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. SHRUTI HIREMATH
W/O DR CHETAN M L
#817/10, B/W 4TH & 5TH CROSS
SHIVAKUMARWSAMY LAYOUT
II STAGE,
DAVANGERE- 577003
2.
Name of the Institution
J.J.M. MEDICAL COLLEGE,
DAVANAGERE
KARNATAKA
PIN - 577004.
3.
Course of the study and subject
POST-GRADUATE (MEDICAL)
M.D. IN ANAESTHESIOLOGY
4.
Date of admission to course
30/07/2013
5.
Title of the topic
“A CLINICAL COMPARATIVE
STUDY OF PROPOFOL AND
KETAMINECOMBINATION
(KETOFOL)VERSUS EITHER DRUG
ALONE IN SHORT SURGERIES &
PROCEDURES”
6.
BRIEF RESUME OF THE INTENDED WORK
6.1 NEED FOR THE STUDY :
When general anaesthesia is provided only with intravenous
(i.v.) agents, this is called total intravenous anaesthesia (TIVA). The TIVA
concept is simple. An i.v. line is the only prerequisite, and everything you need
for general anaesthesia will be supplied through this line. This means that there is
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no need for sophisticated gas delivery systems or scavenger equipment. 1.
TIVA has many advantages over inhalational anesthesia such as no operating
room pollutions, minimal cardiac depression, lesser neurohumoral response,
decreased oxygen consumption 2.
Various drugs have been tried from time to time in TIVA. Since no single drug
can provide all the characteristics of an ideal intravenous agent, several drugs are
used in different combinations to provide balanced anesthesia in TIVA, that is,
amnesia, hypnosis and analgesia 2.
Propofol is a preferred inducing agent for short surgical procedures is a
nonopioid, nonbarbiturate, sedative‑hypnotic agent with rapid induction and
recovery times and antiemetic effects 3. However, adverse effects include
dose‑dependent cardiorespiratory depression, injection pain, and having no
analgesic properties 3, 4,5.
Ketamine causes little or no cardio‑respiratory depression and unlike propofol,
has pain relieving properties. Ketamine use as a single induction agent, however,
is limited by emergence hallucinations, elevation of blood pressure and heart rate
due to its sympathomimetic effects, and increased intracranial pressure 6,7.
Effectiveness of the two agents – propofol and ketamine – in combination
(ketofol) has been recently demonstrated and may provide a novel induction
agent with favorable hemodynamics and reduced side effects attributed to either
drugs8.
By combining propofol and ketamine, there is additive effect of GABA agonism
by propofol and NMDA antagonism by ketamine leading to lesser doses of
propofol required along with ketamine 9.
Ketamine in subanaesthetic doses with propofol has gained attention in total
intravenous anaesthetic technique because of its powerful analgesic action
without causing myocardial or respiratory depression 10,11,12.
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6.2 REVIEW OF LITERATURE :
In a randomized double blind prospective study which included 90 ASA I & II
patients aged between 15 and 50 years scheduled for ambulatory urological;
ambulatory urogynaecological procedures, they concluded tht among the two
admixtures propofol ketamine has an edge over propofol-thiopentone because of
its better hemodynamic stability and superior airway maintenance 9.
In a randomized double blind prospective study which included 100 chidrens
scheduled for LMA insertion the effects of ketofol and propofol were compared
and concluded that ketofol is a safe and effective alternative induction agent for
LMA insertion in children with rapid onset of action and lower incidence of
injection pain. It provided better LMA insertion conditions, improved
hemodynamic stability with less prolonged apnoea when compared with
propofol3.
In a randomized double blind prospective study which included 80 ASA I & II
patients posted for laryngeal tube suctioning compared the effects of propofol and
ketofol and concluded that ketofol provided better insertion summed score for
LTS than propofol with minimal haemodynamic changes 9.
In a randomized double blind prospective study which included 40 female
patients undergoing short gynaecological procedures concluded that the
association propofol-ketamine reach an adequate level of anesthesia with few and
negligible effects on cardiorespiratory system, thus allowing a better operability
and safety. The incidence of post operative psychotic disturbances seems to be
low and moderate.
In a randomized double blind prospective study which included 68 ASA I & II
patients undergoing elective general, orthopaedic & gynaecological procedures
concluded that induction dose of propofol is reduced considerably by prior
administration of small dose of ketamine compared to placebo using loss of
verbal contact as end point of induction. Ketamine had the advantage of better
haemodynamic stability 13.
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In the 10 trials comparing the combination of ketamine and propofol with either
agent alone for procedural sedation in the emergency department were examined.
The evidence reviewed suggests that combining these agents may help to
minimize adverse effects such as hypotension and respiratory depression.
Ketamine is not commonly used as a single agent in adults because of the risk for
emergence reactions; however, when combined with propofol, no significant
increase in this adverse effect was found compared with propofol monotherapy14.
In a randomized double blind prospective study which included 100 children, of
age 3–14 years, American Society of Anesthesiologist physical status IE-IIE,
posted for emergency short surgical procedures concluded that The combination
of low-dose ketamine and propofol is more effective and a safer sedoanalgesia
regimen than the propofol–fentanyl combination in paediatric emergency short
surgical procedures in terms of haemodynamic stability and lesser incidence of
apnoea15
In a randomized double blind prospective study which included 90 adults patients
Posted for LMA insertion concluded that the addition of ketamine 0.5 mg x kg(1) improves haemodynamics when compared to fentanyl 1 microg x kg(-1), with
less prolonged apnoea, and is associated with better LMA insertion conditions
than placebo (saline)16.
In a randomized double blind prospective study which included 60 healthy
women undergoing gynaecological laparoscopy to investigate infertility were
studied, and concluded that use of low-dose ketamine with propofol-fentanyl
anaesthesia in patients undergoing DGL was associated with less pain during
propofol injection, lower incidence of haemodynamic changes, lower total dose
of propofol and improved postoperative analgesia17.
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6.3 AIMS AND OBJECTIVES OF STUDY :
The objectives of this comparative study using propofol, ketamine and ketofol as
an inducing agents in short surgical procedures is to evaluate and compare the
following effects.
 Onset of induction
 Duration
 Quality of analgesia
 Cardiorespiratory stability
 Emergence phenomenon
 Recovery
 Adverse effects
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7.
MATERIALS AND METHODS :
7.1 SOURCE OF DATA :
The study will be conducted on patients with minimum of 50 in each group
i.e propofol alone, ketamine alone and ketofol
aged between18 to 60 years
posted for short surgical procedures at Bapuji Hospital and Chigateri General
Hospital attached to JJM medical college Davanagere.
7.2 METHODS FOR COLLECTION OF DATA :
A minimum of 50 patients in each group will be selected randomly after
taking informed written consent from the relatives.
All patients will be pre medicated.
Patients will be randomly allocated into 3 groups.
Group P-Propofol Group.
Group K – Ketamine group.
Group KP- Combination (ketamine+propofol=ketofol) group.
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Inclusion Criteria
 Age group between 18 to 60 years
 Both sexes
 ASA I, II & III
 Patient scheduled for short surgical procedures lasting for about 20
minutes.
 Patients who have not eaten solid food within 8 hours before or liquids in
the two hours before
Exclusion Criteria
 An acute lung infection
 Procedures involving stimulation of the posterior pharynx
 Coronary heart disease, CHD, and angina or suspected aortic
dissection
 History of uncontrolled hypertension or BP > 140/90mmHg
 Injury cerebral focal neurological deficit or loss of consciousness
 Mass in CNS, hydrocephalus or other conditions with increased
intracranial pressure.
 Glaucoma or eye damage
 Prior hyperthyroidism or thyroid hormone replacement
 Pregnancy or lactation Major psychiatric disorder
 Previous mild allergic reaction to ketamine, propofol, lidocaine, or egg
albumin
 Patient who refuses to provide informed consent
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Procedure:
A prospective, randomised, single blind study will be undertaken
Patients will be randomly allocated into 3 groups.
A minimum of 50 patients in each group will be selected randomly after
taking informed written consent from the patients.
Patients will be randomly allocated into 3 groups
Group P-Propofol Group will receive a Loading dose-2mg/kg body weight.
Group K – Ketamine group will receive a loading dose of 2mg/kg body weight
Group KP- Combination (ketofol) group will receive a dose of ketamine
0.5mg/kg bodyweight
Followed by Propofol 2mg/kg bodyweight
IV line secured and patients will be connected to monitor to record pulse,
NIBP, ECG and SpO2.
Pre medication will be done with injection Glycopyrrolate 0.2mg i.v,
Pentazocine 30mg i.v, & Midzolam 1mg i.v.
Patient will be preoxygenated with 100% oxygen for 3 minutes
The allocated group will receive the specific drug intravenously.
Following this below mentioned parameters were documented
 Onset of action, Duration , Quality of analgesia, Cardiorespiratory
stability, any adverse effects like vomiting, emergence phenomenon,
Recovery at 1min, 5mins, 15mins. 30 mins, and the end of the procedure.
Assessment tools:
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Assessment will be done based on the following scores
 Onset of Induction
Taken by the absence of eyelash reflex/ loss of verbal contact
 Analgesic score
Measured by four point scale by CAMERON et al
0: no pain,
1: mild pain(grimace),
2: moderate pain (grimace + cry),
3: severe pain (cry + withdrawal).
 Apnoea
Defined as absence of spontaneous respiration for > 20 seconds
 Recovery score
Evaluated using Aldrete score (1-10)
Safety will be assessed by monitoring laboratory test results, vital signs,
ECG findings, physical examination findings, withdrawal related events
and adverse events.
Quantitative data will be analysed by suitable statistical tests like chi
square test, ANOVA test, unpaired t test etc..
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7.3 Does the study require any investigations or interventions to be
conducted on patients or other humans or animals? If so, please describe
briefly.
Yes, on Patients.
Investigations:
 Blood:
 Haemoglobin %, Total Count , Differential count.
 Random Blood Sugar (RBS), Blood Urea, Serum creatinine
 ECG
 HIV and HBsAg
 Chest X Ray
 Urine :
 albumin, sugar, microscopy
7.4 Has the ethical clearance been obtained from your institution in case of
7.3?
Yes,
Approval from the ethical committee of J.J.M Medical College, Davangere
has been taken. Side effects of the drugs will be clearly explained to the patients
in the local language and consent will be taken.
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8.
LIST OF REFERENCES:
1. Henrik Eikaas and Johan Raeder; Total intravenous anaesthesia techniques for
ambulatory surgery; Current Opinion in Anaesthesiology; 2009,22:725–729
2. Sukhminder Jit Singh Bajwa,, Sukhwinder Kaur Bajwa1, Jasbir Kaur :Comparison
of two drug combinations in total intravenous anesthesia: Propofol–ketamine and
propofol–fentanyl Vol. 4, Issue 2, May-August 2010:72-79
3. Gamal T. Yousef, Khalid M. Elsayed: A clinical comparison of ketofol (ketamine
andpropofol admixture) versus propofol as an inductionagent on quality of laryngeal
mask airway insertionand hemodynamic stability in children: Anesthesia: Essays and
Researches; 7(2); May-Aug 2013
4. Bassett KE, Anderson JL, Pribble CG, Guenther E. Propofol for procedural
sedation in children in the emergency department. Ann Emerg Med 2003;42:773‑82.
5. Arora S. Combining ketamine and propofol (ketofol) for emergencydepartment
procedural sedation and analgesia: A review. West J Emerg Med 2008;9:20‑3.
6. Strayer RJ, Nelson LS. Adverse events associated with ketamine for procedural
sedation in adults. Am J Emerg Med 2008;26:985‑1028.
7. Morgan GE, Mikhail MS, Murray MJ. Nonvolatile anesthetic agents. Clin
Anesthesiology 2002;8:151‑77.
8. Nathan JS, Michael LB, Thomas MD, Matthew DK. Ketofol as a Sole Induction
Agent is Associated with Increased Hemodynamic Indices in Low‑Risk Patients.
ASA abstracts 2011;16:A485.
9. Kalpana S. Vora, Prabodhachandran M.S., Guruprasad P. Bhosale, Neeta Singhal,
Geeta P. Parikh, Veena R. Shah: Comparison of Admixtures of PropofolThiopentone, Propofol-Ketamine and Propofol in Ambulatory Surgery: J Anaesth Clin
Pharmacol 2005; 21(4) : 413-418.
10. T.W Hui, T G Short, W Hong,m T Suen, T Gin, J Plummer. Additive interactions
between propofol and ketamine when used for anaesthesia induction in female
patients. Anesthesiology 1995; 82: 641-647.
11. Guit JBM, Koning H M, Coster M C, Neimejer R P E, Mackie D P. Ketamine as
analgesia for total intravenous anaesthesia with propofol. Anaesthesia 1990; 46: 2427.
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12. Kaushik Saha, M Saigopal, Rajini Sundar, M palaniappan, Anil C Mathew.
Comparative evaluation of propofol-ketamine and propofol-fentanyl in minor surgery.
Ind. J. Anaesth 2001; 45(2): 100-103.
13. Dr. Uma Srivastava1 Dr. Neeraj Sharma2 Dr. Aditya Kumar3 Dr. Surekha Saxena
small dose propofol or ketamine as an alternative to midazolam co-induction to
propofol :Indian J. Anaesth. 2006; 50 (2) : 112 – 114
14. Thomas MC, Jennett-Reznek AM, Patanwala AE. Combination of ketamine and
propofol versus either agent alone for procedural sedation in the emergency
department. Am J Health Syst Pharm. 2011 Dec 1;68(23):2248-56.
15. Samit Kumar Khutia, Mohan C Mandal, Sabyasachi Das, and SR Basu
Intravenous infusion of ketamine-propofol can be an alternative to intravenous
infusion of fentanyl-propofol for deep sedation and analgesia in paediatric patients
undergoing emergency short surgical procedures; Indian J Anaesth. 2012 Mar-Apr;
56(2): 145–150.
16. Goh PK, Chiu CL, Wang CY, Chan YK, Loo PL. Randomized double-blind
comparison of ketamine-propofol, fentanyl-propofol and propofol-saline on
haemodynamics and laryngeal mask airway insertion conditions. Anaesth Intensive
Care. 2005 Apr;33(2):223-8.
17. Atashkhoyi S, Negargar S, Hatami-Marandi P. Effects of the addition of low-dose
ketamine to propofol-fentanyl anaesthesia during diagnostic gynaecological
laparoscopy. Eur J Obstet Gynecol Reprod Biol. 2013 Aug;170(1):247-50
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9.
SIGNATURE OF THE
CANDIDATE
10.
REMARKS OF THE GUIDE
11.
NAME & DESIGNATION
The present study is undertaken to evaluate
the effectiveness of combination of two
drugs (propofol+ketamine) with respect to
quality
of
analgesia,
duration
&
cardiorespiratory stability in short surgeries .
DR. RAVISHANKAR R B MD.DA.
Professor,
Department Of Anaesthesiology,
J.J.M Medical College,
Davanagere- 577004
11.1 GUIDE
11.2 SIGNATURE
11.3 CO-GUIDE (If any)
-
11.4 SIGNATURE
DR. MANJUNATH JAJOOR., M.D., D.A.
Professor and Head,
Department Of Anaesthesiology,
J.J.M Medical College,
Davanagere- 577004
11.5 HEAD OF THE
DEPARTMENT
11.6 SIGNATURE
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REMARKS OF THE
CHAIRMAN & PRINCIPAL
12.1 SIGNATURE
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