Joseph E. Parrillo from Cecil Medicine, 23rd. Goldman L. Saunders Elsevier. 2007
Shock is a very serious medical condition that results from a profound and widespread reduction in effective tissue perfusion leading to cellular dysfunction and organ failure. Unless it is promptly corrected, this circulatory insufficiency will become irreversible. The most common clinical manifestations of shock are hypotension and evidence of inadequate tissue perfusion. A number of diseases can result in shock, and the specific clinical characteristics of these diseases usually accompany the shock syndrome.
To understand the definition of shock, it is important to comprehend the meaning of effective tissue perfusion ( Table 1 ). Certain forms of shock result from a global reduction in systemic perfusion (low cardiac output), whereas other forms produce shock as a result of maldistribution of blood flow or a defect in substrate utilization at the subcellular level. These latter forms of shock have normal or high global flow to tissues, but this perfusion is not effective because of abnormalities at the microvascular or subcellular level.
TABLE 1 -- DETERMINANTS OF EFFECTIVE TISSUE PERFUSION
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Classification
It is valuable to classify different forms of shock according to etiology and cardiovascular physiology ( Fig. 1 and Table 2 ) because such classification results in appropriate patient management. Hypovolemic shock results from blood or fluid loss, or both, and is due to decreased circulating blood volume, which leads to reduced diastolic filling pressure and volume. The result is inadequate cardiac output, hypotension, and shock. Cardiogenic shock is caused by a severe reduction in cardiac function resulting from direct myocardial damage or a mechanical abnormality of the heart; both cardiac output and blood pressure are reduced. Extracardiac obstructive shock results from obstruction to flow in the cardiovascular circuit, and such obstruction leads to inadequate diastolic filling or decreased systolic function because of increased afterload; this form of shock results in inadequate cardiac output and hypotension. The cardiovascular abnormalities associated with distributive shock are more complex than those in the other shock categories. Distributive shock is characterized by vasodilation: venodilation leads to a decrease in preload, which can be corrected with fluid administration, and arterial vasodilation leads to hypotension with normal or elevated cardiac output. Myocardial depression frequently accompanies distributive shock. The most characteristic pattern is decreased vascular resistance, normal or elevated cardiac output, and hypotension. Distributive shock, which results from mediator effects at the microvascular and cellular levels, may produce inadequate blood pressure and multiple organ system dysfunction without a decrease in cardiac output.
FIGURE 1 Classification of shock showing interrelationships among the different forms of shock. CO = cardiac output; MAP = mean arterial pressure; MODS = multiple organ dysfunction syndrome; SVR = systemic vascular resistance. TABLE 2 -- CLASSIFICATION OF SHOCK
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Pathobiology
Adequate, effective tissue perfusion of organs must be maintained for survival. Perfusion is dependent on a number of variables that are carefully regulated by the body's compensatory mechanisms (see Table 1 ).
Control of Arterial Pressure
One excellent physiologic and clinical measure of perfusion is arterial pressure, which is determined by cardiac output and vascular resistance and can be defined by the following equation:
where MAP is mean arterial pressure, CVP is central venous pressure, CO is cardiac output, and SVR is systemic vascular resistance.
MAP and cardiac output can be measured directly, and these two variables are frequently used to describe tissue perfusion. SVR can be calculated as a ratio of MAP minus central venous pressure divided by cardiac output.
Arterial pressure is regulated by changes in cardiac output or SVR, or both. These regulatory mechanisms consist of neural and hormonal reflexes and local factors. Blood flow to the heart and brain is carefully regulated and maintained over a wide range of blood pressure (from an MAP of 50 to 150 mm Hg); this autoregulation results from reflexes in the local vasculature and ensures the perfusion of these especially vital organs. Failure to maintain the minimal arterial pressure required for autoregulation during shock indicates a severe abnormality that may produce inadequate coronary perfusion and a further reduction in cardiac function as a result of myocardial ischemia.
Cardiac Performance
Cardiac output is a product of heart rate and stroke volume. Stroke volume is determined by preload, afterload, contractility, and ventricular size, whereas preload is dependent on adequate venous return.
Vascular Performance
Effective perfusion requires appropriate resistance to blood flow to maintain arterial pressure. Resistance to flow of blood in a vessel is proportional to the length of the vessel and the viscosity of blood and inversely proportional to the radius of the vessel raised to the fourth power. Therefore, the cross-sectional area of a vessel is by far the most important determinant of resistance to flow. In the systemic vasculature, the major (>80%) site of resistance is at the arteriolar sphincter, and regulation of this arteriolar tone constitutes the major determinant of vascular resistance.
Arteriolar smooth muscle tone is regulated by extrinsic and intrinsic factors. The extrinsic factors consist of sympathetic nervous system innervation of arterioles, which are largely regulated by arterial and cardiopulmonary baroreceptors. Circulating epinephrine and norepinephrine are released into the circulation by stimulation of the adrenal medulla. The intrinsic mechanisms include a vascular smooth muscle (myogenic) response in which blood vessels relax or constrict in response to changes in transmural vessel pressure to maintain vessel blood flow at a constant level despite changes in perfusion pressure. Other intrinsic mechanisms are a metabolic response that results from release of vasodilators in response to increased metabolic activity and an oxygen tension response that results in vasodilation with low oxygen tensions. Vasodilators released locally and systemically include nitric oxide, prostacyclin, eicosanoids, kinins, and adenosine. Vasoconstrictor molecules include norepinephrine, epinephrine, endothelin-1, renin, angiotensin II, thromboxane, vasopressin, and oxygen free radicals.
In addition to vascular tone, the microvasculature also affects perfusion by obstruction to microvascular flow. In shock, this obstruction can be caused by adhesion of leukocytes or platelets to the endothelium, with subsequent sludging and occlusion of microvessels. Leukocyte adhesion and rolling are mediated by integrins and selectins on the surface of activated neutrophils and endothelial cells. Activation of the coagulation system with fibrin deposition and microthrombi can contribute to this process. Shunting around these occluded vessels may occur. Decreased red or white blood cell deformability can also aggravate this microvascular dysfunction. Therapeutic success using activated protein C, an anticoagulant, in severe septic shock emphasizes the importance of the coagulation cascade in the pathogenesis of septic shock.
Microvascular permeability to fluids or other substances may also be altered by vasoactive mediators, activated leukocytes, and damaged endothelial cells. Because intravascular and extravascular fluid is determined by a balance between hydrostatic pressure and colloid osmotic pressure, damage to the endothelium may cause increased extravasation of fluid into the interstitial space and result in tissue edema. This fluid accumulation may further worsen organ dysfunction.
Cellular Function
At the cellular level, a number of factors regulate the unloading of oxygen and other substrates to cells. Shock produces cellular dysfunction through three major mechanisms: cellular ischemia, inflammatory mediators, and free radical injury. Cellular ischemia is probably the major cause of cell damage in shock with low cardiac output. In hypovolemic shock, inadequate perfusion and the resultant lack of oxygen lead to increasing dependence on anaerobic glycolysis, which produces only two adenosine triphosphate (ATP) molecules during the breakdown of one glucose molecule as opposed to 36 ATP molecules produced by aerobic metabolism through the citric acid (Krebs) cycle; the result is depletion of ATP and intracellular energy reserves. Intracellular acidosis occurs, and anaerobic glycolysis leads to the accumulation of lactate. Lack of adequate energy results in failure of energy-dependent ion transport pumps and an inability to maintain normal transmembrane gradients of potassium, chloride, and calcium; the result is mitochondrial dysfunction, abnormal carbohydrate metabolism, and failure of many energy-dependent enzyme reactions. Ultrastructural changes in mitochondria ensue, and the cell dies (cellular necrosis). In addition, shock can damage cells and organs by accelerating cellular apoptosis (programmed cell death).
One important, but controversial hypothesis regarding cellular ischemia in shock is the degree of dependence on oxygen supply. In normal humans, oxygen delivery to tissues (CO × O2 content of arterial blood) is maintained at a high level so that tissue oxygen consumption [CO × (O2 content of arterial blood - O2 content of mixed venous blood)] is not altered or dependent on changes in oxygen delivery. However, if systemic flow drops below a critical value of oxygen delivery, tissues must switch from aerobic metabolism to the less efficient anaerobic metabolism. This deficiency of energy production may lead to multiple organ system dysfunction and death. Below this critical value (estimated to be 8 to 10 mL of oxygen/min/kg in anesthetized humans), oxygen consumption is dependent on oxygen delivery (or supply), a relationship termed physiologic oxygen supply dependency. This process is believed to be an important mechanism of cellular damage in forms of shock that are characterized by low oxygen as a result of inadequate cardiac output, low oxygen saturation, or decreased hemoglobin concentration. The controversy regarding this mechanism stems from the hypothesis that a pathologic oxygen supply dependency exists in patients with sepsis, trauma, or adult respiratory distress syndrome (ARDS). These patients have oxygen delivery in the normal or elevated range but manifest lactate production and organ dysfunction. Some animal and human studies suggest the presence of a pathologic oxygen supply dependency because they demonstrate an increase in oxygen consumption with increases in oxygen delivery, even at elevated levels of oxygen delivery. This finding suggests dependency of consumption on delivery over a wide range of delivery values. Proponents argue that inadequate oxygen delivery is occurring in these forms of shock because of microvascular and cellular abnormalities. This hypothesis has led to the argument that management of sepsis, trauma, and ARDS should include methods to maximize cardiac output and oxygen delivery. In general, these studies have been inconclusive, and the hypothesis of pathologic oxygen supply dependency remains controversial.
Inflammatory mediators are a major cause of cell injury in shock caused by sepsis and trauma, and recent evidence strongly supports a significant role for inflammation in other forms of shock ( Fig. 2 ). These mediators may exert their influence on the vasculature to produce inadequate perfusion, or they may cause direct injury to cells in a number of organs. The cytokines, especially tumor necrosis factor (TNF) and interleukin-1 (IL-1), can produce dysfunction of transmembrane ion gradients similar to that described with cellular ischemia. Administration of TNF to animals leads to a cardiovascular state indistinguishable from septic shock. TNF can also stimulate the release of many other mediators, including other cytokines, platelet-activating factor, leukotrienes, prostaglandins, and thromboxane.
The inflammatory response is a physiologic, homeostatic mechanism designed to respond to injury or infection. Release of inflammatory mediators usually provides beneficial effects such as activating host defense systems and enhancing blood flow to damaged tissues. With a self-limited insult, the inflammatory reaction is carefully controlled by counter-regulatory, anti-inflammatory mechanisms. In shock, the inflammatory response becomes excessive and unregulated, and it contributes to cell injury and tissue damage (see Fig. 2 ).
Free radicals are highly reactive oxygen intermediates that can occur after ischemia with subsequent reperfusion. Cellular ischemia and intracellular accumulation of calcium can result in the formation of xanthine oxidase, which can oxidize purines with formation of the highly toxic superoxide radical. These oxygen products can inactivate proteins, damage DNA, induce lipid peroxidation of cell membranes, and lead to cell lysis and tissue injury.
Altered gene expression may also play a role in the cellular dysfunction during shock. For example, generation of cytokines, adhesion proteins, and inducible nitric oxide synthase enzymes represents upregulation of gene expression. The heat shock proteins may be an especially important genetic response in shock. These proteins are involved in the genetic program of cell death known as apoptosis, a physiologic mechanism that normally functions to remove senescent cells. During shock, the induction of heat shock proteins may interfere with cell synthetic pathways and initiate a heightened activation of programmed cell death. Inappropriate initiation of this mechanism may be an important contributor to cell demise in shock. Recent genetic studies in septic shock have documented an association between the presence of the TNF2 allele, a polymorphism promoter of TNF-α, and a very high relative risk for septic shock and high mortality from this disease. This finding demonstrates the potential predictive ability of genetic studies in shock.
Compensatory Mechanisms
With the onset of hemodynamic dysfunction in shock, homeostatic compensatory mechanisms attempt to maintain effective tissue perfusion, and many of the manifestations of shock represent the body's attempt to correct abnormalities. Most compensatory mechanisms are dependent on various sensing mechanisms designed to recognize hemodynamic or metabolic dyshomeostasis. The sensing mechanisms consist of pressure receptors located in the cardiovascular system (right atrium, pulmonary artery, aortic arch, carotid, and splanchnic baroreceptors) and the kidney (juxtaglomerular apparatus), as well as chemoreceptors sensitive to concentrations of carbon dioxide or oxygen and located in the central nervous system (mostly in the medulla).
The compensatory responses in shock maintain mean circulatory pressure, maximize cardiac performance, redistribute perfusion to the most vital organs, and optimize the unloading of oxygen to tissues. These effects are produced by stimulation of the sympathetic nervous system, release of hormones (angiotensin II, vasopressin, epinephrine, and norepinephrine), and creation of a local tissue environment that enhances the unloading of oxygen to tissues due to acidosis, pyrexia, and increased red blood cell 2,3-diphosphoglycerate. The magnitude of these compensatory mechanisms is dependent on the severity of the hemodynamic or metabolic derangements. Compensation is effective at restoring tissue perfusion for a period during shock; however, if the initiating process is not reversed during this period, shock becomes irreversible as a result of widespread cellular damage.
Clinical Manifestations
Multiple Organ Dysfunction Syndrome
The clinical manifestation of shock is variable and depends on the initiating cause and the response of multiple organs ( Table 3 ). Different organs may be affected minimally, mildly, moderately, or severely. This diffuse damage leads to multiple organ dysfunction syndrome (see Fig. 1 ), which is one of the major causes of death in shock.
TABLE 3 -- ORGAN SYSTEM DYSFUNCTION IN SHOCK
| Organ System | Manifestations |
| Central nervous system | Encephalopathy (ischemic or septic) |
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| Cortical necrosis |
| Heart | Tachycardia, bradycardia |
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| Supraventricular tachycardia |
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| Ventricular ectopy |
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| Myocardial ischemia |
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| Myocardial depression |
| Pulmonary | Acute respiratory failure |
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| Adult respiratory distress syndrome |
| Kidney | Prerenal failure |
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| Acute tubular necrosis |
| Gastrointestinal | Ileus |
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| Erosive gastritis |
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| Pancreatitis |
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| Acalculous cholecystitis |
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| Colonic submucosal hemorrhage |
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| Transluminal translocation of bacteria/endotoxin |
| Liver | Ischemic hepatitis |
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| “Shock” liver |
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| Intrahepatic cholestasis |
| Hematologic | Disseminated intravascular coagulation |
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| Dilutional thrombocytopenia |
| Metabolic | Hyperglycemia |
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| Glycogenolysis |
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| Gluconeogenesis |
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| Hypoglycemia (late) |
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| Hypertriglyceridemia |
| Immune system | Gut barrier function depression |
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| Cellular immune system depression |
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| Humoral immune system depression |
Central Nervous System
The most frequent findings in shock are alterations in the level of consciousness ranging from confusion to coma. Autoregulation protects the ischemia-sensitive neurons by maintaining adequate blood flow down to an MAP of approximately 50 to 60 mm Hg. Below this level, however, tissue ischemia ensues. Acid-base and electrolyte abnormalities also contribute to neuronal damage. Sepsis-related central nervous system dysfunction may occur at a higher MAP as a result of the effects of inflammatory mediators.
Heart
Many of the clinically apparent manifestations of cardiac involvement in shock result from sympathoadrenal stimulation, with tachycardia being the most sensitive indicator that shock is present. As in the brain, autoregulation ensures good coronary perfusion down to an MAP of approximately 50 mm Hg. In low cardiac output forms of shock, myocardial ischemia is prominent and leads to a vicious cycle in which ischemia produces a further reduction in cardiac output, which further aggravates the ischemia. This cycle is believed to be important in producing the high mortality (70 to 90%) rate of cardiogenic shock.
Shock produces complex effects on myocardial contractility. Although sympathoadrenal stimulation should lead to increases in contractility as a result of adrenoreceptor stimulation, there is strong evidence for myocardial depression (decreased ejection fraction) and compliance abnormalities, especially in septic and hypovolemic shock. Septic myocardial dysfunction has been linked to cytokine-induced (specifically, TNF and IL-1) depression of myocardial contraction; this cytokine mechanism produces much of its effect via nitric oxide and cyclic guanosine monophosphate. In addition, there is evidence of decreased β-receptor function. Similar depressant mechanisms may also contribute to myocardial dysfunction in hypovolemic and cardiogenic shock.
Lungs
Acute lung injury causes impaired gas exchange, decreased compliance, and shunting of blood through underventilated areas. The pathologic findings are fibrin-neutrophil aggregates within the pulmonary microvasculature, inflammatory damage to the interstitium and alveoli, and exudation of proteinaceous fluid into the alveolar space; the result is severe hypoxemia with bilateral pulmonary infiltrates, a condition termed adult respiratory distress syndrome. The work of breathing is increased, and respiratory muscle fatigue and ventilatory failure ensue, often requiring mechanical ventilation.
Kidney
Acute renal failure is a major complication of shock and is associated with a high mortality rate. Hypoperfusion of the renal vasculature occurs frequently in shock, in part as a result of preferential direction of blood flow to the brain and heart. Initially, vasoconstriction may maintain glomerular perfusion, but when this compensatory mechanism fails, acute tubular necrosis and renal insufficiency occur. An important clinical challenge is to differentiate between acute tubular necrosis and hypovolemia because both are associated with oliguria.
Gastrointestinal Tract and Liver
Typical clinical manifestations of gut involvement during shock include ileus, erosive gastritis, pancreatitis, acalculous cholecystitis, and submucosal hemorrhage. Some studies suggest that gut barrier integrity may be compromised, thereby leading to translocation of bacteria and their toxins into the blood stream.
The most common manifestation of liver involvement in shock is a mild increase in aminotransferases and lactate dehydrogenase. With severe hypoperfusion, shock liver may be manifested by massive aminotransferase elevations and extensive hepatocellular damage. With an acute insult that resolves, these transaminase elevations peak in 1 to 3 days and resolve by 10 days. Decreased levels of clotting factors and albumin may occur as a result of decreased synthetic function. In septic shock, significant elevations of bilirubin may be seen with only modest elevations of aminotransferases because of dysfunction of bile canaliculi caused by inflammatory mediators or bacterial toxins.
Hematologic
Thrombocytopenia may result from dilution during volume repletion or from immunologic platelet destruction, which is especially common during septic shock. Activation of the coagulation cascade can lead to disseminated intravascular coagulation, which results in thrombocytopenia, decreased fibrinogen, elevated fibrin split products, and microangiopathic hemolytic anemia. Reduced blood levels of protein C are found in the majority of patients with sepsis and are associated with an increased risk for death.
Immune System
Widespread dysfunction of the immune system has been described, especially during hypovolemic and traumatic shock. Abnormalities of function in macrophages, T and B lymphocytes, and neutrophils have been described. These abnormalities are not thought to produce immediate effects but may contribute significantly to late mortality, which is frequently due to complicating infection.
Metabolic
Early in shock, hyperglycemia usually occurs as a result of glycogenolysis and gluconeogenesis mediated by increases in adrenocorticotropic hormone, glucocorticoids, glucagon, and catecholamines, as well as decreases in insulin. Hypertriglyceridemia may also occur. A clinical trial in critically ill surgical patients demonstrated reduced morbidity and mortality associated with administration of insulin to lower blood glucose toward a normal range, but a subsequent study in a medical intensive care unit found no benefit. Later in shock, hypoglycemia may occur as a result of glycogen depletion or failure of glucose synthesis in the liver. In addition, protein catabolism ensues and results in negative nitrogen balance; this catabolism may be an important determinant of late mortality in shock, and some studies suggest that nutritional supplementation is important in shock therapy.
Specific Forms of Shock
Inadequate tissue perfusion results from low cardiac output in hypovolemic, cardiogenic, and extracardiac obstructive forms of shock. In distributive shock, although low cardiac output may occur infrequently as a result of inadequate preload or myocardial depression, most commonly, low SVR and maldistribution of blood flow lead to low blood pressure and shock despite normal or increased cardiac output.
Hypovolemic Shock
Hypovolemic shock is characterized by a decrease in ventricular preload that results in decreased ventricular diastolic pressure and volume, decreased stroke volume and cardiac output, and reduced blood pressure. Patients have pale, cool, clammy skin; tachycardia; a decreased jugular venous pulse; decreased urine output; and altered mental status. The severity of hypovolemic shock is clearly associated with both the magnitude and the rate of fluid loss. Acute loss of 10% of circulating blood volume results in tachycardia and increased SVR with maintenance of blood pressure. Compensatory mechanisms begin to fail with a 20 to 25% volume loss: mild to moderate hypotension and decreased cardiac output occur, SVR is markedly increased, and lactate production may begin. With loss of 40% of circulating blood volume, severe hypotension develops with signs of shock, and cardiac output and tissue perfusion are severely decreased. Hypoperfusion activates the inflammatory cascade (see Fig. 2 ), thereby leading to widespread cellular damage. If this shock state persists for more than 2 hours, sufficient tissue damage occurs that adequate fluid repletion is no longer effective in reversing the shock; that is, the shock is irreversible.
If volume is lost at a slower rate, the compensatory mechanisms are more effective, and similar amounts of volume depletion are better tolerated. Furthermore, a patient's underlying disease, especially a limited cardiac reserve, also influences the response to a hypovolemic insult.
Cardiogenic Shock
Cardiogenic shock is caused by failure of the heart as a pump as a result of myocardial, valvular, or structural abnormalities. Hemodynamically, ventricular filling pressure and volume are increased; cardiac output, stroke volume, and MAP are reduced. Patients manifest signs of peripheral hypoperfusion coupled with evidence of ventricular failure. Recent evidence supports a role for activation of the inflammatory cascade during cardiogenic shock (see Fig. 2 ).
Extracardiac Obstructive Shock
This form of shock results from obstruction to flow in the cardiovascular circuit. Pericardial tamponade and constrictive pericarditis impair diastolic filling of the right ventricle. Massive pulmonary emboli may lead to shock as a result of a severe increase in right ventricular afterload. The hemodynamic pattern is similar to that of other low-output shock states with decreased cardiac output, stroke volume, and MAP. Other hemodynamic variables depend on the site of the obstruction. With pericardial tamponade, increased and equalized right and left ventricular diastolic pressure usually develops. Constrictive pericarditis may produce a similar pattern. Acute pulmonary embolism results in right heart failure with elevated pulmonary artery and right heart pressure and low or normal left heart filling pressure.
The tempo of the disease process influences the clinical manifestations. With pericardial tamponade secondary to myocardial rupture after myocardial infarction, for example, immediate tamponade and shock can occur within minutes with as little as 150 mL of blood in the pericardium. Survival requires immediate drainage and surgery. In patients with malignant or inflammatory causes of pericardial tamponade, fluid accumulates more slowly, and 1 or 2 L of fluid may be necessary to produce shock.
Distributive Shock
The major feature of distributive shock is decreased peripheral resistance. Although anaphylaxis, drug overdose, neurogenic insults, and addisonian crisis can produce this form of shock, the most important and prevalent cause is septic shock. In this form of shock, tissue hypoperfusion results from either microvascular abnormalities (maldistribution or shunting of blood flow) or a mediator-induced metabolic block that prevents cells from adequately using oxygen and other nutrients delivered through the vasculature.
Early in distributive shock, venodilation and leakage of fluid from the microvasculature lead to inadequate intravascular volume and reduced preload. Volume resuscitation corrects this preload abnormality and produces the usual hemodynamic pattern of distributive shock: normal or elevated cardiac output, normal stroke volume, tachycardia, decreased SVR, and decreased MAP. Left and right heart filling pressures are variable and depend on the amount of fluid resuscitation.
In addition, most patients with distributive shock also manifest myocardial depression, which is characterized by a decreased stroke work response to volume loading, biventricular reduction in the ejection fraction, and ventricular dilation. The dilation allows patients to compensate for a depressed ejection fraction and maintain stroke volume, which combined with a high heart rate leads to elevated cardiac output. In approximately 10 to 15% of septic shock patients, the myocardial dysfunction is dominant and severe and results in a hypodynamic low-cardiac output form of shock (see Fig. 1 ).
Clinical Approach to Shock
Shock is a life-threatening emergency. Diagnosis, evaluation, and management most often occur simultaneously, and speed in evaluation is important to achieve a good outcome. The clinical approach must balance two important goals: (1) the need to initiate therapy before shock causes irreversible damage to organs and (2) the need to perform a diagnostic evaluation to determine the cause of the shock ( Fig. 3 ). A reasonable approach is to make a rapid clinical evaluation initially based on a directed history and physical examination and to perform diagnostic tests aimed at determining the cause. In severe shock, initiation of therapy should be based on the initial clinical impression. Certain symptoms and signs are common to all forms of shock. Most patients have hypotension, tachycardia, cool extremities, oliguria, and a clouded sensorium. In general, an MAP less than 60 mm Hg in an adult is considered hypotension. However, blood pressure must be evaluated in terms of previous chronic blood pressure readings. A patient with chronic hypertension may experience shock pathophysiology at higher blood pressure values. A decrease of 50 mm Hg or more from chronic elevated levels is frequently sufficient to produce tissue hypoperfusion. Conversely, in some patients with chronically low blood pressure, shock may not develop until the MAP drops to less than 50 mm Hg.
FIGURE 3 An approach to the diagnosis and treatment of shock. BUN = blood urea nitrogen; CT = computed tomography; ECG = electrocardiogram; LV = left ventricular; MAP = mean arterial pressure; MRI = magnetic resonance imaging; PA = pulmonary artery; PCWP = pulmonary capillary wedge pressure; PT = prothrombin time; PTT = partial thromboplastin time; RV = right ventricular; WBC = white blood cell.
Other clinical manifestations may be useful in differentiating the cause of the shock. Patients with hypovolemic shock frequently manifest evidence of gastrointestinal hemorrhage, bleeding from another site, or vomiting or diarrhea. Patients with cardiogenic shock may have manifestations of heart disease with prior angina or myocardial infarction and often have elevated filling pressure, cardiac gallops, or pulmonary edema. Cardiac murmurs may suggest mechanical causes of cardiogenic shock. Elevated jugular venous pressure and a quiet precordium suggest pericardial tamponade. A site of infection with prominent fever should raise the possibility of septic shock.
Even though the brief history and physical examination are directed at potential causes and signs of shock, blood should be drawn to evaluate hemoglobin, platelets, coagulation, oxygenation and ventilation, electrolytes, kidney function, and blood lactate levels. An electrocardiogram and chest radiograph should be taken.
Simultaneously, venous access with one or two large-bore catheters should be established, and central venous and arterial catheters should be inserted (see Fig. 3 ). Electrocardiographic monitoring and continuous pulse oximetry are usually valuable. If MAP is less than 60 mm Hg or evidence of tissue hypoperfusion is present, an intravenous fluid challenge with 500 to 1000 mL of crystalloid or colloid should be given rapidly (if hemorrhage is likely, blood should be the volume replacement). If the patient remains hypotensive, vasopressors such as dopamine or norepinephrine (or both) should be administered to restore adequate blood pressure while the diagnostic evaluation continues. The shock patient should be admitted to an intensive care unit.
If the diagnosis remains undefined or the hemodynamic status requires repeated fluid challenges or vasopressors, a flow-directed pulmonary artery catheter should be placed to determine cardiac output and ventricular filling pressure ( Table 4 ), and echocardiography should be performed. Echocardiography is valuable in identifying the presence of pericardial fluid, tamponade physiology, ventricular function, valvular heart disease, and intracardiac shunts. Based on these data, patients can usually be classified and managed according to the specific form of shock.
TABLE 4 -- DIAGNOSIS OF SHOCK ETIOLOGY VIA PULMONARY ARTERY CATHETERIZATION
| | | Pulmonary Capillary | | |
| Diagnosis | Wedge Pressure | Cardiac Output | Miscellaneous Comments | |
| CARDIOGENIC SHOCK | ||||
| Cardiogenic shock caused by myocardial dysfunction | ↑↑ | ↓↓ | Usually occurs with evidence of extensive myocardial infarction (40% of the | |
| Cardiogenic shock caused by a mechanical defect | ||||
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| Acute ventricular septal defect | ↑ | LVCO ↓↓ and RVCO > LVCO | Predominant shunt is left to right, pulmonary blood flow is greater than systemic blood flow: oxygen “step-up” occurs at the RV level |
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| Acute mitral regurgitation | ↑↑ | Forward CO ↓↓ | V waves in pulmonary capillary wedge pressure tracing |
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| Right ventricular infarction | | ↓↓ | Elevated RA and RV filling pressure with low or normal pulmonary capillary wedge pressure |
| EXTRACARDIAC OBSTRUCTIVE FORMS OF SHOCK | ||||
| Pericardial tamponade | ↑ | ↓ or ↓↓ | Mean RA, end-diastolic RV, and mean pulmonary capillary wedge pressures are elevated and within 5 mm Hg of one another | |
| Massive pulmonary embolism | | ↓ ↓ | Usual finding is elevated right-sided pressure | |
| HYPOVOLEMIC SHOCK | ||||
| DISTRIBUTIVE FORMS OF SHOCK | ||||
| Septic shock | ↓ or normal | ↑ or normal, rarely ↓ |
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| Anaphylactic shock | ↓ or normal | ↑ or normal |
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Adapted from Parrillo JE, Ayres SM (eds): Major Issues in Critical Care Medicine. Baltimore, Williams & Wilkins, 1984.
| CO = cardiac output; |
TREATMENT
In all forms of shock, restoration of blood pressure and tissue perfusion is a critical goal and commonly requires fluids, vasopressors, inotropic agents ( Table 5 ), mechanical ventilation, and repeated monitoring.
TABLE 5 -- RELATIVE POTENCY OF VASOPRESSORS AND INOTROPIC AGENTS IN SHOCK
| | | Cardiac | Peripheral Vascular[*] | |||
| Agent | Dose | Heart Rate | Contractility | Vasoconstriction | Vasodilatation | Dopaminergic |
| Dopamine | 1–4 μg/kg/min | 1+ | 1+ | 0 | 1+ | 4+ |
|
| 4–20 μg/kg/min | 2+ | 2–3+ | 2–3+ | 0 | 2+ |
| Norepinephrine | 2–20 μg/min | 1+ | 2+ | 4+ | 0 | 0 |
| Dobutamine | 2.5–15 μg/kg/min | 1–2+ | 3–4+ | 0 | 2+ | 0 |
| Isoproterenol | 1–5 μg/min | 4+ | 4+ | 0 | 4+ | 0 |
| Epinephrine | 1–20 μg/min | 4+ | 4+ | 4+ | 3+ | 0 |
| Phenylephrine | 20–200 μg/min | 0 | 0 | 3+ | 0 | 0 |
| Milrinone | 37.5–75 μg/kg via bolus; then 0.375–0.75 μg/kg/min | 1+ | 3+ | 0 | 2+ | 0 |
| Vasopressin | 0.1–0.4 U/min | 0 | 0 | 4+ | 0 | 0 |
Adapted from Parrillo JE, Ayres SM (eds): Major Issues in Critical Care Medicine. Baltimore, Williams & Wilkins, 1984.
| * | The 1 to 4+ scoring system is an arbitrary system to allow a judgment of comparative potency among these vasopressor agents. |
Hypovolemic Shock
The major goal is to infuse adequate volume to restore perfusion before the onset of irreversible tissue damage without raising cardiac filling pressure to a level that produces hydrostatic pulmonary edema, which usually begins at a pulmonary artery occlusion (capillary wedge) pressure greater than 18 mm Hg. In hemorrhagic shock, restoration of oxygen delivery is achieved by transfusion of packed red blood cells with the goal of maintaining the hemoglobin concentration at greater than 10 g/dL. Restoration of intravascular volume must be accompanied by aggressive evaluation to identify a bleeding source and treatment to prevent further bleeding.
In other forms of hypovolemic shock, crystalloid solutions such as normal saline or Ringer's lactate are equivalent to albumin for restoring volume depletion.[2] Because colloids such as albumin and hetastarch are more expensive, crystalloids should be favored unless the serum albumin concentration is low and specific albumin repletion is required. Hypertonic saline, which can provide volume repletion with small volumes of fluid, may be therapeutically useful in burns and head trauma, in which case limitation of free water is often important.
Cardiogenic Shock
In hypotensive patients with cardiogenic shock, pulmonary capillary wedge pressure should be maintained at 14 to 18 mm Hg, and medications should be given in an attempt to restore MAP to greater than 60 mm Hg and the cardiac index (cardiac output divided by body surface area in meters squared) to more than 2.2 L/min/m2. Appropriate patients benefit from an intra-aortic balloon pump or from surgical correction of valvular abnormalities or septal defects. In patients with acute myocardial infarction and cardiogenic shock as a result of myocardial damage, emergency coronary revascularization has been shown to be superior to medical therapy.[3]
Extracardiac Obstructive Shock
In pericardial tamponade, blood pressure can be maintained with fluids and vasopressors in a fashion similar to the method used for cardiogenic shock. However, these measures are only temporizing, and one should move quickly to drain pericardial fluid by needle pericardiocentesis or surgery.
In patients with severe pulmonary embolism producing right ventricular failure and shock, thrombolytic therapy should be considered in addition to conventional anticoagulation with heparin and warfarin. If thrombolysis is contraindicated, emergency surgical pulmonary embolectomy can sometimes produce a successful outcome.
Distributive Shock
For septic shock, principles of management include eliminating the nidus of infection with surgical drainage and antimicrobial therapy, early restoration of blood pressure with fluids and vasopressor agents, and maintenance of adequate tissue perfusion with fluids, inotropic agents, and other supportive measures. Aggressive therapy with fluids, blood transfusions, and inotropic agents in the emergency department significantly lowers the mortality of patients with severe sepsis and septic shock.[4] In patients with a high risk of death, activated protein C therapy also improves survival.[1] Arginine vasopressin appears to be useful in catecholamine-resistant vasodilatory shock.[5]
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