Keywords
pregnancy - shock - emergency medicine - obstetrics - intensive care medicine
Introduction
Statement
There are four main categories of shock, each of which is mainly related to one of
four organ systems:
-
hypovolemic shock relates to the blood and fluids compartment
-
distributive shock relates to the vascular system
-
cardiogenic shock relates to the heart
-
obstructive shock relates to the circulatory system
With the start of pregnancy, the female organism undergoes many different physiological
changes and adaptations which affect all organ systems ([Table 1]) and are aggravated in the event of illness. The revision of the nomenclature, definition,
and classification of different forms of shock into four main categories relates each
one to one of four organ systems systems according to the predominant aspects [1]:
Table 1 Physiological changes of organ function during pregnancy.
|
FRC: functional residual capacity; SVR: systemic vascular resistance; PVR: pulmonary
vascular resistance; CO: cardiac output (l/min); MAC: minimum alveolar concentration
(volatile anesthetics)
|
|
Respiratory system
|
Progesterone-induced increased CO2 sensitivity
|
|
Increase in respiratory volume and respiratory rate by up to 40%
|
|
Increase in respiratory minute volume by up to 50%
|
|
Reduction of FRC by 20%
|
|
Increase in O2 consumption by 20 – 25%
|
|
Mild chronic hyperventilation and respiratory alkolosis
pO2 + 10 mmHg, pCO2 − 10 mmHg, maternal pH between 7.40 – 7.45
|
|
Estrogen-induced increase in perfusion and edema formation in the upper respiratory
tract
|
|
Circulatory system
|
Synthesis of progesterone, prostacyclin PGI2, increased NO
|
|
Decreased vascular smooth musculature tone with SVR − 21% and PVR − 34%
|
|
Decreased effective circulatory blood volume (relative hypovolemia) at the start of
pregnancy
|
|
Activation of the renin-angiotensin-aldosterone system with increased sodium and water
retention (2nd + 3rd trimester of pregnancy)
|
|
Increase of SV + 30%, HR + 17%, CO + 40%, uterine blood flow at the time of delivery
up to 900 ml/min (≈ 14% of CO)
|
|
Blood system
|
Increase in total blood volume by up to 40%, plasma volume by up to 50%, erythrocyte
volume by up to 30% with or 20% without iron substitution
|
|
Anemia (dilution and iron deficiency due to fetal requirements), Hct − 5 to − 10%
(with or without iron substitution, respectively)
|
|
Hypoalbuminemia with tendency to edema formation
|
|
Coagulation system
|
Increase of Factors I, VII, VIII, IX, X, XII
|
|
Decrease of proteins C and S, physiological APC resistance
|
|
Decreased tPA, PTT and clotting time
|
|
Thromboembolism rate in pregnancy 0.05 – 1.8% (~ six times higher)
|
|
Thromboembolism rate peripartum increased up to 14.4-fold
|
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Gastrointestinal system
|
Gastric emptying is not delayed, not even with obesity
|
|
Gastric acid secretion unchanged during pregnancy
|
|
Decreased lower esophageal sphincter pressure due to effect of progesterone, increased
intraabdominal pressure, stomach displacement
|
|
Gastric emptying is delayed after the start of labor, especially under opioid therapy
(IV, s. a. and epidural)
|
|
A light meal 2 – 4 h prior to cesarean section increases the intragastric volume and
reduces pH
|
|
Renal function
|
Increased renal blood flow by up to + 60%
|
|
Increased glomerular filtration rate + 60%
|
|
Elevated aldosterone levels promote Na+ and water retention and edema formation (see above)
|
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Central and peripheral nervous system
|
Sedative effect of progesterone
|
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Reduced MAC for volatile anesthetics − 40%
|
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Increased sensitivity to local anesthetics (respiratory alkalosis increases diffusion
of non-ionized LA to the nerves)
|
|
Increased sensitivity to LA intoxication (relative hypalbuminemia, lower seizure threshold)
|
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hypovolemic shock relates to the blood and fluids compartment
-
distributive shock relates to the circulatory system
-
cardiogenic shock relates to the heart
-
obstructive shock relates to the circulatory system
Hypovolemic shock results from a loss of volume in absolute terms. Distributive shock
leads to relative hypovolemia resulting from a pathological redistribution of intravascular
volumes. Cardiogenic shock is caused by inadequate cardiac function; obstructive shock
is the result of a resistance-related pathology leading to malperfusion. This analysis
of different forms of shock with a focus on particular aspects occurring in pregnancy
aims to facilitate targeted diagnosis and improve the preclinical and clinical management
of shock in pregnant women.
Method
These recommendations were compiled by a working group from the Shock Section of the
German Interdisciplinary Association for Intensive and Emergency Medicine (DIVI) and
the Maternal Disorders Section of the Working Group on Obstetrics and Prenatal Medicine
of the German Society for Gynecology and Obstetrics (AGG i. d. DGGG). It was based
on a selective literature search of the PubMed database up to and including May 2024.
Search terms included “pregnancy AND shock”, “obstetric hemorrhagic shock”, “cardiogenic
shock AND pregnancy”, “septic shock AND pregnancy”, and “obstructive shock AND pregnancy”.
National and international guidelines (e.g., AWMF, NICE, SCCM, Surviving Sepsis Campaign)
were additionally consulted.
The contents of relevant articles identified in the literature were evaluated by the
working group. When the data was contradictory, it was classified according to clinical
relevance, plausibility, and transferability in an obstetric intensive medicine context.
Recommendations and statements were iteratively discussed at several digital consensus
meetings and adopted by consensus. The aim was to formulate practical recommendations
for the differentiated diagnosis and therapy of different forms of shock in pregnancy
which can be applied in both an obstetric and in an intensive medical care setting.
Recommendation
Treatment of hypovolemic shock should consist of rapid hemostasis and intravascular
volume substitution (balanced crystalloid solutions).
Recommendation
A vasoconstrictor (e.g., noradrenaline) should be administered to pregnant patients
with hypovolemic shock and persistent hypotension to achieve a systolic arterial blood
pressure (SAP) of ≥ 100 mmHg.
Recommendation
Tranexamic acid (1 g) with the addition of fibrinogen (2 – 4 g) in cases with persistent
bleeding should be administered early to patients in hypovolemic shock caused by traumatic
or peripartum hemorrhage.
Hypovolemic shock is characterized by critically reduced cardiac preload due to volume
loss [1]. Due to the increase in plasma and erythrocyte volumes, pregnant women can tolerate
a greater loss of blood compared to non-pregnant women.
Obstetric hemorrhagic shock is mainly caused by peripartum bleeding arising from uterine
atony, placental remnants, and childbirth injuries. The risk of bleeding is especially
high when bleeding occurs in the context of placenta accreta spectrum disorders [2]. A critical decrease in circulating blood volume triggers shock; massive erythrocyte
loss intensifies tissue hypoxia.
Traumatic hemorrhagic shock is additionally characterized by significant tissue trauma,
early clotting disorder, and endothelial damage, e.g., arising in the context of polytrauma
[3], [4], [5], [6]. In pregnant women it can be caused by preterm placental abruption, with hemorrhage
and uterine tissue trauma (Couvelaire uterus) leading to hypovolemia [7].
Hypovolemic shock in its narrow defintion and traumatic hypovolemic shock are both
characterized by a relevant loss of fluid (external or internal fluid loss) without
bleeding. Causes can include persistent vomiting, for example due to hyperemesis gravidarum,
and diarrhea as well as uncompensated renal loss (diabetes insipidus, hyperosmolar
diabetic coma). Extravascular sequestration of large fluid volumes due to ileus, acute
pancreatitis, or eclampsia also results in a significant reduction of circulating
plasma volumes.
Hypovolemic shock treatment consists of rapid hemostasis and intravascular volume
substitution. Substitution is done with balanced crystalloid solutions. If hypotension
persists, a vasoconstrictor (e.g., noradrenaline) must be administered to achieve
a systolic arterial blood pressure (SAP) of ≥ 100 mmHg. In cases with traumatic or
excessive peripartum bleeding, tranexamic acid (1 g) must be additionally administered
at an early stage followed by the administration of fibrinogen (2 – 4 g) if bleeding
persists [8]. The treatment of hemorrhagic shock arising in the context of peripartum hemorrhage
has been summarized in the AWMF guideline “Peripartum Haemorrhage, Diagnosis and Therapy”
(S2k, AWMF Registry No. 015 – 063) [2]. The prepartum treatment algorithm must always take the decrease in fetal supply
into account.
Distributive Shock
Statement
Distributive shock arises from a pathological redistribution of initially unchanged
absolute intravascular volumes into the interstitium. Distributive shock is differentiated
into septic shock and neurogenic shock.
Relative hypovolemia is present in distributive shock as a consequence of the pathological
redistribution of initially unchanged absolute intravascular volumes. Causes of distributive
shock are a loss in the regulation of vasotonus followed by a permeability disorder
of the vascular system with redistribution of intravascular volumes into the interstitium
[1].
Septic shock
Statement
Septic shock is defined as a lactate value of > 2 mmol/l with persistent hypotension
which necessitates the administration of vasopressors to maintain a mean arterial
blood pressure of (MAP) > 65 mmHg.
Recommendation
Early recognition of sepsis in patients is important. Scores adjusted to the changes
in pregnant women could be useful to facilitate diagnosis in pregnancy.
Recommendation
The treatment of septic shock in pregnant patients must reconcile concerns about maternal
safety with fetal interests.
Sepsis is a dysregulated bodily response to an infection which results in life-threatening
organ dysfuction. Organ dysfunctions are quantified by increases in the SOFA (sequential
organ failure assessment) score by ≥ 2 points [9]. Septic shock is defined as a lactate value of > 2 mmol/l with persistent hypotension
which necessitates the use of vasopressors to maintain a mean arterial blood pressure
(MAP) of > 65 mmHg [10]. Pathophysiologically, sepsis is the result of immune pathology-triggered endothelial
dysfunction with vasodilation, hypotension, and pathological vascular permeability
which leads to intravascular volume loss (capillary leak syndrome). Sepsis-related
cardiac depression may occur and exacerbate hypotension [11]. Early identification of patients with sepsis is key with regard to the further
course of disease [12].
When caring for pregnant women it is important to be aware that physiologically, tachycardia
> 90/min and tachypnea with leukocyte values of up to 16 000/µl may be classified
as normal findings, which greatly limits the validity of standard scoring systems.
Scores adapted to physiological pregnancy-related changes such as the Maternal Early
Warning Score (MEWS) are useful when making a diagnosis [13]. MEWS includes an assessment and evaluation of blood pressure, heart rate, oxygen
saturation, temperature, and consciousness using a point-based scale, with higher
scores indicating a greater risk. Alternatively, scores with appropriately adapted
thresholds such as the obstetrically modified SOFA score (omSOFA) may be used [14].
Sepsis with Group A Streptococci is a typical complication of puerperium and is associated with an extremely serious
course, especially when the diagnosis is made too late. Infants, older and immune-supressed
persons, and pregnant women all have a high risk of influenza complications and a
fourfold higher risk of requiring admission to hospital, intensive care, or death.
The pregnancy-related changes to the cardiovascular and immune systems result in delayed
recovery after viral infection and a longer and more severe course of disease. Pregnant
women are more affected in the 2nd and 3rd trimester of pregnancy. The most common
comorbidity is bronchial asthma [15]. Cleft lip and palate, neural tube defects, congenital heart defects, neurological
disorders and schizophrenia have all been reported in fetuses after maternal infection
with influenza [16]. Early antiviral therapy is recommended because of the
increased maternal and fetal risk [15]. The majority of pregnant or postpartum patients who require treatment in an intensive
care unit due to infection with influenza A or who died from the infection are not
vaccinated, which is why vaccination is recommended to pregnant women during flu season
[15].
Pregnant women have a higher risk of admission to hospital, treatment in an intensive
care unit, and death compared to non-pregnant women and have a high risk of preterm
or stillbirth following SARS-CoV-2 infection [17]. A retrospective study reported that 5.5% of 793 pregnant women positive for COVID-19
were admitted to an intensive care unit and 1.3% died. Diagnosis of shock in the 3rd
trimester, maternal age, and high maternal BMI have been identified as risk factors
for a severe course of disease [18], [19]. Delivery of the infant only improves oxygenation. Preterm delivery is mainly initiated
for maternal indications. Risk factors for maternal death are high BMI and comorbidities;
risk factors for fetal or neonatal mortality are gestational age at delivery and the
SOFA score in the first 24 hours [18].
In addition to repeat measurements of blood lactate values, culturing blood samples,
and the administration of broad-spectrum antibiotics [20], [21], infusion of balanced crystalloid solutions (30 ml/kg body weight) and the administration
of vasopressors until a MAP of 65 mmHg is reached are the most important therapeutic
measures which should be initiated in the first hour to achieve initial stabilization
of the patient [14]. Vasopressors can result in a decrease in uterine perfusion with reduced fetal blood
supply. But untreated maternal hypotension also has this effect, meaning that the
treatment of pregnant women with septic shock must always try to reconcile concerns
about maternal safety with fetal interests [22].
Neurogenic shock
Statement
Neurogenic shock is characterized by an acute decrease in systolic arterial blood
pressure to less than 100 mmHg and a decreased heart rate of < 60 beats per minute
and is associated with clouding of consciousness and a loss of spinal reflexes in
cases with high spinal cord injury.
Statement
Treatment of the cause is decisive when treating neurogenic shock.
An imbalance between the vegetative regulation of cardiac activity and the vascular
musculature can lead to neurogenic shock. It is characterized by an acute decrease
of the SAP to < 100 mmHg and of the heart rate to < 60/min and is associated with
clouding of consciousness and a loss of spinal reflexes in cases with high spinal
cord injury [1].
The pathomechanisms of neurogenic shock are divided into
-
direct damage to the centers for circulatory control caused by trauma (brainstem trauma) or stroke. The most common causes in pregnancy
or puerperium are preeclampsia/eclampsia, cerebral venous sinus thrombosis, and reversible
cerebral vasoconstriction syndrome (postpartum angiopathy). In addition to excluding
clotting disorders, it is also important to exclude cerebral aneurysm, arteriovenous
malformations, and moyamoya syndrome [23], [24].
-
Afference changes to the cardiovascular regulatory center in the medulla oblongata triggered by fear, stress, or pain, e.g., during delivery,
or
-
interruption of the descending connection between the bulbar region and the spinal cord (quadriplegia syndrome). Neurogenic
shock can also be caused by meningitis (infection and septic shock), seizures (preeclampsia),
or rapidly ascending Guillain-Barré syndrome [25], [26].
Treatment of the cause is decisive when treating neurogenic shock. Initial treatment
must focus on hemodynamic stabilization. In addition to rapid volume therapy, treatment
also consists of administration of noradrenaline which can impair placental perfusion
and may induce fetal bradycardia. In the late stage of pregnancy there may be a risk
of fetal asphyxia due to uterine contractions. Bradycardia is treated with atropine
or glycopyrrolate. Although the overall data are limited, there are no indications
of teratogenicity, and administration of these medications in pregnancy is possible
after careful reviewing the indications [27], [28]. Direct or indirect sympathomimetic drugs such as phenylephrine, cafedrine, theodrenaline,
and droxidopa may be used to restore vascular tone [27]. Mineralocorticoids such as prednisolone and prednisone to increase plasma volume
and prevent sodium
loss are additionally recommended [28].
Cardiogenic Shock
Statement
Clinically, cardiogenic shock is defined as systolic arterial blood pressure < 90 mmHg
or a mean pressure of 30 mmHg below baseline and a cardiac index (CI) < 1.8 l/min/m2 without pharmacological or mechanical support.
Statement
Common peripartum causes of cardiogenic shock are peripartum cardiomyopathy and amniotic
fluid embolism.
Recommendation
If stress apnea is present, it is important to watch for clinical signs of (cardiogenic)
shock as cardiac decompensation is often not recognized.
Cardiogenic shock is primarily a disorder of cardiac function which takes the form
of a critical reduction of cardiac pumping capacity. Clinically, cardiogenic shock
is defined as SAP < 90 mmHg or a mean blood pressure of 30 mmHg below baseline and
a cardiac index (CI) < 1.8 l/min/m2 without pharmacological or mechanical support [1].
One study found that 59% of cases occurred postpartum, 23% during the second stage
of labor, and 18% developed antepartum [29]. The most common cause with an incidence of 1/3000 was peripartum cardiomyopathy,
although 25% of cases developed prepartum. Amniotic fluid embolism is a relatively
common cause of combined forms of shock with a cardiogenic aspect and can develop
both antepartum and peripartum [29]. Shock resulting from acute coronary syndrome develops in around 1/150 000 pregnancies.
In rare cases, mechanical problems can lead to cardiogenic shock in cases with pre-existing
(rheumatic) valvular disease or acute endocarditis.
Physiologically, pregnant women have a higher cardiac output (CO) and lower peripheral
resistance and lower blood pressure. The first peak CO is often reached around the
24th week of gestation: cardiac decompensation therefore often occurs in this period
or immediately postpartum. Pregnancy is often referred to in this context as a form
of “cardiac stress test” [30].
Symptoms are often trivialized when stress apnea is present, and cardiac decompensation
is often not recognized. Dyspnea, a systolic blood pressure < 90 mmHg, a heart rate
> 130/min or < 45/min, a breathing rate > 25/min, oxygen saturation < 90%, lactate
> 2.0 mmol/L or central venous oxygenation saturation < 60% are clinical signs of
(cardiogenic) shock in pregnant women.
After a diagnosis has been made, the cause must be identified. In addition to taking
the patientʼs medical history and a clinical examination, ECG, echocardiography, and
BNP testing are useful for diagnosis. The threshold before carrying out radiological
tests in pregnant women is high. It would therefore be useful to assess the status
of patients with pre-existing cardiac conditions prior to pregnancy. Close cooperation
between the involved medical specialties is always necessary. The threshold before
carrying out invasive coronary diagnostic tests is very high.
Treatment of a pregnant woman must always also take the unborn child and adequate
perfusion of the placenta into consideration. Treatment and care should therefore
be primarily provided by specialized centers where possible; if this is not possible,
a transfer should be requested [31]. Treatment of peripartum cardiomyopathy often consists of timely induction of labor
depending on the fetal development status. Specific treatment of acute coronary syndrome
in pregnant women corresponds to the treatment provided to non-pregnant women [32], [33], including the administration of dual antiplatelet therapy.
Supportive treatment of cardiogenic shock requires the initial optimization of intravascular
volumes as well as the optimization of oxygenation using non-invasive ventilation
or ventilation. Catecholamine therapy in pregnant women can include the administration
of dobutamine, adrenaline or noradrenaline. Data on the use of phenylephrine in pregnant
women is good, especially in the context of cesarean sections [34]. Levosimendan infused over 24 hours can also improve cardiac pumping function [31]. Fetotoxic substances such as ACE inhibitors, AT1 blockers and atenolol should be
avoided. However, loop diuretics, thiazide diuretics, hydralazine, nitrates, and beta
blockers are well tolerated. Bromocriptine may be used to treat peripartum cardiomyopathy
but it must be accompanied by at least prophylactic heparinization [31]. If these specific measures and supportive pharmacological
therapy are unable to terminate cardiogenic shock, mechanical circulatory support
such as use of an Impella pump or extracorporeal membrane oxygenation may be initiated
[35].
Obstructive Shock
Statement
Obstructive shock is a consequence of mechanical intravascular or extravascular factors
obstructing blood flow in the great vessels or cardiac outflow.
Obstructive shock is the result of mechanical intravascular or extravascular factors
obstructing blood flow in the great vessels or cardiac outflow [1]. The most common causes are
The first two causes have already been discussed in detail in earlier articles [1], [36].
Inferior vena cava syndrome is caused by acute pressure created by the fetus which results in a reduction of
venous backflow to the right side of the maternal heart, resulting in low cardiac
output syndrome. This syndrome mostly occurs in the last trimester of pregnancy if
the mother has spent a lot of time lying on her back; the resultant hypotension or
shock may also significantly decrease placental perfusion. Treatment consists of rapid
repositioning of the pregnant woman onto her left side. If cardiopulmonary resuscitation
is required, it should be carried out with the patient in a supine position because
resuscitation in this position is more effective but an assistant must shift the pregnant
uterus to the left during resuscitation (left uterine displacement).
Pulmonary embolisms are relatively common in pregnant women with an incidence of around 1/20 000. As
D-dimer levels are higher in pregnancy and can therefore not be assessed, diagnosis
must be based on arterial blood gas analysis, duplex sonography, a modified Wells
score, and also on low-dose computed tomography or magnetic resonanice imaging if
necessary [31]. In pregnant women, heparin, low molecular weight heparin, or fondaparinux may be
used for specific anticoagulation of pulmonary embolisms.
Amniotic fluid embolism is uncommon and occurs during labor or immediately postpartum within 30 min after
delivery of the placenta with disruption of the fetomaternal barrier and an ingress
of amniotic fluid into the maternal circulation [37]. In addition to obstruction of the pulmonary circulation, the immune system is activated,
resulting in the release of vasoactive, cardiodepressive and procoagulant mediators.
The early stage of this disorder is characterized by pulmonary vasospasm and hypertension
as well as right heart failure. The consumption of coagulation factors directly results
in acute coagulopathy with bleeding (hemorrhagic shock). During the further course
of the disorder, the symptoms “left ventricular insufficiency” and “immune-mediated
vasodilation” (distributive shock) often lead to multiorgan failure. The diagnosis
is based on the sequence of symptoms, beginning with sudden cardiovascular collapse,
followed by acute
coagulopathy, even before any relevant bleeding has occurred. Amniotic fluid embolism
is diagnosed by exclusion. There is currently no causal therapy for amniotic fluid
embolism; treatment of this form of combined shock is purely symptomatic and ranges
from the administration of catecholamines to replacement of clotting factors and cardiopulmonary
resuscitation [38], [39].
Preeclampsia, Eclampsia and HELLP Syndrome
Preeclampsia, Eclampsia and HELLP Syndrome
Statement
Different pathophysiological changes occurring in the context of preeclampsia, eclampsia
or HELLP syndrome may lead to shock.
Different pathophysiological changes arising in the context of hypertensive disorders
of pregnancy and their complications can lead to shock. Progression of preeclampsia
to severe eclampsia results in fluid sequestration in the interstitium (hypovolemic
shock) and often additionally leads to left ventricular insufficiency with pulmonary
edema (cardiogenic shock). Renal vasoconstriction can lead to acute renal failure.
Eclampsia can cause seizures, and intracranial bleeding may develop when blood pressure
increases to > 160/110 mmHg (neurogenic shock).
HELLP syndrome with hemolysis (H), elevated liver enzymes (EL) and low platelets (LP)
occurs in 10 – 20% of cases. The typical symptom of epigastric pain is caused by impaired
hepatic perfusion which may lead, in rare cases, to hepatic rupture with life-threatening
bleeding (hemorrhagic shock). The differential diagnosis of thrombocytopenia must
exclude aHUS (atypical hemolytic uremic syndrome), acute fatty liver of pregnancy,
and TTP (thrombotic thrombocytopenic purpura) [6].
Premature placental abruption can occur in the context of preeclampsia/eclampsia,
leading to impaired fetal supply. Just like hepatic rupture caused by HELLP syndrome,
placental abruption requires immediate emergency cesarean section.
Conclusion
The (patho-)physiological changes of pregnancy result in specific diagnostic and therapeutic
features, even though the basic measures used to rectify the effects of shock do not
differ much from those used when treating non-pregnant women. With all forms of shock
in pregnant women, attention must focus on the fetal outcome. Depending on gestational
age and estimated fetal weight, (emergency) cesarean section may improve the motherʼs
condition and may (also) save the childʼs life.
