Download appendix - iii

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA
SYNOPSIS
OF
DISSERTATION
“COMPARISON OF SINGLE DOSE OF INTRAVENOUS
RAMOSETRON AND RAMOSETRON PLUS
DEXAMETHASONE AS PROPHYLACTIC ANTI- PONV IN
PATIENTS COMING FOR ELECTIVE ENT SURGERIES-A
CLINICAL STUDY”
Submitted by
Dr. AMITHA.S
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
Dr. AMITHA.S
D/O K.C.SEENAPPA ‘BELLI CHUKKI’ SIT
EXTENSION, 16TH CROSS,
GANGOTRI ROAD, TUMKUR,
KARNATAKA- 572102
1
NAME OF THE CANDIDATE
AND ADDRESS
(in block letters)
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
28TH APRIL 2010
5.
“COMPARISON OF SINGLE DOSE OF
INTRAVENOUS RAMOSETRON AND
RAMOSETRON PLUS DEXAMETHASONE
AS PROPHYLACTIC ANTI- PONV IN
PATIENTS COMING FOR ELECTIVE ENT
SURGERIES-A CLINICAL STUDY”
TITLE OF THE TOPIC
BRIEF RESUME OF INTENDED WORK
6.
7
6.1 NEED FOR THE STUDY
APPENDIX-IA
6.2 REVIEW OF LITERATURE
APPENDIX-IB
6.3 OBJECTIVES OF THE STUDY
APPENDIX-IC
MATERIALS AND METHODS
APPENDIX-II
7.1 SOURCE OF DATA
APPENDIX-IIA
7.2 METHOD OF COLLECTION OF DATA
: (INCLUDING SAMPLING PROCEDURE
IF ANY)
APPENDIX-IIB
7.3 DOES THE STUDY REQUIRE ANY
INVESTIGATION OR INTERVENTIONS
TO BE CONDUCTED ON PATIENTS OR
OTHER ANIMALS, IF SO PLEASE
DESCRIBE BRIEFLY.
APPENDIX-IIC
7.4 HAS ETHICAL CLEARENCE BEEN
OBTAINED FROM YOUR INSTITUTION
IN CASE OF 7.3
YES
APPENDIX-IID
1
8.
LIST OF REFERENCES
9.
SIGNATURE OF THE CANDIDATE
10.
REMARKS OF THE GUIDE
11
NAME AND DESIGNATION
(in Block Letters)
APPENDIX - III
STUDY WILL BE CONDUCTED AT A.I.M.S.
11.1 GUIDE
Prof. Dr. RADHA. M.K. M.B.B.S., M.D.
Professor and Head of the Department,
Department of Anaesthesiology,
AIMS, B.G. Nagara-571448
11.2 SIGNATURE OF THE GUIDE
11.3 CO-GUIDE (IF ANY)
NONE
11.4 SIGNATURE
-
11.5 HEAD OF DEPARTMENT
Prof. Dr. RADHA. M.K. M.B.B.S., M.D.
Professor and Head of the Department,
Department of Anaesthesiology,
AIMS, B.G. Nagara-571448
11.6 SIGNATURE
12
12.1 REMARKS OF THE CHAIRMAN
AND PRINCIPAL
12.2 SIGNATURE
2
APPENDIX-I
6.BRIEF RESUME OF THE INTENDED WORK:
APPENDIX –I A
6.1 NEED FOR THE STUDY:
Post operative nausea and vomiting complicates the lives of both patients and health
care providers. The incidence of PONV varies between 20% and 30% depending on surgical
and patient factors1. Nausea is the uncomfortable sensation of impending episode of vomiting
it is often associated with prodromal symptoms such as salivation, swallowing, tachycardia etc.
Vomiting is a complicated process, mediated by a central co-ordinating “Vomiting Center”,
though to reside in the brain stem (close to the Tractus solitarius) called the parvicellular
Reticular formation or the emetic center2.
This is accompanied by multiple autonomic
phenomena including salivation, Shivering and vasomotor changes3,4. During prolonged
episodes, marked behavioral changes including lethargy, depression and withdrawal may
occur3,4. Hence PONV may prolong recovery, delay patient discharge, increase
hospital
expenditure 5 and thereby need to prevent the incidence of PONV.
Several studies were done in comparing ondansetron, dexamethasone and ondansetron
plus dexamethasone as a prophylactic antiemetic therapy in patients undergoing day-case
gynecological
surgeries.
Ondanestron
is
a
selective
5HT3-Receptor
antagonist.
Dexamethasone reduces inflammation and acts on opioids receptor these drugs act in emetic
centre to reduce incidence of PONV and studies showed that combination of drugs would be
better in prevention of PONV than use of either drug alone (ondansetron 4mg, dexamethasone
8mg)6. Studies have also being done in comparing ramosetron versus ondansetron for the
prevention of PONV in patients undergoing gynecological surgery. Ramosetron is a newer
congener of ondansetron having more potency than the latter.
3
The result found to be
ramosetron more potent than ondansetron in reducing nausea severity in female patients
undergoing gynecological surgery7.
In 2003 studies had done, to evaluate the role of dexamethasone in reducing post
operative vomiting & pain after pediatric tonsillectomy. Results found that, pre operative
dexamethasone 0.5mg/kg i.v. reduced both post operative vomiting & pain in children after
electrocautery tonsillectomy 8.
Since very few studies were done in comparing Ramosetron & Ramosetron plus
dexamethasone we have made an attempt to compare whether Ramosetron alone is sufficient
or combination of drugs is effective in prevention of PONV.
APPENDIX –I B
6.2 REVIEW OF LITERATURE
Post operative nausea and vomiting complicates the lives of both patients and health
care providers. The incidence of PONV varies between 20% and 30% depending on surgical
and patient factors. Several studies have been made to know the most economical and most
preferred drug to be opted to prevent PONV.
K.Liu et-al in 19988 did a double blind randomized study to compare the effect of
dexamethasone versus placebo on postoperative emesis and pain in a 60 women undergoing
general anaesthesia for major gynaecology surgery. Dexamethasone 10mg (group D) or saline
(group S) was administered i.v. in a double blind manner during induction of anaesthesia. Post
operative pain relief was controlled with bolus doses of morphine using an i.v. patientcontrolled analgesic device, and patients were assessed for incidence of vomiting, sedation
score, verbal pain rating score, time to first morphine demand & morphine consumption at
4
4,8,12&24 hr after surgery. Six patients in group D & 19 in group S experience vomiting at
least once within 24hr postoperative period; dexamethasone was effective in reducing the
overall incidence of vomiting from 63.3% to 20.0% (p<0.01). Other variables were similar
between the groups, and the influence of dexamethosone on postoperative pain was minimal.
R. Thomas et-al in 20019 performed a prospective randomized, double-blind
comparative study of dexamethasone, ondansetron and ondansetron plus dexamethasone as
prophylactic antiemetic therapy in patients undergoing day case gynecological surgery. In this
study, the effect of combination in comparisons to either of drug alone investigated in day care
gynecological surgery. A total of 177 patients were randomized to three groups:
dexamethasone8mg, ondansetron 4mg, dexamethasone 8 mg plus ondansetron 4mg. The result
found that combination of drug would be better in prevention of PONV than use of either drug
alone.
Dr.Moktar elhakim et-al in 200310 did a double blind study to evaluate the effects of
single dose of dexamethasone on the incidence and severity of post operative vomiting and
pain in children undergoing electro cautery tonsillectomy under standardized general
anesthesia. About 120 patients were randomly allocated either dexamethasone 0.5mg/kg
(maximum 8mg) i.v. or an equivalent volume of saline preoperatively .The incidence of early
and late, need for rescue antiemetic time of first oral intake, time of first demand of analgesia
& analgesic consumption were compared in both groups. Pain score used includes children’s
hospital eastern Ontario pain scale “faces,’’ & a 0-10 visual analogue pain. The results found
that Compared with placebo, dexamethasone significantly decreases the incidence of early
&late vomiting (p<0.005,p<0.001)respectively. .Fewer patient with dexamethasone group
needed antiemetic rescue (p<0.01).the time of first oral intake was shorter, and the time of first
dose of analgesic was longer in the dexamethasone group (p<0.01). Pain scores 30 min after
5
extubation were lower (p<0.005) in dexamethasone group. Hence concluded Preoperative
dexamethasone 0.5mg/kg iv reduces both post operative vomiting & pain in children after
electro cautery tonsillectomy.
Aarti Nandkumar Pawar
et- al in 200911 did
comparative study of single dose
intravenous dexamethasone.Ondansetron And Ondansetron Plus Dexamethasone As
Prophylactic anti-Emetic therapy in Patients Undergoing Laparoscopic Gynecological Surgery.
The study was undertaken on 120 patients in the age group of to 65 years with ASA grades I &
II
undergoing
gynaecologic
laparoscopic
intervention
under
general
anaesthesia.
Group 1 received Inj. Ondansetron 4mg with Inj. Dexamethasone 8mg as single dose I V bolus
5 minutes before induction of anaesthesia. Group 2 received Inj. Ondansetron 4mg as single
dose I V bolus 5 minutes before induction of anaesthesia. Group 3 received Inj.
Dexamethasone 8mg as single dose I V bolus 5 minutes before induction of anaesthesia.
A standard anaesthetic protocol was used in all the patients. 5 min prior, the patients received
the anti – emetic as per their groups Induction of general anaesthesia was done with Inj.
Propofol 2 – 3 mg / kg IV. Intubating conditions were achieved with Inj. Suxamethonium 2 mg
/ kg I V. Trachea was intubated with appropriate sized cuffed PVC endotracheal tube. General
anaesthesia was maintained with O2 + N2O::40:60.,skeletal muscle relaxation was maintained
with of Inj. Atracurium 0.5mg / kg as loading dose and 0.05mg/kg as supplemental doses. The
duration of anaesthesia, surgery, pneumoperitoneum was noted. Nasogastric tube was
introduced after induction & suction of gastric contents was done before recovery & was
removed after extubation.
The patients were evaluated at regular intervals of time in the post operative period for
complaints of nausea, vomiting. The results were found that Combination of Inj. Ondansetron
4mg with Inj. Dexamethasone 8mg proved to be more efficacious over either drug alone.
6
Fujii Y et-al in 199912 compared Ramosetron versus granisetron for the prevention of
postoperative nausea and vomiting after laparoscopic cholecystectomy. In this randomized,
double-blind study, 80 female patients received 3 mg granisetron and 0.3 mg ramosetron i.v.
(n=40 of each) at the completion of surgery. The standardized anesthetic included isoflurane
and nitrous oxide in oxygen. The response found that the incidence of patients with no
complaints PONV during the first 24 hr after anesthesia was 85% with granisetron and 93%
with ramosetron, respectively (P=0.241); the corresponding incidence during the next 24 hr
(24-48 hr) after anesthesia was 63% and 90% (P=0.004). No clinically important adverse
events due to the study drug were observed in any of the groups. This study
showed
Ramosetron was more effective than granisetron for prevention of PONV during 0-48 hr after
anesthesia for laparoscopic cholecystectomy.
Fujii Y et-al in 200013 performed a prospective, randomized, double-blinded study, they
evaluated the efficacy of granisetron and ramosetron for preventing postoperative nausea and
vomiting (PONV) in major gynecologic surgery. The study consist of No clinically serious
adverse events due to the drugs were observed in any of the groups.
120 patients, ASA physical status I or II, aged 23-65 yr, received i.v. granisetron 2.5 mg
or ramosetron 0.3 mg (n = 60 each) at the end of surgery. A standard general anesthetic
technique and postoperative analgesia were used. The incidence of a complete response,
defined as no PONV and no need for another rescue medication, 0-3 h after anesthesia was
87% with granisetron and 90% with ramosetron; the corresponding incidence 3-24 h after
anesthesia was 85% and 90%; the corresponding incidence 24-48 h after anesthesia was 70%
and 92% (P < 0.05). They concluded that prophylactic therapy with ramosetron is more
7
effective than granisetron for the longterm prevention of PONV after major gynecologic
surgery.
Fujii Y
et-al in 200014 did a prospective, randomized, double-blinded, placebo-
controlled trial for Ramosetron in preventing postoperative nausea and vomiting in women
undergoing gynecological surgery. The study consist of One hundred twenty women, ASA
physical status I or II, aged 21-63 yr, received IV either placebo or ramosetron 0.15, 0.3, or 0.6
mg (n = 30 of each) at the completion of surgery. A standard general anesthetic technique and
postoperative analgesia were used. A complete response, defined as no PONV and no need for
another rescue antiemetic, during 0-3 h after anesthesia occurred in 40%, 47%, 87%, and 90%
of patients who had received placebo and ramosetron 0.15, 0.3, and 0.6 mg, respectively.
Corresponding results during 3-24 h after anesthesia were 43%, 50%, 87%, and 90%, and 2448 h after anesthesia were 50%, 53%, 90%, and 93% (P < 0.05). Patients who had received
ramosetron 0.3 or 0.6 mg were satisfied compared with those who had received placebo (P <
0.05). There were no serious clinical adverse events caused by the study drug in any of the
groups.
The report shows that, ramosetron 0.3 mg is an effective antiemetic for preventing
PONV during 0-48 h after anesthesia in female patients undergoing gynecological surgery.
Increasing the dose to 0.6 mg provided no further benefit.
Fujii Y et-al in 200115 performed prospective, randomized, double-blind study,
Comparing granisetron versus ramosetron in Prevention of vomiting after tonsillectomy in
children: Granisetron, a selective 5-hydroxytryptamine type 3 receptor antagonist, is effective
for the prevention of vomiting after tonsillectomy in children. Ramosetron antagonist of 5-
8
hydroxytryptamione type 3 receptor, has more potent and longer-acting properties than
granisetron
Ninety pediatric patients, aged 4 to 10 years, received intravenously granisetron 40
microg/kg or ramosetron 6 microg/kg (n = 45 each) at the end of surgery. The same standard
general anesthetic technique and postoperative analgesia were used throughout. Emetic
episodes and safety assessment were performed during the first 24-hour period and the next
24-hour period after anesthesia.
The authors found that Ramosetron is a better antiemetic than granisetron for the long
term prevention of postoperative vomiting in children undergoing general aneshesia for
tonsillectomy.
Fujii Y et-al in 2003 16performed Randomized, double-blind, placebo-controlled, dosedfinding study of the antiemetic effects and tolerability of ramosetron in adults undergoing
middle ear surgery the study to determine the minimum effective and tolerable dose of
ramosetron needed to prevent postoperative emetic symptoms in adult patients undergoing
middle ear surgery. Patients aged more than 20 years scheduled for middle ear surgery were
randomized to receive either placebo or ramosetron at 1 of 3 doses (0.15, 0.3, or 0.6 mg),
regardless of body weight, i.v. immediately before anesthesia induction. Emetic symptoms
(nausea, retching, or vomiting) occurring from 0 to < 24 and 24 to 48 hours after the start of
anesthesia were recorded. The authors concluded Ramosetron 0.3 mg, regardless of body
weight, was more effective than either ramosetron 0.15 mg or placebo and as effective as
ramosetron 0.6 mg for the prevention of emetic symptoms in the first 48 hours after the start of
anesthesia in this selected population of adult patients who underwent middle ear surgery.
9
Lee D et-al in 200917 studied the effect of oral and IV ramosetron on postoperative
nausea and vomiting in patients undergoing gynecological laparoscopy with total intravenous
anesthesia. The study consists of 120 women were allocated randomly to one of three groups
(n = 40 in each) to receive saline (control), 0.1 mg oral ramosetron (PO), or 0.3 mg IV
ramosetron (IV). Total intravenous anesthesia (TIVA) with propofol and remifentanil was used
in all patients. The results concluded that The effect of oral ramosetron 0.1 mg was comparable
to that of IV ramosetron 0.3 mg on the prevention of PONV in women undergoing
gynecological laparoscopy with TIVA. Both the oral and IV forms were effective at preventing
PONV during the first 1 hr after surgery.
Kim SI et-al in 200918 studied the Comparison of ramosetron with ondansetron for
prevention of postoperative nausea and vomiting in patients undergoing gynaecological
surgery. In this prospective, randomized, double-blinded, placebo-controlled study, 162
healthy patients who were undergoing gynecological operation under general anaesthesia using
sevoflurane were enrolled. Patients were divided into three groups: the ramosetron group (0.3
mg i.v.; n=54), the ondansetron group (8 mg i.v.; n=54), and the placebo group (normal saline
i.v.; n=54). The treatments were given before the end of surgery. The incidence of PONV,
severity of nausea, and the use of rescue antiemetic requirements during the first 24 h after
surgery were evaluated.
The results that found ramosetron 0.3mg i.v. was as effective as ondansetron 8mg i.v. in
decreasing incidence of PONV and reducing nausea severity in female patients during first 24
hr after gynaecological surgery.
10
APPENDIX –IC
6.3 OBJECTIVE OF THE STUDY
To evaluate and compare the efficacy of Ramosetrone and Ramosetrone with
dexamethasone in patient undergoing elective ENT surgery perioperatively period (24 hours).
1. To compare the effficacy of the drugs
2. To compare the vital parameters in terms of Pulse rate,SPO2 and Respiratory rate in
each group.
3. To compare the complications if any.
11
APPENDIX-II
7.0 MATERIALS AND METHODS
APPENDIX-IIA
7.1 SOURCE OF DATA
An open comparative randomised study that will include 60 patients of ASA Grade
I and
II between 20-40 years of age scheduled for ENT elective surgery under general
anaesthesia in Adichunchanagiri Institute of Medical Sciences, Research center and
Hospital.B.G.NAGARA-571448.
Ethics committee’s permission taken.The total study period will be of 18 months of
duration.
A thorough preanaesthetic evaluation with relevent and appropriate investigations
ordered and done in the selected patients for the following study.
Patients wil be divided into two groups of thirty each.
Group A - Injection Ramosetrone – 0.3 mg
Group B - Injection Ramosetrone-0.3 mg with Injection Dexamethasone-8 mg
Premedication:Inj glycopyrolate 0.2mg+ Inj.Midazolam 1mg/kg body wt +Inj.Fentanyl
2 microg/kg body wt will be given and all operations will be performed under general
anaesthesia.In Group A prophylactically Inj Ramosetrone was injected and in Group B Inj
Ramosetrone with Inj Dexamethasone was injected. Anaesthesia will be induced in with
Inj.Thiopentone 5mg/ kg .body.wt.and intubation is achieved with injection Succinyl choline
1.5 mg / kg.body .wt. Maintainance of Anaesthesia will be with inhalation of nitrous oxide
67%+oxygen 33% and halothane 1 % delivered via a Bain coaxial system with controlled
12
ventilation. Muscle relaxation will be facilitated using Inj.Vecuronium bromide 0.02 mg/
kg.body.wt.
APPENDIX-II B
7.2 METHOD OF COLLECTION OF DATA
INCLUSION CRITERIA
1. Patients belonging to ASA grade 1 & 2 undergoing elective ENT surgical procedures.
2. Patients of either sex, between the age group 20-40 years.
3. Patients Body mass index between 18-25
EXCLUSION CRITERIA
1. Patient refusal.
2. Patients belonging to ASA grade III or IV
3. Patients with previous history of allergy to any anaesthetic agents.
4. Patients with Body mass index more than 1.5 times normal.
5. Patient coming for any emergency surgeries
6. Obstetrics patients coming for elective ENT sugeries.
PARAMETERS OBSERVED
1. Vital parameters pulse rate, respiratory rate, blood pressure,
SPO2 after induction
with either of the drug intra operatively at regular intervals.
2. To study any untoward reaction with either of the drug peri operatively.
3. Time at which first rescue antiemetics administered to either of the patietns group.
4. Frequency of rescue antiemetics administered to the patients.
13
STATISTICAL ANALYSES
For this study finally for comparing the efficacy and potency of drugs will be done by
standard deviation + 0.5 and with paired “t” students test.
P value will be considered significant when it is < 0.05
APPENDIX-II C
7.3 Does the study require any investigation or interventions to be conducted on patients
or other animals, if so please describe briefly.
NO
14
APPENDIX-II D
PROFORMA APPLICATION FOR ETHICS COMMITTEE APPROVAL
SECTION A
“COMPARISON OF SINGLE DOSE OF
INTRAVENOUS RAMOSETRON AND
RAMOSETRON PLUS DEXAMETHASONE
AS PROPHYLACTIC ANTI- PONV IN
PATIENTS COMING FOR ELECTIVE ENT
SURGERIES-A CLINICAL STUDY”
Dr. AMITHA. S.
P.G IN ANAESTHESIOLOGY,
ADICHUNCHUNAGIRI INSTITUTE OF
MEDICAL SCIENCES.B.G NAGARA,
MANDYA DISTRICT -571448
a
Title of the study
b
Principle investigator
(Name and Designation)
c
Co-investigator
(Name and Designation)
Prof. Dr. RADHA. M.K. M.B.B.S., M.D.
Professor and Head of the Department,
Department of Anaesthesiology,
AIMS, B.G. Nagara-571448
d
Name of the Collaborating
Department/Institutions
Radiology, Biochemistry and Surgical Faculties
e
Whether permission has been obtained from
the heads of the collaborating departments
& Institution
Section – B
Summary of the Project
YES
APPENDIX - I
Section – C
APPENDIX – IC
Objectives of the study
Section – D
APPENDIX - II
Methodology
Where the proposed study will be
A
undertaken
DEPARTMENT OF ANAESTHESIOLOGY,
S.A.H. & R.C., B.G.NAGARA
B Duration of the Project
18 MONTHS
C Nature of the subjects:
Does the study involve adult patients?
YES
Does the study involve Children?
NO
Does the study involve normal volunteers?
NO
Does the study involve Psychiatric patients?
NO
Does the study involve pregnant women?
NO
15
D If the study involves health volunteers
I.
Will they be institute students?
NO
II.
Will they be institute employees?
NO
III.
Will they be Paid?
NO
IV.
If they are to be paid, how much per
NA
session?
E Is the study a part of multi central trial?
NO
F If yes, who is the coordinator?
(Name and Designation)
NA
Has the trail been approved by the ethics
Committee of the other centers?
-
If the study involves the use of drugs please
indicate whether.
-
I. The drug is marketed in India for the
YES
indication in which it will be used in the study.
II. The drug is marketed in India but not for
the indication in which it will be used in the
study
NA
III. The drug is only used for experimental use
in humans.
NA
IV. Clearance of the drugs controller of India
has been obtained for:
NA
 Use of the drug in healthy volunteers
 Use of the drug in-patients for a new
NA
indication.
 Phase one and two clinical trials
 Experimental use in-patients and healthy
volunteers.
16
G How do you propose to obtain the drug to be
used in the study?
-
Gift from a drug company
-
Hospital supplies
-
Patients will be asked to purchase
-
Other sources (Explain)
NA
H Funding (If any) for the project please state
-
None
-
Amount
-
Source
-
To whom payable
NO
Does any agency have a vested interest in the
I
NO
out come of the Project?
Will data relating to subjects /controls be stored
J
NO
in a computer?
Will the data analysis be done by
K
-
The researcher?
-
The funding agent
YES
NO
L Will technical / nursing help be required form
NO
the staff of hospital.
If yes, will it interfere with their duties?
NO
Will you recruit other staff for the duration of
NO
the study?
If Yes give details of
I.
Designation
II.
Qualification
III.
Number
IV.
Duration of Employment
NA
17
M Will informed consent be taken? If yes
YES
Will it be written informed consent:
YES
Will it be oral consent?
NO
Will it be taken from the subject themselves?
YES
Will it be from the legal guardian? If no, give
NO
reason:
N Describe design, Methodology and techniques
APPENDIX II
Chairman,
P.G Training Cum-Research Institute,
A.I.M.S., B.G.Nagara.
Date :
PS : NA – Not Applicable
18
APPENDIX-III
8. LIST OF REFERENCES
1. WATCHA-MF,WHITE-PF.’’Postoperative nausea and vomiting.its etiology,treatment
& prevention”.Anesthesiology.77:167-87.1992.
2. ANDREW-PL.Physiology of nausea and vomiting BRITISH JOURNAL OF
ANAESTHESIA 69(Suppl):2s-19s.1992.
3. Drugs for emesis,Reflux and digestive disorder.Tripathi KD ,Essentials of medical
pharmacolory.6th edition.
4. Sander-Bush E,Mayer SE 5-(Hydroxytryptamine(serotonin);Receptor agonist and
antagonist.Bruton LL,Lazo JS,Parker kl. GOODMAN AND GILMAN’S The
pharmacology basis of therapeutics.11th edition.
5. WATCHA-MF,WHITE-PF.’’Postoperative nausea and vomiting.its etiology,treatment
& prevention”.Anesthesiology.77:161-184.1992.
6. R.Thomas & N.Jones BRITISH JOURNAL OF ANAESTHESIA 87(4);588-92;2001
7. Kim SL, Kim SC et al ;Br J Anaesth. 2009 Oct;103(4):549-53.
8. K.Liu, c.c. Hsu and Y.Y CHA;BJA 1998;80:85-86
9. R. Thomas and N.Jones BJA 87(4);588-92; 2001
10. Mokhtar Elhakim , Naglaa M;CANADIAN JOURNAL OF ANAESTHESIOLOGY
2003;50:4;392-397.
11. Aarti nandakumar Pawar, Manjula sarkar; The internet journal of anaesthesiology
ISSN: 1092-406X pg 1-7.
12. Fujii Y, Saitoh Y et al; Can J Anaesth. 1999 Oct;46(10):991-3.
13. Fujii Y, Saitoh Y et al; Anesth Analg. 2000 Apr; 90(4); 1004-7
14. Fujii Y, Saitoh Y et al; Anesth Analg. 2000 Feb;90(2):472-5.
19
TM
15. Fujii Y, Saitoh Y et al; Laryngoscope. 2001 Feb;111(2):255-8.
16. Fujii Y, Hiroyoshi Tanaka Clin Ther. 2003 Dec;25(12):3100-8.
17. Lee D, Kim Jy et al J Anesth. 2009;23(1):46-50. Epub 2009 Feb 22.
18. S.I. Kim, S.C.Kim et al Br J Anaesth. 2009 Oct;103(4):549-53.
20