Postpartum Hemorrhage case-based orig.pptx

Maria Virginia M. Santos-Abalos MD FPOGS FPSGE FPIDSOG MBA
Professor IV, Cebu Institute of Medicine
Board of Trustee, POGS National
Medical Director, Chong Hua Hospital Mandaue
Postpartum Hemorrhage:
Challenges & Solutions

Obstetric Hemorrhage Safety Bundle

CBC O Rh(+)
Hgb 9 g/dL
Hct 27.0%
WBC 9,400/mm3
Neutrophils 55%
Lymphocytes 40%
Monocytes 3%
Eosinophils 2%
Platelet 110,000
UA WNL

Maternal Anemia is a Global Health Problem
Global
Health problem
Adverse
Neonatal Effects
Increased
Maternal M&M

Maternal Anemia increases the risk of Cesarean
Section, transfusion & postpartum hemorrhage
12
Mild
anemia
Moderate-severe
anemia
Mild
anemia
Moderate-severe
anemia
Mild
anemia
Moderate-severe
anemia
Cesarean section RBC transfusion Postpartum hemorrhage
Drukker L et al, TRANSFUSION 2015;55;2799–2806

Maternal Anemia increases the risk of postpartum hemorrhage
The rationale behind this
may be
• Decreased Myometrial
Contractility and/or
• Impaired Coagulation
due to low Hb levels.

14
Murray-Kolb L, et al. CHERG Iron Report: Maternal Mortality, Child Mortality, Child
Cognition and Estimates of Prevalence of Anemia due to Iron Deficiency.
Maternal Anemia increases the risk of mothers dying

Recognition Readiness
Recognition
Response
Response
Pillars of PBM (Patient Blood Management)
Anticipation, detection,
and correction of
preoperative-prepartum
anemia
Prevention and reduction
of perioperative-
peripartum RBC loss
Optimizing postpartum
treatment of anemia, incl
the restrictive use of RBC
transfusions
Surbek D et al. Patient blood management (PBM) in pregnancy and childbirth: literature review and expert opinion. Archives of
Gynecology and Obstetrics (2020)
Hgb 9 g/dL
Hct 27.0%

Prenatal
anemia
optimization
pathway
Mirza FG, et al. Expert Rev Hematol.
2018 Sep;11(9):727-736.
Muñoz M, et al. Transfus Med. 2018
Feb;28(1):22-39.

Prenatal
anemia
optimization
pathway
Mirza FG, et al. Expert Rev Hematol.
2018 Sep;11(9):727-736.
Muñoz M, et al. Transfus Med. 2018
Feb;28(1):22-39.
≤34 wk
gestation
>34 wk
gestation
Intravenous iron**
Oral iron (elemental iron 80-
100 mg/day)
Recheck Hb in 2 weeks
Recheck Hb in 4 weeks or at 34
weeks gestation (whichever comes
first)
Hb incremented ≥10 g/L within 14 days or Hb
incremented ≥20 g/L within 28 days
Hb incremented <10 g/L within 14 days or
Hb incremented <20 g/L within 28 days or cannot tolerate
oral iron
Continue oral iron for at least 3 months

CBC O Rh(+)
Hgb 9.2 g/dL
Hct 28.0%
WBC 8,800/mm3
Neutrophils 58%
Lymphocytes 37%
Monocytes 3%
Eosinophils 2%
Platelet 110,000
UA WNL

Assessment of Hemorrhage Risk
ASSESSMENT OF HEMORRHAGE RISK
Before pregnancy
Prenatal
On admission
Ongoing in labor
Postpartum
Active Management of 3rd Stage
(department-wide protocol,
oxytocin after birth)
Measurement of CUMULATIVE blood
loss, as quantitative as possible
Recognition
(Every patient)

22
Admission Risk assessment
LOW-RISK MEDIUM RISK HIGH RISK

Do the appropriate BLOOD BANK REQUEST on admission
LOW-RISK (CLOT TO HOLD) MEDIUM RISK (TYPE & SCREEN) HIGH RISK (TYPE & CROSS)

Hemorrhage Cart & Meds, Procedural Instructions

PPH Kit Contents
Oxytocin
Tranexamic Acid
Methergine
Carboprost
Carbetocin
Large Bore Needles
G16/18
Colloids/Crystalloids
Blood Sample Vials
(Red, Purple & Blue)
Foley Catheter
Urine Bag
Gloves
30/50CC Syringe
(For Tamponade)

ONGOING Risk Assessment:
At least q shift and at every handoff
During Labor
• Prolonged second stage
• Prolonged oxytocin use
• Active bleeding
• Chorioamnionitis
• Magnesium Sulfate treatment
Birth/Postpartum
• Vacuum- or forceps- assisted birth
• Cesarean birth (especially urgent/ emergent
cesarean)
• Retained placenta
ASSESSMENT OF HEMORRHAGE RISK
Before pregnancy
Prenatal
On admission
Ongoing in labor
Postpartum
Active Management of 3rd Stage
(department-wide protocol,
oxytocin after birth)
Measurement of CUMULATIVE blood
loss, as quantitative as possible
Recognition
(Every patient)

What is Postpartum Hemorrhage?
UpToDate

Chance to Alter Outcome by Grouped Cause of Death
Death from Obstetric hemorrhage: Highest chance of being prevented
CA-Pregnancy Associated Mortality Review April 2012

Berg CJ,et al. Preventability of pregnancy-related deaths: results of a state-wide review. Obstet. Gynecol. Dec 2005;106(6):1228-1234.
93%
Death from Obstetric hemorrhage: Highest chance of being prevented

Philippine Data:
Postpartum
Hemorrhage causes
1/5 of our maternal
deaths.
Preventability was
NOT measured

Chance to Alter Outcome by Grouped Cause of Death; 2002-2004 (N=143)
Provider
Issues
Facilities
Issues
Patient
Characteristics
Address
BREAKDOWNS
that we can
control

Addressing the Problem:
Development of
Patient Safety Bundles
37

Bundles represent outlines of
RECOMMENDED
PROTOCOLS & MATERIALS
important to safe care
Development of
38
BUT the specific contents & protocols
should be INDIVIDUALIZED TO
MEET
LOCAL CAPABILITIES

Alliance for Innovation on Maternal Health
1

Obstetrics
Nursing
Anesthesia
Blood
Bank
Laboratory
Operating
Room
Support
Personnel
Disciplines & Departments
Response Team

Design GOALS for
Quality Improvement
Hardwire changes into routine
practice:
Education
Training
Order Sets
Protocols
Environment
Build measurement into the process
Turn-around time
California Maternal Quality care Collaborative 2015
Unit Education: Protocols, Drills Debriefs

2

Pillars of PBM (Patient Blood Management)
Anticipation,
detection, and
correction of
preoperative-
prepartum anemia
Prevention and
reduction of
perioperative-
peripartum RBC loss
Optimizing
postpartum
treatment of anemia,
incl the restrictive use
of RBC transfusions
Recognition Readiness
Recognition
Response
Response
Surbek D et al. Patient blood management (PBM) in pregnancy and childbirth: literature review and expert opinion.
Archives of Gynecology and Obstetrics (2020)

Global Health problem
An important global
health problem that
affects about 500
million women of
reproductive age.
Stevens GA et al. Lancet Glob
Health. 2013;1:e16-e25
Neonatal Effects
Increases the risks of
low birthweight,
preterm birth, perinatal
mortality, and neonatal
mortality.
Rahman MM et al. Am J Clin Nutrit. 2016;
103: 495-504
Maternal M&M
Places the mother at
increased risk of death
during and after
childbirth
Black RE et al. Lancet. 2013; 382: 427-451
Maternal Anemia is a Global Health Problem

TRANSFUSION Volume 55, December 2015
Maternal Anemia increases the risk of Cesarean Section

TRANSFUSION Volume 55, December 2015
Monitoring/correction of hemoglobin concentrations even
in late pregnancy may prevent these adverse events

Women diagnosed with anemia during pregnancy were more likely to
experience a SEVERE COMPLICATION at the time of delivery
Study
Consortium on Safe Labor database (19 US Hospitals),
n= 109,832, 10,217 (6.1%) anemia
Maternal Outcome No Anemia Anemia P value
Severe maternal morbidity
Composite outcome
4.0 7.5 <.001
Transfusion during labor 1.0 2.9 <.001
Transfusion postpartum 3.7 6.7 <.001
Hysterectomy 0.1 0.3 <.001
Postpartum hemorrhage 6.9 13.8 <.001
Cesarean delivery 28.4 36.7 <.001
Baystate Medical Center, Springfield, Massachusetts; Cedars-Sinai Medical Center Burnes Allen Research Center, Los Angeles, California; Christiana Care Health System,
Newark, Delaware; The EMMES Corporation, Rockville, Maryland (Data Coordinating Center); Georgetown University Hospital, MedStar Health, Washington, DC; Indiana
University Clarian Health, Indianapolis, Indiana; Intermountain Healthcare and the University of Utah, Salt Lake City, Utah; Maimonides Medical Center, Brooklyn, New
York; Metro Health Medical Center, Cleveland, Ohio; Summa Health System, Akron City Hospital, Akron, Ohio; University of Illinois at Chicago, Chicago, Illinois; University
of Miami, Miami, Florida; and University of Texas Health Science Center at Houston, Houston, Texas.
Harrison RK et al. Am J Obstet Gynecol MFM 2021;3:100395.
Conclusion
Diagnosis and
treatment of anemia
during the antepartum
period is essential to
optimize maternal
health and may
contribute to a
decrease in maternal
morbidity & mortality

≤34 wk
AOG
>34 wk
AOG
Intravenous
iron**
Oral iron
(elemental iron
80-100 mg/day)
Recheck Hb in 2
wks
Recheck Hb in 4 wks
or at 34 wks AOG
(whichever comes
first)
Hb incremented
• ≥10 g/L within 14 days
• ≥20 g/L within 28 days
Hb incremented
• <10 g/L within 14 days
• <20 g/L within 28 days
• cannot tolerate oral iron
Continue oral iron for at
least 3 months

Repeat screening with
a CBC at week 24 to 28
1st trim 1-2 mg/d
2nd trim 4-5 mg/day
3rd trim 6-7 mg/d

Reduce the rate of Operative Delivery
Safe Prevention of the Primary
Cesarean Delivery
External cephalic version for
breech presentation
Trial of labor after Cesarean
Section (TOLAC)

Timing of delivery & Surgical planning

ONGOING Risk Assessment:
At least every shift and at every handoff

CONCLUSIONS:
• PPH is a relatively common complication of delivery and is
associated with substantial maternal morbidity and mortality.
• PPH caused by uterine atony resulting in transfusion often occurs in
the absence of recognized risk factors.
(Anesth Analg 2010;110:1368 –73)

Assessment of Hemorrhage Risk
Belfort MA et al. UpToDate 2021
CMQCC OB Hemorrhage Emergency Management Plan 2015

Practice Active Management of the
3rd stage of Labor

PREVENTION
ACTIVE MANAGEMENT OF THE 3RD STAGE OF LABOR
• ADMINISTRATION OF
UTEROTONIC AGENTS
Within the FIRST MINUTE
after delivery Carbetocin 100 mcg single
dose via bolus inj slowly over 1
min within 1st minute fter
delivery

Quantify blood loss with every delivery

“QUANTIFY”
Blood Loss
Laminated chart in
the Hemorrhage kit

Assessment of
Blood Loss
Symptoms related to blood loss with postpartum hemorrhage
Bonnar J. Massive obstetric haemorrhage. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14:1.

3

Prepare your Unit’s Management plan
and Checklist
CMQCC OB Hemorrhage Emergency
Management Plan 2015

103
Assess Cause
Institute immediate medical management
• Uterotonics
• Fluid management
• Oxygenation
Consider blood transfusion, as needed
Optimize Clinical Management

Timely
appropriate
medication
Mechanical
and surgical
interventions
Rapid
thorough
examination
Assess Cause :
Tone
Trauma
Tissue
Thrombin
Uterotonics
Fluid management
Oxygenation
Blood transfusion,
as needed
Balloon tamponade
Compression sutures
Uterine vessel mass
ligation
Uterine artery
embolization
Hysterectomy

• 1 %
• 20 %
• 10 %
•70 %
TONE
(uterine atony)
TISSUE
(retained
placenta)
THROMBIN
(coagulo-pathy)
TRAUMA
(lacerations,
uterine rupture)
70 %
TONE
(uterine
atony)
POSTPARTUM HEMORRHAGE: 4 Ts

Uterotonics
for
Postpartum
Hemorrhage
WHO 2019

Postpartum Hemorrhage: what works, which one?
Are skilled health personnel
who can administer injectable
uterotonics available
Is cold chain transport &
storage available?
Is oxytocin available?
NO
NO
NO
Heat-stable Carbetocin 100ug IM/IV
(where its cost is comparable to other effective uterotonics)
Misoprostol 400/600 ug PO
Heat-stable Carbetocin 100ug IM/IV
Ergometrine
Fixed dose combination Oxytocin-Ergometrine
Misoprostol 400/600 ug PO by trained community health workers
YES
YES
YES
OXYTOCIN
10U IV OR IM

Study
30 trials
RCTs, comparing carbetocin to any other uterotonic agent
Management of cesarean and vaginal deliveries
Parameter RR 95% CI
Carbetocin vs
Oxytocin
Need for additional
uterotonic use
Cesarean delivery 0.43 0.30-0.59
Vaginal delivery 0.56 0.34-0.94
Postpartum blood
transfusion
0.57 0.33-0.96
Carbetocin vs other
uterotonic agents Risk of PPH
Cesarean delivery 0.69 0.45-1.05
Vaginal delivery 0.61 0.32-1.14
Kalafat E et al. J Matern Fetal Neonatal Med. 2021 Jul;34(14):2303-2316.
Efficacy of Carbetocin in the prevention of postpartum
hemorrhage

Conclusion:
Carbetocin is effective in REDUCING the
need for additional uterotonic use and
postpartum blood transfusion
in high-risk women undergoing Cesarean delivery.

Fluid management during severe PPH

Fluid management during severe PPH
Belfort MA et al. Postpartum hemorrhage: Medical and minimally invasive management. UpToDate. Feb 21, 2022
Shock index
Heart rate divided by systolic blood
pressure
SI above 1.1 is considered a helpful
marker to identify relevant
hypovolemia in pregnancy
Maternal lactate
Used by anesthetists to monitor
tissue hypoperfusion in case of
significant blood loss.

A large-bore IV
Gauge can
deliver the
volume if and
when needed
Get 2nd Line In
before vaso-
constriction
develops!
Establish adequate intravenous access

Maintain oxygenation

Avoid hypothermia and acidosis
Avoid hypothermia and acidosis (T ≥35.5°C)
● Warming devices for
IVF, blankets
● Hypothermia assd with
coagulopathy
● Bicarbonate for pH
<7.1

Blood Transfusion, as needed
There are no universally accepted guidelines for
replacement of blood components in patients
with PPH.
Recommendations are usually based upon
expert opinion since there is no strong evidence
from randomized trials, and these opinions are
often extrapolated from data from studies in
trauma patients.
Fuller AJ Bucklin B. Blood component therapy in obstetrics.
Obstet Gynecol Clin North Am. 2007;34(3):443.

Blood Transfusion CLINICAL ASSESSMENT
Acute Phase of PPH Later Phase of PPH
More liberal policy on
blood transfusion
Highly dynamic
situation
Timely transfusion can
be life-saving
Restrictive policy on
blood transfusion
Ongoing blood loss is
excluded
Hb 6-8 g/dl: assess clinical
situation & symptoms
Consider IV iron

Patient with persistent hypotension and/or
oliguria despite reasonable volume replacement
 Massive hemorrhage
Replace with blood components and fibrinogen as
necessary, rather than crystalloid, which may
result in a dilutional coagulopathy and worsen
bleeding.

Fresh Frozen Plasma
To reverse dilutional
coagulopathy
Start early in abruption,
amniotic fluid embolism, or
prolonged hemorrhage
NSS 2-3L
Ratio varies
2:1 FFP:pRBC
Massive transfusion:
Calcium Gluconate
1 to 2 grams x 2-3 min
for q4u pRBC
Fuller AJ Bucklin B. Blood component therapy in obstetrics.
Obstet Gynecol Clin North Am. 2007;34(3):443.

Mechanical & Surgical Interventions
External Aortic Compression

Hysterectomy
Hysterectomy is a DEFINITIVE TREATMENT
of uterine bleeding.
Placenta accreta spectrum and uterine rupture:
Early resort to hysterectomy may prevent deaths and
morbidity caused by delays
Improved prenatal diagnosis of placental attachment
disorders: hysterectomy can be discussed with the
patient before PLANNED CESAREAN BIRTH.

How did we do?
How can we improve?
What drills should we practice some more?

Obstetric Hemorrhage Safety Bundle
Denial Delay
Avoid these two common errors

Maria Virginia M. Santos-Abalos MD FPOGS FPSGE FPIDSOG MBA
Board of Trustees, POGS National
Challenges & Solutions

Death
Multi-organ
failure
Loss of
fertility
Complications
of multiple
blood
transfusions
Unintended
damage to
pelvic organs
Psychological
sequelae
Peripartum
hysterectomy
Postpartum Hemorrhage: Mortality and Morbidities

Treatment of PPH

Tranexamic acid

Red blood cell transfusion

Transfusion of fresh frozen plasma

Recombinant activated human factor VII (rhFVIIa)

Surgical/interventional strategies as second‐line
treatments for PPH
Uterine balloon tamponade

Embolization

Uterine compression sutures

Prenatal assessment and planning
Identify and prepare for
patients at risk
Placenta previa/accreta
Bleeding disorder
Refuse transfusion
Screen and treat for
anemia
Iron panel
Hemoglobin
electrophoresis Consider
oral versus IV iron

Risk stratification for PPH
HIGH
Placenta previa
Suspected accreta
Abruption
Coagulopathy
LOW
≤4 vaginal births
Singleton
<2 prior CS
No previous PPH
No known bleeding disorder
MEDIUM
Hgb <8
Platelets <100,000
≥3 prior CS or previous myomectomy
>4 vaginal births
Chorioamnionitis
Magnesium sulfate use
Multiple gestation
Large uterine fibroids
EFW >4250 g
History of PPH
Morbid obesity (BMI >40)

OB Hemorrhage Cart
Set of vaginal retractors
long right angle
long weighted speculum
Sponge forceps (minimum: 2)
Sutures (for cervical laceration repair and B-Lynch)
Vaginal Packs
Uterine balloon
Banjo curettes, several sizes
Long needle holder
Uterine forceps
Bright task light on wheels
Diagrams depicting various procedures (e.g. B-Lynch, uterine artery
ligation, Balloon placement)

OB Hemorrhage Medication Kit
Pitocin 20 units per liter NS 1 bag
Hemabate 250 mcg/ml 1 ampule
Cytotec 200mg tablets 5 tabs
Methergine 0.2 mg/ml 1 ampule
OB Hemorrhage Tray: Available on Postpartum Floor
IV start kit
16 gauge angiocath
1 liter bag lactated Ringers
IV tubing
Sterile Speculum
Urinary catheter kit with urimeter
Flash light
Lubricating Jelly
Assorted sizes sterile gloves
Lab tubes: red top, blue top, tiger
top

Disclosure
I receive honoraria for lectures and
advisory board memberships from
Abbott Pharma
Bayer Healthcare Pharmaceuticals
BioFemme Inc
Folares Pharma
MSD Pharmaceuticals

Outline
• General Approach to Postpartum Hemorrhage
• The Role of Carbetocin as a Uterotonic agent
• Cost-effectiveness of Carbetocin

Comprehensive
maternal
hemorrhage
protocols
2015

Comparative Trial n=>60,000 births
Pre and Post protocol implementation % Change p value
Blood product use per 1000 births -25.9 % <.01
Puerperal hysterectomy -14.8% 0.2
PPH PROTOCOL
Shields LE et al. Am J of Obs Gyn 2015

179
Development of
The bundles represent outlines of
recommended protocols & materials
important to safe care BUT the specific
contents & protocols should be individualized
to meet local capabilities

180
Do we have a MATERNAL HEMORRHAGE
PATIENT SAFETY BUNDLE in our own hospitals?

POSTP
ARTU
M
HEMO
RRHAG
E
PPH
Identify
patients at
risk
Use a multi-
disciplinary
approach
Optimize
Clinical
Manage-
ment

POSTP
ARTU
M
HEMO
RRHAG
E
RRR
Identify
patients at
risk
Use a multi-
disciplinary
approach
Optimize
Clinical
Manage-
ment
OB Hemorrhage Patient Safety Bundle

HALT
HELP
HEAD
HOLD
ETIOLOGY
EVALUATE
MANAGE
OBSERVE
ASSESS
ALERT
ASK

Risk Factors for
Postpartum Hemorrhage
Prior
Postpartum
Hemorrhage
Placental
abnormalities
Operative
delivery
Parity Macro-somia
Multiple
gestation
Polyhy-dramnios
Prolonged
Precipitous labor Coag defects
Identify
patients at
risk
1

• 1 %
• 20 %
• 10 %
•70 %
TONE
(uterine atony)
TISSUE
(retained
placenta)
THROMBIN
(coagulo-pathy)
TRAUMA
(lacerations,
uterine rupture)
POSTPARTUM HEMORRHAGE: 4 Ts
70 %
TONE
(uterine
atony)
Identify
patients at
risk
1

187
Pre-delivery Management
Prepare for PPH:
• Personnel, Blood Bank
• Equipment and Medications: Hemorrhage Cart & Kit
Optimize patient’s hemodynamic status
Anesthesia / IV access / Invasive monitoring
Modify obstetrical management
Increased postpartum / postoperative surveillance
Prepared Mind, Prepared Team, Full range of possible Tx
Use a multi-
disciplinary
approach
2

188
Pre-delivery
Management
Use a multi-
disciplinary
approach
1. Prepare for PPH:
2

189
Admission Risk assessment & BLOOD BANK REQUEST
LOW-RISK (CLOT TO HOLD) MEDIUM RISK (TYPE & SCREEN) HIGH RISK(TYPE & CROSS)
Use a multi-
disciplinary
approach
HR >110/min
BP <85/45 mm Hg
O2 saturation ≤94%
Shortness of breath
Confusion, Agitation
2

PPH Kit Contents
Oxytocin
Tranexamic Acid
Methergine
Carboprost
Carbetocin
Large Bore Needles G16/18
Colloids/Crystalloids
Blood Sample Vials
(Red, Purple & Blue)
Foley Catheter
Urine Bag
Gloves
30/50CC Syringe
(For Tamponade)

192
Use a multi-
disciplinary
approach
2. Optimize patient’s hemodynamic status
Identify and treat anemic patients
Volume resuscitation pre-transfusion
Component therapy: pRBC
2

193
Use a multi-
disciplinary
approach
Placenta accreta 34 – 35 6/7 wks
Placenta previa
36 – 37 6/7 wks
Prior classical CS
Prior myomectomy 37 – 38 6/7 wks
If extensive 36 – 37 wks
GET HELP!
3. Timing of delivery & Surgical planning
Patients Who Decline Blood
Products
Antepartum:
Maximize Hb/Hct
Consult MFM, Anes
Identify risk factors
Do not delay definitive surgical
intervention
Faster progression of care: 
observation/fluid replacement
 mechanical hemostasis 
hysterectomy
2

194
Pre-delivery Management
Prepare for PPH:
Optimize patient’s hemodynamic status
Anesthesia / IV access / Invasive monitoring
Modify obstetrical management
Increased postpartum / postoperative surveillance
Prepared Mind, Prepared Team, Full range of possible Tx
Use a multi-
disciplinary
approach
4. Anesthesia / IV access / Invasive monitoring
5. Modify obstetrical management
6 Increased postpartum / postoperative surveillance
2

195
Active Management of Third stage of Labor
Assess Cause
Institute immediate medical management
• Uterotonics
• Fluid management
• Oxygenation
Consider blood transfusion, as needed
Optimize
Clinical
Manage-
ment
3

What do the international societies
recommend?
FIGO, ACOG, RANZCOG, RCOG, SOGC, WHO
198

PPH in Low-
resource
settings
FIGO 2012

Active management of the 3rd stage of labor
PREVENTION
Active vs Physiologic management of PPH
5.9%
6.8%
17.9%
16.5%
3.13 (2.3-4.2)
2.42 (1.78- 3.3)
Active Management Expectant Management
Odds ratio
(95% CI)

HOW TO USE UTEROTONIC AGENTS
• Give oxytocin 10 IU IM within 1 minute of delivery of
the infant
• Oxytocin is preferred over other drugs
• It is effective 2–3 minutes after injection
• Has minimal adverse effects
• Can be used in all women.
• Options: Ergometrine, Syntometrine, Misoprostol
PREVENTION
• ADMINISTRATION OF UTEROTONIC
AGENTS

PREVENTION
• Administration of uterotonic agents
• Controlled cord traction
• Uterine massage after delivery of the placenta, as
appropriate
PREVENTION
• ADMINISTRATION OF
UTEROTONIC AGENTS
Within the FIRST MINUTE
after delivery
PREVENTION
• ADMINISTRATION OF UTEROTONIC
AGENTS

PREVENTION
• CONTROLLED CORD TRACTION
CONTROLLED CORD TRACTION Adverse Effects
NOT RECOMMENDED in the
• Absence of uterotonic drugs
• Prior to signs of separation of the placenta
• Partial placental separation
• Ruptured cord
• Excessive bleeding
• Uterine inversion

PPH
FIGO Recommendations:
TREATMENT OF PPH
DEFINITION
ACUTE MANAGEMENT
TREATMENT

Uterine Atony Retained Placenta Uterine Inversion Lacerations

206
Ergot alkaloids are
CONTRAINDICATED
• High blood pressure,
• Cardiac disease,
• Pre-eclampsia/Eclampsia
If 1 of the listed treatment options is
NOT EFFECTIVE,
• Administer another depending on
the severity of hemorrhage
• Consider non-pharmaceutical
interventions
Drug Regimens for
TREATMENT of PPH

207
MAIN UTEROTONIC AGENTS:
Oxytocin Ergonovine
Carboprost Carbetocin
Misoprostol
PROBLEMS:
Side-effects
Contraindications
Storage
Administration
Search for the IDEAL
UTEROTONIC AGENT

Prevention and management of postpartum hemorrhage:
a comparison of 4 national guidelines
Oxytocin 10-40 units IV
or 10 units IM
Dose not specified,
IV/IM
5 units IV, may repeat
40 units IV in 500 mL at
125 mL/hr
10 units IM or 5 units IV
20-40 units IV at 500 -1000
mL/hr
Carbetocin 100 mg IV over 1 minute
Ergots Methyl-ergonovine 0.2
mg IM Q2-4H
Ergometrine, dose not
specified
Ergometrine 0.5 mg IV/IM Ergonovine 0.25 mg IM or
IV every 2 hr
Prostaglandins
F2a-carboprost
0.25 mg IM q15-90 min
8 dose maximum
500 μg IM incrementally
up to 3 mg
0.25 mg IM q15, Max 8x or
0.5 mg intramyometrial
0.25 mg IM q 15, Max X 8
Prostaglandins E2-
dinoprostone
20mg PV or PR q2hr
Prostaglandins E1-
misoprostol
800-1000 mg rectal 1000 mg rectal 1000 mg rectal 400-1000 mg oral or rectal
ACOG 2013 RANZCOG 2014 RCOG 2011 SOGC 2009
Oxytocin 10-40 units IV
or 10 units IM
Dose not specified,
IV/IM
5 units IV, may repeat
40 units IV in 500 mL at
125 mL/hr
10 units IM or 5 units IV
20-40 units IV at 500 -1000
mL/hr
Carbetocin 100 mg IV over 1 minute
Ergots Methyl-ergonovine 0.2
mg IM Q2-4H
Ergometrine, dose not
specified
Ergometrine 0.5 mg IV/IM Ergonovine 0.25 mg IM or
IV every 2 hr
Prostaglandins
F2a-carboprost
0.25 mg IM q15-90 min
8 dose maximum
500 μg IM incrementally
up to 3 mg
0.25 mg IM q15, Max 8x or
0.5 mg intramyometrial
0.25 mg IM q 15, Max X 8
Prostaglandins E2-
dinoprostone
20mg PV or PR q2hr
Prostaglandins E1-
misoprostol
800-1000 mg rectal 1000 mg rectal 1000 mg rectal 400-1000 mg oral or rectal
SOGC 2009
ACOG 2013

Prevention and management of postpartum hemorrhage: a comparison of 4 national guidelines
Uterine packing 4-inch gauze, 5000 units
thrombin in 5 mL saline
solution
Balloon tamponade Foley: 60-80 mL saline
solution (≥1)
Blakemore tube: Sengstaken
technique not specified
Bakri: 300-500 mL saline
solution
Type or technique not
specified
First-line “surgical”
intervention if caused
by atony: 4-6 hr, ideally
remove during daytime,
deflate but leave in place
Ensure entire balloon
is positioned past the cervical
canal, consider antibiotic
prophylaxis, 8-48 hr
Brace suture B-Lynch, square B-Lynch B-Lynch, square B-Lynch, square
Vessel ligation Uterine artery
Internal iliac artery
Uterine artery
Uterine artery
Uterine artery
Hysterectomy Indication not specified Indication not specified “Sooner rather than later”
second consultant
recommended
Indication not specified
Embolization If bleeding stable, persistent,
nonexcessive
Yes, does not preclude
surgical management
Yes, consider Yes, if stable, ongoing & no
surgical options
SURGICAL
MANAGEMENT
ACOG 2013 RANZCOG 2014 RCOG 2011 SOGC 2009
Dahlke. Postpartum hemorrhage guidelines. Am J Obstet Gynecol 2015.
Uterine packing 4-inch gauze, 5000 units
thrombin in 5 mL saline
solution
Balloon tamponade Foley: 60-80 mL saline solution
(≥1)
Blakemore tube: Sengstaken
technique not specified
Bakri: 300-500 mL saline
solution
Type or technique not
specified
First-line “surgical”
intervention if caused
by atony: 4-6 hr, ideally
remove during daytime,
deflate but leave in place
Ensure entire balloon
is positioned past the cervical
canal, consider antibiotic
prophylaxis, 8-48 hr
Brace suture B-Lynch, square B-Lynch B-Lynch, square B-Lynch, square
Vessel ligation Uterine artery
Uterine artery
Uterine artery
Uterine artery
Hysterectomy Indication not specified Indication not specified “Sooner rather than later”
second consultant
recommended
Indication not specified
Embolization If bleeding stable, persistent,
nonexcessive
Yes, does not preclude
surgical management
Yes, consider Yes, if stable, ongoing & no
surgical options

National
Guidelines
2015
Substantial variation exists in
PPH prevention & management guidelines
among 4 national organizations.
It highlights the need for
BETTER EVIDENCE & MORE CONSISTENT SYNTHESIS
of the available evidence

what works, which one?
storage available?
NO
NO
NO
Heat-stable Carbetocin 100ug IM/IV (where its cost
is comparable to other effective uterotonics)
Heat-stable Carbetocin 100ug IM/IV (where its cost is
comparable to other effective uterotonics)
Ergometrine (where its cost is
Fixed dose combination Oxytocin-Ergometrine (where its cost is
YES
YES
YES
OXYTOCIN
10U IV OR IM

214
Is this
CURRENT?
What does the
EVIDENCE say?

216
Globally, access to effective
uterotonics remains a key
barrier to reducing maternal
mortality

OXYTOCIN is the standard therapy
for the PREVENTION of postpartum
hemorrhage

OXYTOCIN is the standard therapy for the
PREVENTION of postpartum hemorrhage. BUT it
requires cold storage, which is not available in
many countries.
Questionable Real-World Efficacy

25
Heat-related degradation of oxytocin is well-
documented
Hogerzeil HV, Walker GJ, De Goeje MJ, World Health Organization. Stability of injectable oxytocics in tropical climates: results of field surveys and
simulation studies on ergometrine, methylergometrine and oxytocin. Geneva: World Health Organization; 1993.
Oxytocin injection
Martindale 1989 Store at 2-80 C; Expiry 3Y
Stored <250 C; Expiry 2Y
BP 1988 Store 2-150C; pH between 3.5-4.5
Sandoz Australia 1989 Stored <250C, protected fr light; Exp 3Y
Stored at 300C, 50% loss of potency after 4Y
5000k, 150W light; Stable 96H
Sandoz UK 1989 Stored 8-220C, protected from light; 3Y
Medisca 1989 Stored <250C, pH 3.1-4.9, no change
Short period of >250C is possibly harmful
Scanboharm 1988 Stored at 230C: no change observed after 10 min

26
Oxytocinstorage
Widmer M, Piaggio G, Nguyen TM, Osoti A, Owa OO, Misra S, Coomarasamy A, Abdel-Aleem H, Mallapur
AA, Qureshi Z, Lumbiganon P. Heat-stable carbetocin versus oxytocin to prevent hemorrhage after vaginal birth. New
England Journal of Medicine. 2018 Aug 23;379(8):743-52.
United Nations Commission for Life-
Saving Commodities:
oxytocin be supplied and stored between
2°C and 8°C to ensure efficacy.
In many settings, oxytocin is still stored
at room temperature degradation and
loss of efficacy in approximately 1/3 of
ampules

Lots of researches were conducted:
Is (heat stable) CARBETOCIN
an under-utilized option for
prevention of PPH?

32
Carbetocin: Mechanism of Action
Carbetocin
•Synthetic oxytocin analogue
•Binds to the same oxytocin receptors
in the myometrium with an affinity
similar to that of oxytocin.
Carbetocin
Cordovani, D., Carvalho, J. C. A., Boucher, M., & Farine, D.
Carbetocin for the Prevention of Postpartum Hemorrhage.

32
Carbetocin
induces a
PROLONGED
UTERINE
RESPONSE
Carbetocin has a four-fold longer
uterotonic activity compared to
oxytocin which precludes the
necessity of
•Repeated administration
• Continuous infusion
It is administrated as a single 100-
μg slow IV bolus
Cordovani, D., Carvalho, J. C. A., Boucher, M., & Farine, D.
Carbetocin for the Prevention of Postpartum Hemorrhage.

55
The better alternative
Carbetocin is a
MORE HEAT
STABLE
MOLECULE with
EQUIVALENT
EFFICACY

Which drug is
BEST
for reducing
excessive
blood loss
after birth?
Cochrane
2018
NHS UK 2019

Misoprostol
Carbetocin
NETWORK
Meta-Analysis

Systematic review, NMA, 137 RCTs, Prophylactic use, n= 87,466
Systematic review, NMA, 196 RCTs, Prophylactic use, n= 135,559
PRIMARY OUTCOME SECONDARY OUTCOMES PATIENT-REPORTED OUTCOMES
Prevention of PPH blood
loss of ≥ 500 ml
Maternal mortality or morbidity Sx of excessive blood loss
Additional uterotonics Nausea & vomiting
Prevention of PPH blood
loss of ≥ 1000 ml
Transfusion Hypertension
Manual removal of placenta Headache
Mean volumes of blood loss Tachycardia
Mean durations of the third
stage
Hypotension
Changes in Hgb measurements Abdominal pain
Fever/shivering 1st 24H post partum

231
Oxytocin and Carbetocin are both better
than Ergometrine & Misoprostol
OXYTOCIN
(NS)
Ergometrine vs Oxytocin
1.17 (0.90 -1.52)
1.31 (0.88 - 1.92)
Misoprostol vs Oxytocin
1.08 (0.95 – 1.23)
1.07 (0.92 – 1.24)
CARBETOCIN Ergometrine vs Carbetocin
1.61 (1.06- 2.45)
NA
Misoprostol vs Carbetocin
1.49 (1.05 – 2.11)
NA

232
Carbetocin is better than Oxytocin (NS)
Carbetocin
vs Oxytocin
NMA 0.72 (0.52 - 1.00)
0.69 (0.45 - 1.07)
Pairwise

233
COMBINATION TX is BETTER than
Oxytocin, Ergometrine and Misoprostol alone
Combination
vs
Oxytocin
Misoprostol + Oxytocin
vs Oxytocin
0.73 (0.60 – 0.90)
0.74 (0.62 – 0.88)
Ergometrine + Oxytocin
vs Oxytocin
0.69 (0.57 – 0.83)
0.72 ( 0.56 – 0.92)
Ergometrine
and
Misoprostol vs
Combination
Ergometrine vs
1.69 (1.24 – 2.29)
0.16 (0.00 - 4.05)
Misoprostol vs
1.56 (1.29 – 1.89)
1.74 ( 1.34 - 2.26)
Ergometrine vs
1.58 (1.14 – 2.21)
NA
Misoprostol vs
1.47 (1.16 – 1.86)
1.92 (0.98 – 3.76)

234
Carbetocin is NOT INFERIOR to Combination treatment
Carbetocin vs
Combination
Carbetocin
vs
1.04 (0.73 – 1.49)
0.95 (0.43 – 2.08)
Combination
vs Carbetocin
vs
Carbetocin
1.01 (0.69 – 1.49)
NA

235
Effectiveness of uterotonic agents forPPH >500 ml
SUCRA method (SUrface underneath this Cumulative Ranking)
SUCRA
Ergometrine + Oxytocin 87.6%
Carbetocin 81.0%
Misoprostol + Oxytocin. 80.4%

236
Effectiveness of uterotonic agents forPPH>1000
SUCRA
Carbetocin 84.8%
Misoprostol + Oxytocin 64.1%

237
Requirement of ADDITIONAL UTEROTONICS
36
Gallos ID, Papadopoulou A, Man R, Athanasopoulos N, Tobias A, Price MJ, Williams MJ, Diaz V, Pasquale J,
Chamillard M, Widmer M. Uterotonic agents for preventing postpartum haemorrhage: a network meta-analysis.
Cochrane Database of Systematic Reviews. 2018(12).
SUCRA
Carbetocin 92.8%
Misoprostol + Oxytocin 83.6%

238
Conclusions
Ergometrine + Oxytocin More effective uterotonic drug
strategies for preventing PPH than the
current standard, oxytocin.
Carbetocin
Ergometrine + Oxytocin Cause significant side effects.
Carbetocin has a favourable side-effect profile,
which was similar to oxytocin.

Do we have direct comparisons between
Oxytocin and Carbetocin?
WHO CHAMPION TRIAL

Randomized, double-blind, noninferiority trial n=29645
Carbetocin 100 ug Oxytocin 10 IU Carbetocin Oxytocin RR
Blood loss of at least 500 ml
Non-inferiority margin = 1.16
14.5% 14.4% 1.01
0.95 - 1.06
1.51% 1.45% 1.04
0.87 - 1.25
Use of additional uterotonic agents 10.4% 10.4% 1.00
(0.94 - 1.07)
Interventions to stop bleeding 1.1% 0.9% 1.15
(0.92 - 1.44)
WHO CHAMPION Trial: Efficacy
Use of additional uterotonic agents
Interventions to stop bleeding

Randomized, double-blind, noninferiority trial n=29645
WHO CHAMPION Trial: Safety

Carbetocin is
as SAFE as
Oxytocin

Broader collaboration involving
Regulatory (World Health Organization)
Advocacy (Merck for Mothers)
Manufacturing (Ferring Pharmaceuticals)
To make heat stable carbetocin accessible in
the public sector of low and lower-middle income
countries at an affordable and sustainable price.

The iMox
Study
2019
No results yet

How do the uterotonic agents perform vs
oxytocin on BENEFICIAL OUTCOMES?
250
EFFICACY

Network Meta-
analysis
2019
Treatment effects of uterotonic agents vs oxytocin on beneficial outcomes
Desirable
Outcomes
Oxytocin
Absolute risk
Carbetocin Misoprostol Prostaglandi
ns, injectable
Ergometrine Oxytocin +
ergometrine
Misoprostol
+ Oxytocin

Does the balance between
DESIRABLE & UNDESIRABLE EFFECTS favor
different uterotonics over Oxytocin?
252
SAFETY

Balance between desirable and undesirable effects
Carbetocin
Misoprostol
Injectable
Prostaglandins
Ergometrine
Oxytocin +
Ergometrine
Misoprostol +
Oxytocin
Probably
favors
carbetocin
Favors
Oxytocin
Favors
Oxytocin
Probably
Favors
Oxytocin
Favors
Oxytocin
Favors
Oxytocin

Heat-stable carbetocin is a promising alternative
to oxytocin
The balance of effects favors carbetocin
over oxytocin.
Good Practice Point

22.3 UTEROTONICS
Carbetocin Injection (heat stable): 100 ug/ml

Postpartum Hemorrhage: what works, which one? (WHO 2018)
storage available?
NO
NO
NO
Heat-stable Carbetocin 100ug IM/IV (where its cost
is comparable to other effective uterotonics)
Heat-stable Carbetocin 100ug IM/IV (where its cost is
Ergometrine (where its cost is
Fixed dose combination Oxytocin-Ergometrine (where its cost is
YES
YES
YES
Oxytocin
10u IV or IM
Heat-stable Carbetocin 100ug IM/IV (where its
cost is comparable to other effective uterotonics)
Heat-stable Carbetocin 100ug IM/IV (where its
cost is comparable to other effective uterotonics)

Today, most trials point to the advantages of Carbetocin.
(heat stability, efficacy, favorable side-effect profile)
The decision to maintain Oxytocin as the standard drug despite
current data is due to
Small trials done with Carbetocin
Premium cost of Carbetocin
258

Does the cost–effectiveness of the following
uterotonics favour the uterotonic or oxytocin?
PREMIUM COST OF CARBETOCIN
259
COST-EFFECTIVENESS

260
Cost-effectiveness against Oxytocin
Carbetocin
Misoprostol
Injectable
Prostaglandins
Ergometrine
Oxytocin +
Ergometrine
Misoprostol +
Oxytocin
Probably
favors
oxytocin
Favors
Oxytocin
Favors
Oxytocin
Probably
favors
oxytocin
Varies
Varies

263
Carbetocin versus Oxytocin
The supply cost of carbetocin is
approximately 20 times more
than that of oxytocin

264
Carbetocin versus Oxytocin
Probable cost-savings with Carbetocin:
• Reduction in the use of additional uterotonics by about half
• Avoid the need for a cold chain will enable lower- cost transport
and storage
• Reduce the waste associated with heat-exposure–related
degradation and loss of active ingredient.

47
How cost-effective is carbetocin?
van der Nelson, H. A., Draycott, T., Siassakos, D., Yau, C. W., & Hatswell, A. J. (2017). Carbetocin versus
oxytocin for prevention of post-partum haemorrhage at caesarean section in the United Kingdom: An47 economic impact
analysis. European Journal of Obstetrics & Gynecology and Reproductive Biology, 210, 286-
291.
Total Cost - £ 27,518

Today, most trials point to the advantages of Carbetocin.
(heat stability, efficacy, favorable side-effect profile)
The decision to maintain Oxytocin as the standard drug despite
current data is due to
SMALL TRIALS DONE WITH CARBETOCIN
266

Saving Mothers
from Hemorrhage
Ma. Virginia M. Santos-Abalos MD MBA

Postpartum Hemorrhage case-based orig.pptx

Postpartum Hemorrhage case-based orig.pptx

Recommended

Recommended

More Related Content

Similar to Postpartum Hemorrhage case-based orig.pptx

Similar to Postpartum Hemorrhage case-based orig.pptx (20)

Recently uploaded

Recently uploaded (20)

Postpartum Hemorrhage case-based orig.pptx