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Staged repair of acute type aortic dissection and correlation in pregnancy . Ann Thorac Surg 2000 ; 69 : 1945 – 1947 . 93 Zeebregts C , Schepeus M , Hamceteman T , Morshires N , de la Riviere AB . Acute aortic dissection complicating pregnancy . Ann Thorac Surg 1997 ; 64 : 1345 – 1348 . 94 Katy N , Cullen J , Morout M , et al. Aortic dissection during preg- nancy: treatment by emergency caesarean section immediately fol- 571 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 41 Septic Shock 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 Chapter 41 572 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. Type of shock Physiologic variable Causes Preload Pump function Afterload Tissue perfusion Clinical measurement Pulmonary capillary wedge pressure Cardiac output Systemic vascular resistance Mixed venous oxygen saturation Hypovolemic shock Ø ↓ ↑ ↓ Hemorrhage Fluid loss Cardiogenic shock ↑ Ø ↑ ↓ Cardiomyopathy Arrhythmias Valvular disease Obstruction Distributive (vasodilatory) shock ↓ or ↔ ↑ Ø ↑ Septic shock 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. Septic Shock 573 ate 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 antigenic toxins released by some Staphylococcus and Streptococcus species can directly activate T - lymphocytes without involving intermedi- Table 41.2 Defi nitions. * Defi nition Is a positive blood/tissue culture 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 Bacteremia The presence of viable bacteria in the blood 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. Chapter 41 574 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 develop- Figure 41.1 Pathophysiology of septic shock. DIC, disseminated intravascular coagulopathy; MDF, Myocardial depressant factor; O 2 , oxygen. Septic Shock 575 tates 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, facili- Chapter 41 576 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 amplify- ing 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 Septic Shock 577 obstetric 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 Chapter 41 578 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. Incidence (%) Chorioamnionitis 0.5 – 1.0 Postpartum endometritis – After cesarean delivery 0.5 – 85 – After vaginal delivery < 10 Urinary tract infection 1 – 4 Pyelonephritis 1 – 4 Septic abortion 1 – 2 Necrotizing fasciitis (postoperative) < 1 Toxic shock syndrome < 1 Non - pregnant Pregnant Relative change Cardiac output (L/min) 4.3 6.2 +43% Heart rate (bpm) 71 83 +17% Systemic vascular resistance (dyne/sec/cm 5 ) 1530 1210 +21% Pulmonary vascular resistance (dyne/sec/cm 5 ) 119 78 +34% COP (mmHg) 20.8 18.0 +14% COP – PCWP gradient (mmHg) 14.5 10.5 +18% Mean arterial pressure (mmHg) 86.4 90.3 No change Central venous pressure (mmHg) 3.7 3.6 No change PCWP (mmHg) 6.3 7.5 No change 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. . & 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,. dissection during preg- nancy: treatment by emergency caesarean section immediately fol- 571 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy 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: