RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA
PROFORMA FOR REGISTRATION OF DISSERTATION

TOPIC
COMPARISON OF EQUICONCENTRATION OF
BUPIVACAINEFENTANYL AND
ROPIVACAINE-FENTANYL FOR EPIDURAL LABOUR ANALGESIA:
A PROSPECTIVE RANDOMISED COMPARATIVE STUDY.

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA.

BANGALORE

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. Name of the Candidate

DR. BHAVNA P SINGH,

and Address

NO.12, SAI CHARAN,

(in block letters)

1ST MAIN, 3RD CROSS,

ASHWINI LAYOUT,
EJJIPURA EXTENSION,
BANGALORE-560047.

2. Name of the Institution

ESIC MEDICAL COLLEGE - POST GRADUATE INSTITUTE OF

MEDICAL SCIENCE & RESEARCH ,RAJAJINAGAR, BENGALURU-10

3. Course of study and

subject

MD, ANAESTHESIOLOGY

4. Date of Admission to
course

30/05/2012

5. Title of the Topic

COMPARISON OF EQUICONCENTRATION OF BUPIVACAINE

FENTANYL AND ROPIVACAINE-FENTANYL FOR EPIDURAL
LABOUR ANALGESIA: A PROSPECTIVE RANDOMISED
COMPARATIVE STUDY

Brief Resume of the intended work :

6.1

Need for the study :

THE DELIVERY OF THE INFANT INTO THE ARMS OF A CONSCIOUS AND PAIN FREE
MOTHER IS ONE OF THE MOST EXCITING AND REWARDING MOMENTS IN MEDICINE.
- MOIR
Pain relief in labour has always been surrounded with myths and controversies and providing
effective and safe analgesia during labour has remained an ongoing challenge. Advances in the field of
labour analgesia have tread a long journey from the days of ether and chloroform in 1847 to the present
day practice of comprehensive program of labour pain management using evidence based medicine.
Neuraxial techniques were introduced for pain relief in labour in 1950. Modern neuraxial
labour analgesia reflects a shift in obstetrical anesthesia, thinking away from a simple focus on pain
relief towards a focus on the overall quality of analgesia.(1)
In our country the awareness of regional analgesia for labour is still lacking and except a few
centres that run a comprehensive labour analgesia programme, the national awareness or acceptance of
pain relieving options for women in labour virtually does not exist. Central neuraxial analgesia is the
most versatile method of labour analgesia and the gold standard technique for pain control in obstetrics
that is currently available.(2) The satisfaction of birth experience is greater with neuraxial techniques.
Epidural blockade is an effective means of providing analgesia during labour.(2)
Bupivacaine and Ropivacaine are widely used to provide efficient epidural analgesia in labour.
The value of bupivacaine is limited by the risks of motor blockade and toxicity. There have been
conflicting comparisons of ropivacaine and bupivacaine for labour analgesia.(3-5) Some studies have
suggested that ropivacaine produces less motor block than bupivacaine while others found the drugs to
be indistinguishable. Dilute solutions of epidural local anesthetics combined with opioids may be used
to minimize unwanted motor block. The amount by which fentanyl reduces local anesthetic dose
requirement depends on dose of fentanyl.(6)
Present day epidural local anesthetic for labour is low and minimal dose and volume with
opioids. The present study is taken up to provide labour analgesia service to our patients and compare
the analgesic requirement and hemodynamic effects of bupivacaine and ropivacaine.

Review of literature :
6.2

GREG.C.MEISTER et al (2000) (7) compared 0.125% Ropivacaine with 2g/ml Fentanyl and
0.125% Bupivacaine with 2g/ml Fentanyl for epidural Labour Analgesia. They chose 50 laboring
women and randomized them to receive either 0.125% Ropivacaine with Fentanyl 2g/ml or 0.125%
Bupivacaine with Fentanyl 2g/ml by using patient controlled epidural analgesia (PCEA) technique.
They found no differences in verbal pain scores; local anesthetic used patient satisfaction or side effects
between the groups. However the Ropivacaine/Fentanyl group developed significantly less motor block
than Bupivacaine/Fentanyl group. They concluded that although Ropivacaine/Fentanyl group developed
less significantly less motor blockade whether these results are applicable to anesthesia practices which
do not use PCEA remains to be determined.
HELENE FINEGOLD et al (2000)(8) conducted a double blind randomized study in 100 term
nulliparous women to compare the analgesic efficacy of ropivacaine 0.1% with 2g/ml fentanyl and
Bupivacaine 0.125% with 2g/ml fentanyl infusion for epidural labor analgesia. They found the onset
time and visual analogue scale were not different in both the groups, 80% of the patients in the
ropivacaine group had no demonstrable motor block after first hour compared with only 55% of patients
in bupivacaine group. They concluded that both bupivacaine and ropivacaine produced satisfactory
labor analgesia and ropivacaine produced significantly less motor block during first stage of labor.
CAMPBELL et al (2000)(9) conducted a prospective randomized double blinded study to compare
the efficacy of 0.08% Bupivacaine and 2g/ml Fentanyl or 0.08% Ropivacaine and 2g/ml Fentanyl to
initiate ambulatory labour epidural analgesia. 40 nulliparous women in early labour <5cm cervical
dilation received either 20ml of 0.08% Bupivacaine and 2g/ml Fentanyl (BF) or 20ml of 0.08%
Ropivacaine and 2g/ml Fentanyl (RF) to initiate epidural analgesia. They found that 0.08%
Ropivacaine and 2g/ml Fentanyl provides consistent, effective labour analgesic without causing
clinically significant adverse maternal/fetal effects while concurrently preserving maternal ability to
void urine and ambulate.
P.D.W. FETTES et al (2006) (10) conducted a randomized double blinded trial with 40 primigravid
patients to compare intermittent bolus vs. continuous administration of epidural Ropivacaine with
Fentanyl for epidural analgesia. Plain Ropivacaine 0.2%, 15-20 ml was titrated until analgesia and
bilateral sensory block to T10 was produced (Time Zero).Patients were then given either an infusion of
Ropivacaine 2mg/ml with 2g/ml Fentanyl or hourly boluses of 10ml of the same solution and on
request additional 10ml were given for analgesia. They found no differences between the two groups in
patient characteristics, obstetric/neonatal outcome, and sensory/motor block. However the total drug
dose used in the intermittent group was lower and duration of uninterrupted analgesia (time to 1 st rescue

bolus) was longer. They concluded that intermittent bolus is a more efficacious mode of analgesia.
NEERA SHAH et al (2007)(11) conducted a prospective randomized double blinded study in 162
ASA-I and II full term primiparous laboring women to compare the efficacy of

Ropivacaine,

Bupivacaine and Levobupivacaine. All patients received 8ml of local anesthetic + fentanyl (100g)
followed by infusion of 12 ml/hr of local anesthetic with 2g/ml of fentanyl. Patients were allocated to
one of the three groups, group 1 received bolus infusion of Bupivacaine 0.125%, group 2 received bolus
and infusion of Levobupivacaine 0.125%, and group 3 received bolus of ropivacaine 0.2% and infusion
of ropivacaine 0.1%. Vital signs, VAS score, sensory and motor block were recorded every hour. They
found no statistically significant difference in pain (VAS) / motor (Bromage) score among the 3 groups.
WANG Li ZHONG et al (2010)

(12)

conducted a randomized clinical trial in 450 nulliparous

parturients to compare Ropivacaine, Bupivacaine and Levobupivacaine with Sufentanyl for PCEA
during labour. A concentration of 0.05%, 0.075%, 0.125% or 0.15% of either Ropivacaine (group R),
Bupivacaine (group B) and Levobupivacaine (group L) with Sufentanyl 0.5g/ml was epidurally
administered by PCEA mode. Effective analgesia was defined as VAS score 30mm. The relative
median potency for each local anesthesia was calculated using a probit regression model. They found no
significant difference among groups in the numbers of effective analgesia, pain scores, hourly local
anesthesia concentration used and sensory/motor blockade. They concluded that by using PCEA lower
concentration of Ropivacaine, Bupivacaine and Levobupivacaine with Sufentanyl produced similar
analgesia and motor blockade. Analgesic efficacy mainly depends on concentration rather that type of
anesthetics.
SUMIT KALRA et al (2010) (13) compared the efficacy of low concentration of Bupivacaine with
Fentanyl and Bupivacaine with Sufentanyl for epidural labour analgesia. 50 full term parturients
received a initial bolus dose of a 10ml of 0.125% Bupivacaine. The patients were randomly divided into
two groups: Fentanyl group (F) received 0.0625% Bupivacaine + 2.5g/ml Fentanyl. Sufentanyl group
(S) received 0.625% Bupivacaine + 0.25g/ml Sufentanyl. Verbal analogue pain scores, need of
supplementary boluses, mode of delivery and maternal satisfaction neonatal APGAR scores were
recorded. No significant difference was observed in the 2 groups. They concluded that both Fentanyl
and Sufentanyl were equally effective in providing labour analgesia with hemodynamic stability,
maternal satisfaction without serious maternal / fetal side effects.

Objectives of the study :

The present study is carried out to compare Bupivacainefentanyl and Ropivacainefentanyl in

primigravid full term parturients for epidural labour analgesia. The following parameters are compared:
6.3

Analgesic efficacy

Onset, duration of action, total dose of local anesthetic used

Motor blockade intensity

Hemodynamic parameters

Maternal satisfaction.

MATERIALS AND METHODS :

7.1 SOURCE OF DATA :Data will be collected from patients coming for delivery at ESIC Medical College PGIMSRRajajinagar Bangalore.
7

SAMPLE SIZE
60 patients with below mentioned inclusion and exclusion criteria will be enrolled, 30 in each
group.

STUDY DESIGN
Prospective randomized double blind controlled study
INCLUSION CRITERIA
1. ASA physical status I-II
2. Primigravida women with gestational age 36 weeks
3. Singleton pregnancy with vertex presentation
4. Uncomplicated pregnancy with normal fetal heart rate
5. Cervical dilatation < 5cm.

EXCLUSION CRITERIA
1. ASA physical status III or IV
2. Multiple or preterm gestation
3. Allergy to any study drug

4. Contra indications or patients unwilling for labour analgesia

5. Cervical dilatation > 5cm.
7.2 METHOD OF STUDY AND COLLECTION DATA:
After obtaining ethical committee approval, a written informed consent is obtained. A detailed
examination of the patient is done and the following parameters are recorded: Demographic data, parity,
gestational age, condition of membranes, vital parameters and fetal heart rate.
Patients are randomized into two groups based on a computer generated randomization
table. (Group B -will receive 0.125% Bupivacaine with 2g/ml Fentanyl and Group R- will receive
0.125% Ropivacaine with 2g/ml Fentanyl). An intravenous access is secured with an 18G cannula and
the parturient is preloaded with 500 ml of Ringers lactate solution. 3 lead electrocardiogram (ECG),
pulse oximeter and non invasive blood pressure are connected and baseline vitals are recorded. The
parturient and anesthesiologist performing the technique and administering the study drug are blinded to
the drug. Under

aseptic precautions epidural space is identified in sitting position with midline

approach using 18 gauge Tuohys needle in L3-4 or L4-5 interspace with loss of resistance to air technique
and catheter is threaded cephalad 3 to 4 cms into epidural space. After negative aspiration for blood and
CSF, a test dose of 3ml of lignocaine 1.5% with 1:2,00,000 adrenaline is administered through the
catheter. Intravascular spread of the drug is detected by a change in heart rate of more than 30 beats per
minute from baseline within 20-40 seconds. (14) Intrathecal spread is detected by appearance of motor
blockade within five minutes. Subjects with positive test dose response are excluded from the study.
Five minutes after administering the test drug, 10-15 ml of study drug of either 0.125% Bupivacaine
with Fentanyl 2g/ml or 0.125% Ropivacaine with Fentanyl 2g/ml is given in 5 ml increments over
10 min. Patients not experiencing analgesia within 20 min of initial bolus are supplemented with
additional 5 ml of the solution.
Analgesia is maintained by continuous epidural infusion of the solution at the rate of 10 ml/hr
after 30 min of the initial bolus by using a syringe infusion pump. Patients who experienced inadequate
analgesia (VAS > 4) during the process are supplemented with additional 5 ml of solution up to a
maximum of 10 ml/hr.

The following parameters are noted:

1. Oxygen saturation
2. Heart rate
3. Non invasive blood pressure and
4. Fetal heart rate
All these parameters are monitored continuously before insertion and after insertion of catheter.
These parameters are recorded at 5, 10, 20, 30, 45, 60 min and every 30 min after that, until delivery.

Adverse effects like hypotension, arterial desaturation are noted and managed if necessary.
Hypotension is defined as fall of systolic blood pressure 20% of base line or < 90 mmHg, is managed
with left uterine displacement, accelerating IV fluid administration and IV Bolus ephedrine 3-5 mg as
required.
After administration of bolus dose and starting infusion the following parameters are noted:
5. Pain score - assessed by using visual analogue scale (VAS) 0-10, where 0- no
pain and 10worst possible pain.
6. Highest level of sensory block - assessed by loss of temperature discrimination to
alcohol swab.
7. Degree of motor blockade is assessed by using Bromage scale.
8. Total dose of local anesthetic consumed per hour and number of additional
supplements is recorded.
All these parameters are assessed at twenty minutes after the initial bolus
and every thirty minutes thereafter.
After delivery the following are noted.
1. Patients satisfaction - assessed as excellent, good, fair or poor.
2. The mode of delivery - spontaneous, vaginal, instrumental vaginal, caesarean
section, and
3.

Total dose of local anesthetic is note.

STATISTICAL ANALYSIS:
Done using analysis of variance X2, and Fischers exact tests as appropriate. P < 0.05 is considered
significant. Group size was selected by using proportions sample size estimates (power = 80%).

8.

REFERENCES :

1. Wong CA. Advances in labour analgesia. Int J Womens Health 2009;1:139-54.

2. Hawkins JL. Epidural analgesia for Labour and delivery. N Engl J Med 2010;362: 1503-10.
3. .Polley L S, Columb M O, Naughton N N, Wagner D S, van de Ven C J. Relative analgesic
potencies of ropivacaine and Bupivacaine for epidural analgesia in labor: implications for
therapeutic indexes. Anesthesiology 1999; 90: 944-50.
4 Capogna G, Celleno D, Fusco P, Lyons G, Columb M. Relative potencies of Bupivacaine and
ropivacaine for analgesia in labour. Br J Anesth 1999; 82: 371-73.
5.Owen M D, D Angelo R, Gerancher J C. 0.125% ropivacaine is similar to 0.125% Bupivacaine
for labor analgesia using patient controlled epidural infusion. Anesth Analg 1998; 86: 527-31.
6.Lyons G, Columb M, Hawthorne L, Dresner M. Extradural pain relief in labour: Bupivacaine
sparing by extradural fentanyl is dose dependent. Br J Anaesth 1997; 78: 493-97.
7. Meister G C, D Angelo R, Owen M, Nelson K E, Gaver R. A comparison of epidural analgesia
with 0.125% Ropivacaine with Fentanyl versus 0.125% Bupivacaine with Fentanyl during labor.
Anesth Analg 2000; 90: 632-37.
8. Helene Finegold, Gordon Mandell, Sivam Ramanathan. Comparison of ropivacaine 0.1%fentanyl and bupivacaine 0.125% -fentanyl infusions for epidural labour analgesia. Can J Anesth
2000; 47(8): 74045.
9. David C. Campbell, Rhonda M. Zwack, Lesley-Ann L. Crone, Ray W. Yip. Ambulatory labor
epidural analgesia: bupivacaine versus ropivacaine. Anesth Analg 2000; 90: 13849.
10. P. D. W. Fettes, C. S. Moore, J. B. Whiteside, G. A. Mcleod, J. A. W. Wildsmith. Intermittent vs
continuous administration of epidural ropivacaine with fentanyl for analgesia during labour. Br J
Anaesth 2000; 97: 35964.
11. Neera Sah, Manuel Vallejo, Amy Phelps, Helene Finegold, Gordon Mandell, Sivam
Ramanathan. Journal of Clinical Anesthesia 2007; 19: 21417.
12. WANG Li-zhong, CHANG Xiang-yang, LIU Xia, HU Xiao-xia and TANG Bei-lei. Comparison
of bupivacaine, ropivacaine and levobupivacaine with sufentanil for patient-controlled epidural
analgesia during labor: a randomized clinical trial. Chin Med J 2010;123(2):178-83.
13. Sumit Kalra, Namita Saraswat, G. S. Agnihotri. Comparison of Bupivacaine and fentanyl with
Bupivacaine and sufentanil for epidural labor analgesia. Saudi Journal of Anesthesia 2010; 4(3):
178-81.
14. Linda S, Beth Glosten. Epidural and spinal analgesia/anesthesia: local anesthetic techniques.
In:Natasha Andjelkovic, Donna Morrissey. Chestnut: Obstetric Anesthesia. Philadelphia,
Pennsylvania: Mosby Inc; 2004. p325-42.

9.

Signature of candidate

10. Remarks of the guide

11.

Name & Designation of

block letters)
11.1 Guide

THIS STUDY WILL BE CONDUCTED UNDER MY

DIRECT SUPERVISION AND GUIDANCE. VERY
RELEVANT TOPIC IN DAY TO DAY PRACTICE.
(in DR. PRASAD .C.G.S. MD,
ASSOCIATE PROFESSOR,
DEPARTMENT OF ANESTHESIOLOGY PAIN AND
CRITICAL CARE,

11.2 Signature

11.3 Co-Guide

DR. RENUKA RAMAIAH

PROFESSOR AND HEAD OF DEPARTMENT OF
OBSTETRICS AND GYNAECOLOGY.

11.4 Signature

11.5 Head of department

11.6 Signature
12

12.1. Remarks of the

Chairman & Principal

12.2. Signature.

DR. N.S. KODANDA RAM, MD DA,

PROFESSOR AND HEAD OF DEPARTMENT OF
ANESTHESIOLOGY, PAIN AND CRITICAL CARE.

APPENDIX

BROMAGE SCORE
Grade 0- Patient able to move at all the joints (Hip, Knee, and Ankle)
Grade 1- Unable to move at hip joint
Grade 2- Unable to move at both hip and knee joint
Grade 3- Unable to move at all the 3 joint hip, knee and ankle

VISUAL ANALOGUE SCALE

PROFORMA

Sl. No.

Date of Admission :

Name:

IP No:

Age:
Sex:

Occupation:

Address:
Parity:
Weight:
Height:

BMI:

ASA physical Status:

Informed Consent:
Group: Bupivacaine (B) / ropivacaine (R):
HISTORY
General ExaminationVital signs: pulse- /min, blood pressure- /
temperature,
SPO2- %
Systemic ExaminationInvestigations:
Haemoglobin:
Coagulation profile:
Blood Sugar:
Blood Group:
Urine analysis:

Preloading:

mm Hg, respiratory rate- /min,

MONITORING CHART
Parameters are monitored continously and recorded as follows

PARAMETER
Heart rate
(bpm)
SBP mm Hg
DBP mm Hg
MAP mm Hg
SPO2 %
FHR (bpm)

0 min

5min

PARAMETER
Visual analogue
scale
Highest sensory
level
Degree of motor
block

10min

20min

30min

45min

60min

90min

120min

150min

180min

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

20 min

30 min

60 min

90 min

120 min

150 min

180 min

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

PARAMETER
Number of additional
supplements
Total dose of local
anesthetic used

1st hour

2nd hour

3rd hour

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

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

AFTER DELIVERY:
PATIENT SATISFACTION: Excellent/ good/ fair/ poor
MODE OF DELIVERY: Spontaneous, vaginal, instrumental vaginal, caesarean section
GRAND TOTAL OF LOCAL ANESTHETIC USED:

CONSENT FORM
INFORMATION TO THE PARTICIPANT:
Our aim is to provide a pain free labour and make delivery a pleasant experience for you.
Epidural labour analgesia has been proven to be one of the best ways of doing it. We will be introducing a
catheter into your back and infuse drug through the catheter.
We have undertaken a study to compare the merits & de-merits of 0.125% Bupivacaine with
Fentanyl 2g/ml and 0.125% ropivacaine with 2g/ml fentanyl. You will not know which of the two
drugs you will be receiving. We thus request your participation in the study. The procedure will be
performed by a qualified Anesthesiologist (Principal / Co-Investigator).
IF YOU AGREE TO PARTICIPATE IN THE STUDY, THE FOLLOWING WILL BE DONE:
With aseptic precautions epidural catheter will be threaded through lumbar L 3-4 or L4-5 space with
18G Tuohy needle. After a negative test dose response the test drug will be given as a continuous infusion

through the epidural catheter. You will have analgesia approximately below your umbilicus and will be
conscious throughout the procedure. You will be monitored continuously till the time of delivery.
BENEFITS & RISKS OF PROCEDURE:-

Benefits- pain free labour and pleasant memory of birth experience.

Risks-like any other procedure epidural labour analgesia is associated with some side and
adverse effects.
Side effects include hypotension (decrease in blood pressure) and bradycardia (decrease in heart
rate) which will be treated immediately as and when it occurs if necessary.
Adverse effects include dural puncture incidence (<1%) (a hole in one of the membranes
covering spinal cord). This may lead to post procedure headache which will be treated.
Very rare complications include intravascular injection of drug, subarachnoid injection (spinal
anesthesia) and total spinal.

UNDERTAKING BY THE INVESTIGATOR:

Your consent to participate in the above study is sought. You have the right to refuse consent or
withdraw the same during the study without giving any reason. If you have any doubts about the study
you are free to contact any of the investigators Dr Prasad C.G.S, Assoc Professor & Dr Bhavna.P.Singh,
Junior Resident of Anesthesia Dept of ESIC PGIMSR, Rajajinagar, Bangalore for clarification if you so
desire. If you withdraw from the study, all your information will be destroyed.
CONFIDENTIALITY:
All the information/data collected from you, the results of the test will be kept in strict
confidence. The information provided/obtained by the study will be kept separate from your medical
records. A serial number will indicate your identity on records. Your research results will not be provided
to your relatives, personal physician, insurance companies or any other third party unless you give a
written consent for this to be done. Information about you will be available to the investigators & the
research associates, no person or family will be identified in any report or publications from the study.
Your identity or that of your family will not be revealed in any description unless you agree for other
studies related to the similar procedure.
Result of the analysis:- The results will not be disclosed to you.

Patient consent form

Name of the participant: ____________________________________________

Name of the Principal (Co-) Investigator: ______________________________

Name of the Institution: ____________________________________________

Name and address of the sponsoring (funding) agency/ies (if any): ________________

________________________________________________________________________

Documentation of the informed consent

I, ., have read the information in this form (or it has been read to me). I was free to ask
any questions and they have been answered. I am over 18 years of age and, exercising my free power of choice,
hereby give my consent to be included as a participant in .
. (title of the study)
..

(1) I have read and understood this consent form and the information provided to me.
(2) I have had the consent document explained to me.
(3) I have been explained about the nature of the study.
(4) My rights and responsibilities have been explained to me by the investigator.
(5) I have been advised about the risks associated with my participation in the study.
(6) I have informed the investigator of all the treatments I am taking or have taken in the past .
months including any desi (alternative) treatments.
(7) I agree to cooperate with the investigator and I will inform him/her immediately if I suffer unusual
symptoms.
(8) I have not participated in any research study within the past .. month(s).
(9) I am aware of the fact that I can opt out of the study at any time without having to give any reason
and this will not affect my future treatment in the hospital.
(10) I am also aware that the investigators may terminate my participation in the study at any time, for
any reason, without my consent.
(11) I hereby give permission to the investigators to release the information obtained from me as result of
participation in this study to the sponsors, regulatory authorities, Government agencies, and ethics
committee. I understand that they may inspect my original records.
(12) My identity will be kept confidential if my data are publicly presented.
(13)If, despite following the instructions, I am physically harmed because of any substance or any
procedure as stipulated in the study plan, [my treatment will be carried out free at the investigational
site / the sponsor will bear all the expenses], if they are not covered by my insurance agency or by a
Government program or any third party.
(14) I have had my questions answered to my satisfaction.
(15) I have decided to be in the research study.

WITNESS SIGNATURE

PARTICIPANTS SIGNATURE

1.
Date
2.

Place