activity
Able to move all extremities on command 2
Some weekness in movement of extremities 1
Unable to voluntarily move extremities 0
Hemodynamic stability
Blood pressure ,15% of baseline MAP value 2
Blood pressure 15-30 % of baseline MAP value 1
Blood pressure 30% below baseline MAP value 0
14
Respiratory stability
Able to breathe deeply 2
Tachypnea with good cough 1
Dyspneic with weak cough 0
Oxygen saturation status
Maintains value .90% on room air 2
Requires supplemental oxygen (nasal prongs ) 1
Saturation 90 % with syupplemental oxygen 0
Postoperative pain assessment
None or mild discomfort 2
Moderate to severe pain controlled with iv analgesics 1.
Persistent severe pain 0
Postoperative emetic symptoms
None or mild nausea with no active vomiting 2
Transient vomiting or retching 1
Persistent moderate to severe nausea and vomiting 0.
Total score 14
MAP 5 mean arterial pressure.
References
1. Aldrete JA. The post-anaesthesia recovery
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