PROFORMA FOR

THE THESIS OF MASTER OF SURGERY

DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY

S. N. MEDICAL COLLEGE AGRA

AFFILIATED WITH
ATAL BIHARI VAJPAYEE MEDICAL UNIVERSITY
LUCKNOW, UTTAR PRADESH
(2022-2025)

TITLE
CARBETOCIN VERSUS OXYTOCIN USE IN STANDARD
ACTIVE MANAGEMENT OF THIRD STAGE OF LABOUR
(AMTSL) FOR PROPHYLAXIS OF POSTPARTUM
HEMORRHAGE IN VAGINAL DELIVERY

BY:
Dr. SHIKHA SINGH
DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY
S.N. MEDICAL COLLE GE
 PROFORMA FOR THE THESIS FOR MASTER OF SURGERY
(OBSTETRICS AND GYNAECOLOGY)
ATAL BIHARI VAJPAYEE MEDICAL UNIVERSITY, LUCKNOW, UTTAR PRADESH
(2022-2025)
TITLE : CARBETOCIN VERSUS OXYTOCIN USE IN ACTIVE MANAGEMENT OF
THIRD STAGE OF LABOUR (AMTSL) FOR PROPHYLAXIS OF POSTPARTUM
HEMORRHAGE IN VAGINAL DELIVERY

HEAD OF DEPARTMENT Prof. RICHA SINGH

M.S. D.N.B. M.N.A.M.S,
F.I.C.O.G F.M.A.S.I., F.I.C.M.CH
Professor and Head of Department
Department of Obstetrics and Gynaecology
S.N. Medical College, Agra
GUIDE: Dr. DIVYA YADAV
M.S ,F.I.C.O.G ,F.M.A.S. , F.I.C.M.C.H., M.N.A.M.S.
Associate Professor
Department of Obstetrics and Gynaecology
S. N. Medical College, Agra
CO-GUIDE: Prof. RICHA SINGH
M.S. D.N.B. M.N.A.M.S,
F.I.C.O.G F.M.A.S.I., F.I.C.M.CH
Professor And Head of Department
Department of obstetrics and gynaecology
S.N Medical College , Agra

CO- GUIDE :. Dr. ABHILASHA YADAV

M.S , F.M.A.S.
Assistant Professor
Department of obstetrics and gynaecology
S.N. Medical College ,Agra

NAME OF THE STUDENT: Dr. SHIKHA SINGH(JUNIOR RESIDENT 1)

PLACE OF WORK: DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY

CERTIFICATE:- It is certified that Aims , objectives, material and methods have been checked and approved.
The work is feasible and statistician has been consulted .
 INTRODUCTION

Postpartum haemorrhage is an obstetric emergency complicating 1-10% of all

deliveries.1 It continues to be the leading obstetric cause of maternal death.
Almost 500,000 women die for this potentially preventable cause each year,
and up to an estimated quarter of these deaths occur as a consequence of
hemorrhage at time of delivery.2 Prevention of post-partum hemorrhage
(PPH) is of utmost importance due to its impact on maternal morbidity
and mortality. Non-fatal PPH can result in further interventions, severe
anemia, need of blood transfusion, Sheehan’s syndrome (pituitary infarction),
coagulopathy and organ damage due to hypotension and shock.
The most common cause of hemorrhage at the time of delivery is uterine
atony, therefore active management of the third stage of labor rather than
expectant management is recommended by WHO.3-5 If third stage of labor is
effectively managed, it is possible to reduce postpartum blood loss by
316.5%.6 The administration of uterotonic drugs widely prevents the PPH,
significantly decreases the incidence of PPH and therefore it is the main point
of active management. The recommended uterotonic is Oxytocin (10 IU)
administered intra-muscularly immediately after delivery of the baby for the
prevention of PPH in low-risk vaginal and caesarean deliveries.

The incidence of PPH has been reported to be 3.9 % in women who delivered
vaginally.7

Oxytocin binds to oxytocin receptors in the myometrium to stimulate uterine

smooth muscle. It has a fast onset but is of short duration and a maintenance
infusion in the immediate perioperative period is recommended. Although
oxytocin is the most widely accepted uterotonic agent, however other drugs
are available and which agent is ideal for prophylactic use is far to be clearly
stated.
Carbetocin is a long-acting synthetic oxytocin analogue, 1-deamino-
1monocarbo-(2-O-Methyltyrosine)-oxytocin, firstly described in 1987. It has
a half-life of 40 minutes (around 4–10 times longer than oxytocin) and uterine
contractions occur in less than two minutes after intravenous administration
of optimal dosage of 100 μg.8
Recent trials suggest that carbetocin may be just as effective as oxytocin, with
less adverse effects, avoiding a continuous infusion and greater heat stability,
particularly where maintaining a cold supply chain is not feasible.
Prophylactic administration of carbetocin may be a good alternative to
oxytocin to prevent post-partum hemorrhage.
In the proposed study we will evaluate and compare the efficacy of carbetocin
versus oxytocin for prevention of postpartum hemorrhage in vaginal delivery.
 AIM AND OBJECTIVES

Aim:

To compare the effectiveness of carbetocin versus oxytocin use in standard

AMTSL for prophylaxis of postpartum hemorrhage after vaginal delivery.

Objectives:

• To assess the efficacy and side effects of carbetocin for

prophylaxis of post-partum hemorrhage in vaginal delivery.

• To assess the efficacy and side effects of oxytocin for

prophylaxis of post-partum hemorrhage in vaginal delivery.

• To compare the efficacy of carbetocin with oxytocin in

prophylaxis of post-partum hemorrhage in vaginal delivery.
 REVIEW OF LITERATURE

The most common cause of maternal mortality is obstetrics bleeding. Postpartum

hemorrhage accounts for 72% of all obstetric haemorrhages.1 The most common
cause of postpartum bleeding is uterine atony. If the third stage of labor is
effectively managed, it is possible to reduce postpartum blood loss by 3-16.5
percent.6

During the second half of the 20th century, a package of interventions performed
during the third stage of labour became the cornerstone for the prevention of PPH.
According to the WHO and other professional organisations, third-stage labour
should be actively managed to prevent PPH. This approach became known as the
”Active management of the third stage of labour(AMTSL)-” and consisted
initially of the following components:13 -
UTEROTONIC-Administration of a prophylactic uterotonic immediately after
the delivery of the baby.
DELAYED CORD CLAMPING-Delayed clamping the cord for at least 1-3
minutes.
-Controlled traction of the umbilical cord perform ,if required.
POSTPARTUM VIGILANCE-Immediately assess uterine tone to ensure a
contracted uterus ,continue to check every 15 minutes for 2 hours, If there is
uterine atony ,perform fundal massage and monitor more frequently.
In contrast to active management, expectant management involves instead
waiting for signs of placenta separation and allows for the placenta to be delivered
spontaneously, or aided by nipple stimulation or gravity. Compared with
expectant management, the active management of the third stage of labour is
associated with a substantial reduction in the occurrence of PPH.

A set of initial measures also seems to be consensual in most guidelines and

consist of maintenance of two large IV lines, supplementation of oxygen, strict
monitoring of vitals, crystalloids infusion, and measures to avoid hypothermia
and evaluate the PPH cause.
Oxytocin
Oxytocin is a hormone produced by the posterior pituitary of brain. It is used as
a uterotonic agent in prevention of PPH (active management of 3rd stage of
labor) or treatment of atonic PPH. It is recommended by the majority of clinical
guidelines as the first-line uterotonic for PPH prevention and treatment in both
caesarean and vaginal delivery. It is either given by IV or IM route.
Oxytocin has a rapid onset of action (causing an almost immediate effect after
IV administration and after approximately 2 minutes following IM injection)
and a short duration of action (15-20 minutes).Due to its short duration of
action, multiple doses of Oxytocin have to be administered . Oxytocin acts on
receptors in the uterine smooth muscle to stimulate contraction of the
myometrium .
Oxytocin is a heat-sensitive uterotonic drug; has to be stored in 2 to 8°C to ensure
efficacy. In settings where oxytocin is used, attention should be paid to the
oxytocin cold chain (i.e. the requirements of a temperature-controlled supply
chain).
Despite being first-line of treatment, Oxytocin has certain limitations that are
mentioned below:-
• Requires cold chain storage
• No consistent administration method or dose
• Need for appropriate training to clinical staff
• Regular patient monitoring
• Short acting (half life 1 to 6 minutes)
• Long Infusion time
• Need for other Uterotonic agents
• High affinity to the vasopressin V2 receptor (antidiuretic effects of
oxytocin )

• This led to the development of carbetocin, a long-acting analogue of

oxytocin, which is now available in a heat-stable formulation.
Carbetocin

Carbetocin is a long-acting synthetic oxytocin analogue, 1-deamino-1monocarbo-

(2-O-Methyltyrosine)-oxytocin, firstly described in 1987.
Carbetocin is a long-acting synthetic oxytocin analogue has a half-life of
40minutes (around 4-10 times longer than oxytocin) and uterine contractions
occur in less than two minutes after intravenous administration of optimal dosage
of 100mcg. It requires single dose administration.8

Optimal dosage of 100 μg of carbetocin is well established through studies.8 Due

to the structural changes in carbetocin it has lower affinity to vasopressin receptor
and less anti-diuretic effect.
It also has some additional desirable effects compared with oxytocin and a very
favourable side effect profile similar to oxytocin
Like oxytocin, carbetocin selectively binds to oxytocin receptors present in
uterus, resulting in rhythmic contractions of the uterus, increased frequency of
existing contractions, and increased uterine tone.
Carbetocin is associated with substantial reduction of blood loss >500 ml
compared to oxytocin.
 MATERIALS AND METHOD

Place of study: Department of Obstetrics and Gynaecology, S.N. Medical

College, Agra.

Study design: A Randomized Comparative and Interventional Study.

Study population: Antenatal women of 37 to 40 weeks of gestation undergoing

vaginal delivery will be selected from labor room of Department of Obstetrics
and Gynaecology ,SNMC Agra for the study.

Duration of study: 18 months from May 2023 to August 2024

Sample size :Appoximately 400

Group A -200 women will receive injection carbetocin 100 micrograms I.M
Group B -200 women will receive injection oxytocin 10 I.U I.M

Sampling: simple random sampling

Inclusion criteria: All antenatal women of 37-40 weeks of gestation

undergoing vaginal delivery .

Exclusion criteria:
• Pulmonary edema
• Severe cardiovascular disorders
• Hypersensitivity to oxytocin.
• Epilepsy
• Renal or hepatic disorder ( risk benefit ratio can be assessed).
• Coagulopathy.
• All contraindications of vaginal delivery.

All selected women will be subjected to detailed history taking, and complete
General and Obstetrics examination and routine investigations. Vaginal
examination will be done under strict aseptic precautions.
After careful selection, the women undergoing vaginal delivery will be randomly
divided into 2 groups by simple Randomization.
Study Group A: Inj. Carbetocin 100 micrograms I.M/I.V given
Control Group B: Inj. Oxytocin 10 I.U I.M given
Either of the drugs will be administered within one minute of delivery of the
baby, In case of twin pregnancy the drugs will be given after delivery of the
second twin.
ESTIMATION OF BLOOD LOSS – Once the umbilical cord would be clamped
and cut, Volumetric and gravimetric estimation of blood loss would be
calculated. Volumetric estimation in CHATTISGARH – Drape (CG -Drape).
will be added to gravimetric blood loss. The gravimetric assessment will be done
by weighing the dressing pads with an electric scale before and after being used
to wipe blood during episiotomy repair ,difference of each gram will be taken as
one ml .Blood loss will be measured for atleast one hour but if bleeding continued
after one hour ,until active bleeding has stopped. Study would be aborted if
patient lands in PPH and PPH will be managed according to institutional protocol.
All participants would be followed up for 24 hr. The uterine tone and amount of
bleeding would be noted

Vitals (Pulse ,BP, SpO2,Bleeding per vaginum) and Uterine tone will be
monitored immediately after delivery, 30 and 60min after delivery. Possible
complications like nausea, vomiting, tachycardia, flushing, dizziness, headache,
shivering, metallic taste, dyspnea, palpitation and itching.
Data will be statistically described in terms of mean±standard deviation (±SD),
or frequencies (number of cases) and percentages when appropriate. Comparison
of numerical variables between the study groups will be done using independent
t-test. For comparing categorical data, Chi square test will be performed.

Reyes et al.9 performed a prospective double-blinded randomized controlled trial

in 60 women with severe preeclampsia who were randomized to receive either
oxytocin or carbetocin during the third stage of labor. They found that carbetocin
was as effective as oxytocin in the prevention of PPH . Carbetocin had a safety
profile similar to that of oxytocin, and it was not associated with the development
of oliguria or hypertension. They concluded that carbetocin is an appropriate
alternative to oxytocin for the prevention of PPH in women with severe
preeclampsia.
Boucher et al.10 have randomized 160 women undergoing vaginal delivery with
at least one risk factor for PPH to receive either carbetocin 100 mcg IM or
oxytocin 10 IU iv oxytocin infusion over2h.The need for uterine massage and
other uterotonics were significantly lower in the carbetocin group. However, they
found no significant difference in the amount of bleeding or the hemoglobin
difference before and after delivery between the groups.
Attilakos et al.11 have randomized 377 women undergoing cesarean section to
receive either IV carbetocin 100mg or IV oxytocin 5IU after the delivery of the
baby. The carbetocin group needed significantly less uterotonic results, which
agrees with our findings On the other hand, they found no significant difference
in the blood loss or difference n hemoglobin before and after the operation
between the two groups.
Moertl et al.12 studied 56 women undergoing elective cesarean section after
spinal anesthesia. They measured hemodynamic parameters taken for 500s upon
administration of a slow intravenous bolus of 100mg of carbetocin or 5IU of
oxytocin to prevent PPH. They found a non significant difference in the
hemodynamic effects of both drugs, with a maximal effect at about 30–40s: HR
increased 17.98±2.53bpm for oxytocin and 14.20±2.45bpm for carbetocin.
Systolic blood pressure (sBP) decreased (26.80±2.82mmHg for oxytocin versus
22.98± 2.75mmHg for carbetocin). Following the maximal effect, women treated
with carbetocin recovered slowly to baseline values asymptotically (HR and BP),
whereas women treated with oxytocin displayed a slight rebound bradycardia at
200s (6.8±1.92bpm). They concluded that both oxytocins have comparable
hemodynamic effects and are uterotonic drugs with an acceptable safety profile
for prophylactic use.

The WHO CHAMPION (Carbetocin HAeMorrhage PreventION) TRIAL

was a large study enrolling 29,645 women across 23 sites in 10 countries
(Argentina, Egypt, India, Kenya, Nigeria, Singapore, South Africa, Thailand,
Uganda and the United Kingdom- between July 7, 2015 and January 30,2018) in
randomized, double-blind, noninferiority trial comparing intramuscular
injections of HS carbetocin (at a dose of 100 μg) with oxytocin (at a dose of 10
IU) administered immediately after vaginal birth .
The primary outcomes of the WHO CHAMPION trial were the proportion of
women who experienced > 500 ml blood loss or had use of additional uterotonics;
and the proportion of women who experienced > 1000 ml blood loss.
The secondary outcomes included the proportion of women requiring use of
additional interventions to stop bleeding and those having anticipated side effects
amongst several others.
The trial showed that HS carbetocin was noninferior to oxytocin for the
prevention of blood loss of at least 500 ml or the use of additional uterotonic
agents and failed to show noninferiority for the outcome of blood loss of at least
1000 ml.
 REFERENCES

1. Lalonde A. Prevention and treatment of postpartum hemorrhage in

lowresource settings. Obstetric Anesthesia Digest. 2013 Sep 1;33(3):136-
7.
2. World Health Organization. The World health report: 2005: make every
mother and child count. World Health Organization; 2005.
3. Knight M, Callaghan WM, Berg C, Alexander S, Bouvier-Colle MH, Ford
JB, Joseph KS, Lewis G, Liston RM, Roberts CL, Oats J. Trends in
postpartum hemorrhage in high resource countries: a review and
recommendations from the International Postpartum Hemorrhage
Collaborative Group. BMC pregnancy and childbirth. 2009 Dec;9(1):1-0.
4. Cotter A, Ness A, Tolosa JE. Prophylactic oxytocin for the third stage of
labour Cochrane Database of Systematic Reviews.
5. Su LL, Chong YS, Samuel M. Oxytocin agonists for preventing postpartum
haemorrhage. Cochrane database of systematic reviews. 2007(3).
6. Leduc D, Senikas V, Lalonde AB, Ballerman C, Biringer A, Delaney M,
Duperron L, Girard I, Jones D, Lee LS, Shepherd D. Active management
of the third stage of labour: prevention and treatment of postpartum
hemorrhage. Journal of obstetrics and gynaecology Canada. 2009 Oct
1;31(10):980-93.
7. Naef 3rd RW, Chauhan SP, Chevalier SP, Roberts WE, Meydrech EF,
Morrison JC. Prediction of hemorrhage at cesarean delivery. Obstetrics and
gynecology. 1994 Jun 1;83(6):923-6.
8. Sweeney G, Holbrook AM, Levine M, Yip M, Alfredsson K, Cappi S,
Ohlin M, Schulz P, Wassenaar W. Pharmacokinetics of carbetocin, a long-
acting oxytocin analogue, in nonpregnant women. Current Therapeutic
Research-Clinical and Experimental. 1990;47(3):528-40.
9. Reyes OA, Gonzalez GM. Carbetocin versus oxytocin for prevention of
postpartum hemorrhage in patients with severe preeclampsia: a
doubleblind randomized controlled trial. Journal of Obstetrics and
Gynaecology Canada. 2011 Nov 1;33(11):1099-104.
10.Boucher M, Nimrod CA, Tawagi GF, Meeker TA, White RE, Varin J.
Comparison of carbetocin and oxytocin for the prevention of postpartum
hemorrhage following vaginal delivery: a double-blind randomized trial.
Journal of Obstetrics and Gynaecology Canada. 2004 May 1;26(5):481-8.
11.Attilakos G, Psaroudakis D, Ash J, Buchanan R, Winter C, Donald F, Hunt
LP, Draycott T. Carbetocin versus oxytocin for the prevention of
postpartum haemorrhage following caesarean section: the results of a
double‐blind randomised trial. BJOG: An International Journal of
Obstetrics & Gynaecology. 2010 Jul;117(8):929-36.
12.Moertl MG, Friedrich S, Kraschl J, Wadsack C, Lang U, Schlembach DJ.
Haemodynamic effects of carbetocin and oxytocin given as intravenous
bolus on women undergoing caesarean delivery: a randomised trial. BJOG:
An International Journal of Obstetrics & Gynaecology. 2011
Oct;118(11):1349-56.
CASE PERFORMA

Study group:
Case number:
OPD/Registration number:
• Name:
• Age:
• Sex:
• Address:
• Date:
• Weight:
• Height:
• BMI:
• Chief complaints:
• Personal history
• Obstetrical history:
1. LMP:
2. EDD:
3. POG/S:
4. POG/D:
5. Gravida, parity ,live issue,abortion(GPLA):
• Past history:
• Personal history:
1. occupation:
2. addiction:
3. dietary history:
Examination:
1. general condition:
2. pulse rate:
3. blood pressure:
4. respiratory rate:
5. temperature:
6. pallor:
7. icterus:
8. cyanosis:
9. clubbing:
10. lymphadenopathy:
11. edema:
Systemic examination:
1. CNS:
2. CVS:
Per abdominal examination:
1. Fundal height.
2. Lie.
3. Presentation.
4. FHS.
5. Uterine contraction.

Per vaginal examination (Modified Bishop’s score):

1. Cervical dilatation
2. Cervical length
3. Cervical consistency
4. Cervical position
5. Head station Investigations:
1.CBC
2.LFT
3.KFT
4. RBS
5. USG
6. USG colour
Name of uterotonic given- Carbetocin or Oxytocin Presence
/ Absence of post partum hemorrhage(>1000ml):
Additional uterotonic given:
Estimated blood loss:
Pre Delievery Post Delievery (after 24 hrs)
Hb:
Hct:
Need for blood transfusion:
Side effects:
Haemodynamic changes:
Participant Information Sheet

1. STUDY TITLE:
2. STUDY INVESTIGATORS:
3. Student: (Name, Department)
4. Guide (Name, Department):
5. Co- Guide/s (Name, Department):
6. Introduction:
[Provide a simple background about the research topic in non-technical
language from perspective of participant such as: We are conducting a research
study to
………………………………………………………………………………in
SNMC Agra . We would like to …………….……...
……………………………………………………….. If you agree to take part
voluntarily, we will ask you to sign a consent form.]
7. Purpose of the study:
[Write the main aim / objective of study and why is it being done in simple
language such as: The aim of our study is
to…………………...…………………………………….............. This will help
us find..……………………………………………………………………… ]
8. Taking part – what it involves:
a. Do I have to take part?
Participation in this research is entirely voluntary. A decision to not take part, or
to withdraw at any time, will not affect your rights or medical care in any way.
b. What is expected of me if I take part?
If you participate, we
will.……………………………………………………………………… [either
collect information about……………………………(in case of observational
studies) or give you / administer …………………………………………(in
case of interventional studies) or collect sample of
……………………………………………. (in case of diagnostic purposes).]
c. How long will my part in the study last?
Your participation in the study would last for …………….(Mention duration,
whether it is one time, or multiple visits – mention follow-up time points)
d. Do I have to come for extra visits or undergo extra investigations for the
study?
[Include point if applicable to your study. Mention no additional visits or extra
investigations in case of observational studies, or specify non-routine visits or
investigations.]
e. What are the possible benefits in taking part?
[Outline any direct or indirect benefits such as: Taking part will help gain
knowledge about…………………………..which may result in improvement of
management / outcomes for you / patients like yourself (modify according to
your study)]
f. What are the possible disadvantages and risks of taking part?
[In case of observational study: There are no major foreseeable disadvantages or
risks because of the study. There may be risk of loss of privacy and
confidentiality of information collected even though all possible measures will
be taken to ensure safe data storage and access. (In case of interventional study:
mention any specific risks / adverse effects associated with intervention being
studied)]
g. What happens to the information collected from me?
All information collected will be kept strictly confidential and not shared with
anyone. Results from the study will be reported as group data and will not
identify you in any way.
h. What if I change my mind regarding participation in the study?
You are entitled to change your mind and withdraw at any time during the study
without any disadvantage or penalty.
i. Whom do I contact for more information or if I have further questions or
concerns?
If you want any information or have questions or concerns, you can contact:

Dr. (Student Name)

Post graduate student,
Department of …………,
(Mobile no, Email id)
 Consent Form

I have willingly agreed to participate in the research study titled “

CARBETOCIN VERSUS OXYTOCIN USE IN AMTSL IN
PROPHYLAXIS OF POSTPARTUM HEMORRHAGE IN VAGINAL
DELIEVERY under the guidance of Prof. Dr. Richa Singh . All the risk and
benefits of procedures, investigations and drugs associated with this research
have been explained. I am ready to go through all the procedures and
investigations as and when required. I can quit this study, if I wish to do so. I
am not been influenced by any person associated with this hospital.

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or

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