3. Major Obstetric Haemorrhage 4. Uterotonics Flashcards
Objectives
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.
Key points
- Major obstetric haemorrhage (MOH) is the leading
cause of global maternal morbidity and mortality,
yet most deaths can be prevented. - Early recognition is key to the effective management of patients with MOH.
- The choice and dose of uterotonic drug depend on
the clinical context. - Massive transfusion protocols should be adopted
locally, as deaths occur from inadequate volume
replacement and failure to correct coagulopathy - Anaesthetists should be familiar with the range
of mechanical and surgical options to treat postpartum haemorrhage.
Burden
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
Definitions of maternal haemorrhage
APH
vs massive
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
PPH
Primary
Mod
Severe
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).
Pathophysiology of MOH
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
Aetiology
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.
Causes of APH
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.
1* PPH
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.
2* PPH
Endometritis or retained products of conception are
the most common causes of secondary PPH
Accreta
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)
Clinical assessment of blood loss
- 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 - 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
Preparation
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
Initial clinical management
- The causes of haemorrhage should be considered and simultaneously investigated while being treated
- 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. - 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 - Rapid infusion systems offer the possibility of very high flow rates.
- Central venous access should
be considered if you anticipate that vasopressors might be
needed. - Left lateral tilt or uterine displacement is required in antepartum cases to optimise preload to the right side of the
hear
Initiial piece
- 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. - Blood should be sent for a full blood count, a coagulation
screen and four units of blood should be cross-matched as a
minimum - 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 - 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 - 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
Flow chart
- Major obstetric haemorrhage call
* Mobilise obstetrics and anaesthesia
* Summon senior help
* Initiate massive transfusion protocol– laboratory
+ transport staff alerted: immediate issuance of
blood components - Blood loss ≥1000 ml +/– signs of hypovolaemia
- Immediate resuscitation
* Airway: assessment
* Breathing: 100% F2
* Circulation: wide bore IV access, warmed i.v. fluid or blood if available
Interventions
Clinical
- External uterine massage
- Bimanual uterine compression
3* Active warming
- If uterus contracted- transfer to theatre
Pharmacological
* Uterotonics
* TXA
Blood component
therapy
- PRC
- FFP
- Cryoprecipitate/ fibrinogen conc.
- Platelet
Assessment + investigation of bleeding
- Blood tests: X Match, FBC, Coag,
Fibrinogen, U+E, LFTs
- Blood tests: X Match, FBC, Coag,
- Assess QBL
3 * Point-of-care echocardiography
4 * Thromboelastography
5 * Point-of-care Hb
6 * Consider invasive monitoring
- Assess QBL
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
Control of uterine tone
- Oxytocin
- Carbetocin
- Prostaglandins
- Ergot alkaloids
Oxytocin
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
Carbetocin
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
- Prostaglandins
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
- Ergot alkaloids
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
Control of uterine tone
- 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
- process in which expulsion of the placenta and
membranes is achieved proactively with
early cord clamping,
controlled cord traction (CCT
use of uterotonic drugs
Control of uterine tone
- 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
- 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.
Uterine Muscle + Activity
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).
Oxytocin
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
Carbetocin
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
Prostaglandins
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.
Prostaglandins
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.
Ergometrine
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
Blood transfusion and haemostasis
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.
Red cell transfusion
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
ICS
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
Plasma and fibrinogen products
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
Targets
Changes in pregnancy
Rate of progression
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.
Platelets
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
Tranexamic acid
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
Mechanical and surgical intervention
Anaesthesia for surgical intervention
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.
Interventions to control haemorrhage
- 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.
- 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
- 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.
- 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.
In more severe cases
- 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
- 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 - . Selective radiological embolisation
of the uterine artery may be used to treat haemorrhage.
Complications including ischaemia, thrombosis and arterial
rupture have also been reported. - 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
Conclusions
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
RF
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
