Three broad types of shock are recognized characterized by one of three primary physiologic derangements: i decreased preload hypo-volemic shock; ii pump failure cardiogenic shock; and i
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Trang 3fol-Critical Care Obstetrics, 5th edition Edited by M Belfort, G Saade,
M Foley, J Phelan and G Dildy © 2010 Blackwell Publishing Ltd.
Errol R Norwitz 1 & Hee Joong Lee 2
1 Department of Obstetrics and Gynecology, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA
2 Department of Obstetrics and Gynecology, The Catholic University of Korea, Seoul, Korea
Introduction
Shock is a generalized physiologic state characterized by a signifi
-cant reduction in tissue perfusion resulting in decreased tissue
oxygen delivery Although the effects of inadequate tissue
perfu-sion are initially reversible, prolonged oxygen deprivation leads
to generalized cellular hypoxia, end - organ damage, multiple
organ system failure, and death [1] For these reasons, prompt
recognition and appropriate management of shock is crucial Any
classifi cation scheme simplifi es the complex pathophysiology
underlying the many individual causes of shock Three broad
types of shock are recognized characterized by one of three
primary physiologic derangements: (i) decreased preload
(hypo-volemic shock); (ii) pump failure (cardiogenic shock); and (iii) a
severe drop in systemic vascular resistance with a compensatory
increase in cardiac output (known as distributive or vascular
shock) (Table 41.1 )
Septic shock describes the constellation of clinical fi ndings that
results from the systemic infl ammatory response to an infectious
insult (defi ned in Table 41.2 ) It is characterized by an inability
of the host to maintain vascular integrity and fl uid homeostasis
resulting in inadequate tissue oxygenation and circulatory failure
The spectrum of host response ranges from simple sepsis to septic
shock with multiple - organ system dysfunction and death Patients
with septic shock require early and aggressive intervention, and
often succumb despite timely and appropriate therapy The
annual incidence of sepsis is estimated at 50 – 95 cases per 100 000,
and has increased over the past 20 years by 9% per annum [2]
Sepsis accounts for 2% of overall hospital admissions Roughly
9% of patients with sepsis progress on to severe sepsis, and 3%
of those with severe sepsis develop septic shock [3] Septic shock
accounts for approximately 10% of admissions to non - coronary
intensive care units (ICUs) and is the 13th leading cause of death
in the United States Its incidence appears to be increasing [4] After correcting for the increased age of the population, the rate
of septic shock reported by the Centers for Disease Control and Prevention of the United States (CDC) more than doubled between 1979 and 1987 Moreover, this increased rate of septic shock was observed regardless of age group or geographic area [5] While improvements in care have led to a decrease in septic shock mortality rates over the past two decades [6,7] , the overall number of patients dying from sepsis is growing as more patients are affected Moreover, despite improvements in ICU care, the mortality rate from septic shock remains at 40 – 50% in most series [8] , and an additional 20% of hospital survivors may succumb within the following year [9] Short - term mortality appears to be related to the number of organ systems affected The average risk
of death increases by 15 – 20% with failure of each additional organ system [10] If there is evidence of renal, pulmonary, and cerebral dysfunction, mortality may be as high as 70% [2] Although septic shock remains an uncommon event in the obstetric population, factors that contribute to the increased rate
of sepsis in the general population are also more common in women of reproductive age Additionally, because maternal mortality is so uncommon, sepsis remains an important overall cause of maternal mortality [11]
Systemic i nfl ammatory r esponse s yndrome
The systemic infl ammatory response syndrome (SIRS) describes
a generalized infl ammatory response of the host to a variety of insults Its etiology is not limited to infection, since burn injuries, trauma, and infl ammatory conditions (such as pancreatitis) can elicit a similar clinical picture It is characterized by two or more
of the following cardinal signs: (i) a body temperature less than
36 ° C or more than 38 ° C; (ii) a pulse rate greater than 90 beats per minute (bpm); (iii) tachypnea manifesting as a respiratory rate exceeding 20 breaths per minute or a P a CO 2 less than
32 mmHg; and/or (iv) a circulating leukocyte count less than 4000/ µ L, greater than 12 000/ µ L, or more than 10% immature
Trang 4Chapter 41
Pathophysiology of s eptic s hock
Infection with a pathogenic organism results in cellular activation
of monocytes, macrophages, and neutrophils and induction of a proinfl ammatory cascade triggered by interaction between the organism and a number of pathogen recognition receptors in the host [14] The proinfl ammatory mediators, in turn, induce a systemic response (characterized by tachycardia, tachypnea, and hypotension) and – if excessive or uncontrolled – can lead to end - organ dysfunction, including ARDS and acute renal failure [15] In such patients, the severity of the clinical presentation [16] and the mortality rate [8] is dependent largely on the vigor of the
host ’ s infl ammatory response and not on the virulence of the
inciting infection
For the most part, Gram - negative sepsis has been the model used to study this phenomenon in experimental animals In this model, endotoxin – a complex lipopolysaccharide (LPS) present
in the cell wall of aerobic Gram - negative bacteria that is released
at the time of the organism ’ s death – appears to be a critical factor
in inducing the pathophysiologic derangements associated with septic shock [11] A similar mechanism may also be responsible for the development of shock in the setting of Gram - positive sepsis [17] Indeed, Cleary et al [18] demonstrated that patients
forms on the differential count A consensus committee in
1991 concluded that evidence of SIRS in the setting of suspected
or proven infection should be regarded as diagnostic of sepsis
[12]
Severe sepsis is diagnosed when SIRS is associated with organ
dysfunction, tissue hypoperfusion, and/or hypotension Useful
indicators of tissue hypoperfusion include lactic acidosis,
oligu-ria, or an acute alteration in mental status Hypotension may not
be present if the patient is on exogenous vasopressor support
Other features of severe sepsis may include acute lung injury
(acute respiratory distress syndrome [ARDS]), coagulopathy,
thrombocytopenia, and acute renal, liver, or cardiac failure
[1,12,13] Multiple - organ system dysfunction syndrome (MODS)
is the terminal phase of this spectrum, represented by the
pro-gressive physiologic deterioration of interdependent organ
systems such that homeostasis cannot be maintained without
active intervention If hypotension and reduced tissue perfusion
persists despite adequate fl uid resuscitation, then a diagnosis of
septic shock (severe sepsis with cardiovascular failure) should be
made Refractory hypotension is defi ned as a systolic blood
pres-sure less than 90 mmHg, mean arterial pressure less than
65 mmHg, or a decrease of 40 mmHg in systolic blood pressure
compared to baseline which is unresponsive to a crystalloid fl uid
challenge of 20 – 40 mL/kg
Table 41.1 Pathophysiology and hemodynamic profi le of shock states
Clinical measurement Pulmonary capillary
wedge pressure
Cardiac output Systemic vascular
resistance
Mixed venous oxygen saturation
Fluid loss
Arrhythmias Valvular disease Obstruction
Toxic shock syndrome Anaphylaxis Drug/toxin reaction Myxedema coma Neurogenic shock Burn shock Adapted from Gaieski D, Manaker S General evaluation and differential diagnosis of shock in adults UpToDate, 2007 The primary pathophysiologic defect for each type
of shock is highlighted
Trang 5ate antigen - processing cells such as macrophages [24] This abbreviated mechanism of T - lymphocyte activation may explain the rapid progression and fulminant clinical course seen with some Gram - positive bacterial infections
The series of events initiated by endotoxin is presented sche-matically in Figure 41.1 The fi rst event is a local activation of the immune system at the site of infection in an attempt to confi ne its spread If the ability to contain the infection is lost, systemic activation of effector cells leads to the production of proinfl am-matory cytokines with widespread systemic effects and end - organ injury [25] In this way, the initial infectious insult primes the immune system for an exaggerated and disproportionate response
to any subsequent insult [26 – 30] with an outpouring of copious amounts of proinfl ammatory mediators [31] Activation of the complement cascade also plays a central role in activation of the immune system [32] and can itself lead to the hemodynamic changes characteristic of sepsis in animal models [33]
infected with Streptococcus pyogenes are only at risk of
develop-ing septic shock if the isolates from the patients were able to
produce exotoxin Exotoxins released by Clostridium perfringens ,
Staphylococcus aureus , and Group A β - hemolytic streptococcus
can cause rapid and extensive tissue necrosis and gangrene,
espe-cially of the postpartum uterus, leading to profound
cardiovas-cular collapse and maternal death [19,20] In addition to exotoxin,
Gram - positive microorganisms also release peptidoglycans and
lipoteichoic acid which can induce the production of proinfl
am-matory mediators associated with sepsis [21] The clinical
presen-tation of septic shock is generally not helpful in identifying the
underlying pathogenic mechanism
Although the response of the host innate immune system is
generally similar for all microorganisms, there are some
patho-gen - specifi c responses [17,22,23] For example, highly antipatho-genic
toxins released by some Staphylococcus and Streptococcus species
can directly activate T - lymphocytes without involving
Table 41.2 Defi nitions *
required for the diagnosis?
Infection A microbial phenomenon characterized by an infl ammatory response to the presence of
micro - organisms or the invasion of normally sterile host tissue by those organisms
Yes
Systemic infl ammatory
response syndrome
(SIRS)
SIRS is a widespread infl ammatory response to a variety of severe clinical insults This syndrome is clinically recognized by the presence of two or more of the following:
– Temperature > 38 ° C or < 36 ° C – Heart rate > 90 beats/min – Respiratory rate > 20 breaths/min or PaCO 2 < 32 mmHg – WBC > 12,000 cells/mm 3 , < 4000 cells/mm 3 or with > 10% immature (band) forms
Yes
Sepsis Sepsis is the systemic response to infection Thus, in sepsis, the clinical signs describing
SIRS are present together with defi nitive evidence of infection In contrast to the lactic acidosis typically associated with septic shock, early sepsis may be associated with acute respiratory alkalosis due to stimulation of ventilation
No (a clinical diagnosis)
Severe sepsis Sepsis is considered severe when it is associated with organ dysfunction, hypoperfusion or
hypotension The manifestations of hypoperfusion may include, but are not limited to, lactic acidosis, oliguria or an acute alteration in mental status
No (a clinical diagnosis)
Septic shock Septic shock is sepsis with hypotension despite adequate fl uid resuscitation combined with
perfusion abnormalities that may include, but are not limited to, lactic acidosis, oliguria
or an acute alteration in mental status Patients who require inotropic or vasopressor support despite adequate fl uid resuscitation are in septic shock Septic shock is one of the forms of vasodilatory or distributive shock It results from a marked reduction in systemic vascular resistance, often associated with an increase in cardiac output
No (a clinical diagnosis)
* Data from: American College of Chest Physicians and Society of Critical Care Medicine Consensus Conference: Defi nitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis Crit Care Med 1992; 20: 864; Balk RA Severe sepsis and septic shock Defi nitions, epidemiology, and clinical manifestations Crit Care Clin 2000; 16: 179; Levy MM, Fink MP, Marshall JC, et al 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Defi nitions Conference Crit Care Med 2003; 31: 1250
Trang 6Chapter 41
ment of sepsis leading to decreased mortality [42,43] At a cellular level, LPS bound to a carrier protein interacts with pattern rec-ognition molecules or receptors on the surface of target cells, such
as CD14 and Toll - like receptors (TLRs) Activation of these receptors induces transcription of infl ammatory and immune response genes typically by way of nuclear factor - κ B (NF κ B) -mediated mechanisms Activation of this signal transduction cascade triggers the production and release of endogenous medi-ators, such as TNF - α and interleukin - 1 β (IL - 1 β ), which amplify the LPS signal and transmit it to other cells and tissues Currently, more than 10 TLR isoforms have been described in humans and the list of their specifi c microbial ligands is growing [44] The presence of numerous TLR complexes on the surface of immune cells allows these cells to recognize many conserved microbial
Various proinfl ammatory mediators have been implicated in
the pathogenesis of septic shock Several lines of experimental
evidence in both humans and animal models support a central
role for tumor necrosis factor - α (TNF - α ) in the pathophysiology
of sepsis [34] Large amounts of TNF - α are produced in response
to LPS administered to healthy human subjects [35,36] and
administration of either endotoxin or TNF - α provokes similar
physiologic derangements to that seen in sepsis [37] Elevated
levels of TNF - α in animals are associated with irreversible shock
and death [38,39] , and infusion of TNF - α into experimental
animals produces the pulmonary, renal, and gastrointestinal
his-topathology observed at autopsy in septic patients [40,41] In
similar experimental models, early and adequate administration
of anti - TNF - α antiserum is able to protect against the
Figure 41.1 Pathophysiology of septic shock DIC,
disseminated intravascular coagulopathy; MDF, Myocardial depressant factor; O 2 , oxygen
Trang 7tates the infl ammatory cascade and worsens the clinical syn-drome As our understanding of this process grows, opportunities will be identifi ed for targeted intervention to abort this systemic infl ammatory cascade that leads to progressive multiorgan dys-function [53]
Tumor necrosis factor - α and activated complement fragments attract neutrophils whose products exacerbate endothelial injury [54] This results in altered ability of the host to maintain tissue perfusion through regulation of blood pressure, cardiac output (CO), and systemic vascular resistance (SVR) [15] The produc-tion of IL - 1 β by macrophages also promotes procoagulant activ-ity, which results in fi brin deposition in the microvasculature leading to further perturbations of organ perfusion [55 – 57] Activation of the microvasculature endothelium by TNF - α and
IL - 1 β produces capillary leak and increased leukocyte receptor expression Leukocyte migration and activation result in release
of vasoactive substances such as histamine, serotonin, and brady-kinin These substances, in turn, increase capillary permeability, induce endothelial damage, and promote vasodilation [26] Neutrophil activation stimulates a respiratory burst with increased production and release of lysosomal enzymes and toxic oxygen species such as superoxide, hydroxyl, and peroxide radicals This can have deleterious effects on the vasculature as well as other organs and is especially detrimental in the lung, where it is felt to play a key role in the pathogenesis of ARDS [50] Stimulation of neutrophils by activated complement fragments also leads to leu-kotriene secretion, further affecting capillary permeability and blood fl ow distribution [57] At the same time, the damage to the vascular endothelium stimulates platelet aggregation Complement activation ensues, with microthrombus formation and fi brin deposition leading to further derangements of perfusion [58]
As discussed above, disruption of the endothelium and vascu-lar smooth muscle is a well - recognized component of septic shock This results also in a blunting of the response to vasoactive drugs Because these effects can be blocked in experimental animal models by treatment with inhibitors of nitric oxide syn-thesis, alterations in nitric oxide metabolism are felt to play a role
in the development of refractoriness to endogenous catechol-amines and exogenous vasopressors [59] The elaboration of infl ammatory mediators may also affect sympathetic vasomotor tone resulting in impaired vasoconstriction to sympathetic stim-ulation The combination of a leaky vasculature and loss of smooth muscle tone results in refractory hypotension [59,60]
An intact sympathetic refl ex response to a local infl ammatory event may produce profound vasoconstriction in some organ systems leading to a reduction in tissue perfusion [26] Alternatively, a localized loss of control of vascular tone can result
in a failure of arterioles to dilate in response to physiologic vaso-active substances such as histamine and bradykinin [61] , leading
to increased capillary leak and intravascular fl uid depletion The net result is a marked reduction in peripheral vascular resistance with extensive capillary pooling of blood Cellular hypoxia and acidosis further disrupt the ability of individual cells to utilize
molecules Lipopolysaccharide also binds to soluble CD14 to
facilitate interaction with tissues lacking the CD14 receptor, such
as vascular endothelium [45] The production of TNF - α , in turn,
stimulates the secretion of interleukins, prostaglandins,
leukotri-enes, and other infl ammatory mediators These infl ammatory
products cause the clinical symptoms associated with sepsis as
well as capillary leak, hypotension, and activation of the
coagula-tion system [46] In a rabbit model of IL - 1 β - induced
hypoten-sion, the lung was the primary organ injured Although both
cytokines were able to produce massive pulmonary damage,
TNF - α produced more injury than IL - 1 β Moreover, these
studies suggested that TNF - α and IL - 1 β may act synergistically
to disrupt vascular endothelial integrity [47] Additional evidence
for the role of cytokines in mediating lung injury in ARDS
includes the increased production of IL - 1 β and TNF - α by lung
macrophages in response to LPS administration [48] and the in
vivo observation that alveolar macrophages from ARDS patients
produce increased amounts of IL - 1 β [49]
Vascular endothelium is a metabolically active tissue that
exerts a pivotal role in the regulation of underlying vascular
smooth muscle tone, the maintenance of vessel integrity and
fl uidity of blood, and the regulation of leukocyte adhesion
Maintenance of vascular homeostasis is regulated in large part by
production of nitric oxide (originally identifi ed as endothelium
derived relaxing factor) [50] TNF - α stimulation of macrophages
causes a sustained increase in nitric oxide production resulting in
profound effects on vascular tone and permeability This nitric
oxide excess, in turn, leads to microvascular damage, vascular
hyporeactivity, and multiorgan dysfunction likely through
induc-tion of apoptosis [51] Cyclooxygenase is also activated, and the
elaboration of prostaglandins contributes to the misdistribution
of blood fl ow [52]
Stimulation of endothelial cells by several cytokines including
IL - 1 α , IL - 1 β , and TNF - α results in endothelial activation, and
alters the structural and metabolic functions of the endothelium
Rather than its usual anticoagulant properties, the endothelial
lining of blood vessels becomes a procoagulant surface with
upregulation of adhesion molecule expression, increased
produc-tion of chemoattractant and vasoactive substances, and decreased
expression of anticoagulants Specifi cally, there is evidence of
activation of the extrinsic pathway of the coagulation cascade
with increased production of tissue factor (a critical promoter of
the procoagulant pathway) and suppression of a number of key
anticoagulant factors, including thrombomodulin, heparan
sulfate, and protein C In the normal state, few adhesion
mole-cules are expressed on vascular endothelium After activation by
proinfl ammatory mediators, increased amounts of P - selectin,
E - selectin, intercellular adhesion molecule - 1, and other adhesion
molecules are expressed on the surface of vascular endothelial
cells Leukocytes adhere and transmigrate into the infl amed
tissues This mechanism is designed to confi ne and localize the
infection, but may also lead to endothelial dysfunction with
capil-lary leakage Systemic endothelial activation, with its associated
outpouring of proinfl ammatory mediators and cytokines,
Trang 8facili-Chapter 41
The clinical manifestations of septic shock fall into three broad categories, which correlate with progressive physiologic
derange-ment (summarized in Table 41.3 ) Early ( warm ) shock is
charac-terized by a hyperdynamic circulation and decreased SVR The
hallmark of late ( cold ) shock is abnormal tissue perfusion and
oxygenation due to regional (peripheral) vasoconstriction and myocardial dysfunction Secondary ( irreversible ) shock is fre-quently a terminal condition associated with multiple - organ system dysfunction Each phase represents a continued down-ward progression in the course of this disease process
In the early phase of septic shock, bacteremia is heralded typi-cally by shaking chills, a sudden rise in temperature, tachycardia, and warm extremities Although the patient may appear ill, the diagnosis of septic shock may be elusive until hypotension is evident In addition, patients may present initially with non specifi c complaints such as malaise, nausea, vomiting, or even profuse diarrhea Abrupt alterations in behavior and mental status changes, which have been attributed to a reduction in cerebral blood fl ow, may also herald the onset of septic shock Tachypnea or dyspnea may be present with no objective fi ndings
on physical examination These symptoms likely represent a direct effect of endotoxin on the respiratory center and may precede the development of clinical ARDS
Laboratory fi ndings are highly variable during the early stages
of septic shock The circulating WBC count may initially be depressed, although a marked leukocytosis is a more common
fi nding Although there may be a transient increase in circulating blood glucose levels due to catecholamine release, hypoglycemia
available oxygen [62] , leading to worsening tissue and organ
damage
Direct effects of bacterial immunologic complexes are also
thought to play an important role in tissue injury [63] Immune
complex precipitants have been identifi ed within the lung
vascu-lature and are thought to contribute to the development of ARDS
Similarly, focal areas of acute tubular necrosis seen in the kidney
have been associated with the deposition of infl ammatory
infi ltrates
Disseminated intravascular coagulopathy (DIC) frequently
complicates septic shock DIC involves activation of both the
coagulation and fi brinolytic cascades leading to depletion of
cir-culating coagulation factors (a consumptive coagulopathy)
Tissue factor is released by TNF - α stimulation of monocytes and
by exposure of subendothelial tissue factor following injury to the
vascular endothelium with activation of the extrinsic pathway
Microvasculature fi brin deposition compromises end - organ
per-fusion At the same time, TNF - α also inhibits the production and
action of regulatory proteins such as protein C, thereby
amplifying the procoagulant state Although its role in DIC is not signifi
-cant, activation of the intrinsic pathway provides a powerful
stimulus to the production of kinins, such as bradykinin, thus
contributing to hypotension and disruption of vascular
homeo-stasis Derangements in the coagulation system are magnifi ed by
the ability of endotoxin to rapidly activate and then suppress
fi brinolysis, which again appears to be mediated by TNF - α [64]
Clinical p resentation of s eptic s hock
The clinical presentation of shock varies with the type and cause,
but several features are common including hypotension (defi ned
as systolic blood pressure less than 90 mmHg), cool clammy skin
and oliguria (due to redistribution of blood), changes in mental
status (confusion, delirium, or coma), and metabolic acidosis
Sepsis refers to a clinical syndrome that encompasses a variety of
host responses to systemic infection As discussed above, the
clinical spectrum of sepsis depends primarily on the host response
to infection rather than the severity of the infection itself [16,65]
Because the clinical manifestations of sepsis can be recapitulated
experimentally by infusing proinfl ammatory mediators (such as
interleukins and TNF - α), an exaggerated host infl ammatory
response is felt to be central to its pathophysiology [43,47]
Although various risk factors have been identifi ed and scoring
systems developed, there is as yet no effective method to predict
which patients will progress from bacteremia to septic shock and
MODS [66] In general, however, more severe infl ammatory
responses appear to be accompanied by progressively greater
mortality rates [67] The timing of onset of infection may also
infl uence the clinical outcomes A recent study showed that
patients who developed septic shock within 24 hours of ICU
admission were more severely ill but had better outcomes than
patients who became hypotensive later during their ICU stay
[68]
Table 41.3 Clinical features of septic shock
Early (warm) shock Altered mental status Peripheral vasodilation (warm skin, fl ushing) Tachypnea or shortness of breath Tachycardia
Temperature instability Hypotension Increased cardiac output and decreased peripheral resistance
Late (cold) shock Peripheral vasoconstriction (cool, clammy skin) Oliguria
Cyanosis ARDS Decreased cardiac output and decreased peripheral resistance
Secondary (irreversible) shock Obtundation
Anuria Hypoglycemia Disseminated intravascular coagulation Decreased cardiac output and decreased peripheral resistance Myocardial failure
Trang 9obstetric patients with septic shock managed with pulmonary artery (PA) catheters [76]
Predisposing f actors in o bstetrics
The ability of both Gram - positive and Gram - negative organisms
to systematically activate the infl ammatory cascade has particular relevance in the obstetric patient, in whom mixed polymicrobial infections are commonly identifi ed [77] Although Gram negative coliforms make up a signifi cant portion of the organisms recovered in bacteremic obstetric patients, other organisms,
including aerobic and anaerobic streptococci, Bacteroides fragilis , and Gardnerella vaginalis , are found frequently Septic shock in
pregnancy associated with legionella pneumonia has also been described [78] As in other areas of medicine, the number of cases
of obstetric sepsis associated with Group A streptococcus appears
to be increasing [79] Pregnancy has been described as an immunocompromised state, although little objective evidence exists comparing the ability of pregnant and non - pregnant individuals to process bac-terial antigens and elicit an appropriate immune response Pregnant women remain at risk for common medical and surgical illnesses (such as pneumonia and appendicitis) as well as condi-tions unique to pregnancy (for example, intra - amniotic infection and septic abortion), all of which may result in sepsis If the pregnancy is not the cause of the infection, delivery is not gener-ally indicated Supportive care should include control of fever with antipyretics, cooling blankets, or both The fetus should be
resuscitated in utero with correction of maternal acidosis,
hypox-emia, and systemic hypotension, which will usually improve any abnormalities in the fetal heart tracing Although genital tract infections are common on an obstetric service [80 – 82] , septic shock in this same population tends to be an uncommon event When an obstetric patient has clinical evidence of local infection, the incidence of bacteremia is approximately 8 – 10% [77,83 – 86] Overall, rates of bacteremia of 7.5 per 1000 admissions to the obstetrics and gynecology services at two large teaching hospitals have been reported [83,84] More striking is that patients with bacteremia rarely progress to develop more signifi cant complica-tions, including septic shock Ledger and colleagues [83]
identi-fi ed only a 4% rate of septic shock in pregnant patients with bacteremia This value is in agreement with that of other investi-gators, who have reported a 0 – 12% incidence of septic shock
in bacteremic obstetric and gynecologic patients [77,83 – 87] Obstetric conditions that have been identifi ed as predisposing to the development of septic shock are listed in Table 41.4 [84,87,88 – 92]
The physiologic changes that accompany pregnancy may place the gravida at greater risk for morbidity than her non - pregnant counterpart Elevation of the diaphragm by the gravid uterus, delayed gastric emptying, and the emergent nature of many intu-bations in obstetrics dramatically increases the risk of aspiration pneumonitis (Mendelson ’ s syndrome) Although the pregnant
is more likely to prevail later due to hepatic dysfunction and a
reduction in gluconeogenesis Evidence of a decreased platelet
count, decreased fi brinogen, elevated fi brin split products, and
elevated prothrombin time may suggest the presence of DIC
Initial arterial blood gas may show an initial transient respiratory
alkalosis due to tachypnea, but this is likely to evolve with time
into a metabolic acidosis with increased circulating levels of lactic
acid resulting from tissue hypoxia
In the setting of undiagnosed and untreated septic shock,
pro-found and progressive myocardial depression will develop with
a marked reduction in CO and SVR [69] This will manifest
clinically as cold extremities, oliguria, and peripheral cyanosis
Prolonged tissue hypoxia will lead to worsening metabolic
acidosis, electrolyte imbalance, DIC, and mental status changes,
which with time will become irreversible The etiology of this
myocardial depression is not clear In contrast to patients with
myocardial failure due structural heart disease or myocardial
infarction [70] , extensive studies in both humans and animal
point to a circulating myocardial depressant factor or toxin as the
cause of myocardial depression rather than an alteration in
coro-nary fl ow or insuffi cient myocardial oxygenation [71] In support
of this hypothesis, infusion of endotoxin in healthy human
sub-jects results in a decrease in myocardial performance and left
ventricular dilation similar to that seen in patients with septic
shock [72]
Echocardiography in women with septic shock may be helpful
Cardiac output and cardiac index (CI) are initially increased in
women with septic shock due to a profound decrease in SVR and
a compensatory increase in heart rate However, this increase in
CO is typically inadequate to meet the patient ’ s metabolic needs
As a result, with time, both the left and right ventricles dilate, and
the ejection fraction decreases [72] Cardiac output is maintained
despite the low ejection fraction because ventricular dilatation
permits a normal stroke volume The limitation in cardiac
per-formance and ejection fraction is greater than that seen in equally
ill non - septic patients [73] Ventricular compliance is also affected
in women with sepsis as evidenced by a decreased ability of the
myocardium to response to an increase in preload [74]
To better understand the hemodynamic response to sepsis,
Parker & Parillo [69] studied 20 subjects with septic shock By
conventional criteria, 95% of the patients would have been
clas-sifi ed as hyperdynamic, but 10 of the 20 (50%) had abnormally
depressed ejection fractions that could not be accounted for by
differences in preload, afterload, or positive end - expiratory
pres-sure (PEEP) In the acute phase of septic shock, dilatation of the
left ventricle appears to represent an adaptive response that
confers a survival advantage, since it allows for the CO to be
maintained in the face of a declining ejection fraction [73] Two
discrete subsets of patients were identifi ed based on their response
to volume loading: those who respond with ventricular dilation
and increased CO (better prognosis) and those who respond with
increased pulmonary capillary wedge pressure (PCWP) and no
increase in CO (poorer prognosis) [75] Cardiac depression of
similar magnitude and frequency has also been reported in
Trang 10Chapter 41
specialties, tends to be an infrequent event in obstetrics and gyne-cology The incidence of death from sepsis is estimated at 0 – 3%
in obstetric patients as compared with 10 – 81% in non - obstetric patients [83,84,90,99] Suggested reasons for this observation of
a more favorable outcome in pregnant woman include: (i) younger age group; (ii) transient nature of the bacteremia; (iii) type of organisms involved; (iv) a primary site of infection (pelvis) that is more amenable to both surgical and medical intervention; and (v) lack of associated medical diseases that could adversely impact the prognosis for recovery Evidence in support of the latter explanation comes from earlier studies demonstrating increased mortality in septic non - pregnant patients with underly-ing comorbid disease [100]
Pregnancy and s eptic s hock
The pregnant host may be different from the traditional septic shock host in ways other than the difference in microbiologic pathogens involved Physiologic adaptations to pregnancy designed to promote favorable maternal and fetal outcome occur
in almost every organ system (summarized in Table 41.5 ) [94,98,101 – 103] Some of these changes, such as a dramatic increase in pelvic vascularity, promote maternal survival after infection They may also infl uence the presentation and course
of septic shock in the gravida, although this idea has received little attention in the published literature On the other hand, other physiologic adaptations to pregnancy (e.g ureteral dilatation) may predispose the gravid female to more signifi cant infectious morbidity than her non - pregnant counterpart
In an animal model of endotoxin - induced septic shock, Beller and coworkers [104] compared pregnant and non - pregnant responses to fi xed doses of LPS The pregnant animals had a much more pronounced respiratory and metabolic acidosis than did the controls, and they died signifi cantly faster than did non -pregnant controls due primarily to cardiovascular collapse
patient has been previously identifi ed as being at increased risk
of pulmonary sequelae from systemic infection such as
pyelone-phritis, the pathophysiologic mechanisms have been known only
for the past decade [93] Hemodynamic investigation in normal
women using fl ow - directed PA catheters has quantifi ed the
physi-ologic alterations that place the patient at increased risk for
pul-monary injury Pregnancy decreases the gradient between colloid
osmotic pressure (COP) and PCWP [94] This increases the
pro-pensity for pulmonary edema if pulmonary capillary permeability
changes or the PCWP increases In the critically ill, non - pregnant
patient, decreases in the COP – PCWP gradient predict an
increased propensity for pulmonary edema [95,96,97] The
intra-pulmonary shunt fraction (Q S /Q T ) is also increased in normal
pregnancy [98] , which may further increase the risk of
pulmo-nary morbidity
Fortunately, mortality from septic shock, which is extremely
high in the setting of bacteremia in other medical and surgical
Table 41.4 Bacterial infections associated with septic shock in the obstetric
population
– After vaginal delivery < 10
Necrotizing fasciitis (postoperative) < 1
Systemic vascular resistance (dyne/sec/cm 5 ) 1530 1210 +21%
Pulmonary vascular resistance (dyne/sec/cm 5 ) 119 78 +34%
Left ventricular stroke work index (g/m/m 2 ) 41 48 No change
From Clark SL, Cotton DB, Lee W, et al Central hemodynamic assessment of normal term pregnancy Am J
Obstet Gynecol 1989; 161: 1439 – 1442
COP, colloid osmotic pressure; PCWP, pulmonary capillary wedge pressure
Table 41.5 Hemodynamic and ventilatory
parameters in pregnancy