Ketofol (1:1 Combination of Ketamine and Propofol)

KETOFOL (1:1 COMBINATION OF KETAMINE AND PROPOFOL)

VERSUS PROPOFOL FOR SHORT SURGICAL PROCEDURES:

A COMPARISON OF QUALITY OF ANESTHESIA,

CHARACTERISTICS ADVERSE EVENTS, AND RECOVERY

BY

Dr. B PRAVEEN KUMAR

SYNOPSIS FOR REGISTRATION OF SUBJECT FOR DISSERTATION

TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

IN PARTIAL FULFILLMENT OF REGULATIONS FOR THE

AWARD OF

DOCTOR OF MEDICINE

IN

ANAESTHESIOLOGY

DEPARMENT OF ANAESTHESIOLOGY

COMMAND HOSPITAL (AIR FORCE), BANGALORE – 560 007

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

SYNOPSIS

DISSERTATION TOPIC

KETOFOL (1:1 COMBINATION OF KETAMINE AND PROPOFOL)

VERSUS PROPOFOL FOR SHORT SURGICAL PROCEDURES:

A COMPARISON OF QUALITY OF ANESTHESIA,

CHARACTERISTICS, ADVERSE EVENTS, AND RECOVERY

By

Dr.B PRAVEEN KUMAR

PG student (Anaesthesiology)

Command Hospital (Air Force),

Bangalore.

Course

2013-2016

Rajiv Gandhi University of Health Sciences, Bangalore,Karnataka

Annexure-A

1.Name of candidate :Dr.B Praveen Kumar

2. Name of Institution :Command Hospital (Air Force), Bangalore

3. Course of study and subject :M.D. (Anaesthesiology)

4. Date of admission :1 st July 2013

5. Title Of Topic : Ketofol (1:1 combination of

Ketamine & Propofol) versus

Propofol alone for Short

Surgical Procedures-A

Comparison of Adverse Event

Recovery characteristics and

Quality of Anesthesia

6. Brief resume of intended work

Need for the study : APPENDIX ‘A’

Objective of study : APPENDIX ‘B’

Review of literature : APPENDIX ‘C’

7. Material and Methods : APPENDIX 'D'

Source of data : APPENDIX ‘D’

Method of collection of data : APPENDIX ‘D’

8. Does the study require any investigation

and interventions to be conducted

on patients or other animals? : YES/NO

Has ethical clearance been obtained

from your institution? : YES/NO

9. Patient Performa : APPENDIX ‘E’

10. Statistical Analysis : APPENDIX ’F’

11. List Of References : APPENDIX ‘G’

12. Patient Consent Form : APPENDIX ‘H’

13. Study Information Sheet : APPENDIX ‘I’

14. Signature Of Candidate

15. Remarks of guide

16. Name and designations

Guide Col (Dr.)P V Madhu

Associate professor & Cardiac Anaesthesiologist,

Dept of Anaesthesiology

& Critical Care

Command Hospital (Air Force)

Bangalore

Signature

17. Head of the Department Col (Dr.) K Prabhakaran

Senior Advisor & Head of

Dept of Anaesthesiology

& Critical Care

Command Hospital (Air Force)

Bangalore

Signature

18.Remarks of the chairman and principal

Signature

Appendix ‘A’

Need for the study

Total Intravenous Anesthesia is often used for short surgical and day care procedures. Ketamine and propofol are two medications commonly used for this purpose because they possess many of the desired characteristics including rapid induction and recovery. However, ketamine has lost favor with anesthesiologists due to propensity to cause emesis and recovery agitation, and its prolonged recovery time compared with that of propofol. Propofol, on the other hand, is limited by dose dependent hypotension and respiratory depression, especially when combined with opioids. The opposing physiologic effects of ketamine and propofol suggest the potential for synergy, and this has led to interest in their combined use, commonly termed “ketofol”. The potential advantages of ketofol over propofol alone include the provision of deep sedation with lower doses of propofol, thus potentially limiting propofol-associated adverse respiratory effects; the provision of ketamine analgesia without the increased adverse respiratory effects associated with concomitant opioid administration; and the mitigation of propofol-induced hypotension. The potential advantages of ketofol over ketamine-alone procedural sedation include shorter recovery time and a lower incidence of ketamine-associated emesis and recovery agitation. This study will establish if the purported benefits are actually seen in clinical practice.

Appendix 'B'

Aims and Objectives of study

(a)Aim: To compare incidence of adverse events, recovery characteristics and quality of anesthesia with ketofol (1:1 combination of ketamine and propofol) versus propofol alone for short surgical procedures (anticipated duration of surgery less than 30 minutes.)

(b)Objectives: To establish whether anesthesia with ketofol is superior to propofol alone and is associated with fewer side effects.

Appendix ‘C

Review of literature

As per the below mentioned articles, the induction properties, hemodynamic changes of ketofol and propofol have been mentioned

1. Hui TW, Short TG, Hong W, Suen T, Gin T, Plummer J. Additive interactions between Propofol and Ketamine when used for anesthesia induction in female patients. Anesthesiology. 1995;82:641-48.

1. Calimaran A, Lancaster K, Lerant A, et al. Compatibility of propofol and ketamine in propofol-ketamine mixture. Anesthesiology. 2008;109:A694-A695.

c.Andolfatto G, Riyad B Abu Laban, Zed PJ, Staniforth SM, Stackhouse S, Moadebi S, Willman

1. Ketamine-Propofol Combination (Ketofol) Versus Propofol Alone for Emergency Department Procedural Sedation and Analgesia: A Randomized Double-Blind Trial. Ann Emerg Med. 2012;59:504-512.

e. Green SM, Andolfatto G, Krauss B. Ketofol for procedural sedation? Pro and Con. Ann Emerg Med. 2011;57;444-448

Ketofol appears to be the ideal anesthetic agent theoretically as the disadvantages of one agent are easily offset by the other. Whereas propofol is known to cause pain on injection, hypotension, respiratory depression and no analgesia (thus requiring co-administration of opioids), ketamine maintains blood pressure and respiration and possesses excellent analgesic properties. However, ketamine is known to cause emergence reactions, nausea and vomiting and delayed recovery. Propofol on the other hand, is an anti-emetic and can also reduce emergence reactions by limiting the total dose of ketamine administered. The combination of both these agents in a single polypropylene syringe has been found to be chemically stable and physically compatible. These theoretical advantages have led to ketofol being increasingly used for short surgical procedures and sedation.

Recent articles have refuted these claims and have shown no benefit of the combination as compared to propofol alone for sedation in the emergency department. However, the benefits of the combination may be more evident in the operating room as a deeper plane of anesthesia is maintained for a longer period and requirement of analgesics is also usually higher in the operating room. Hence even subtle differences in the incidence of respiratory adverse events, quality of anesthesia and analgesia or recovery characteristics may be amplified and may be significant.

Appendix ‘D’

Materials and Methods

300 consenting adult ASA I and II patients posted for short surgeries (anticipated time less than 30 minutes) will be randomly assigned into one of two groups and administered TIVA with 1:1 combination of ketamine and propofol or propofol alone, after appropriate premedication. Two different groups have made based on medication used for induction. Ketamine & propofol combination is taken under Group I.Propofol is taken under Group II. Complications occurring during induction, intraoperative &post-operative period especially agitation, desaturation ,nausea and vomiting will be noted.

INDUCTION CHARACTERISTICS

BP(mmhg) / PR(mmhg) / RR(/min) / TIME OF LOSS OF EYE LASH REFLEX
(sec) / TIME FOR INCISION (min) / TOTAL DRUG USED
? / ADVERSE EVENTS
Pre op / Post
op / pre op / post op / Pre op / Post op
GP I
(KETOFOL)
GP II
(Propofol)

INTRA OP CHARECTERISTICS

Pulse(min) / BP(mmhg) / Supplementation of Opioids / Addition of drugs / Adverse effects
Gp I
Gp II

POST OP CHARACTERSTICS

HR(mmhg) / BP(mmhg) / Pulse(/min) / PONV / Responding to Verbal Command / Return of airway reflex
GP1(10 min)
GP I (30 min)
Gp II (10 min)
GP II (30 min)

Inclusion criteria

A .Patient of either sex, aged between 20-60 yrs

B .Patient belonging to american society of anaesthesiologists grade I&II

C. Short surgical procedures duration of <30 min

 Exclusion criteria

A .Patient refusal for the procedure

B .Patient with psychiatric history

 C .Patient allergic to Ketamine & Propofol
Appendix ‘E’

PATIENT PERFORMA

Pt Name:…………………………..Age/Sex……………….Wt………...... Sr. No……

Diagnosis……………………………………ASA………….Group……..………………………

S No / Name / Age / Sex / Diagnosis / Recovery Time (min) / PONV / Home ready By
(min)

Appendix ‘F’

Statistical analysis

In the present study,the data is collected & analyzed statistically by computing the mean, standard deviation & 95% confidence interval wherever necessary and the inference drawn accordingly.

Appendix ‘G’

References

1. Hui TW, Short TG, Hong W, Suen T, Gin T, Plummer J. Additive interactions between Propofol and Ketamine when used for anesthesia induction in female patients. Anesthesiology. 1995;82:641-48.
2. Calimaran A, Lancaster K, Lerant A, et al. Compatibility of propofol and ketamine in propofol-ketamine mixture. Anesthesiology. 2008;109:A694-A695.
3. Andolfatto G, Riyad B Abu Laban, Zed PJ, Staniforth SM, Stackhouse S, Moadebi S, Willman E. Ketamine-Propofol Combination (Ketofol) Versus Propofol Alone for Emergency Department Procedural Sedation and Analgesia: A Randomized Double-Blind Trial. Ann Emerg Med. 2012;59:504-512.
4. Green SM, Andolfatto G, Krauss B. Ketofol for procedural sedation? Pro and Con. Ann Emerg Med. 2011;57;444-448.
5. Bell RF, Dahl JB, Moore RA, Kalso EA. Perioperative ketamine for acute postoperative pain. Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD004603. DOI: 10.1002/14651858.CD004603.pub2.

Appendix ‘H’

COMMAND HOSPITAL AIR FORCE, BANGALORE

INFORMED CONSENT FORM FOR ADMINISTRATION OF ANAESTHESIA

Patient’s name:……………………………………………………………….. Relationship:……………Rank:……………Service no:……………………..

Name:…………………………Age:………………….Unit:…………………Date:…………………

1. I understand that the performance of(Surgical procedure)shall require administration of general anesthesia. As a part of the institutional study I will be administered either Ketofol or propofol.Both of these procedures though are relatively safe have their own advantages as well as disadvantages like transient respiratory depression, inadequate analgesia, postoperative confusion, and nausea and vomiting which have been fully explained to me in detail in language I understand best. I have been assured that all the necessary precautions will be undertaken to prevent any adverse outcome. The queries have been fully explained to me & all the questions & doubts about the administration of anaesthesia have been cleared to my satisfaction.

1. I accept the administration of anaesthesia & the risks involved. I also give consent to change the plan of anaesthesia during the course of the procedure if the need arises for my safety & well being. I agree to be a part of this project & fully co-operate with the anaesthesiologist & follow his/her instructions.

1. This document has been signed by my own free act of will.

Signature of the patient

Name & Sign of the witness Signature of next of kin

Name

Relationship

Appendix ‘I’

Study Information Sheet for Patients/NOK

1.Name of study: Ketofol (1:1 combination of ketamine and propofol) versus propofol alone for short surgical procedures: A comparison of adverse events, recovery characteristics and quality of anesthesia.

2.Purpose of study: Research

3.Number of participants: 300

4.Procedures to be followed: All patients who are scheduled to undergo short surgical procedures expected to last less than 30 minutes and who are otherwise fit for general anesthesia, will be given either propofol or a mixture of propofol and ketamine. Both drugs have been proven to be safe and effective, but it remains to be seen whether the combination is actually better in terms of fewer side effects and quality of anesthesia. This study will aim to answer that question.

5.Special investigations: Nil

6.Foreseeable risks and discomfort: Usually, patient will not come to know which drug is being administered. There may be pain on injection of propofol in less than 10 % of patients.

7.Benefits to participants, community or medical profession as may be applicable: Haemodynamic stability and faster recovery with good analgesia.

8.Policy on compensation: NA

9.Availability of medical treatment for such injuries or risk management: Available

10.Alternative treatment if available: Yes

11.Steps taken to ensure confidentiality: As per SOP for patients undergoing

surgeries

12.No loss of benefit on withdrawal: No Loss to patient

13.Benefit sharing in the event of commercialisation: NA

14.Voluntary participation: Yes

15.If test for genetics and HIV is to be done,counselling for consent for testing must be given as per national guidelines: NA

16.Storage period of biological sample and related data with choice offered to participant regarding future use of sample, refusal for storage and receipt of its results. NA

17.Contacts:If you have any further questions, any time during the course of the study you can contact the following

Dr B Praveen kumar

Resident

Dept. of Anaesthesiology and Critical Care

Command Hospital Air force

Bangalore 560007

Col (Dr) P V Madhu

Associate Professor & Cardiac Anaesthetist

Dept. of Anaesthesiology and Critical Care

Command Hospital Air force

Bangalore 560007

CERTIFICATE FROM THE HEAD OF THE INSTITUTION

Permission is hereby accorded to the student Dr.B Praveen Kumar, to undergo MD (Anaesthesiology) course being conducted at Command Hospital (Air Force) Bangalore affiliated to the Rajiv Gandhi University of Health Sciences commencing from Jul 2013 under the guidance of Col(Dr.)PV Madhu (Associate Professor & Cardiac Anaesthesiologist), Dept of Anaesthesiology, Command Hospital

(Air Force) Bangalore.

Date: (R Bhalwar)

Air Vice Marshal

Commandant and Principal

Command Hospital, Air Force

Bangalore - 560007

CERTIFICATE FROM ETHICAL COMMITTEE

1.The committee has examined the scope including the need, objectives, methods and human /animal interventions and the follow-up study to be carried out by Dr.B Praveen Kumar, MD student (Anesthesiology) under guidance of Col PV Madhu, the title of which is Ketofol versus Propofol alone for short surgical procedures: A comparison of adverse events, recovery characteristics and quality of anesthesia.

2.The committee has no objections for undertaking this study at Command Hospital (Air force) Bangalore.

(Salini Chaudhary) (S Kaistha) (SK Jha) (SC Dash) (MS Prakash) (H Sahni)

Sq Leader Wg Cdr Col Col Brig Gp Capt

OIC Legal Cell Rep of AFWWA OIC Prof & HOD Prof & HOD OIC AFMRC Member Member Member PG Cell Surgery Medicine Member

Member Member Secretary

(Mrs. Vasantha kishore) (Dr V Sinha)

Counsellor Scientist ‘D’ Physiologist

E- support Member

Member

(MK Bedi)

Air Cmde

AOC MTC

Chairman Ethical Committee

Command Hospital (Air Force)

Bangalore – 560007

CERTIFICATE OF ACCEPTANCE BY THE GUIDE

1. I, Col PV Madhu, hereby accept Dr B Praveen Kumaras a candidate of MD (Anaesthesiology ) course. The title of his dissertation is as follows:-
2. “KETOFOL (1:1 COMBINATION OF KETAMINE AND PROPOFOL) VERSUS PROPOFOL FOR SHORT SURGICAL PROCEDURES: A COMPARISON OF ADVERSE EVENTS, RECOVERY CHARACTERISTICS AND QUALITY OF ANESTHESIA ”

2. He will be under my guidance during the period of his study and thesis work.

Date: Col (Dr) PV Madhu

Associate professor & Cardiac Anaesthesiologist

Dept of Anaesthesiology &

Critical Care

Command Hospital Air Force

Bangalore 560007