SYNOPSIS

For the award of Degree of Doctor of Medicine

(M.D. Anaesthesiology)
SESSION: 2018-2021

TITLE:
EFFECT OF SINGLE DOSE GABAPENTIN ON POST OPERATIVE PAIN AND
MORPHINE CONSUMPTION AFTER MASTECTOMY

INDIRA GANDHI INSTITUTE OF

MEDICAL SCIENCES, PATNA
Thesis protocol
Name of the candidate : Dr Sunny Kumar
Subject : Anaesthesiology
Date of joining : 01-06-2018
Institute : Indira Gandhi Institute of Medical
Sciences, Patna

Guide : Dr AJIT GUPTA

Professor and head of the
department
Dept. of Anaesthesiology
I.G.I.M.S, Patna

Co-Guide :

Signature of candidate Signature of co-guide

Signature of Guide Signature of the Head of Dept.

Signature of the dean of the Institution

INTRODUCTION :
Gabapentin, a structural analogue of gamma amino butyric acid, is used
as an analgesic adjunct to reduce the post-operative pain and
post-operative morphine consumption. Initially introduced as an
antiepileptic, it soon found use in treating neuropathic pain associated
with post-herpetic neuralgia, post-poliomyelitis neuropathy and reflex
sympathetic dystrophy. Experimental and clinical studies have
demonstrated antihyperalgesic effects in models involving central
neuronal sensitization. It has been suggested that central neuronal
sensitization may play an important role in postoperative pain. The aim
of the study was to investigate the effect of gabapentin on morphine
consumption and postoperative pain in patients undergoing radical
mastectomy.

REVIEW OF LITERATURE:-
The anticonvulsant gabapentin is widely used for treatment of chronic
pain and has reduced neuropathic pain in three large placebo-
controlled clinical trials. (1–3) Despite intensive investigation, the
molecular mechanism of action of gabapentin remains unsettled (for
review, see Taylor et al.4). Suman Chauhan et al. [5] demon- strated that
L-amino acids potently inhibited binding of an active enantiomer of
gabapentin ([3 H]gabapentin). This was further supported by Taylor et
al. [4] who showed that the potent anticonvulsant, 3-isobutyl GABA (an
analogue of gabapentin) potently and stereoselectively bound to the
same receptor. Early studies [6] indicated that gabapentin had only a
central anti-allodynic effect, gabapentin has been shown to inhibit
ectopic discharge activity from injured peripheral nerves. Experimental
studies have demonstrated antihyperalgesic effects of gabapentin in
models involving central neuronal sensitization, without affecting acute
pain transmission(7)In healthy volunteers, gabapentin enhanced the
effect of morphine in the cold pressor test,(8)reduced primary
mechanical allodynia in acute inflammation following a thermal injury,
(9)and reduced secondary hyperalgesia following sensitization with
combined heat and capsaicin, without affecting acute nociceptive
thresholds.(10) It has been suggested that central neuronal sensitization
may amplify postoperative pain, although the relative contribution of
various pain mechanisms to postoperative pain has not been
established.(11) The hypothesis of the present study is that gabapentin,
due to its potent antihyperalgesic effects, may reduce postoperative
pain.
 AIMS AND OBJECTIVES

Primary objectives
The aim of the study is to investigate the effect of single dose of
1200mg gabapentin on morphine consumption and postoperative pain
in patients undergoing radical mastectomy.

Secondary objective
To look for any significant adverse effect of these drugs.

METHODS:
In this study, 70 patients will receive a single dose of oral gabapentin
(1,200 mg) 1 h before surgery. Patients will receive analgesia with
morphine at doses of 2.5 mg postoperatively. Pain will be assessed on a
visual analog scale at rest and during movement, and side effects were
assessed on a four-point verbal scale 2 and 4 h postoperatively.

MATERIAL AND METHODS

Ethics statement
This study will be conducted after obtaining ethical clearance from the
Institute Ethics Committee, IGIMS, Patna. Written informed consent will
be obtained from all the patients before enrolling them for the study.
a) Place of Study : Indira Gandhi Institue of Medical
Sciences, Patna, India
b) Study duration : Pre induction time to induction of
anaesthesia
c) Type of study :

d) Inclusion Criteria :
i) Patients between 18-75 yr scheduled for unilateral radical
mastectomy
ii) Patients willing to participate.
e) Exclusion Criteria :
i) Patient's refusal to participate
ii) Patients with known allergy to gabapentin or morphine
iii) Patient with daily intake of analgesics or corticosteroids
,diabetes or impaired kidney function
iv) Patients with an intake of NSAIDs or paracetamol 24 hr prior
to operation
v) Patients with an intake of antacids 48 hr prior to operation
a) Outcome parameters : .
b) Sample size : Based on previous study keeping alpha error <0.05
and beta error <0.2, power of study 80%, 70 patients will be
required in the group.
c) Sampling type :
d) Details of materials : Patient admitted for radical mastectomy
procedure under general anaesthesia, who are willing to
participate and fulfil the inclusion criteria will be enrolled in the
study.
Intervention & data collection methods: Patients will receive 1,200 mg
oral gabapentin 1 h before surgery. Anaesthetic technique will be
standardised for all the patients. Standard anaesthesia monitoring
comprising of pulse oximetry, 5 lead electrocardiogram, automated
non-invasive blood pressure will be initiated and continued to the
post-operative period up to 24 h. End tidal carbon dioxide, train-of-four
neuromuscular response and nasopharyngeal temperature will be
monitored after induction of anaesthesia. Following pre-oxygenation,
anaesthesia will induced with intravenous (IV) fentanyl 2 μg/kg and
propofol (loss of verbal response taken as end point of induction).
Ability to mask ventilate will checked before injecting 0.1 mg/kg of
vecuronium for neuromuscular blockade. Following 3 min of ventilation
with 1–2% isoflurane in 100% oxygen, trachea will be intubated with
appropriate sized tracheal tube. Anaesthesia will be maintained with
isoflurane in 33% oxygen and 66% nitrous oxide aiming a minimum
alveolar concentration of 1.3. Vecuronium will be repeated as
appropriate. Concerned consultant anaesthesiologist started an infusion
of morphine at 20 μg/kg/hr through a dedicated IV line, 30 min after
induction of anaesthesia and stopped infusion at start of skin
closure.loading dose of 2 mg was set. The demand bolus dose of
morphine was set at 1 mg (1 mg/ml) with a lock out period of 10 min.
No background infusion of morphine was administered. Only during the
1st h following surgery, the nurse will be allowed to give morphine
boluses upon patient’s request . Time to first analgesic request will be
recorded (duration between completion of surgery and request for first
analgesic). Pain will assessed at intervals of 1, 2, 6 and 24 h following
surgery by the blinded investigator. The ward nurse also assessed the
pain every hour, when the patient will be not sleeping; and encouraged
the patient to use PCA if pain score was ≥4. Total morphine consumed
at the end of 24 h will recorded. Sedation level will be assessed at each
interval. Patients will be encouraged to report any side effects
experienced by them. Specific enquiry will be made regarding nausea,
vomiting, dizziness, headache and pruritus. PCA will be terminated at
the end of 24 h and the subsequent analgesia will managed by the
treating surgeon.

REFERENCE
1. Rowbotham M, Harden N, Stacey B, Bernstein P, Magnus-Miller L: Gabapentin
for the treatment of postherpetic neuralgia: A randomized controlled trial.
JAMA 1998; 280:1837–42

2. Backonja M, Beydoun A, Edwards KR, Schwartz SL, Fonseca V, Hes M,

LaMoreaux L, Garofalo E: Gabapentin for the symptomatic treatment of painful
neuropathy in patients with diabetes mellitus: A randomized controlled trial.
JAMA 1998; 280:1831–6

3. Rice AS, Maton S: Gabapentin in postherpetic neuralgia: A randomised,

double blind, placebo controlled study. Pain 2001; 94:215–24

4. Taylor CP, Vartanian MG, Yuen P, Bigge C, Suman-Chauhan N, Hill DR. Potent and
stereospecific anticonvulsant activity of 3-isobutyl GABA relates to in vitro binding at a novel
site labelled by tritiated gabapentin.Epilepsy Research 1993; 14: 11±1

5. suman-Chauhan N, Webdale N, Hill DR, Woodruff GN.Characterisation of [3H]-gabapentin

binding to a novel site in rat brain: homogenate binding studies. European Journal of
Pharmacology 1993; 244: 293±301.
6.Petioff OA, Rothnan DL, Behan KL. The effect of gabapentin on brain gamma-aminobutyric
acid in patients with epilepsy. Annals of Neurology 1996; 39: 95±9.

7. Mao J, Chen LL: Gabapentin in pain management. Anesth Analg 2000;

91:680–7

8. Eckhardt K, Ammon S, Hofmann U, Riebe A, Gugeler N, Mikus G: Gabapentin

enhances the analgesic effect of morphine in healthy volunteers. Anesth
Analg 2000; 91:185–91

9. Werner MU, Perkins FM, Holte K, Pedersen JL, Kehlet H: Effects of gabapentin
in acute inflammatory pain in humans. Reg Anesth Pain Med 2001; 26:322–8

10. Dirks J, Petersen KL, Rowbotham MC, Dahl JB: Gabapentin suppresses
cutaneous hyperalgesia following heat/capsaicin sensitization. ANESTHESIOLOGY
2002;97:102–6

11. Woolf CJ, Chong MS: Preemptive analgesia-treating postoperative pain by

preventing the establishment of central sensitization. Anesth Analg 1993; 77:362–79

To,

The Chairman

Institute ethics sub committee

I.G.I.M.S. PATNA
 Through: proper channel

Subject: Submission of thesis for M.D (Anaesthesiology) course, session

2018-2021

Sir,

As per your guidelines, I Dr Sunny Kumar, M.D(anaesthesiology) student

here by submit the thesis titled “EFFECT OF SINGLE DOSE GABAPENTIN ON POST OPERATIVE
PAIN AND MORPHINE CONSUMPTION AFTER MASTECTOMY ” for M.D. Anaesthesiology course
session 2017-2020 for your kind approval

Yours sincerely,

(Dr Sunny Kumar)

INDIRA GANDHI INSTITUTE OF MEDICAL SCIENCES SHEIKHPURA,
PATNA - 800014
FORMAT FOR SUBMISSION OF PROTOCOL INVOLVING RESEARCH IN HUMAN SUBJECTS FOR
CLEARANCE BY INSTITUTE ETHICS SUB-COMMITTEE OF IGIMS FOR DM /M.Ch/ MD / MS /
MHA / MDS /M.Sc / M. Biotech./MBBS AND Ph.D STUDENTS (FOR THESIS OR DISSERTATION)

Submit fourteen (14) copies of the Research Project along with Covering letter and ‘soft
copy’ on CD with following information to the Member Secretary, Institute Ethics Sub-
Committee IGIMS. The Investigator must submit protocol through Chief Guide and Head
of Department who ensures that the project has been wetted both from the scientific
and ethical point of view.

No research project shall be / can be started unless ethics clearance/approval is

obtained. Please bear in mind that no retrospective / post facto ethical clearance can be
provided to research projects which were neither submitted nor wetted by the ethics
committee.

All submissions should be made in the prescribed Format of the Institute Ethics Sub-
Committee with signatures of all the investigators. The submission must be accompanied
with Participant Informed Consent Form (PICF) and Participant Information Sheet (PIS),
both in English and Hindi, in an understandable layman’s language. Also ensure that all
the pages are numbered.

Project Submission Time: Submissions will be received on all working days. Proposals
received till 15th of any month will be processed in the coming Institute Ethics Sub-
Committee meetings and those received after 15 th will be processed in the next Institute
Sub-Committee meetings.

Next meetings of Institute Ethics Sub-Committee on the first Monday in the month of
February.
While submitting replies raised by the Sub-Committee, the candidates are advised to
mention the Institute Ethics Committee/Sub-Committee reference number/s and also
attach a copy of the comments of the Institute Ethic Committee/Sub-Committee.

It is desirable that topics pertaining to clinical/drug trials should be avoided as thesis

topics to Ph.D / DM / M.Ch / MD / MS / MHA / MDS / M.Sc. / M.Biotech and MBBS
students. In case these are given, appropriate DCGI permission should be available.

Reply Submission: While submitting reply raised by the Sub-Committee, the Investigators are
advised to submit these through Chief-Guide. They should also mention the Sub-Committee
Reference number/s and also attach a copy of the comments of the Sub-Committee. These
changes should be incorporated as a soft copy in the CD.

Amendment Submission: While submitting amendments in protocols a covering letter

should be provided clearly stating the changes and soft copy of the same should be
submitted in a CD.
The research projects proposal submitted should be as follows:

1. Full Title of Study:

2.1 Name & signatures of the

Candidate 2.1________________Signatures_____________

2.2 Department 2.2_____________________________________

2.3 Degree/course 2.3

B.Sc/MBBS/M.Sc/MD/MS/MHA/MDS/M.Biotech/MCh/

2.4 Batch of admission to course DM/ Ph.D (encircle)

2.5 Month & year of submission of 2.4 January/July ________ (year)

Thesis
2.5 June/November ________(year)

3. Name of Faculty & Department Signatures (Guide/Co-Guides)

(Guide/Co-guide)

3.1______________________
3.1______________________________________

3.2 ______________________
3.2 _____________________________________

3.3 ______________________
3.3______________________________________

3.4 ______________________
3.4 _____________________________________

3.5______________________________________
3.5_________________________

(Expand if any more co-guides)

4. Objectives of the study 4.1________________________________________

4.2________________________________________
 4.3________________________________________

4.4________________________________________

4.5________________________________________

5. Why this study is required?

Please provide brief justification.

6. Methodology 6.1. Number of Patients:

6.2. Inclusion criteria

a)_________________________________________

b)________________________________________

c)_________________________________________

d)________________________________________

6.3. Exclusion criteria

a)_________________________________________

b)________________________________________
 c)_________________________________________

d) ________________________________________

6.4. Control(s)

6.5. Study design

6.6. Dosages of drug

6.7. Duration of treatment

6.8. Investigation specifically related to projects

6.9 Permission To Use copyrighted

Questionnaire/profrom
a

6.9. Others

6.10 Brief Methodology

7.Permission From Drug 1.Required 2.Not required

Controller 3.Received 4. Applied when:

General of India (DCGI)

8. Permission from DGFT , if 1.Required 2. Not required

Required 3.Received 4.Applied when:

9. a) Safety measures for a)_________________________________________

Proposed b)________________________________________

interventions c)________________________________________

b) Results of relevant laboratory

Tests

c) Result of studies in human

10. Plans to withdraw standard Yes No

Therapy Remarks:_________________________________
in research

11. Plan for provision of coverage

For

medical risk

12. How you will maintain

Confidentiality of subject?

13. Costs Involved (Appx. in 13.1_______________________________________

Rs.)

13.1 Investigations 13.2_______________________________________

13.2 Disposables

13.3 Implants 13.3_______________________________________

13.4 Drugs / Contrast Media

Who will bear the costs of the 13.4_______________________________________

requirements? (mark √ )
1. Patient 2. Project 3.Exempted

4. Other Agencies

(Name)________________________

14. Participant Information Sheet Attached English version

(mark √ if yes) Attached Hindi version

Certified that Hindi version is a true translation of English

version
 Attached English version

15. Participant Informed Consent Attached Hindi version

Form Certified that Hindi version is a true translation of English

(mark √ if yes) Version

16. Whether any work on this (mark √ if yes, X if no)

(Please enclose a separate certificate to this

Project effect).

has started or not?

17.Attached documents 17.1 Covering letter, through proper channel.

(If any) 17.2 Copy of the detailed protocol is mandatory

17.3 Undertaking that the study shall be done

in

Accordanc
e

with ICMR and GCP guidelines

17.4 In case of multicentric study, IEC clearance

of

Other

centers must be provided

17.5
Definite
undertaki
ng as to
who will
bear the

expenditu
re of
injury
related to
the
project
 INDIRA GANDHI INSTITUTE OF MEDICAL SCIENCES,
PATNA - 800014

PARTICIPANT INFORMATION SHEET (PIS)

The protocol must be accompanied by the Participant Information Sheet addressed to the
patient or participant or parent/guardian, in case of minor. While formulating the participant
information sheet, investigator must provide the subjects with the following information in
simple understandable layman’s language in English & Hindi, which can be understood by them:

Title of the study/project.

IGIMS and methods of the research.

Expected duration of the subject participation.

The benefits to be expected from the research to the subject or to others.

Any risk to the subject associated with the study.

Maintenance of confidentiality of records.

Provision of free treatment for research related injury.

Compensation of subjects for disability or death resulting from such injury.

Freedom of individual to participate and to withdraw from research at any time.
Withoutpenalty or loss of benefits to which the subject would otherwise be entitled.

Amount of blood sample to be taken should be mentioned in PIS in Tea Spoon Full.

Costs and source of investigations, disposables, implants and drugs / contrast

mediamust be mentioned in the PIS.

Telephone number/contact number of the candidate and one of the

investigatorsmust be mentioned in the PIS.

 In case of drug trials: The chemical name of the drug, date of its manufacturing and batch
number must be mentioned

 Initial Bio equivalent study of the drug / references should be provided

 Self certification should be given that translation to vernacular is accurate.

 INDIRA GANDHI INSTITUTE OF MEDICAL SCIENCES, PATNA - 800014

PARTICIPANT INFORMED CONSENT FORM (PICF)

Participant identification number for this trial: _______________________

Title of Project: _______________________________________________

Name of Principal Investigator: ____ ___ __Tel.No(s).__________________

The contents of the information sheet dated ……………….. that was provided have been

read carefully by me / explained in detail to me, in a language that I comprehend, and I have
fully understood the contents. I confirm that I have had the opportunity to ask questions.

The nature and purpose of the study and its potential risks / benefits and expected duration
of the study, and other relevant details of the study have been explained to me in detail. I
understand that my participation is voluntary and that I am free to withdraw at any time,
without giving any reason, without my medical care or legal right being affected.

I understand that the information collected about me from my participation in this research
and sections of any of my medical notes may be looked at by responsible individuals from
IGIMS. I give permission for these individuals to have access to my records.
I agree to take part in the above study.

Date:
(Signatures--------------------------------------------- /Left Thumb Impression) Place:

Name of the Participant: ____________________________________

Son / Daughter / Spouse of: __________________________________

Complete postal address: _____________________________________

This is to certify that the above consent has been obtained in my presence.

------------------------------

Date:

Signatures of the Principal Investigator

Place:

1) Witness – 1 2) Witness – 2

------------------------------ -------------------------------

Signatures Signatures

Name: Name:

Address: Address:

NB Three copies should be made, for (1) patient, (2) researcher, (3) Institution (Students
are requested to prepare the translation in simple understandable Hindi of their own)
 PATIENT CONSENT FORM

I……………………………………………………….s/o………………………

…………………………………………………………………………………

Resident

of …………………………………………………………………………………

Exercising my power of choice hereby give my consent for me/my

son/daughter/mother/ included as a subject in the study.

“EFFECT OF SINGLE DOSE GABAPENTIN ON POST OPERATIVE PAIN AND MORPHINE CONSUMPTION
AFTER MASTECTOMY”

I have been informed to my satisfaction by Dr.Sunny kumar, the purpose and

the risk involved in the Study. I am also aware of my right to opt out of the
study at any time during course without having to give reasons for doing so.

Date Signature of parent/guardian

Date Signature of the witness

Date Signature of the investigator
 PATIENT INFORMATION SHEET
TITLE OF STUDY: “EFFECT OF SINGLE DOSE GABAPENTIN ON POST OPERATIVE PAIN AND
MORPHINE CONSUMPTION AFTER MASTECTOMY”

If you agree to participate in the study, information provided by you will be

recorded in a proforma and will be kept confidential. You will continue to
receive routine hospital care. There are no potential risks to you being enrolled
in this study.

You are free not to participate in the study or withdraw from the study
anytime. If you choose not to participate in the study or withdraw from study
anytime, patient care and treatment at IGIMS hospital will continue as earlier.

If you have any questions, please feel free to ask.

CONTACTS: At any time in course of study, you wish to get information kindly
contact the following:

Name of Principal Investigator Name of Supervisor

Dr. Sunny Kumar Dr.AJIT GUPTA

MD Student Professor

Department of Anaesthesiology IGIMS, Patna Mob: Department of Anaesthesiology

9686475418 IGIMS, Patna
 Undertakings
I Dr. Sunny Kumar agree to abide by the ethical guidelines for
biomedical research on human subject (as per the ICMR guidelines) while
conducting the research project being submitted for Ethical Committee
consideration:-

1. Project is considered to be absolutely essential for the advancement of

knowledge and for the benefit of all.
2. Only subject, who volunteer for the project, will be included. Their
informed consent shall be obtained prior to commencement of the research
Project, and subjects will be kept fully appraised of all the consequences.
3. Privacy and confidentially of the subjects shall be maintained and without
the consent of the subjects no disclosure will be made.
4. Proper precautions shall be taken so as to minimize risk and prevent
irreversible adverse effects.
5. Research will be conducted by the professionally competent person

6. Research will be conducted in a fair, honest, impartial and transparent

manner.
7. Research will be accountable for maintaining proper records.

8. Research will be conducted keeping in view the public interest at large.

9. Research reports, materials and data will be preserved (as per the
institutional guidelines).
10. Result of research will be made through scientific publications.

11. Professional and moral responsibilities will be the researchers, directly or

indirectly connected with the research.

Approval of ethical committee and its composition
Approval of Scientific committee and its composition
 DECLARATION

We have read and agree to comply with the procedures details in this
document. All the relevant standard procedures will be adopted to
conduct this study with the highest ethical standards.

We have read Helsinki declaration (for clinical studies), ICP- GCP

guidelines/CPCSEA guidelines/ICMR ethical guidelines and other
applicable guidelines and undertake to follow them strictly in
performance in this study. The study will be performed as per
approved permission will be obtained from ethical committee for any
deviations. The study will be terminated immediately in case of any
unforeseen adverse consequences and the ethical committee
informed immediately.
Date: Signature of the investigator
 ந

Helsinki for clinical studies) ICP ந GCP CPCSEA

ICMR

ந
 CERTIFICATE (FOR STUDY)

This is certified that the study “EFFECT OF SINGLE DOSE GABAPENTIN ON POST
OPERATIVE PAIN AND MORPHINE CONSUMPTION AFTER MASTECTOMY ” will be done as
per ICMR/GCP guidelines.

Signature of Head of department Signature of Investigator

Department of Anaesthesiology

IGIMS, Patna
 CERTIFICATE (FOR STUDY)

This is to certify that no work has been started regarding the study
“EFFECT OF SINGLE DOSE GABAPENTIN ON POST OPERATIVE PAIN AND MORPHINE CONSUMPTION
AFTER MASTECTOMY”

before clearance from the ethical committee.

Signature of Head of department

Department of Anaesthesiology
IGIMS, Patna
INDIRA GANDHI INSTITUTE OF MEDICAL SCIENCES SHEIKHPURA, PATNA – 800014

Six Monthly Progress Of Project

Institute Ethics Sub-Committee No._________________________

Study title: ______________________________________________

Name of the Principal Investigator ______________________________

Designation / Department _____________________________________

Duration of Study ____________________________________________

Date of Starting of the Study ___________________________________

Period of Six monthly progress report: from ___________________ to _______

Progress:
 Side Effect if any:

Any serious adverse event:

Amendments if any:

Discontinuation reasons:

Progress:

Signatures of Guide _____________ Signatures of Investigator____

Date: _________