We use cardiac function curves and venous return relations in the following discussion to compare and contrast cardiovascular mechanisms responsible for cardiogenic shock (Fig. 21-2), hypovolemic shock (Fig. 21-3), and septic shock (Fig. 21-4). The goal is to link pathophysiology of the circulation to the broader differential diagnosis of the types of shock presented in Table 21-4 to facilitate the accurate etiologic diagnosis and management based on additional hemodynamic measures as required by the response to urgent resuscitation.
Shock caused by decreased pump function of the heart is commonly cardiogenic shock resulting from left ventricular ischemia. For high right atrial pressure hypotension not obviously caused by left ventricular ischemia, greatly elevated pulmonary arterial pressure (most commonly pulmonary embolism), right ventricular ischemia, and dysfunction of heart valves must be excluded. Of course, right atrial pressure may be increased by abnormal pressures surrounding the heart in the absence of ventricular dysfunction. Because of this clinical presentation, I have included cardiac tamponade in the category of high right atrial pressure hypotension. Tamponade and pulmonary embolism might have been classified as decreased venous return due to obstruction of the circulation (see Table 21-1). Decreased venous return despite normal pump function is most commonly due to hemorrhagic or dehydration hypovolemia, but I emphasize other mechanisms including decreased venous tone caused by drugs, neurologic injury, and adrenal insufficiency, particularly for nonresponsive hypovolemia. Septic shock is the most common cause of high cardiac output hypotension resulting from abnormal arterial tone and blood flow distribution, although other causes such as severe liver failure, severe pancreatitis, trauma with tissue damage eliciting a significant inflammatory response, anaphylactic shock, thyroid storm, Paget disease, and other peripheral shunts share this mechanism. Defining shock as anaerobic metabolism of multiple organ systems, often signaled by lactic acidosis, allows classification of the shock state associated with metabolic poisons such as carbon monoxide that results in histotoxic hypoxia caused by inadequate uptake of oxygen by the mitochondria (see Table 21-4). Other shock states, in particular septic shock, may also involve an inability of tissues to extract delivered oxygen, but the lactic acidosis of sepsis is not necessarily caused by anaerobic metabolism.
Decreased Pump Function—Cardiogenic Shock
Pump function is measured as the output of a pump for a given input. The diagnosis of decreased pump function as the cause of shock is made by finding evidence of inappropriately low output (cardiac output) despite normal or high input (right atrial pressure). Cardiac output is the most important “output” of the heart and is clinically assessed in the same way that perfusion was assessed during the urgent initial examination. Better estimates are later obtained by thermodilution measurement using a pulmonary artery catheter, nuclear medicine scans, and Doppler echocardiographic techniques. Right atrial pressure or CVP is the most easily measured “input” of the whole heart and is initially assessed by examination of jugular veins. After catheter insertion, CVP can be measured accurately. Other outputs, such as stroke work or left ventricular ejection fraction, and other inputs, such as left ventricular end-diastolic pressure (LVEDP) or volume (LVEDV), are useful to determine the specific cause of decreased pump function. Left and right ventricular dysfunction can be caused by decreased systolic contractility, increased diastolic stiffness, greatly increased afterload (including obstruction), valvular dysfunction, or abnormal heart rate and rhythm.
Causes of Left Ventricular Failure
Acute or acute-on-chronic left ventricular failure resulting in shock is the classic example of cardiogenic shock and is identified as a subset of decreased pump function by evidence of a low cardiac output in relation to high left ventricular filling pressures. Clinical findings of low cardiac output and increased left ventricular filling pressures include, in addition to assessment of perfusion, pulmonary crackles in dependent lung regions, a laterally displaced and diffuse precordial apical impulse, elevated jugular veins, and presence of a third heart sound.20 These findings are not always present or unambiguous. Therefore, echocardiography or pulmonary artery catheterization is helpful and often essential in establishing the diagnosis and titrating therapy. Cardiogenic shock then is usually associated with a cardiac index lower than 2.2 L/m2 per minute when the pulmonary artery occlusion pressure has been raised above 18 mm Hg.21
Figure 21-2 illustrates the pathophysiologic abnormalities of cardiogenic shock resulting from decreased left ventricular contractility. The primary abnormality is that the relation of end-systolic pressure to volume is shifted down and to the right (see Fig. 21-2, upper panel) so that, at the same afterload, the ventricle cannot eject as far (decreased contractility). It follows that pump function is also impaired, indicated by a shift down and to the right (see Fig. 21-2, lower panel) so that at similar preloads cardiac output is reduced. Three mechanisms that counter the decrease in cardiac output are illustrated. The diastolic ventricle becomes more compliant, possibly from stress relaxation of the pericardium and myocardium, so that stroke volume increases at the same end-diastolic pressure (rightward shift of the diastolic pressure-volume relation in the upper panel). Afterload decreases, resulting in increased stroke volume (see Fig. 21-2, upper panel). Mean systemic pressure rises (see Fig. 21-2, lower panel), aided by avid fluid retention by the kidneys and by increased venous tone mediated by the sympathetic nervous system. Thus, the Frank-Starling mechanism of increasing cardiac output by increasing diastolic filling is used.
As a result of a decrease in contractility, the patient presents with elevated left and right ventricular filling pressures and a low cardiac output. Mixed venous oxygen saturation may be well below 50% because cardiac output is low. In the presence of physiologic pulmonary shunt that accompanies pulmonary edema, the low saturation of mixed venous blood shunting by the lung contributes to substantial arterial desaturation. Accordingly, arterial desaturation aggravates the low oxygen delivery due to reduced cardiac output, as does intercurrent anemia.
Acute myocardial infarction or ischemia is the most common cause of left ventricular failure leading to shock. The principal effect of myocardial infarction is to depress systolic contractility, which in completely infarcted areas becomes zero or even negative (paradoxical regional wall motion). Earlier series described shock occurring in 10% to 20% of patients with transmural myocardial infarction.22 However, the recent use of fibrinolytic therapy and early angioplasty or surgical revascularization has reduced the incidence of cardiogenic shock to less than 5%.23 Infarction greater than 40% of the myocardium is often associated with cardiogenic shock;24 anterior infarction is 20 times more likely to lead to shock than is inferior or posterior infarction.25 Details of the diagnosis and management of ischemic heart disease are discussed in Chap. 25; other causes of decreased left ventricular contractility in critical illness are discussed in more detail in Chaps. 22 and 23, and each may contribute to shock.
Increased left ventricular diastolic chamber stiffness contributing to cardiogenic shock occurs during myocardial ischemia and in a range of less common disorders including late stages of hypovolemic shock and septic shock (see Table 21-4); all causes of tamponade listed in Table 21-4 need to be considered in a systematic review of causes of diastolic dysfunction.26 Cardiac function is depressed because stroke volume is decreased by decreased end-diastolic volume caused by increased diastolic chamber stiffness. Diastolic dysfunction in a hypotensive patient with low cardiac output and high filling pressures is often identified by a small (rather than large) LVEDV by bedside echocardiography. Conditions resulting in increased diastolic stiffness are particularly detrimental when systolic contractility is decreased because decreased diastolic stiffness (increased compliance; see Fig. 21-2, upper panel) is normally a compensatory mechanism. Increased diastolic chamber stiffness contributing to hypotension in patients with low cardiac output and high ventricular diastolic pressures is best identified echocardiographically by small diastolic volumes.
Treatment of increased diastolic stiffness is approached by first considering the potentially contributing reversible causes. Acute reversible causes include ischemia and the many causes of tamponade physiology listed in Table 21-4. Fluid infusion results in large increases in diastolic pressure without much increase in diastolic volume. Positive inotropic agents and afterload reduction are generally not helpful and may decrease blood pressure further. If conventional therapy of cardiogenic shock aimed at improving systolic function is ineffective, then increased diastolic stiffness should be strongly considered as the cause of decreased pump function. Cardiac output responsiveness to heart rate is another subtle clue suggesting impaired diastolic filling. Heart rate does not normally alter cardiac output (which is normally set by and equal to venous return) except at very low heart rates (maximally filled ventricle before end diastole) or at very high heart rates (incomplete ventricular relaxation and filling). However, if diastolic filling is limited by tamponade or a stiff ventricle, then very little further filling occurs late in diastole. In this case, increasing heart rate from 80 to 100 or 110 beats/min may result in a significant increase in cardiac output, which may be therapeutically beneficial and also a diagnostic clue.
Acute mitral regurgitation, due to cordal or papillary muscle rupture or papillary muscle dysfunction, most commonly is caused by ischemic injury. The characteristic murmur and the presence of large V waves on the pulmonary artery occlusion pressure trace suggest significant mitral regurgitation, which is quantified by Doppler echocardiographic examination. Rupture of the ventricular septum with left-to-right shunt is detected by Doppler echocardiographic examination or by observing a step-up in oxygen saturation of blood from the right atrium to the pulmonary artery.27 Rarely, acute obstruction of the mitral valve by left atrial thrombus or myxoma may also result in cardiogenic shock. These conditions are generally surgical emergencies.
More commonly, valve dysfunction aggravates other primary etiologies of shock. Aortic and mitral regurgitation reduces forward flow and raises LVEDP, and this regurgitation is ameliorated by effective arteriolar dilation and by nitroprusside infusion. Vasodilator therapy can effect large increases in cardiac output without much change in mean blood pressure, pulse pressure, or diastolic pressure, so pulmonary artery catheterization and repeat echocardiography, to confirm increased cardiac output and reduced valvular regurgitation, are essential to titrating effective vasodilator doses. In contrast, occasional patients develop decreased blood pressure and cardiac output on inotropic drugs such as dobutamine; in this case, excluding dynamic ventricular outflow tract obstruction by echocardiography or treating it by increasing preload, afterload, and end-systolic volume are essential.
Not infrequently, arrhythmias aggravate hypoperfusion in other shock states. Ventricular tachyarrhythmias are often associated with cardiogenic shock; sinus tachycardia and atrial tachyarrhythmias are often observed with hypovolemic and septic shock. Specific therapy of tachyarrhythmias depends on the specific diagnosis, as discussed in Chap. 24. Inadequately treated pain and unsuspected drug withdrawal should be included in the intensive care unit differential diagnosis of tachyarrhythmias; whatever their etiology, the reduced ventricular filling time can reduce cardiac output and aggravate shock. Bradyarrhythmias contributing to shock may respond acutely to atropine or isoproterenol infusion and then pacing; hypoxia or myocardial infarction as the cause should be sought and treated. Symptomatic hypoperfusion resulting from bradyarrhythmias, even in the absence of myocardial infarction or high-degree atrioventricular block, is an important indication for temporary pacemaker placement that is sometimes overlooked.
Treatment of Left Ventricular Failure
After initial resuscitation, which includes consideration of early institution of thrombolytic therapy in acute coronary thrombosis and revascularization or surgical correction of other anatomic abnormalities where appropriate,3 management of patients with cardiogenic shock requires repeated testing of the hypothesis of “too little versus too much.” Clinical examination is not accurate enough; when the response to initial treatment of cardiogenic shock is inadequate, a pulmonary artery catheter may be required. Therapy for cardiogenic shock follows from consideration of the pathophysiology illustrated in Fig. 21-2 and includes optimizing filling pressures, increasing contractility by improving the ratio of myocardial oxygen supply to demand, or by using inotropic drugs, and optimizing afterload. Temporary mechanical support using an intraaortic balloon pump is often extremely useful in cardiogenic shock and should be considered early as a support device in patients who may benefit from later surgical therapy.28 Cardiac transplantation and mechanical heart implantation are considered when other therapy fails.
Filling pressures are optimized to improve cardiac output but avoid pulmonary edema. Depending on the initial presentation, cardiogenic shock frequently spans the spectrum of hypovolemia (so fluid infusion helps) to hypervolemia with pulmonary edema (where reduction in intravascular volume results in substantial improvement). If gross fluid overload is not present, then a rapid fluid bolus should be given. In contrast to patients with hypovolemic or septic shock, a smaller bolus (250 mL) of crystalloid solution should be infused as quickly as possible. Immediately after infusion, the patient's circulatory status should be reassessed. If there is improvement but hypoperfusion persists, then further infusion with repeat examination is indicated to attain an adequate cardiac output and oxygen delivery while seeking the lowest filling pressure needed to accomplish this goal. If there is no improvement in oxygen delivery and evidence of worsened pulmonary edema or gas exchange, then the limit of initial fluid resuscitation has been defined. Crystalloid solutions are used particularly if the initial evaluation is uncertain because crystalloid solutions rapidly distribute to the entire extracellular fluid compartment. Therefore, after a brief period only one-fourth to one-third remains in the intravascular compartment, and evidence of intravascular fluid overload rapidly subsides.
Contractility increases if ischemia can be relieved by decreasing myocardial oxygen demand, by improving myocardial oxygen supply by increasing coronary blood flow (coronary vasodilators, thrombolytic therapy, surgical revascularization, or intra-aortic balloon pump counterpulsation), or by increasing the oxygen content of arterial blood. Inotropic drug infusion attempts to correct the physiologic abnormality by increasing contractility (see Fig. 21-2). However, this occurs at the expense of increased myocardial oxygen demand. Afterload is optimized to maintain arterial pressures high enough to perfuse vital organs (including the heart) but low enough to maximize systolic ejection. When systolic function is reduced, vasodilator therapy may improve systolic ejection and increase perfusion, even to the extent that blood pressure rises.29 In patients with very high blood pressure, end-systolic volume increases considerably so that stroke volume and cardiac output decrease unless LVEDV and LVEDP are greatly increased; this sequence is reversed by judicious afterload reduction.
Diagnosis and Management of Right Ventricular Failure
Right ventricular failure as a cause of cardiogenic shock is often identified by elevated right atrial pressure and low cardiac output not explained by left ventricular failure or cardiac tamponade. The most common causes of shock owing to right ventricular failure are right ventricular infarction and pulmonary embolism resulting in greatly increased right ventricular afterload.
Right ventricular infarction is found in approximately half of inferior myocardial infarctions and is complicated by shock only 10% to 20% of the time.30 Isolated right ventricular infarction with shock is uncommon and has a mortality rate ∼50% comparable to left ventricular infarction shock.25 The hemodynamic findings of right ventricular infarction must be distinguished from cardiac tamponade and constrictive pericarditis and include Kussmaul sign, low cardiac output, high filling pressures, and often equalization of right atrial, right ventricular diastolic, pulmonary artery diastolic, and pulmonary artery occlusion pressures. Pulmonary crackles are classically absent. Early recognition of right versus left ventricular infarction as the cause of shock is important, so potentially dangerous therapy, including vasodilators, morphine, and β blockers, are avoided. Therapy includes infusion of dobutamine and volume expansion, although excessive volume can aggravate shock by shifting the intraventricular septum from right to left.31 Because bradyarrhythmias are common and atrioventricular conduction is frequently abnormal, atrioventricular sequential pacing may preserve right ventricular synchrony and often dramatically improves cardiac output and blood pressure in shock caused by right ventricular infarction.31 Afterload reduction using balloon counterpulsation may also be useful,25 as are early fibrinolytic therapy and angioplasty when indicated (see Chap. 25).
Right ventricular ischemia, with or without coronary artery disease, probably is a more important cause of right ventricular dysfunction than generally recognized. In shock states systemic arterial pressure is often low, and right ventricular afterload (pulmonary artery pressure) may be high owing to emboli, hypoxemic pulmonary vasoconstriction, acidemic pulmonary vasoconstriction, sepsis, or ARDS. Therefore, right ventricular perfusion pressure is low leading to right ventricular ischemia and decreased contractility, which, in the face of normal or high right ventricular afterload, results in right ventricular dilation. Subsequent right-to-left shift of the interventricular septum limits left ventricular filling. Cardiac output is then limited by right ventricular systolic ejection and left ventricular diastolic filling.
Therapy of right ventricular failure caused by decreased right ventricular perfusion and increased afterload is evolving. Animal studies suggest that, acutely in right ventricular shock caused by pulmonary embolism, interventions such as norepinephrine infusion may increase systemic arterial pressure more than pulmonary arterial pressure, resulting in improved right ventricular perfusion. Improved right ventricular function and total cardiac function may result. This approach has not been carefully tested in patients in shock owing to right ventricular failure.32 Established approaches include verifying that pulmonary emboli are present and initiating therapy with anticoagulation, fibrinolytic agents for submassive pulmonary embolism or shock, or surgical embolectomy as necessary.33 Hypoxic pulmonary vasoconstriction may be reduced by improving alveolar and mixed venous oxygenation. More aggressive correction of acidemia should be considered in this setting. Pulmonary vasodilator therapy may be useful in some patients if pulmonary artery pressures can be lowered without significantly lowering systemic arterial pressures. Inhaled nitric oxide, prostaglandin E1, and many other agents have been variably successful. Measurements of pulmonary artery pressure, systemic pressure, cardiac output, and oxygen delivery before and after a trial of a specific potential pulmonary vasodilator are essential (see Chap. 26).
Compression of the Heart by Surrounding Structures
Compression of the heart (cardiac tamponade) limits diastolic filling and can result in shock with inadequate cardiac output despite very high right atrial pressures. Diagnosis of cardiac tamponade is made physiologically by using pulmonary artery catheterization to demonstrate a low cardiac output in addition to elevated and approximately equal right atrial, right ventricular diastolic, pulmonary artery diastolic, and pulmonary artery occlusion pressures (particularly their waveforms). The diagnosis is often best confirmed anatomically by using echocardiographic examination to demonstrate pericardial fluid, diastolic collapse of the atria and right ventricle, and right-to-left septal shift during inspiration. Septal shift during inspiration and increased afterload that accompany decreased intrathoracic pressure during inspiration account for the clinically observed pulsus paradoxus. Although pericardial tamponade by accumulation of pericardial fluid is the most common cause of cardiac tamponade, other structures surrounding the heart may also produce tamponade. Tension pneumothorax, massive pleural effusion, pneumopericardium (rarely), and greatly elevated abdominal pressures may also impair diastolic filling.
Decreasing the pressure of the tamponading chamber by needle drainage of the pericardium, pleural space, and peritoneum can rapidly and dramatically improve venous return, blood pressure, and organ system perfusion. Therefore, the goal of therapy is to accomplish this decompression as rapidly and safely as possible. In patients who are hemodynamically stable, fluid infusion is a temporizing therapy that increases mean systemic pressure so that venous return increases even though right atrial pressure is high. In hemodynamically stable patients, if it is safe to take the time needed to get ultrasonic guidance for needle aspiration or surgical drainage, then this should be done. Otherwise, in an emergency, blind needle drainage is necessary.
Decreased Venous Return—Hypovolemic Shock
The pressure driving venous return to the right atrium is described as mean systemic pressure minus right atrial pressure, where the mean systemic pressure is determined by the vascular volume and by the unstressed volume and capacitance of the systemic vessels. Venous return to the heart when right atrial pressure is not elevated may be inadequate owing to decreased intravascular volume (hypovolemic shock), to decreased tone of the venous capacitance bed so that mean systemic pressure is low (e.g., drugs, neurogenic shock), and occasionally to increased resistance to venous return (e.g., obstruction of the inferior vena cava by abdominal compartment syndrome). In the presence of shock, decreased venous return is determined to be a contributor to shock by finding low left and right ventricular diastolic pressures, often in an appropriate clinical setting such as trauma or massive gastrointestinal hemorrhage.
Hypovolemia is the most common cause of shock caused by decreased venous return and is illustrated in Fig. 21-3. Intravascular volume is decreased, so the venous capacitance bed is not filled, leading to a decreased pressure driving venous return back to the heart. This is seen as a left shift of the venous return curve in Fig. 21-3, lower panel, so that cardiac output decreases at a low end-diastolic pressure (intersection of the venous return curve and cardiac function curve). Endogenous catecholamines attempt to compensate by constricting the venous capacitance bed, thereby raising the pressure driving venous return back to the heart, so that 25% reductions in intravascular volume are nearly completely compensated for. Orthostatic decrease in blood pressure by 10 mm Hg or an increase in heart rate of more than 30 beats/min34 may detect this level of intravascular volume reduction. When approximately 40% of the intravascular volume is lost, sympathetic stimulation can no longer maintain mean systemic pressure, resulting in decreased venous return and clinical shock.
After sufficient time (>2 hours) and severity (>40% loss of intravascular volume), patients often cannot be resuscitated from hypovolemic shock.35 This observation highlights the urgency with which patients should be resuscitated. A “no reflow” phenomenon is described in microvascular beds, gut ischemia with systemic release of inflammatory mediators,36 and increased diastolic stiffness (see Fig. 21-3) contribute to the pathophysiology.37
Shock after trauma is a form of hypovolemic shock in which a significant systemic inflammatory response, in addition to intravascular volume depletion, is present. Intravascular volume may be decreased because of loss of blood and significant redistribution of intravascular volume to other compartments, i.e., “third spacing.” Release of inflammatory mediators may result in pathophysiologic abnormalities resembling septic shock. Cardiac dysfunction may be depressed from direct damage from myocardial contusion, from increased diastolic stiffness, from right heart failure, or even from circulating myocardial depressant substances. Shock related to burns similarly is multifactorial with a significant component of intravascular hypovolemia and a systemic inflammatory response (see Chaps. 98, 99, and 100).
Other causes of shock caused by decreased venous return include severe neurologic damage or drug ingestion resulting in hypotension caused by loss of venous tone. As a result of decreased venous tone, mean systemic pressure decreases, thereby reducing the pressure gradient driving blood flow back to the heart so that cardiac output and blood pressure decrease. Obstruction of veins owing to compression, thrombus formation, or tumor invasion increases the resistance to venous return and occasionally may result in shock.
The principal therapy of hypovolemic shock and other forms of shock caused by decreased venous return is rapid initial fluid resuscitation. Warmed crystalloid solutions are readily available. Colloid-containing solutions result in a more sustained increase in intravascular volume. However, in the setting of demonstrated or potential leaking endothelial surfaces (e.g., ARDS), the colloid rapidly redistributes into the entire extravascular water compartment. Pulmonary edema and tissue edema may be aggravated. Overall, no benefit of colloid over crystalloid has been convincingly demonstrated. The role of hypertonic saline and other resuscitation solutions is currently uncertain. Alternatively, transfusion of packed red blood cells increases oxygen-carrying capacity and expands the intravascular volume and is therefore a doubly useful therapy. In an emergency, initial transfusion often begins with type-specific blood before a complete cross-match is available. During initial resuscitation, the Early Goal-Directed Protocol suggests that achieving a hematocrit greater than 30% may be beneficial when ScvO2 is less than 70%. However, after initial resuscitation, maintaining hemoglobin above 90 g/L does not appear to be better than maintaining hemoglobin above 70 g/L. After a large stored red blood cell transfusion, clotting factors, platelets, and serum ionized calcium decrease and therefore should be measured and replaced if necessary (see Chap. 68).
Recognizing inadequate venous return as the primary abnormality of hypovolemic shock alerts the physician to several commonly encountered and potentially lethal complications of therapy. Airway intubation and mechanical ventilation increase negative intrathoracic pressures to positive values and thus raise right atrial pressure. The already low pressure gradient driving venous return to the heart worsens, resulting in marked reduction in cardiac output and blood pressure. However, ventilation treats shock by reducing the work of respiratory muscle, so ventilation should be implemented early with adequate volume expansion. Sedatives and analgesics are often administered at the time of airway intubation, resulting in reduced venous tone because of a direct relaxing effect on the venous capacitance bed or because of a decrease in circulating catecholamines. Thus, the pressure gradient driving venous return decreases. Therefore, in the hypovolemic patient, these medications may markedly reduce cardiac output and blood pressure and should be used with caution and with ongoing volume expansion.
High Cardiac Output Hypotension—Septic Shock
Septic shock is the most common example of shock that may be caused primarily by reduced arterial vascular tone and reactivity, often associated with abnormal distribution of blood flow. Gram-negative bacilli account for half of all cases of sepsis and approximately 50% of these patients develop septic shock.38 In contrast, shock accompanies only 5% to 10% of gram-positive or fungal bloodstream infections,38 although candida infections are emerging as an important cause of attributable mortality.39 Evidence of end-organ hypoperfusion and dysfunction may be present at low, normal, and high cardiac outputs and oxygen deliveries. During evaluation and resuscitation, normal or increased cardiac output with low SVR hypotension is manifested by a high pulse pressure, warm extremities, good nail bed capillary filling, and low diastolic and mean blood pressures. This high cardiac output hypotension is often accompanied by an abnormal temperature and white blood cell count and differential and an evident site of sepsis. However, the diagnosis is sometimes initially unclear when septic shock is combined with cardiogenic or hypovolemic shock, which limit the usual increase in cardiac output, oxygen delivery, and mixed-venous oxygen saturation.
Several pathophysiologic mechanisms contribute to inadequate organ system perfusion in septic shock. There may be abnormal distribution of blood flow at the organ system level, within individual organs, and even at the capillary bed level. The result is inadequate oxygen delivery in some tissue beds.
The cardiovascular abnormalities of septic shock (see Fig. 21-4) are extensive and include systolic and diastolic abnormalities of the heart, abnormal arterial tone, decreased venous tone, and abnormal distribution of capillary flow leading to regions of tissue hypoxia. In addition, there may be a cellular defect in metabolism so that even cells exposed to adequate oxygen delivery may not maintain normal aerobic metabolism. Depressed systolic contractility illustrated as a rightward shift of the end-systolic pressure-volume relation in Fig. 21-4, upper panel, occurs in septic shock40 due to circulating proinflammatory cytokines and other mediators, nitric oxide production by activated endothelial cells and cardiomyocytes, and reactive oxygen intermediate generation by retained leukocytes and other cells.41 Decreased systolic contractility associated with septic shock is reversible over 5 to 10 days as the patient recovers.40 Systolic and diastolic dysfunctions during sepsis that progress to the point that high cardiac output (hyperdynamic circulation) is no longer maintained (normal or low cardiac output is observed) are associated with poor outcome.40
Decreased arterial resistance is almost always observed in septic shock. Early in septic shock, a high cardiac output state exists with normal or low blood pressure. The low arterial resistance is associated with impaired arterial and precapillary autoregulation and may be due to increased endothelial nitric oxide production and opening of potassium adenosine triphosphate channels on vascular smooth muscle cells. Redistribution of blood flow to low-resistance, short time-constant vascular beds (such as skeletal muscle) results in decreased resistance to venous return, as illustrated in Fig. 21-4 (lower panel) by a steeper venous return curve. As a result, cardiac output may be increased even when cardiac function is decreased (see Fig. 21-4, lower panel) because of decreased contractility (see Fig. 21-4, upper panel). Hypovolemia, caused by redistribution of fluid out of the intravascular compartment and to decreased venous tone, impedes venous return during septic shock.
Early institution of appropriate antibiotic therapy and surgical drainage of abscesses or excision of devitalized and infected tissue is central to successful therapy. Activated protein C and low-dose steroids therapy in patients with inadequate adrenal responses to ACTH stimulation improve outcome. Many other anticytokine and anti-inflammatory therapies and inhibition of nitric oxide production have not been successful in improving outcome.
As detailed in Table 21-4, there are many less common etiologies of shock, and the diagnosis and management of several causes of high right atrial pressure hypotension are discussed elsewhere in this book (see Chaps. 22, 26, and 28). A few other types of hypovolemic shock merit early identification by their characteristic features and lack of response to volume resuscitation including neurogenic shock and adrenal insufficiency. Anaphylactic shock results from the effects of histamine and other mediators of anaphylaxis on the heart, circulation, and the peripheral tissues (see Chap. 106). Despite increased circulating catecholamines and the positive inotropic effect of cardiac H2 receptors, histamine may depress systolic contractility via H1 stimulation and other mediators of anaphylaxis. Marked arterial vasodilation results in hypotension even at normal or increased cardiac output. Like septic shock, blood flow is redistributed to short time-constant vascular beds. The endothelium becomes more permeable, so fluid may shift out of the vascular compartment into the extravascular and intracellular compartments, resulting in intravascular hypovolemia. Venous tone and therefore venous return are reduced, so the mainstay of therapy of anaphylactic shock is fluid resuscitation of the intravascular compartment and includes epinephrine and antihistamines as adjunctive therapy.42
Neurogenic shock is uncommon. In general, in a patient with neurologic damage that may be extensive, the cause of shock is usually associated with blood loss. Patients with neurogenic shock develop decreased vascular tone, particularly of the venous capacitance bed, which results in pooling of blood in the periphery. Therapy with fluid will increase mean systemic pressure. Catecholamine infusion also will increase mean systemic pressure, and stimulation of α receptors will increase arterial resistance, but these are rarely needed once circulation volume is repleted.
Several endocrinologic conditions may result in shock. Adrenal insufficiency (Addison disease, adrenal hemorrhage and infarction, Waterhouse-Friderichsen syndrome, adrenal insufficiency of sepsis, and systemic inflammation) or other disorders with inadequate catecholamine response may result in shock or may be important contributors to other forms of shock.17 Whenever inadequate catecholamine response is suspected, diagnosis should be established by measuring serum cortisol and conducting an ACTH stimulation test, whereas presumptive therapy proceeds using dexamethasone (see Chap. 79). Hypothyroidism and hyperthyroidism may in extreme cases result in shock; thyroid storm is an emergency requiring urgent therapy with propylthiouracil or other antithyroid drug, steroids, propranolol, fluid resuscitation, and identification of the precipitating cause43 (see Chap. 80). Pheochromocytoma may lead to shock by markedly increasing afterload and by redistributing intravascular volume into extravascular compartments.44 In general, the therapeutic approach involves treating the underlying metabolic abnormality, resuscitating with fluid to produce an adequate cardiac output at the lowest adequate filling pressure, and infusing inotropic drugs, if necessary, to improve ventricular contractility if it is decreased. Details of diagnosis and therapy of shock associated with poisons (carbon monoxide, cyanide) are discussed in Chap. 102.