3. Major Obstetric Haemorrhage 4. Uterotonics

Question 1

Objectives

Answer 1

1 Define major obstetric haemorrhage (MOH) and
understand its epidemiology.

2 Initiate an appropriate strategy for resuscitation
with fluids and blood products.

3 Explain the rationale for the medical, pharmacological and surgical treatment options for patients with MOH.

Question 2

Key points

Answer 2

1. Major obstetric haemorrhage (MOH) is the leading
   cause of global maternal morbidity and mortality,
   yet most deaths can be prevented.
2. Early recognition is key to the effective management of patients with MOH.
3. The choice and dose of uterotonic drug depend on
   the clinical context.
4. Massive transfusion protocols should be adopted
   locally, as deaths occur from inadequate volume
   replacement and failure to correct coagulopathy
5. Anaesthetists should be familiar with the range
   of mechanical and surgical options to treat postpartum haemorrhage.

Question 3

Burden

Answer 3

However, MOH results in severe morbidity in all healthcare
settings, including multiorgan failure, postpartum hysterectomy and long-term psychological trauma, contributing to
enormous economic and social costs

In the UK and Ireland’s most recent Mothers and Babies:
Reducing Risk through Audits and Confidential Enquiries
(MBRRACE) report, deaths from haemorrhage were the second
most common cause of direct maternal deaths with a rate of
0.64 (0.35e1.08) per 100,000.

In resource-rich healthcare settings, an increase in the
incidence of PPH has been primarily caused by an increasing
incidence of uterine atony.7 Rates of severe PPH requiring interventions, such as blood transfusion and surgery, are also
increasing in many countries

Question 4

Definitions of maternal haemorrhage

APH

vs massive

Answer 4

Definitions of what constitutes maternal haemorrhage are not
universally agreed. Antepartum haemorrhage (APH) occurs
from 24 weeks’ gestation, and occurs in between 3% and 5% of
all pregnancies.

Defined major APH as bleeding
of 50-1000mL with no signs of shock,

and massive APH as
bleeding 1000 mL and/or bleeding of any volume with clinical signs of shock

Question 5

PPH

Primary

Mod

Severe

Answer 5

Primary PPH occurs within the 24 h after delivery

and
secondary PPH occurs between 24 h and 12 weeks after delivery.

The WHO defines PPH as 500 ml blood loss.

However, it is recognised that using a definition with a higher threshold of 1000 ml may be more relevant clinically

In the UK, the RCOG stratifies their definitions of
PPH by severity. Major PPH may be defined as moderate
(1000e2000 ml) or severe (2000 ml).

Question 6

Pathophysiology of MOH

Answer 6

High-flow, low-resistance vascular bed and by term receives 25% of the cardiac output.

Both plasma and red cell mass increase
throughout pregnancy, leading to a 50%
increase in maternal blood volume.

volume is greater than red cell mass leading to a ‘physiological
anaemia of pregnancy’, thereby offering an evolutionary
advantage in which less red cell mass is lost per millilitre of
blood during haemorrhage.

Involution of the uterus and
termination of the placental circulation after delivery results
in autotransfusion of approximately 500 ml

Question 7

Aetiology

Answer 7

Aetiology

Early identification of women who are at

risk of haemorrhage allows for safe birth planning

and strategic mobilisation of resources;

yet, risk stratification for maternal haemorrhage is
fraught with difficulty as most women who present with PPH
have no discernible risk factors.

Question 8

Causes of APH

Answer 8

Causes of APH include

placenta praevia,

placental abruption,

uterine rupture and

bleeding from the vulva, vagina or cervix,

although a cause is often not found.

Question 9

1* PPH

Answer 9

PPH is uterine atony, which accounts for approximately 80% of cases of primary PPH

Trauma and injury to the
genital tract, retained invasive placenta and coagulopathy are
other common causes of PPH.

Question 10

2* PPH

Answer 10

Endometritis or retained products of conception are
the most common causes of secondary PPH

Question 11

Accreta

Answer 11

Placenta accreta spectrum (PAS) is a common cause of
MOH, and the incidence of this condition is increasing

placenta that is morbidly adherent to the myometrium (accreta vera),

to that which invades into the myometrium (increta)

through the myometrium into surrounding organs (percreta)

Question 12

Clinical assessment of blood loss

Answer 12

1. A higher resting heart rate and a lower mean arterial blood pressure compared with the non-pregnant state may contribute to failure to
   detect signs of haemorrhage
2. Visual estimation of blood loss is variable and often
   underestimated. Quantitative blood loss measurement offers
   a more objective and scientific approach to visual assessment

Quantitative blood loss can be used as part of an alert system
with the aim of preventing the progression of minor bleeding
to more severe bleeding, and has been successfully incorporated into the Welsh Obstetric Bleeding Strategy

Question 13

Preparation

Answer 13

This includes individual risk stratification, optimisation before delivery, and preparing obstetric units and
healthcare staff for massive transfusion events.

Bundles of
care such as the Safe Motherhood Initiative (SMI) aid in both
the planning and execution of safe management by delineating standards and minimising variability in care between
obstetric units

Early identification of haemorrhage risk in the antenatal
period enables the effective mobilisation of healthcare resources

In those with abnormal placentation, prior
structured multidisciplinary planning can reduce blood loss,
blood transfusions and emergency Caesarean delivery - appropriate site

Women who may refuse blood products in an emergency,
including Jehovah’s witnesses, should be identified early in
the antenatal period and counselled appropriately.

Screening for anaemia and the optimisation of haemoglobin in the antenatal period is essential to prevent unnecessary
blood transfusion in cases of postpartum bleeding, as there
are opportunities to maximise maternal red cell mass through
improved nutrition, iron supplementation or the use of recombinant erythropoietin.

multidisciplinary involvement including obstetrics, anaesthesia, midwifery, obstetric-trained nurses and
transfusion medicine specialists. It is recommended that from
the outset a senior clinician should supervise the overall
management plan, in order to coordinate all aspects of care and
avoid fragmentation of decision making

Question 14

Initial clinical management

Answer 14

1. The causes of haemorrhage should be considered and simultaneously investigated while being treated
2. The goal during resuscitation is restoration of blood volume and oxygen-carrying capacity. The SMI has categorised
   obstetric haemorrhage into four stages based on volume of
   blood loss, the presence of abnormal physiology and the
   requirement for transfusion.
3. Wide bore i.v. access should be
   established early in at least two sites and a high flow of
   warmed i.v. crystalloid fluid should be infused until blood
   products are available
4. Rapid infusion systems offer the possibility of very high flow rates.
5. Central venous access should
   be considered if you anticipate that vasopressors might be
   needed.
6. Left lateral tilt or uterine displacement is required in antepartum cases to optimise preload to the right side of the
   hear

Question 15

Initiial piece

Answer 15

1. Management of the airway is the first priority followed by
   respiratory support if needed. High-flow oxygen via facemask
   should be started in all cases of MOH in awake patients.
   Tracheal intubation may be required to protect the airway in
   women with a reduced level of consciousness.
2. Blood should be sent for a full blood count, a coagulation
   screen and four units of blood should be cross-matched as a
   minimum
3. liver and renal function tests, electrolytes and fibrinogen concentrations.
   Point-of-care testing for haemoglobin and viscoelastic assays
   may be useful to detect and monitor ongoing losses
4. initial haemoglobin concentration may not reflect the amount of blood lost and therefore
   clinical judgement is paramount when initiating and calculating needs for blood transfusion
5. The body temperature
   should be measured frequently and active warming is
   mandatory. Extracorporeal membrane oxygenation (ECMO)
   may offer life-saving support for patients who fail to recover
   from reversible cardiocirculatory failure

Question 16

Flow chart

Answer 16

1. Major obstetric haemorrhage call
   * Mobilise obstetrics and anaesthesia
   * Summon senior help
   * Initiate massive transfusion protocol– laboratory
   + transport staff alerted: immediate issuance of
   blood components
2. Blood loss ≥1000 ml +/– signs of hypovolaemia
3. Immediate resuscitation
   * Airway: assessment
   * Breathing: 100% F2
   * Circulation: wide bore IV access, warmed i.v. fluid or blood if available

Interventions

Clinical

1. • External uterine massage
2. • Bimanual uterine compression

3* Active warming

4. • If uterus contracted- transfer to theatre

Pharmacological
* Uterotonics
* TXA

Blood component
therapy

1. • PRC
2. • FFP
3. • Cryoprecipitate/ fibrinogen conc.
4. • Platelet

Assessment + investigation of bleeding

1. • Blood tests: X Match, FBC, Coag,
     Fibrinogen, U+E, LFTs
2. • Assess QBL
     3 * Point-of-care echocardiography
     4 * Thromboelastography
     5 * Point-of-care Hb
     6 * Consider invasive monitoring

Transfer to operating theatre
* Examination under anaesthesia
* If uterine inversion: reduce
* Genital tract trauma - repair +/– pack
* Intrauterine balloon tamponade
* Haemostatic compression sutures
* Uterine artery ligation
* Hysterectomy

interventional
radiology
* Selective endovascular balloon occlusion

• Selective radiological embolisation

Post
HDU
* ICU

Question 17

Control of uterine tone

Answer 17

1. Oxytocin
2. Carbetocin
3. Prostaglandins
4. Ergot alkaloids

Question 18

Oxytocin

Answer 18

First-line therapy

Via oxytocin receptors on myometrial cell membrane

After vaginal delivery: 5 IU i.v. slowly.

Elective Caesarean delivery (CD): bolus 1 IU
oxytocin;
then infusion at 2.5-7.5 IU h1
.
Intrapartum CD: 3 IU
oxytocin over 30 s; then
infusion at 7.5e15 IU h1
.
If required after 2 min after
initial bolus, give a further
dose of 3 IU over 30 s.

Extreme caution in context of
haemodynamic instability or
cardiovascular disease e deliver
drug slowly

Question 19

Carbetocin

Answer 19

First-line therapy

Via oxytocin receptors on myometrial cell membrane

After vaginal delivery: 100 mg over 30 s.

Elective CD: 100 mg over 30 s.

Intrapartum CD: 100 mg over 30 s.

Smaller doses may be sufficient at CD (as low as
20 mg) and may be repeated
up to 100 mg.

Do not exceed
100 mg in any setting.

Extreme caution in context of haemodynamic instability or
cardiovascular disease e deliver drug slowly

Question 20

3. Prostaglandins

Answer 20

Second-line therapy:

misoprostol may be
used as first line where
oxytocin/carbetocin
unavailable

Via prostaglandin receptors PGE1, PGE2,
and PGF2a subtypes

Misoprostol 400e600 mg:
sublingual, rectal, vaginal,
oral; repeat after 15 min if
required, maximum dose
800 mg.

Carboprost 250 mg: i.m. or
intramyometrial
(contraindicated i.v.); up to
every 15 min if required,
maximum eight doses.

Asthma/obstructive lung disease

Question 21

4. Ergot alkaloids

Answer 21

Second-line therapy

Via dopamine, aadrenergic and 5-HT3 receptors

Ergometrine (ergonovine) 200e500 i.m. or
slow i.v. in exceptional
circumstances;

may be repeated after 2 h.

Hypertension
Myocardial ischaemia
Cardiovascular disease

Question 22

Control of uterine tone

Answer 22

1. More than 80% of cases of PPH are
   attributable to poor uterine
   tone after delivery.

Traditionally, active management of the third stage of labour
(AMTSL) is a

3. process in which expulsion of the placenta and
   membranes is achieved proactively with
   early cord clamping,
   controlled cord traction (CCT
   use of uterotonic drugs

Question 23

Control of uterine tone

Answer 23

1. More than 80% of cases of PPH are
   attributable to poor uterine
   tone after delivery.

Traditionally, active management of the third stage of labour
(AMTSL) is a

3. process in which expulsion of the placenta and
   membranes is achieved proactively with
   early cord clamping,
   controlled cord traction (CCT
   use of uterotonic drugs
   =
   Reduce Incidence of primary PPH by 70% compared with expectant
   management

delayed cord clamping has significant benefits for the
neonate, and CCT may only be beneficial in the event of a
delayed third stage.

Uterotonic drug prophylaxis against PPH is required for all women,
as many who suffer PPH have no identifiable risk factors.

Question 24

Uterine Muscle + Activity

Answer 24

uterine smooth muscle demonstrates considerable spontaneous
electrical and contractile activity.

Gap junctions between myometrial cells enhance
the spread of electrical activity, and these junctions increase during pregnancy to
provide a low resistance pathway. Depolarization takes place in response to the influx
of sodium ions, while the availability of calcium ions enhances the response of
uterine smooth muscle.

These cross the cell membrane to stimulate further release
of calcium from the sarcoplasmic reticulum. The uterus contains α1-adrenergic
(excitatory), β2-adrenergic (inhibitory) and serotoninergic receptors, as well as specific
excitatory receptors for oxytocin.

These increase in number in late pregnancy
(after 37 weeks’ gestation).

Question 25

Oxytocin

Answer 25

Oxytocin and its analogue carbetocin are recommended as
first-line uterotonic prophylaxis and treatment for PPH

Oxytocin should be given initially as a small bolus and then
as a titrated infusion.

There is significant variability in the dose of oxytocin recommended,
with most of the major obstetric society guidelines recommending doses of between

5 - and 10 IU after both vaginal and Caesarean delivery
(5 IU is the maximum allowable i.v. bolus in the UK).

However, there is evidence to suggest that these drugs are as effective for prophylaxis in much lower doses

Caesarean delivery (prior oxytocin exposure)
because of oxytocin receptor desensitisation

oxytocin leads to desensitisation of receptors on the myometrium and failure of oxytocin to
stimulate effective myometrial contractions

Side effects

cardiovascular system and commonly causes tachycardia and hypotension.
Chest pain, ECG ST-T segment changes and dysrhythmias
may also occur
~~
Dose and speed of administration.

A reduced
dose should be given slowly in those women with cardiac
disease. As oxytocin is given via infusion, and has an
antidiuretic-like effect in which there is a risk of fluid overload and hyponatraemia in susceptible women

Question 26

Carbetocin

Answer 26

Carbetocin is an oxytocin analogue that is at least as effective
as oxytocin, with a favourable adverse effect profile, but its
use has been limited by its relatively high cost

duration
of action approximately 4e7 times that of oxytocin and so can
be given as a slow i.v. bolus without the need for an infusion

heat stable formulation

Question 27

Prostaglandins

Answer 27

Prostaglandins act via stimulation of prostaglandin receptors
and are unaffected by prior exposure to oxytocin

contraindicated in patients with
asthma as they may cause bronchospasm. Other adverse effects include hypertension, hypotension, pulmonary oedema,
diarrhoea, nausea, vomiting, flushing, pyrexia and myalgia.

Misoprostol is a prostaglandin E1 analogue and may be given
by oral, sublingual, rectal or vaginal routes. It is recommended
as first-line treatment for PPH where oxytocin is not available.

~~ Efficacy
Increased s/e profile

Carboprost
and sulprostone are prostaglandins used to treat PPH where
first-line agents have failed, and are not used currently as
first-line prophylaxis because of their significant adverse effects.

250 mg i.m.
every 15 min up to a maximum of eight doses, and i.v. use is
contraindicated as it may result in bronchospasm, hypertension or pulmonary oedema.

Question 28

Prostaglandins

Answer 28

Prostaglandins act via stimulation of prostaglandin receptors
and are unaffected by prior exposure to oxytocin

contraindicated in patients with
asthma as they may cause bronchospasm. Other adverse effects include hypertension, hypotension, pulmonary oedema,
diarrhoea, nausea, vomiting, flushing, pyrexia and myalgia.

Misoprostol is a prostaglandin E1 analogue and may be given
by oral, sublingual, rectal or vaginal routes. It is recommended
as first-line treatment for PPH where oxytocin is not available.

~~ Efficacy
Increased s/e profile

PGE2 and PGF2α
mediate strong uterine contractions

Carboprost
and sulprostone are prostaglandins used to treat PPH where
first-line agents have failed, and are not used currently as
first-line prophylaxis because of their significant adverse effects.

250 mg i.m.
every 15 min up to a maximum of eight doses, and i.v. use is
contraindicated as it may result in bronchospasm, hypertension or pulmonary oedema.

Question 29

Ergometrine

Answer 29

Ergometrine

Ergometrine is currently recommended as a second-line agent
for the treatment of PPH.

Ergometrine combined with oxytocin has additional benefit compared with oxytocin alone, but has more adverse effects, especially nausea

via α1-adrenergic and also serotoninergic myometrial receptors,

Contraindicated where hypertensive disorders are present, as a-adrenergic receptor activation may
precipitate or exacerbate hypertension

Guidelines recommend a dose range of 200e500 mg,
and this may be given via either the i.v. (with caution) or i.m.
routes.20 The duration of action of ergometrine is from 45 min

Question 30

Blood transfusion and haemostasis

Answer 30

Delays in accessing blood components for life-threatening
haemorrhage leading to unnecessary morbidity and mortality are often reported, including in the 2020 Serious Hazards of
Transfusion (SHOT) report

Blood transfusion may be lifesaving but has
risks including transfusion reactions, infection and red cell
alloimmunisation. Blood product management is often
extrapolated from the trauma literature

Blood transfusion may be lifesaving but has
risks including transfusion reactions, infection and red cell
alloimmunisation. Blood product management is often
extrapolated from the trauma literature

Fib dilution is a concern if large volumes of products with a low concentration of fibrinogen are used such as FFP.

Question 31

Red cell transfusion

Answer 31

When MOH is suspected,

the decision to transfuse red cells should be made on clinical grounds,

avoiding any delay in waiting to

confirm transfusion thresholds on laboratory tests.

ABOe, rhesus De (RhDe) and Ke (Kelle) compatible
red cell units should be transfused

At least four units of O-negative packed red cells
should be readily available in each obstetric unit at all times

Question 32

ICS

Answer 32

If blood loss is anticipated during
surgery, cell salvage may be useful for autologous transfusion

major haemorrhage, but no benefit has been demonstrated from its routine use and it may increase the risk of
maternal alloimmunisation

who would not otherwise accept blood
transfusion, for example Jehovah’s Witnesses

A perceived risk of amniotic fluid embolisation
is often cited against the
use of cell salvage,

yet there is little evidence to support this in
practice and safety has been demonstrated robustly

A double
suction technique is often used, with the aim of using one
suction for amniotic fluid and another for suctioning uncontaminated blood

Cell salvage requires training and experience must be demonstrated in the low risk setting in order to
ensure proficiency amongst staff in an emergency

Question 33

Plasma and fibrinogen products

Answer 33

Inadequate provision of coagulation products,

particularly fibrinogen was highlighted as a concern
in recent MBRRACE reports,

and many women who died had delayed
or inadequate correction of their coagulopathy

The risk of coagulopathy increases with bleeding >2000 ml

aetiology of haemorrhage and may be
dilutional, consumptive or attributable to DIC

Haemorrhage Caused:
by amniotic fluid embolism, uterine rupture or
placental abruption may be associated with early onset DIC

Question 34

Targets

Changes in pregnancy

Rate of progression

Answer 34

The coagulation target should be to maintain PT and APTT
at less than 1.5x normal.

Pregnancy is a prothrombotic state with higher baseline
fibrinogen concentrations of 4-6g
compared with 2-4 g L-1 in non-pregnant patients,
acting as a physiological buffer for haemorrhage.

Fibrinogen concentrations decrease more
rapidly than other coagulation factors, and this is often a
predictor of progression to severe PPH.

Question 35

Platelets

Answer 35

The platelet count, if low, may indicate a consumptive process
and be associated with a coagulopathy.

A platelet transfusion trigger of 75x109 is recommended as a transfusion trigger during haemorrhage

Question 36

Tranexamic acid

Answer 36

Tranexamic acid (TXA) reduces bleeding by inhibiting the
enzymatic breakdown of fibrin,

thereby stabilising blood clot architecture
and is well established in many non-obstetric
situations including trauma and elective surgery

he World
Maternal Antifibrinolytic Trial (WOMAN) showed that by giving TXA, deaths from bleeding were reduced by 20% and the
greatest benefit was seen when TXA was given within 3 h of
childbirth

Question 37

Mechanical and surgical intervention
Anaesthesia for surgical intervention

Answer 37

Women may need examination under anaesthesia to evaluate
the cause of haemorrhage, repair tears to the genital tract,
drain a haematoma or other interventions to control bleeding.

Women may need examination under anaesthesia to evaluate
the cause of haemorrhage, repair tears to the genital tract,
drain a haematoma or other interventions to control bleeding.

The choice and dose of i.v. anaesthetic
for induction should avoid cardiovascular decompensation,
and ‘cardiostable’ induction agents such as ketamine may be
preferred.

Invasive arterial pressure monitoring will allow
detection of rapid shifts in arterial pressure and close titration
of vasopressors and fluid balance. Women who suffer MOH
should be managed in a high-dependency area with the capacity to deliver high-quality maternal critical care in the
presence of the infant, where possible.

Question 38

Interventions to control haemorrhage

Answer 38

1. Bimanual uterine compression

is recommended as a temporising measure
until definitive care is available for the treatment of
PPH resulting from uterine atony after vaginal delivery

and acts by stimulating contraction of uterine muscle fibres.

2. Balloon

Intrauterine balloon catheters such as the Bakri, Rusch and
Foley catheters may be used to achieve uterine tamponade,
and is effective in 97% of cases of PPH in resource-poor settings

he balloon should be deflated preferably during the
daytime when there is a full complement of staff available
because of the risk of rebleeding

3. SUTURES

Haemostatic compression sutures are most commonly
used at Caesarean delivery to arrest haemorrhage,
particularly in the setting of refractory uterine atony.

They are safe and may be fertility preserving.

4. Blood supply

Ligation of the uterine and utero-ovarian arteries
can reduce uterine bleeding by
obtunding myometrial blood flow.

Cross-clamping of the aorta may be
used as a temporising measure to control
bleeding in the setting of massive haemorrhage.

Question 39

In more severe cases

Answer 39

1. Interventional radiology offers a minimally invasive,
   fertility preserving method to treat refractory haemorrhage.

Selective arterial occlusion using balloons may be used to
stem blood flow to the common internal iliac artery or the
aorta to either prevent or treat PPH

2. REBOA
   resuscitative endovascular balloon occlusion of the aorta (REBOA) has
   resulted in better outcomes than standard therapy without
   REBOA, but has also been associated with serious complications including ischaemia
3. . Selective radiological embolisation
   of the uterine artery may be used to treat haemorrhage.
   Complications including ischaemia, thrombosis and arterial
   rupture have also been reported.
4. Peripartum hysterectomy is the definitive last resort to
   control obstetric haemorrhage and is associated with significant morbidity. The recent MBRRACE report acknowledges
   that hysterectomy should be resorted to sooner rather than
   later, especially in cases of accreta or uterine rupture

Question 40

Conclusions

Answer 40

Major obstetric haemorrhage is a significant global burden
and a preventable cause of maternal morbidity and mortality.

Early identification of haemorrhage, followed by
simultaneous investigation and management, is the key to
effective treatment.

Uterotonic drugs should be chosen based
on the clinical context.

Intravascular volume resuscitation
and blood transfusion should be driven by a protocol with
clear local guidelines agreed at each obstetric unit, as many
women who have died had delayed or inadequate correction
of their coagulopathy.

Early senior decision making is critical to coordinate and optimise care.

Anaesthetists should familiarise themselves with the range of mechanical and surgical options available to treat haemorrhage.

Coordinated preparation, including simulation training, is essential to deliver
high-quality care in a crisis

Question 41

RF

Answer 41

there is a strong association with augmentation of labour. It may
also follow uterine overdistension by multiple births, by polyhydramnios and by
delivery of babies weighing greater than 4 kg. It is associated with protracted
labour, with the use of tocolytic drugs and also with maternal hypotension