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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA, BANGALORE
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR
DISSERTATION
1.

NAME OF THE CANDIDATE


AND ADDRESS (IN BLOCK
LETTERS)

DR.RADHIKA D.
POST GRADUATE IN
ANAESTHESIOLOGY
KIMS, HUBLI-580021

2.

NAME OF THE
INSTITUTION

KARNATAKA INSTITUTE OF MEDICAL


SCIENCES
HUBLI-580021

3.

COURSE OF STUDY AND


SUBJECT

M.D IN ANAESTHESIOLOGY

4.

DATE OF ADMISSION TO
COURSE

21st MAY 2012

5.

TITLE OF THE TOPIC

A RANDOMIZED DOUBLE BLIND


COMPARISON OF TWO DIFFERENT
PROPORTIONS OF
KETOFOL(KETAMINE-PROPOFOL)
WITH FENTANYL-PROPOFOL FOR
SEDATION-ANALGESIA IN TUBAL
STERILIZATION BY
MINILAPAROTOMY

6.

BRIEF RESUME OF THE INTENDED WORK:


6.1 NEED FOR THE STUDY:
Ketofol is a combination of ketamine and propofol in a single syringe and
can be prepared in any desired concentration.1 Ketamine and propofol are
physically compatible for 1 hour at 23C.2 Ketofol has been used for several
years in Procedural Sedation and Analgesia (PSA). It has been found to produce
effective sedation and analgesia in gynecologic, opthalmologic, orthopedic and
1

cardiovascular procedures in all age groups.1,3,4


Propofol and ketamine combination has been found to oppose the
respiratory and haemodynamic effects of each other. These two drugs have been
combined in different proportions and the effectiveness of this combination has
been studied by several people.1,2,5&6
Combination of fentanyl with propofol in place of ketamine decreases
hospital stay and increases patient satisfaction.3
Several gynecological procedures like tubal sterilization are of short
duration and just require analgesia and moderate sedation. Minilaparotomy is
one of the methods by which female sterilization is conducted in India. Local
anaesthesia has proven to be the most appropriate anaesthesia for
minilaparotomy. It is cost effective and safe. Several drugs like pentazocine,
promethazine, pethidine have been used for providing sedation during tubal
sterilization by minilaparotomy.7 Ketofol has fast onset and good analgesic and
sedative properties1 thus making it ideal for this procedure.
Keeping this in mind this study is designed to compare ketofol in two
different proportions with the well tried propofol-fentanyl combination in minor
gynecological procedures like minilaparotomy for tubal sterilization.
.
6.2 REVIEW OF LITERATURE:

A randomized, double blind study on 100 female patients of age 18-40 years
who underwent Medical Termination of Pregnancy (MTP) showed ketofol in
1:2 ratio had higher sedation, recovery and discharge times compared to other 4

groups which were ketofol 1:3, 1:4, propofol-fentanyl and propofol alone.1
A randomized study on 100 children who underwent procedural operation with
ketofol 1:1 and 1:4 showed increase in postoperative nausea, psychomimetic

side effects and delay in discharge times with the largest ketamine dosage.2
A randomized study on 114 patients of all ages for procedural sedation with
ketofol 1:1 showed decreased requirement of both drugs. No hypotension,

vomiting or need for intubation was noted.4


A randomized study in minor orthopedic procedures showed that ketofol 1:2
infusion is appropriate for Procedural Sedation in comparison with ketofol 1:1

& 1:3.5
A randomized study on 105 patients posted for transrectal prostate biopsy
2

showed that ketofol provides effective sedation and analgesia with high patient
safety profile and the 1:2 ratio of ketamine:propofol shortens the discharge
time.8

6.3 OBJECTIVES OF STUDY


1

To evaluate the effectiveness of combining ketamine and propofol in two


different proportions that is, ketamine:propofol 1:1, ketamine:propofol 1:2 on
the duration and level of sedation.

To evaluate the effectiveness of combining ketamine and propofol in 1:1 and


1:2 proportions on the quality of analgesia.

To study the effects of combining ketamine and propofol in 1:1 and 1:2
proportions on haemodynamic parameters like blood pressure & heart rate.

To evaluate the effects of combining ketamine and propofol in 1:1 and 1:2
proportions on respiratory parameters.

7.

Comparison of all the above effects with combination of fentanyl-propofol.

MATERIALS AND METHOD

7.1 SOURCE OF DATA:


Adult female patients (18-40 years) of physical status I & II scheduled to
undergo elective tubal sterilization by minilaparotomy at Karnataka Institute
of Medical Sciences, Hubli from 1st of January 2013 to 31st of December
2013.
7.2METHOD OF COLLECTION OF DATA
A prospective, double blind, randomized study is planned in 60 patients
undergoing elective tubal sterilization by minilaparotomy with average
duration of surgery 20minutes. Patients should satisfy the following inclusion
criteria.

INCLUSION CRITERIA
1. ASA grades I & II.
2. Aged between 18-40 years.
3. Patients giving informed consent.
4. Patients scheduled to undergo elective tubal sterilization by minilaparotomy.
EXCLUSION CRITERIA
1. ASA grades III & IV.
2. Emergency procedure.
3. Pregnancy.
4. Chronic drug abuse.
5. Allergy to egg.
6. Hypersensitivity to ketamine or propofol.
7. Head injury patients and patients with raised intracranial tension.
8. Weight more than 70kgs.
9. Patients with psychiatry disorders.
10. Laparoscopic sterilization procedure.
11.Deep scars on abdomen with 2 or more previous LSCS and any pelvic
pathology.
METHODS

All patients satisfying above criteria will be evaluated day prior to surgery and

informed written consent will be obtained.


Patients will be then randomly assigned into 3equal groups A, B & C (n=20
per group) according to computer generated list. The procedure will be double

blinded and randomization list will be maintained by the pharmacist.


In the operation theatre temperature will be kept at 23C. Baseline blood

pressure, heart rate and oxygen saturation will be recorded.


Intravenous access will be obtained by cannulating a peripheral vein with an

18 gauge cannula.
All patients will receive i.v. ketorolac 0.5mg/kg pre operatively on the table

before induction.
Equipment to protect airway like facemasks, airways, endotracheal tubes and

laryngeal mask airway will be kept ready.


Using syringes up to 12ml calibrations, under aseptic precautions the
following preparations will be freshly prepared by the pharmacist and both the

anaesthetist and patient will be blinded to the procedure.


A. KETOFOL (1:1)-2ml of ketamine (50mg/ml) that is 100mg is mixed with
10ml of 100mg propofol 1% such that each ml contains 8.3mg of ketamine
4

and 8.3mg of propofol.


B. KETOFOL (1:2)-1ml of Ketamine (50mg/ml) is mixed with 10ml of 100mg
propofol 1% and 1ml of D5W such that each ml contains 4.16mg ketamine
and 8.3mg propofol.
C. FENTANYL PROPOFOL-2ml of fentanyl (50g/ml) is mixed with 10ml
of 100mg propofol 1% such that each ml contains 8.3g fentanyl and 8.3mg
propofol.

All 3 syringes will appear milky and similar from outside and will be labeled

as A, B and C.
All patients will be pre medicated with injection midazolam 0.03mg/kg and

injection glycopyrolate 0.2mg on the table before induction.


Surgeon will be asked to paint and drape the abdomen.
The patients in group A will receive drug from syringe A, group B from

syringe B and group C will receive drug from syringe C intravenously.


The study drug will be given by a qualified anaesthetist as 3ml starting dose
over 1minute. Dose will be titrated to effect repeating 1-3ml of study drug
every 3 to 5 minutes until adequate sedation that is until a Ramsay Sedation
Score of 5-6 will be achieved and the procedure can be safely executed

without any visible pain (grimacing, protective limb movement and moaning).
Surgeon will be asked to give local infiltration with 10ml of injection
lidocaine (1%) without adrenaline at surgery site and will be allowed to start
the procedure once Ramsay Sedation Score of 5-6will be achieved. Response

to local anaesthesia infiltration will be noted.


A maximum dose of 0.25ml/kg of study drug solution will be allowed.
In case of failed sedation (defined as failure to achieve the desired level of
sedation) the case will be converted to general anaesthesia and patient will be

intubated with endotracheal tube or laryngeal mask airway will be inserted.


Supplementary oxygen will be administered via oxygen mask 6L/min

throughout the procedure.


Maximum duration of surgery will be 20minutes and cases which require

more than 20minutes or extension of incision will be considered as drop outs.


After completion of the study the drug group will be revealed to the
anaesthetist.

THE PARAMETERS OBSERVED WILL BE:


1. Time of administering starting dose
5

2. Time to sedation will be recorded as time from starting dose till a Ramsay
Sedation Score of 5-6 is achieved.
3. Non Invasive Blood Pressure(NIBP),Heart rate,Oxygen saturation(SPO2)
This will be recorded before sedation then every 5minutes during procedure
till 15minutes after end of procedure.
Hypotension will be defined as a decrease in Mean Arterial Pressure of 20%
than pre procedural levels and will be treated with 6mg of injection Ephedrine
i.v.
Bradycardia will be defined as decrease in heart rate 20% of baseline and will
be treated with injection Atropine 0.01mg/kg i.v.
Hypoxia will be defined as SPO2 less than 90% at any time during the
procedure.
4. Surgeon Satisfaction will be rated from 0 to 4 where 0=unsatisfied and
4=satisfied.
5. Ramsay Sedation Score2 will be measured every 5minutes during procedure.
The goal will be to maintain a Ramsay Sedation Score of 5-6 with no limb
movement and/or no patient grimacing.
6. Duration of procedure will be noted from local anaesthesia infiltration till
last skin stitch.
7. Recovery time will be recorded as time taken from the administration of last
dose of the study drug to achieve a Modified Aldrete Score of 9-10, when the
patient can be transferred to recovery room.
8. Total sedation time will be the time from the first administration of drug to
first eye opening for verbal stimulation.
9. Total amount of each component of the drug (ketamine, propofol and fentanyl)
in milligrams per kg of body weight required for the procedure will be
recorded.
10. Number of cases having failed sedation will be noted in each group.
Sedation consistency- number of patients maintaining Ramsay Sedation
Score of 5 or greater throughout the procedure and not requiring general
anaesthesia.
Sedation efficacy- sedation is efficacious if no general anaesthesia is
needed and there is no sedation related adverse events resulting in
abandonment of procedure or unplanned prolonged patient observation.
11. ADVERSE EVENTS
Minor adverse event will be defined as an event not resulting in a
change in vital signs and requiring no more than minimal interventions
6

(airway positioning, physical stimulation). Minor adverse events like


myoclonus, rash, tongue fall will be noted.
Significant adverse event is one requiring interventions such as
intravenous fluids, oral airway devices, ventilator assistance. Severe
emergence reactions like agitations, hallucinations, vomiting, prolonged
recovery time more than 3hours, hypotension, hypoxia, seizure, apnea
(defined as cessation of breathing for at least 20seconds with or without
oxygen desaturation ) will be recorded as significant adverse events.
12. VERBAL RATING SCALE FOR POSTOPERATIVE PAIN:
This will be recorded 15minutes after the end of the procedure. This will be
rated from 0 to 10 where, 0=no pain and 10=unbearable pain.

STATISTICAL ANALYSIS
Appropriate statistical analysis of data will be done using the following tests:
1. Student t test for parametric data.
2. Chi square test for nonparametric data.
P<0.05 will be considered statistically significant.
Parametric data include heart rate, blood pressure, O2 saturation, total dose
of each drug, Ramsay sedation score, recovery time, total sedation time, time
to sedation.
Non parametric data include hallucinations, agitation, vomiting and apnea.
7.3 DOES THIS STUDY REQUIRE ANY INVESTIGATIONS OR
INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR
ANIMALS SPECIFY?
No specific test or investigations are required to collect data for achieving the
objectives.
7.4 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM THE
ETHICAL COMMITTEE OF YOUR INSTITUTION IN THE CASE
OF 7.3?
Yes, ethical clearance has been obtained from the ethical committee of
KIMS, Hubli.

8.

LIST OF REFERENCES:
1. Yanfen Wang, Xi Jiang, Lei Pang, Su Dong, Yanhua Feng, Sujan Surya
Prajapati. A randomized double blind controlled study of the efficacy of ketofol
with propofol-fentanyl and propofol alone in termination of pregnancy. African
Journal of Pharmacy and Pharmacology Sep 2012;6(34):2510-14.
2. Daabiss M, Elsherbiny M, AlOtibi R. Assessment of different concentrations of
Ketofol

in procedural operation. British Journal Of Medical Practitioners

2009;2(1):27-31.
3. Akin A, Guler G, Esmaoglu A, Bedirli A. A comparison of fentanyl-propofol
with a ketamine-propofol combination for sedation during endometrial biopsy.
Journal of Clinical Anaesth.2005 May;17(3):187-190.
4. Willman EV, Andolfatto G. A Prospective evaluation of
ketofol(ketamine/propofol combination) for procedural sedation and
analgesia in the emergency department. Ann Emerg Med. 2007;49(1):23-30.
5. Saeed E. Ketofol infusion as a procedural sedation and analgesia modality for
minor orthopedic surgeries: evaluation of dose-outcome relation. Ain Shams
Journal of Anaesthesiology Jan 2011;4(1):63-74.
6. Erden IA, Pamuk AG, Akinci SB, Koseoglu A, Aypar U. Comparison of two
ketamine-propofol dosing regimens for sedation during interventional
radiology procedures. Minerva Anestesiologica April 2010;76(4):260-5.
7. Reference manual for Minilap tubectomy. Family planning division Ministry
Of Health and Family Welfare- Government of India Nov 2009;Chapter 6:1821.
8. Ayman A. Abdellatif. Ketofol for outpatient transrectal ultrasound guided
8

prostate biopsy.Ain Shams Journal of Anaesthesiology Jan 2012;5(1):11-22.

9.

SIGNATURE OF THE
CANDIDATE:

10. REMARKS OF THE GUIDE:

KETAMINE AND PROPOFOL ARE


TWO VERY POPULAR DRUGS USED
FOR SEDATION AND
ANAESTHESIA.THEIR
COMBINATION IN THE SINGLE
SYRINGE MAY BE LIKE TWO
GREAT TASTES THAT TASTE
GREATER TOGETHER.THIS STUDY
WILL HELP TO WIDEN THE
CLINICAL APPLICATION OF
KETOFOL.

11. NAME AND DESIGNATION OF

DR. MADHURI. S. KURDI M.D.


PROFESSOR,DEPARTMENT OF
ANAESTHESIOLOGY, KIMS, HUBLI

11.1 GUIDE

11.2 SIGNATURE:

11.3 HEAD OF THE


DEPARTMENT:

DR. SAFIYA SHAIKH M.D.


PROFESSOR& HEAD,
DEPARTMENT OF
ANAESTHESIOLOGY, KIMS,
HUBLI.

11.4 SIGNATURE:

12.

12.1

REMARKS OF THE
CHAIRMAN & PRINCIPAL:

12.2 SIGNATURE:

10