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RAGIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGLORE
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1. NAME OF THE CANDIDATE
AND ADDRESS
:
2. NAME OF THE INSTITUTION
: MYSORE MEDICAL COLLEGE AND
RESEARCH INSTITUTE
MYSORE
3. COURSE OF STUDY AND
SUBJECT
4. DATE OF ADMISSION TO
THE COURSE
5. TITLE OF THE TOPIC
DR. G.B.SUMALATHA
C/O G.B.VIJAYKUMAR,ASST TEACHER,
MCC A BLOCK, 3RD MAIN
CHURCH ROAD, #2110, DAVANGERE,
KARNATAKA.
: M D ANAESTHESIOLOGY
: 9th MARCH 2009
: “ATTENUATION OF HAEMODYNAMIC
RESPONSE TO LARYNGOSCOPY AND
TRACHEAL INTUBATION IN ADULT
PATIENTS WITH A SINGLE
INTRAVENOUS DOSE OF 0.6ug/kg OF
DEXMEDETOMIDINE”
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6. BRIEF RESUME OF THE INTENDED WORK
6.1
NEED FOR THE STUDY:
Laryngoscopy and endotracheal intubation are employed for safe conduct of general
anaesthesia. However both laryngoscopy and intubation are noxious stimuli and are
associated with stress responses & haemodynamic responses in the form of laryngosympathetic stimulation which is manifested as hypertension, tachycardia & arrhythmias.
These haemodynamic responses are well tolerated in otherwise healthy individuals, but in
patients with hypertension, coronary heart disease, cerebrovascular disease & intracranial
aneurysm these transient changes can result in potentially deleterious effects like left
ventricular failure, pulmonary edema, myocardial ischemia, ventricular dysrhythmias &
cerebral haemorrhage1
Attempts were made as early as in 1960’s by various investigators to reduce the
sympathetic response to laryngoscopy & intubation. These include:
1. deepening the plane of anaesthesia with inhalational & intravenous
anaesthetic agents.1
2. Decreasing the duration of laryngoscopy to less than 15 seconds.
3. usage of drugs like lidocaine, sedatives, opioids, vasoactive drugs like sodium
nitroprusside, calcium channel blockers, beta blockers1 and other drugs
especially alpha 2 agonists like clonidine & dexmedetomidine.2
Intravenous Dexmedetomidine, a central alpha 2 agonist is being used in anaesthesia
practice as a premedicant. The advantages of Dexmedetomidine as premedicant in
anaesthesia setting include sedation, analgesia, anxiolysis & improved hemodynamic
stability. Because of these beneficial properties it has been found that the minimum alveolar
2
concentration (MAC) of volatile anaesthetics also decreases significantly up to 90% and
hence decreases the requirement of anaesthetics.3 It has also been found that it can decrease
the haemodynamic response to laryngoscopy and intubation. 4,5
Dexmedetomidine is being used in other countries since many years as
premedicant. Since it has been introduced recently in India, (only in2009) and not many
studies have been done in our country, there is a need to study the effectiveness of
Dexmedetomidine in obtunding the hemodynamic response to laryngoscopy & intubation
The present study is aimed at attenuation of haemodynamic response to laryngoscopy
& intubation in adult patients with single intravenous bolus dose of Dexmedetomidine
0.6ug/kg given 10 min prior to induction.
REVIEW OF LITERATURE
1. Pharmacology & physiology in anaesthesia practice, by Robert K. Stoelting & Simon
C. Hillier, Philadelphia, Lippincott Williams and Wilkins ( 4th edition 2006),2
Dexmedetomidine is a highly selective, specific, and potent alpha 2 adrenergic agonist
(1,620:1 alpha 2 to alpha 1)(Bloor et al, 1992;Sandler, 1996). This drug is the dextroisomer
and pharmacologically active component of medetomidine, which has been used for many
years in veterinary practice for its hypnotic, sedative, and analgesic effects. Compared with
clonidine, Dexmedetomidine is 7-10 times more selective for alpha 2 receptors and has a
shorter duration of action than clonidine. In this regard Dexmedetomidine is considered full
agonist at the alpha 2 receptors, whereas clonidine is a partial agonist ,( ratio of alpha 2:alpha
1 activity for clonidine is 220:1)(Sandler,1996). The elimination half time of
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Dexmedetomidine is 2-3 hours compared with 6-10 hours of clonidine. Dexmedetomidine is
highly protein bound (90%) and undergoes extensive hepatic metabolism.
As with clonidine, pretreatment with Dexmedetomidine attenuates responses to
tracheal intubation, decreases plasma catecholamine concentrations during anaesthesia,
decreases perioperative requirements for inhaled anaesthetics and opioids and increases the
likelihood of hypotension. Dexmedetomidine decreases MAC for volatile anaesthetics in
animals by >90% compared with a plateau effect between 25% to 40% for clonidine. Despite
marked dose dependant analgesia and sedation produced by this drug, there is only mild
depression of ventilation. The preservation of breathing provides a potential anaesthetic
technique for patients with difficult upper airway.
2. Martina Aho, A.M.Lehinten, O.Erkola et al
6
in the year 1991, conducted a
double blind, randomized study in 96 women undergoing abdominal hysterectomy to
evaluate the effect of intravenously administered Dexmedetomidine on perioperative
hemodynamics & isoflurane requirements. Here they studied the effect of 2 doses of
Dexmedetomidine 0.3ug/kg & 0.6ug/kg, fentanyl 2ug/kg & saline as a single intravenous
bolus dose which were administered 10 min prior to induction of anaesthesia. They found
that in all groups BP & HR increased after tracheal intubation. However increase in BP &
HR was significantly less in Dexmedetomidine group which received 0.6µg/kg than in saline
group. At the same time they noted that in patients receiving Dexmedetomidine 0.3µg/kg, the
increase in HR & BP did not differ from that of saline group. The major findings of this
study were that Dexmedetomidine administered before induction at a dose of 0.6µg/kg
blunted the tachycardiac response during endotracheal intubation.
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3. M.L.Jaakola, T.Ali-melkkila, J.Kanto et al5 in year 1992, studied the effect of a
single intravenous bolus dose of Dexmedetomidine on intraocular pressure, hemodynamic &
sympathoadrenal responses to laryngoscopy & tracheal intubation. The effects were studied
in a randomized placebo contolled, double blind trial in 30 ASA I patients undergoing
cataract surgery. The groups were allocated to receive Dexmedetomidine 0.6ug/kg and saline
placebo intravenous 10 min before induction of anaesthesia, In group receiveing
Dexmedetomidine there was 34% reduction in intraocular pressure & 62% reduction in
plasma nor-adrenaline concentrations. After intubation maximum heart rate was 18% less in
Dexmedetomidine group compared with placebo. They also noted that there was a significant
decrease
in
blood
pressure
in
Dexmedetomidine
group.
They
concluded
that
Dexmedetomidine may be a useful adjunct in ophthalmic surgery.
4. B.Scheinin, L.Lindgren, T.Randell et al4 in the year 1992, evaluated the effect
of Dexmedetomidine in attenuating sympathoadrenal responses to tracheal intubation &
requirements of Thiopentone and fentanyl perioperatively. They studied the effect in a
randomized placebo controlled, double blind trial in 24 ASA – I patients. Dexmedetomidine
0.6ug/kg or saline was given 10 min before induction of anaesthesia. They concluded that
required dose of Thiopentone was significantly smaller in Dexmedetomidine group than in
control group. They also concluded that the drug attenuated the cardiovascular responses to
laryngoscopy and tracheal intubation.
5.
Basar H, Akpinar S, Doganci N et al7 in 2008, evaluated the effects of
preanaesthetic single dose Dexmedetomidine on induction, hemodynamic & cardiovascular
parameters. The effects were studied in randomized double blind trial in 40 ASA I & II
patients scheduled for Cholecystectomy. Patients were divided randomly into two groups to
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receive 0.5ug/kg of Dexmedetomidine ( Group D) 10 minutes before anaesthesia, slowly
over 60 seconds or saline (Group C). Measurements of mean arterial pressure, heart rate,
ejection fraction, end diastolic index. Cardiac index & stroke volume index were recorded at
every 10 min intervals. The time for patients to “open eyes on verbal command” & post op
Aldrete recovery scores were also recorded. In Group C , increase in heart rate & mean
arterial pressure(MAP) occurred after endotracheal intubation. In group D heart rate(HR)
significantly decreased after Dexmedetomidine. The end diastolic index (EDI), cardiac
index(CI), stroke volume index(SVI) and ejection fraction(EF) values were similar in groups
D and C.The modified Aldrete recovery scores of patients were similar in groups C and D.
They concluded that a single dose of Dexmedetomidine given prior to induction of
anaesthesia decreased thiopental requirements without serious hemodynamic effects or any
effect on recovery time.
6. Yildiz M, Tavlan A, Tuncer S et al8 in 2006 evaluated the effect of a single
preinduction intravenous dose of Dexmedetomidine 1 ug/kg on cardiovascular responses
resulting from laryngoscopy & tracheal intubation, need for anaesthetic agent &
perioperative haemodynamic stability. Here fifty patients scheduled for minor surgery were
randomized in to two groups, Dexmedetomidine group & placebo group, n=25 in each group.
During and after drug administration, the Ramsay sedation scale was applied every 5 min.,
haemodynamic parameters and adverse effects were recorded every 10 min for 1 hour after
surgery. The results were, during intubation the need for thiopental and sevoflurane
concentration were decreased by 39% & 92% respectively in Dexmedetomidine group
compared with placebo group. In all groups blood pressure & heart rate increased after
tracheal intubation; both were significantly reduced in Dexmedetomidine group than in
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placebo group. Hence they concluded that preoperative administration of single dose of
Dexmedetomidine resulted in progressive increase in sedation, blunted the haemodynamic
response to laryngoscopy and reduced opioids and anaesthetic requirements.
OBJECTIVES
1. To study changes in heart rate, systolic blood pressure, diastolic blood pressure & mean
arterial blood pressure associated with laryngoscopy & intubation.
2. To evaluate the efficacy of Dexmedetomidine in the dose of 0.6ug/kg as a single bolus
dose in attenuating hemodynamic response to laryngoscopy & tracheal intubation in adult
patients.
3. To study the effect of Dexmedetomidine in decreasing the requirements of induction
agent, Thiopentone.
4. To study any adverse effects associated, such as perioperative hypotension, bradycardia,
post op recovery & post op excessive sedation.
MATERIALS & METHODS
Source of Data
100 patients aged between 18yrs and 50yrs of ASA class I for various elective surgeries
requiring general anaesthesia at Krishnarajendra & Cheluvamba hospital attached to Mysore
medical college & Research institute, Mysore, will be randomly selected for the study. This
prospective, randomized, double blind study will be conducted from Nov 2009 to July 2011.
The study population will be divided into 2 groups of 50 patients each.
a. Group D ( n=50) = Dexmedetomidine group
b. Group C ( n=50) = control group
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Preoperative assessment will be done for each patient and written consent will be taken.
Patients will be premedicated on the night before surgery with Tablet Ranitidine 150mg and
Tablet Alprazolam 0.5mg. Intravenous line obtained with 18 guage cannula The study drug
Dexmedetomidine will be given to group ‘D’ as a bolus dose of 0.6ug/kg diluted in normal
saline to 5 ml and injected intravenously slowly over one minute, 10 minutes before
induction.
Group C patients will be given 5ml of normal saline, 10 min before induction.
The double blind design of study is assured by the fact that an anesthesiologist not
further involved in the study prepared syringes immediately before induction of anaesthesia.
The syringes are marked Dexmedetomidine/placebo together with the name of the patient.
The anaesthesiologist responsible for the anaesthetic technique is thus kept unaware of the
content of the syringes.
Both the groups will be premedicated with 0.2 mg glycopyrollate, 1 mg midozolam & 15 mg
pentazocine given intravenously before induction.
General anaesthesia will be induced with 2.5% Thiopentone in incremental doses till
the eyelash reflex is lost. The loss of eyelash reflex is taken as criteria for end of induction.
The dose of Thiopentone required for induction is noted down in both the groups.
Succinylcholine 1.5mg/kg is given for intubation.Both groups of patients will be intubated
with appropriate sized cuffed endotracheal tubes with gentle laryngoscopy. Anaesthesia will
be maintained with oxygen + nitrous oxide + Inj Vecuronium bromide + 0.5% halothane.
After the surgical procedure patients of both the groups will be reversed with
Inj.Neostigmine 2.5mg + Inj Glycopyrollate 0.5mg intravenously.
INCLUSION CRITERIA
8
-
Healthy adult patients aged between 18 – 50 yrs
-
Patients belonging to ASA class I
EXCLUSION CRITERIA
-
Patients with hypertension, cardiac, renal, hepatic & cerebral diseases,
-
Patients with difficult airway and obese patients
-
Patients with endocrinal diseases like hyperthyroidism, hypothyroidism and
diabetes mellitus.
METHODS OF COLLECTION OF DATA
A. Hemodynamic responses are compared in both groups by measuring
1. Heart rate
2. Systolic blood pressure
3. diastolic blood pressure
4. mean arterial pressure
These parameters are measured using automatic multiparameter monitor at following
intervals
1. Before giving the test drug
2. After administration of test drug at 2 min, 5 min & 8 min.
3. Just before induction
4. After induction
5. After intubation at 1 min, 3min, 5 min & 10 min
6. Heart rate, systolic blood pressure, diastolic blood pressure and mean arterial
pressure every 10 min throughout the surgery.
B. Post operative recovery and sedation will be studied.
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Time of recovery from anaesthesia is the interval from injecting the reversal agent to the
spontaneous eye opening.
Sedation scoring will be done as per Ramsay sedation scale:
Score
response
1
anxious or restless or both
2
co-operative, oriented & tranquil
3
responding to commands
4
brisk response to stimulus
5
sluggish response to stimulus
6
no response to stimulus
The results of intended study between the two groups will be compared statistically using ‘p’
value obtained from Student‘t’ test.
7.2 Does the study require any investigation/intervention to be conducted on
patients/human/animals? If so describe briefly.
No
7.3 Has ethical clearance been obtained from your institution in case of 7.3?
Yes obtained. (copy enclosed)
8.LIST OF REFERENCES
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1. King BD, Harris LC, “Reflex circulatory responses to Direct laryngoscopy and Tracheal
intubation performed during General anaesthesia”, Anesthesiology, 1951;12: 556-566
2. Stoelting RK, Hiller SC, “ Pharmacology and physiology in anesthetic practice”,
Philadelphia, Lippincott Williams and Wilkins,2006,340
3. Bloor BC, Ward DS, Belleville JP, Maze M. Effects of intravenous dexmedetomidine in
humans. II Haemodynamic changes. Anaesthesiology 1992;77:1134-1142.
4. Scheinin B, Lindgren L, Randell T, Scheinin H, Scheinin M. Dexmedetomidine attenuates
sympathoadrenal responses to tracheal intubation and reduces the need for thiopentone &
peroperative fentanyl. British journal of anaesthesiology 1992;68:126-131
5. Jakola ML, Ali-Melkkila T, Kanto J, Kallio A, Scheinin H, Scheinin M. Dexmedetomidine
reduces intraocular pressure, intubation response and anaesthetic requirements in patients
undergoing ophthalmic surgery. British journal of anaesthesiology 1992;68:570-575
6. Martina Aho, Lehinten AM, Erkola O, Kallio A, Korttila K. The effects of intravenously
administered dexmedetomidine on perioperative hemodynamics and isoflurane requirements
in patients undergoing abdominal hysterectomy. Anaesthesiology 1991;74:997-1002
7.
Basar H, Akpinar S, Doganci N, Buyukkocak U, Kaymak C et al. The effects of
preanaesthetic,
single-dose
dexmedetomidine
on
induction,
hemodynamic,
and
cardiovascular parameters. Journal of clinical anaesthesia,2008 Sep;20(6):431-436
8.
Yildiz M, Tavlan A, Tuncer S, Reisli R, Yosunkaya A, Otelcioglu S. Effect of
dexmedetomidine on haemodynamic responses to laryngoscopy and intubation, perioperative
haemodynamics and anaesthetic requirements. Drugs R D 2006;7:43-52
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9. Signature of the Candidate
:
10. Remarks of the Guide
:
11. NAME AND DESIGNATION OF
11.1 Guide
: Dr.ARUNA T.M.
ASSISTANT PROFESSOR
DEPARTMENT OF
ANAESTHESIOLOGY
MYSORE MEDICAL COLLEGE AND
RESEARCH INSTITUTE, MYSORE
11.2 Signature of Guide
:
11.3 Co-guide (if any)
:
11.4 Signature of Co-Guide
:
12
11.5 Head of the Department
:
PROF.DR.C.L.GURUDATT M.D . D.A.
PROFESSOR AND HEAD
DEPARTMENT OF ANAESTHESIOLOGY,
MYSORE MEDICAL COLLEGE AND
RESEARCH INSTITUTE, MYSORE
11.6 Signature of
Head of the Department :
12. REMARKS
12.1Remarks of the
Dean and Director
12.2 Signature
:
:
13
ETHICAL COMMITTEE CLEARANCE
1. TITLE OF DISSERTATION
: “ATTENUATION OF
HAEMODYNAMIC RESPONSE TO
LARYNGOSCOPY AND TRACHEAL
INTUBATION IN ADULT
PATIENTS WITH A
SINGLE INTRAVENOUS
BOLUS DOSE OF
0.6 µg / kg BODY WEIGHT OF
DEXMEDETOMIDINE.”
2. NAME OF THE CANDIDATE
: DR.G.B.SUMALATHA
3. SUBJECT
: M.D. ANAESTHESIOLOGY
4. NAME OF THE GUIDE
:Dr.ARUNA T.M.
ASSISTANT PROFESSOR
DEPARTMENT OF
ANAESTHESIOLOGY
MYSORE MEDICAL COLLEGE AND
RESEARCH INSTITUTE, MYSORE
5. APPROVED/NOT APPROVED
(If not approved, suggestion)
: APPROVED
14
MEDICAL SUPERINTENDENT
MEDICAL SUPERINTENDENT
KR Hospital
Mysore
Cheluvamba Hospital
Mysore
PROFESSOR AND HOD
PROFESSOR AND HOD
Depart ment of medicine
Mysore Medical College and
Research institute, Mysore
Department of Surgery
Mysore Medical College and
Research institute, Mysore
MEDICAL SUPERINTENDENT
P.K.T.B and CHEST DISEASES
HOSPITAL, MYSORE
LAW EXPERT
DEAN AND DIRECTOR
MYSORE MEDICAL COLLEGE
AND RESEARCH INSTITUTE, MYSORE
15