Trauma, 7th Ed.

CHAPTER 12. Management of Shock

Louis H. Alarcon, Juan Carlos Puyana, and Andrew B. Peitzman

Shock is defined as the inadequate delivery of oxygen to tissues leading to cellular dysfunction and injury. In 1872 Gross described shock as a “rude unhinging of the machinery of life.”1 Although this definition is less than precise, to this day it illustrates the physiologic derangements of decompensated shock. Significant hypoperfusion and cellular injury may occur despite normal systemic blood pressure, so equating shock with hypotension and cardiovascular collapse is a vast oversimplification and results in delayed recognition of early shock, when intervention may be most effective at preventing end-organ dysfunction.

Shock is most precisely defined as inadequate delivery of oxygen and nutrients necessary for normal tissue and cellular function. The initial cellular injury that occurs is reversible. However, this injury will become irreversible if tissue hypoperfusion is prolonged or severe enough such that, at the cellular level, compensation is no longer possible. Rapid recognition of the patient in shock and the prompt institution of steps to correct shock is a critical skill for the trauma surgeon. Surgeons caring for injured patients must initiate active treatment empirically, prior to a definitive diagnosis of the cause of shock.

The management of the patient in shock has been an integral component of the surgeon’s realm of expertise for centuries. Bernard suggested that an organism attempts to maintain constancy in the internal environment despite external forces that attempt to disrupt the milieu intérieur.2 In the intact animal, the failure of physiologic systems to buffer the organism against these external forces results in the shock state. Cannon described the “fight or flight response” generated by elevated levels of catecholamines in the bloodstream and introduced the term homeostasis in 1926. He spent 2 years on the battlefields of Europe and published his classic monograph, Traumatic Shock, in 1923. Cannon’s observations led him to propose that shock was due to a disturbance of the nervous system that resulted in vasodilatation and hypotension. He proposed that secondary shock with its attendant capillary permeability leak was caused by a “toxic factor” released from the tissue.3,4 Interestingly, Cannon is also credited with first proposing deliberate hypotension in patients with penetrating wounds of the torso to minimize internal bleeding since “if the pressure is raised before the surgeon is ready to check the bleeding that may take place, blood that is sorely needed may be lost.”5

Blalock documented that shock after hemorrhage was associated with reduced cardiac output and that hemorrhagic shock was due to volume loss, not a “toxic factor.”6 He also noted, however, that toxins could be important initiators of shock. In 1934, Blalock proposed the following four categories of shock that are still utilized today: hypovolemic, vasogenic, cardiogenic, and neurogenic (Table 12-1). Hypovolemic shock, the most common type, results from loss of circulating blood or its components. Thus, loss of circulating volume may be due to decreased whole blood (hemorrhagic shock), plasma, interstitial fluid, or a combination thereof. Vasogenic shock as seen in sepsis results from decreased resistance to blood flow within capacitance vessels of the circulatory system causing an effective decrease in circulating volume. Neurogenic shock is a form of vasogenic shock in which spinal cord injury (or spinal anesthesia) causes vasodilatation. Cardiogenic shock results from failure of the pump function as may occur with arrhythmias or acute heart failure. Two additional categories of shock have been added to those originally proposed by Blalock. Obstructive shock occurs when circulatory flow is mechanically impeded as with pulmonary embolism or a tension pneumothorax. Laboratory experiments and clinical experience have also confirmed the appropriateness of Cannon’s proposal of traumatic shock as a unique entity. Injuries to soft tissue and fractures of long bones that occur in association with multisystem trauma can produce an upregulation of proinflammatory mediators that can create a state of shock that is more complex than simple hemorrhagic shock.

TABLE 12-1 Forms of Shock


In addition to seminal observations on the clinical syndrome of shock on the battlefield, the early and mid-20th century witnessed important laboratory contributions to our understanding of shock. In 1947, Wiggers developed a model of graded hemorrhagic shock based on the uptake of shed blood into a reservoir to maintain a prescribed level of hypotension.7 Shires and coworkers performed a series of classical laboratory studies in the 1960s and 1970s that demonstrated that a large extracellular fluid (ECF) deficit occurred in severe hemorrhagic shock that was greater than could be attributed to vascular refilling alone.8 A triple isotope technique in dogs revealed that this ECF deficit persisted when shed blood or shed blood plus plasma was used in resuscitation. Only the infusion of both shed blood and lactated Ringer’s solution (an ECF mimic) repleted the red blood cell mass, plasma volume, and ECF.9Mortality after hemorrhage dramatically illustrated the importance of this observation: resuscitation with blood alone (80%), blood plus plasma (70%), and blood plus lactated Ringer’s solution (30%). The existence of this ECF deficit was subsequently confirmed in patients. Additional studies by this group demonstrated significant dysfunction of the cellular membrane in prolonged hemorrhagic shock.10 Depolarization of the cell membrane resulted in an uptake of water and sodium by the cell and loss of potassium in association with the loss of membrane integrity.10 The depolarization of the cell membrane was proportional to the degree and duration of hypotension. Studies in red blood cells, hepatocytes, and skeletal muscle suggested that an abnormality in membrane active transport (Na-K-ATPase pump) was the basis of the cellular membrane dysfunction.10 In addition, the uptake of fluid by the intracellular compartment was a major site of fluid sequestration following prolonged hemorrhagic shock. These changes were reversible with appropriate resuscitation. Thus, the importance of fluid resuscitation of severe hemorrhagic shock with isotonic saline or lactated Ringer’s solution in addition to red blood cells was confirmed. These studies also emphasized the important cellular effects from what had previously appeared to be a global circulatory phenomenon.

With advances in our understanding of the pathophysiology and treatment of shock, new clinical problems soon became apparent. The Vietnam War provided a clinical laboratory for the rapidly expanding field of shock research. Aggressive fluid resuscitation with red blood cells, plasma, and crystalloid solutions allowed patients who previously would have succumbed to hemorrhagic shock to survive. Renal failure became a less frequent clinical problem, but fulminant pulmonary failure appeared as an early cause of death after severe hemorrhage. Initially labeled “shock lung” or “DaNang lung,” the clinical problem soon became recognized as the acute respiratory distress syndrome (ARDS). Flooding of the lung with large volumes of crystalloid solution was initially proposed as the primary mechanism of ARDS. Currently, ARDS is seen as a component of the multiple organ dysfunction syndrome (MODS), a result of the complex upregulation of proinflammatory mediators and mechanisms of the homeostatic response. The concept of MODS will be discussed in a subsequent chapter (see Chapter 61).

Several decades of research utilizing modified Wiggers’ models of hemorrhagic shock emphasized the importance of early control of hemorrhage in conjunction with restoration of intravascular volume with red blood cells and crystalloid solutions. Studies over the past decade have extended the observations initially made by Cannon in 1918 on the futility of vigorously resuscitating patients with ongoing bleeding and have challenged traditional thinking on the appropriate end points of resuscitation from uncontrolled hemorrhage.11 The concepts of delayed fluid resuscitation and hypotensive resuscitation are still being debated, fueled by the clinical study by Bickell et al. of patients with penetrating torso trauma.12 Several essential concepts in the management of shock in the trauma patient, however, have withstood the test of time: (a) early definitive control of the airway must be achieved; (b) delays in control of active hemorrhage increase mortality; (c) poorly corrected hypoperfusion increases morbidity and mortality, that is, inadequate resuscitation results in avoidable early deaths; and (d) excessive fluid resuscitation exacerbates problems, that is, uncontrolled resuscitation is harmful.


Image Pathophysiology of Shock

Shock exists when the delivery of oxygen and metabolic substrates to tissues and cells is insufficient to maintain normal aerobic metabolism. This concept implies an imbalance between substrate delivery (supply) and substrate requirements (demand) at the cellular level. Tissue hypoperfusion is associated with cardiovascular and neuroendocrine responses designed to compensate for and reverse inadequate tissue perfusion. The pathophysiologic sequelae of shock may be due to either the direct effects of inadequate tissue perfusion on cellular and tissue function or the body’s adaptive responses producing undesirable consequences. The magnitude of the shock insult and, therefore, the magnitude of the response varies depending on the depth and duration of shock.13,14 The consequences of shock may also vary from minimal physiologic disturbance with complete recovery at one end of the spectrum to profound circulatory disturbance, end-organ dysfunction, and death at the other (Fig. 12-1). The accumulating evidence suggests that, while the quantitative nature of the host response to shock may differ between the various etiologies of shock, the qualitative nature of the body’s response to shock is similar regardless of the cause of the insult. This response consists, in part, of profound changes in cardiovascular, neuroendocrine, and immunologic function. Furthermore, the pathophysiologic responses vary with time and in response to resuscitation. For example, in hemorrhagic shock, the initial compensation for blood loss occurs primarily through the neuroendocrine responses to maintain hemodynamics. This represents the compensated phase of shock. With ongoing hypoperfusion, cellular death and injury are ongoing and the decompensated phase of shock ensues. Microcirculatory dysfunction, cellular injury, and activation of inflammatory cells can perpetuate the hypoperfusion and exacerbate tissue injury. The ischemia/reperfusion injury will often further exacerbate the initial insult. Persistent hypoperfusion results in further hemodynamic derangements and cardiovascular collapse, which has been termed the irreversible phase of shock. At this point, extensive parenchymal and microvascular injury has occurred, such that further volume resuscitation fails to reverse the process, leading to death of the patient.


FIGURE 12-1 A rodent model of hemorrhagic shock depicting the relation between volume loss, duration of shock, and transition from reversible to fatal, irreversible shock. (Reproduced with permission from Peitzman AB, Harbrecht BG, Udekwu AO, et al. Hemorrhagic shock. Curr Probl Surg. 1995;32:974, © Elsevier.)


Afferent impulses transmitted from the periphery are processed within the central nervous system (CNS) and activate the reflexive effector responses or efferent impulses designed to expand plasma volume, maintain peripheral perfusion and tissue oxygen delivery, and reestablish homeostasis. The afferent impulses that initiate the body’s intrinsic adaptive responses converge in the CNS and originate from a variety of sources. The initial inciting event is often loss of circulating blood volume; other stimuli that can produce the neuroendocrine response include tissue trauma, pain, hypoxemia, hypercarbia, acidosis, infection, change in temperature, emotional arousal, or hypoglycemia. The sensation of pain from injured tissue is transmitted via the spinothalamic tracts and activates the hypothalamic–pituitary–adrenal axis.15 The sensation of pain can also activate the autonomic nervous system (ANS) and increase direct sympathetic stimulation of the adrenal medulla to release catecholamines.

Baroreceptors represent an important afferent pathway in initiating adaptive or corrective responses to shock. Volume receptors are present within the atria of the heart and are sensitive to changes in both chamber pressure and wall stretch.15 They become activated with low-volume hemorrhage or mild reductions in right atrial pressure. Receptors in the aortic arch and carotid bodies respond to alterations in pressure or stretch of the arterial wall and respond to greater reductions in intravascular volume or changes in pressure. These receptors normally inhibit activation of the ANS. When these baroreceptors are activated, their output is diminished. Thus, there is increased ANS output principally via sympathetic activation at the vasomotor centers of the brainstem, and this produces centrally mediated constriction of peripheral vessels.

Chemoreceptors in the aorta and carotid bodies are sensitive to changes in oxygen tension, H+ ion concentration, and CO2 level.16 These receptors also provide afferent stimulation when the circulatory system is disturbed and activate effector response mechanisms. In addition, a variety of protein and nonprotein mediators produced at the site of injury and inflammation act as afferent impulses and induce a host response to shock and trauma. Some of these compounds are components of the host immunologic response to shock and include histamine, cytokines, eicosanoids, endothelins, and others that will be discussed in greater detail both in this chapter and in subsequent chapters.


Image Cardiovascular Response

The neuroendocrine and ANS responses to shock result in changes in cardiovascular physiology, which constitute a prominent feature in the body’s adaptive response and the clinical presentation of the patient in shock. Stimulation of sympathetic fibers innervating the heart leads to activation of β1-adrenergic receptors that increase heart rate and contractility in an attempt to increase cardiac output.16 Increased myocardial oxygen consumption occurs as a result of the increased workload. Myocardial oxygen supply must be maintained or myocardial ischemia and dysfunction will develop.

Direct sympathetic stimulation of the peripheral circulation via the activation of α1-adrenergic receptors on arterioles increases vasoconstriction and causes a compensatory increase in systemic vascular resistance and blood pressure. Selective perfusion of tissues due to regional variations in arteriolar resistance from these compensatory mechanisms occurs in shock. Blood is shunted away from organs such as the intestine, kidney, and skin that are less essential to the body’s immediate need to correct and respond to shock.17 Organs such as the brain and heart have autoregulatory mechanisms that attempt to preserve their blood flow despite a global decrease in cardiac output. Direct sympathetic stimulation also induces constriction of venous vessels, decreasing the capacitance of the circulatory system, and accelerating blood return to the central circulation.

Increased sympathetic output increases catecholamine release from the adrenal medulla. Catecholamine levels increase and peak within 24–48 hours of injury before returning to baseline.16 Most of the epinephrine that circulates systemically is produced by the adrenal medulla, while norepinephrine is derived from synapses of the sympathetic nervous system.17 Catecholamines also have profound effects on peripheral tissues in ways that support the organism’s ability to respond to shock and hypovolemia. They stimulate hepatic glycogenolysis and gluconeogenesis to increase the availability of circulating glucose to peripheral tissues, increase glycogenolysis in skeletal muscle, suppress the release of insulin, and increase the release of glucagon.15 These responses increase the availability of glucose to the tissues that require it for maintenance of essential metabolic activity.

Image Neuroendocrine Response

As discussed earlier, a variety of afferent stimuli lead to activation of the hypothalamic–pituitary–adrenal axis that functions as an integral component of the adaptive response of the host following shock. Shock stimulates the hypothalamus to release corticotrophin-releasing hormone, which results in the release of adrenocorticotropin hormone (ACTH) by the pituitary. ACTH subsequently stimulates the adrenal cortex to release cortisol. Cortisol acts synergistically with epinephrine and glucagon to induce a catabolic state.16 It stimulates gluconeogenesis and insulin resistance, resulting in hyperglycemia. It also induces protein breakdown in muscle cells and lipolysis, which provide substrates for hepatic gluconeogenesis. Cortisol causes retention of sodium and water by the kidney that aids in restoration of circulating volume. In the setting of severe hypovolemia, ACTH secretion occurs independently of negative feedback inhibition by cortisol. Absence of appropriate cortisol secretion during critical illness or after injury has been postulated as a contributor to ongoing circulatory instability in critically ill patients.1820

The pituitary also releases vasopressin or antidiuretic hormone (ADH) in response to hypovolemia, changes in circulating blood volume sensed by baroreceptors and stretch receptors in the left atrium, and increased plasma osmolality detected by hypothalamic osmoreceptors.15 Epinephrine, angiotensin II, pain, and hyperglycemia enhance the production of ADH. ADH levels remain elevated for about 1 week after the initial insult, depending on the severity and persistence of the hemodynamic abnormalities. ADH acts on the distal tubule and collecting duct of the nephron to increase water permeability, decrease losses of water and sodium, and preserve intravascular volume. Also known as arginine vasopressin, ADH acts as a potent mesenteric vasoconstrictor, shunting circulating blood away from the splanchnic organs during hypovolemia.21 The intense mesenteric vasoconstriction produced by vasopressin may contribute to intestinal ischemia and predispose to dysfunction of the intestinal mucosal barrier in shock states. Vasopressin also regulates hepatocellular function by increasing hepatic gluconeogenesis and hepatic glycolysis.

The renin–angiotensin system is activated in shock, as well. Decreased perfusion of the renal artery, β-adrenergic stimulation, and increased sodium concentration in the renal tubules cause the release of renin from the juxtaglomerular cells.16 Renin catalyzes the conversion of angiotensinogen (produced by the liver) to angiotensin I, which is then converted to angiotensin II by angiotensin-converting enzyme (ACE) produced in the lung. While angiotensin I has no significant functional activity, angiotensin II is a potent vasoconstrictor of both splanchnic and peripheral vascular beds and also stimulates the secretion of aldosterone, ACTH, and ADH. Aldosterone, a mineralocorticoid, acts on the nephron to promote reabsorption of sodium and, as a consequence, water in exchange for potassium and hydrogen ions that are lost in the urine.

Image Immunologic and Inflammatory Response

The inflammatory and immune responses are a complex set of interactions between circulating soluble factors and cells that can arise in response to trauma, infection, ischemia, toxic, or autoimmune stimuli.22The function of the host’s immune system after shock is intimately related to alterations in the production of mediators generally considered part of the body’s response to localized inflammation and infection. When these mediators gain access to the systemic circulation, they induce changes in a number of tissues and organs. Therefore, activation of proinflammatory pathways is an integral component of the host response to shock. While proinflammatory activation is a central feature of septic shock, proinflammatory cytokine production and mediator release also occurs in other forms of shock such as hypovolemic shock.2325 As initially proposed by Cannon in the early part of the 20th century, inflammatory mediators can be a cause of shock as well as a by-product of the body’s response to shock. Most mediators have a variety of effects due to the redundant and overlapping nature of the host response to injury. Therefore, in addition to regulating immune function in the host, many of these mediators have effects on the cardiovascular system, cellular metabolism, and cellular gene expression. It deserves to be mentioned, however, that many compounds already discussed that have substantial effects on the cardiovascular or neuroendocrine response to shock, such as catecholamines, can also have effects on immune function and the activation of proinflammatory cytokines.26 Cytokines are small polypeptides and glycoproteins that exert most of their actions in a paracrine fashion and are responsible for fever, leukocytosis, tachycardia, tachypnea, and the upregulation of other cytokines. Their levels are elevated in hemorrhagic, septic, and traumatic shock.22 The overexpression of certain cytokines is associated with the metabolic and hemodynamic derangements often seen in septic shock or decompensated hypovolemic shock, and cytokine production after shock correlates with the development of the MODS.23–25,27 The immune response to injury and infection is discussed in greater detail in Chapter 61. A brief review of several of the key components of the immune response is provided below.

Tumor necrosis factor-α (TNF-α) is one of the earliest proinflammatory cytokines released by monocytes, macrophages, and T cells in response to injurious stimuli.28 The classic model of TNF-α production is the injection of bacterial endotoxin in an animal or human subject. Under these controlled conditions, TNF-α levels peak within 90 minutes of the insult and return to baseline within 4 hours. Endotoxin stimulates TNF-α release and may be a primary inducer of cytokines, as in the case of septic shock. TNF-α release may also be a secondary event following the release of bacteria from the intestinal lumen that may occur after hemorrhage and ischemia.29,30 Also, TNF-α levels are increased after hemorrhagic shock,31 and TNF-α levels correlate with mortality in animal models of hemorrhage.32 In humans, TNF-α, interleukin-6 (IL-6), and IL-8 levels increase during hemorrhagic shock, although the magnitude of the increase is less than that seen in septic patients.33 Once released, TNF-α can cause peripheral vasodilation, activate the release of other cytokines such as IL-1β and IL-6, induce procoagulant activity, and stimulate a wide array of cellular metabolic changes.28 TNF-α has also been associated with mechanisms of host defense against infection by promoting activation of macrophages and intracellular killing of pathogens.34 During the stress response, TNF-α contributes to breakdown of muscle protein and cachexia, as well.28 Despite being linked to tissue injury and dysfunction, TNF-α may be essential in combating bacterial infection since neutralizing TNF-α in infection models using live bacteria (peritonitis, pneumonia) increases mortality.3537

IL-1β has actions that are similar to TNF-α and can cause hemodynamic instability and vasodilation.28 It has a very short half-life (6 minutes) and primarily acts locally in a paracrine fashion. IL-1β produces a febrile response by activating prostaglandins in the posterior hypothalamus and causes anorexia by activating the satiety center. This cytokine also augments the secretion of ACTH, glucocorticoids, and β-endorphins.28 In conjunction with TNF-α, IL-1β can induce the release of other cytokines such as IL-2, IL-4, IL-6, IL-8, granulocyte/macrophage colony-stimulating factor (GM-CSF), and interferon-γ (IFN-γ). IL-2 expression is important for the cell-mediated immune response, and its attenuated expression has been associated with transient immunosuppression of injured patients. IL-6 has consistently been shown to be elevated in animals subjected to hemorrhagic shock or trauma and in patients with major surgery or trauma. And elevated IL-6 levels correlate with mortality in some forms of shock.38 IL-6 contributes to neutrophil-mediated injury to the lung after hemorrhagic shock39 and may play a role in the development of diffuse alveolar damage and ARDS. IL-6 and IL-1β are mediators of the hepatic acute phase response to injury and enhance the expression and/or activity of complement, C-reactive protein, fibrinogen, haptoglobin, amyloid A, and α1-antitrypsin. Activation of neutrophils is promoted by IL-6, IL-8, and GM-CSF, and IL-8 also serves as a potent chemoattractant to neutrophils.

The complement cascade is activated by injury and shock and contributes to proinflammatory activation in both animal models and human patients. Complement consumption can occur after hemorrhagic shock and may contribute to the hypotension and metabolic acidosis observed following resuscitation.40 The degree of complement activation is proportional to the magnitude of the traumatic injury and may serve as a marker for severity of injury in trauma patients.41 Patients in septic shock also demonstrate activation of the complement pathway with elevation of the activated complement proteins C3a and C5a.42 Activation of the complement cascade can contribute to the development of organ dysfunction.43,44 The development of ARDS and MODS in trauma patients correlates with the intensity of complement activation.23,25

Activation of neutrophil is one of the early changes induced by the inflammatory response, and neutrophils are the first cells to be recruited to sites of injury and inflammation. These cells are important in the clearance of infectious agents, foreign substances that have penetrated host barrier defenses, and nonviable tissue. On the other hand, activated neutrophils and their products may also produce cell injury and organ dysfunction. Activated neutrophils generate and release a number of substances such as reactive oxygen species, lipid peroxidation compounds, proteolytic enzymes (elastase, cathepsin G), and vasoactive mediators (leukotrienes, eicosanoids, and platelet-activating factor [PAF]). Oxygen radicals such as superoxide anion, hydrogen peroxide, and the hydroxyl radical are potent inflammatory molecules that activate peroxidation of lipids, inactivate cellular enzymes, and consume cellular antioxidants (such as glutathione and tocopherol). Intestinal ischemia and reperfusion cause activation of neutrophils and induce neutrophil-mediated organ injury in experimental animal models.45 In animal models of hemorrhagic shock, activation of neutrophils correlates with irreversibility of shock and mortality,46 and neutrophil depletion prevents the pathophysiologic sequelae of hemorrhagic and septic shock.47,48 Human data corroborate the activation of neutrophils in trauma and shock and suggest that neutrophil activation may play a role in the development of MODS after injury.49 Plasma markers of neutrophil activation such as elastase may correspond to phagocytic activity or correlate with severity of injury.24 In this context, elastase and other markers of neutrophil activation may predict the development of ARDS and MODS after shock.

Interactions between endothelial cells and leukocytes are important in host defense and the initiation and perpetuation of the inflammatory response in the host. The vascular endothelium regulates blood flow, adherence of leukocytes, and activation of the coagulation cascade. Adhesion molecules such as intercellular adhesion molecules (ICAMs), vascular cell adhesion molecules (VCAMs), and the selectins (E-selectin, P-selectin) are expressed on the surface of endothelial cells and are responsible for the adhesion of leukocytes to the endothelium. The interaction of surface proteins on leukocytes and vascular endothelial cells allows activated neutrophils to marginate into the tissues in order to engulf invading organisms. Unfortunately, the migration of activated neutrophils into tissues can also lead to neutrophil-mediated cytotoxicity, microvascular damage, and tissue injury.50 This tissue damage may contribute to organ dysfunction after shock.

Image Cellular Effects

Depending on the magnitude of the insult and the intrinsic compensatory mechanisms present in different cells, the response at the cellular level may be one of adaptation, dysfunction and injury, or death. The aerobic respiration of the cell, that is, oxidative phosphorylation by mitochondria, is the pathway most susceptible to inadequate oxygen delivery. As oxygen tension within cells decreases, oxidative phosphorylation decrease and the generation of adenosine triphosphate (ATP) slows or stops. The loss of ATP, the cellular “energy currency,” has widespread effects on cellular function, physiology, and morphology.51 As oxidative phosphorylation slows, the cells shift to anaerobic glycolysis that generates ATP from the rapid breakdown of cellular glycogen.52 However, anaerobic glycolysis is much less efficient than oxygen-dependent mitochondrial pathways. Under aerobic conditions, pyruvate, the end product of glycolysis, is fed into the Krebs cycle for further oxidative metabolism. Under hypoxic conditions, the mitochondrial pathways of oxidative catabolism are impaired and pyruvate is instead converted to lactate. The accumulation of lactic acid and inorganic phosphates is accompanied by a reduction in pH resulting in intracellular metabolic acidosis. As cells become hypoxic and ATP depleted, other ATP-dependent cell processes are affected: synthesis of enzymes and structural proteins, repair of deoxyribonucleic acid (DNA) damage, and intracellular signal transduction. Tissue hypoperfusion also results in decreased availability of metabolic substrates and the accumulation of metabolic by-products such as oxygen radicals and organic ions that may be toxic to cells.

The consequences of intracellular acidosis on cell function can be quite profound. Decreased intracellular pH can alter the activity of cellular enzymes, lead to changes in cellular gene expression, impair cellular metabolic pathways, and interfere with ion exchange in the cell membrane.5355 Acidosis can also lead to changes in cellular calcium (Ca2+) metabolism and Ca2+-mediated cellular signaling that can, by itself, interfere with the activity of specific enzymes and alter cell function.53,56 These changes in normal cell function can produce cellular injury or cell death.57 Changes in both cardiovascular function and immune function in the host can be induced by acidosis,58,59although translating these in vitro effects to the physiologic sequelae of shock produced in the intact organism may be difficult.

As cellular ATP is depleted under hypoxic conditions, the activity of the membrane Na+, K+-ATPase slows and thus the regulation of cellular membrane potential and volume is impaired.10 Na+ accumulates intracellularly while K+leaks into the extracellular space. The net gain of intracellular sodium is accompanied by an increase in intracellular water and the development of cellular swelling. This cellular influx of water is associated with a corresponding reduction in ECF volume.60 Swelling of the endoplasmic reticulum is the first ultrastructural change seen in hypoxic cell injury. Eventually, swelling of the mitochondria and cells is observed. The changes in cellular membrane potential impair a number of cellular physiologic processes such as myocyte contractility, cell signaling, and the regulation of intracellular Ca2+ concentrations. Once intracellular organelles such as lysosomes or cell membranes rupture, the cell will undergo death by necrosis.61

Hypoperfusion and hypoxia can induce cell death by apoptosis, as well. Animal models of shock and ischemia/reperfusion have demonstrated apoptotic cell death in lymphocytes, intestinal epithelial cells, and hepatocytes.62Apoptosis has also been detected in trauma patients with ischemia and reperfusion injury. Apoptosis of lymphocytes and intestinal epithelial cells occurs within the first 3 hours of injury.63Apoptosis in intestinal mucosal cells may compromise barrier function of the intestine and lead to translocation of bacteria and endotoxin into the portal circulation during shock. Also, lymphocyte apoptosis has been hypothesized to contribute to the immune suppression that is observed in trauma patients.

Tissue hypoperfusion and cellular hypoxia result not only in intracellular acidosis but also in systemic metabolic acidosis as metabolic by-products of anaerobic glycolysis exit the cells and gain access to the circulation. In the setting of acidosis, oxygen delivery to the tissues is altered as the oxyhemoglobin dissociation curve is shifted toward the right.15 The decreased affinity of hemoglobin for oxygen in erythrocytes results in increased tissue O2 release and increased tissue extraction of oxygen. In addition, hypoxia stimulates the production of erythrocyte 2,3-diphosphoglycerate (2,3-DPG), which also contributes to the shift to the right of the oxyhemoglobin dissociation curve and increases O2 availability to the tissues during shock.

Epinephrine and norepinephrine released after shock have a profound impact on cellular metabolism in addition to their effects on vascular tone. Hepatic glycogenolysis, gluconeogenesis, ketogenesis, breakdown of skeletal muscle protein, and lipolysis of adipose tissue are all increased by these catecholamines.21 Cortisol, glucagon, and ADH also participate in the regulation of catabolism during shock. Epinephrine induces the release of glucagon while inhibiting the release of insulin by pancreatic β-cells. The result is a catabolic state with glucose mobilization, hyperglycemia, protein breakdown, negative nitrogen balance, lipolysis, and insulin resistance during shock and injury.21,60 The relative underutilization of glucose by peripheral tissues preserves it for the glucose-dependent organs such as the heart and brain. In addition to inducing changes in cellular metabolic pathways, shock also induces changes in cellular gene expression. The DNA-binding activity of a number of nuclear transcription factors is altered by the production of oxygen radicals, nitrogen radicals, or hypoxia that occurs at the cellular level in shock.64 The expression of other gene products including heat shock proteins,65 vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), and cytokines is also increased in shock.6668 Many of these shock-induced gene products, such as cytokines, have the ability to subsequently alter gene expression in specific target cells and tissues.28 These pathways will be discussed in greater detail elsewhere but they emphasize the complex, integrated, and overlapping nature of the response to shock.

Shock induces profound changes in tissue microcirculation that may contribute to organ dysfunction, and the systemic sequelae of severe hypoperfusion. These changes have been studied most extensively in the microcirculation of skeletal muscle in models of sepsis and hemorrhage. Whether microcirculatory changes are primarily a result of the development of shock or a pathophysiologic response that promotes tissue injury and organ dysfunction has been difficult to determine. Intuitively, it would seem that both are likely to be true. After hemorrhage, larger arterioles vasoconstrict, most likely due to sympathetic stimulation, while smaller distal arterioles dilate, presumably due to local mechanisms.69 Flow at the capillary level, however, is heterogeneous with swelling of endothelial cells and the aggregation of leukocytes producing diminished capillary perfusion in some vessels both during shock and following resuscitation.70,71 Hemorrhage-induced microcirculatory dysfunction also occurs in vascular beds besides skeletal muscle and may contribute to tissue injury and organ dysfunction.72,73 In sepsis, similar changes in microcirculatory function occur. Regional differences in blood flow can be demonstrated after proinflammatory stimuli, and the microcirculation in many organs is heterogeneous.7478 Aggregation and sludging of neutrophils in the microcirculation can aggravate shock-induced hypoperfusion, induce direct cellular injury via toxic neutrophil-dependent processes such as production of oxygen radicals or release of proteolytic enzymes, and impair cellular metabolism.79

The decreases in microcirculatory blood flow and capillary perfusion result in decreased capillary hydrostatic pressure. The changes in hydrostatic pressure promote an influx of fluid from the extravascular or extracellular space into the capillaries in an attempt to increase circulating volume. These changes are associated, however, with additional decrements in the volume of ECF due to increased cellular swelling. These basic cellular and microcirculatory changes have significant physiologic importance in the ability of the organism to recover from circulatory shock. Resuscitation with volumes of fluid sufficient to restore the ECF deficit is associated with improved outcome after shock as described earlier.9

Image Quantifying Cellular Hypoperfusion

Hypoperfused tissues and cells experience what has been called oxygen debt, a concept first proposed by Crowell.80 The oxygen debt is the deficit in tissue oxygenation over time that occurs during shock. When oxygen delivery (DO2) is limited, oxygen consumption (VO2) may be inadequate to match the metabolic needs of cellular respiration creating a deficit in oxygen at the cellular level. The measurement of oxygen deficit is calculated by taking the difference between the estimated oxygen demand and the actual value obtained for oxygen consumption (VO2). Under normal circumstances, cells can “repay” the oxygen debt during reperfusion. The magnitude of the oxygen debt correlates with the severity and duration of hypoperfusion. In a canine model of hemorrhagic shock, Crowell and Smith demonstrated a direct relation between survival and degree of shock.81 They determined that a marker of mortality was the inability to repay the oxygen debt. The median lethal dose (LD50) occurred at 120 mL/kg of oxygen debt. Dunham et al. showed via regression analysis that the probability of death could be directly correlated to the calculated oxygen debt in a canine model of hemorrhagic shock.82 Their study demonstrated that the LD50 for oxygen debt was similar (113.5 mL/kg) to that found by Crowell in their earlier studies. Dunham et al. were also able to confirm a relation between the rate of accumulation of the oxygen debt and survival. In human patients a relation between oxygen debt and survival has also been shown. In over 250 high-risk surgical patients, the calculated oxygen debt correlated directly with organ failure and mortality.83 The maximum oxygen debt in nonsurvivors (33.2 L/m2) was greater than that of survivors with organ failure (21.6 L/m2) and survivors without organ failure (9.2 L/m2). In addition, the total duration of oxygen debt and the time required to repay it correlated with outcome in this study. Survivors were able to repay the oxygen debt while the hallmark of nonsurvivors was the inability to repay the oxygen debt. Thus, the magnitude of the oxygen debt, its rate of accumulation, and the time required to correct it may all correlate with survival.

It is difficult to directly measure the oxygen debt in the resuscitation of trauma patients. The easily obtainable parameters of arterial blood pressure, heart rate, urine output, central venous pressure, and pulmonary artery occlusion pressure are poor indicators of the adequacy of tissue perfusion. Therefore, surrogate parameters have been sought to estimate the oxygen debt. Experimental animal studies show that serum lactate and base deficit (BD) correlate with oxygen debt.82 Cardiac output, blood pressure, and shed blood volume were all inferior to the BD and lactate in estimating the oxygen debt and in predicting mortality in hemorrhaged animals.82 Dunham et al. showed a direct correlation between arterial lactate and probability of survival in a model of canine hemorrhage (Fig. 12-2).82 The LD50 for lactate was 12.9 mmol/L in hemorrhaged dogs.


FIGURE 12-2 The relation between mortality and serum lactate levels is described by data generated in a canine hemorrhagic shock model. (Reproduced with permission from Dunham CM, Siegel JH, Weireter L, et al. Oxygen debt and metabolic acidemia or quantitative predictors of mortality and the severity of the ischemic insult in hemorrhagic shock. Crit Care Med. 1991;19:231.)

BD is the amount of base in millimoles that is required to titrate 1 L of whole blood to a pH of 7.40 with the blood fully saturated with O2 at 37°C (98.6°F) and a PaCO2 of 40 mm Hg. It is usually measured by arterial blood gas analysis using automated devices and has a rapid turnaround time. Good correlation between the BD and survival has been shown in patients with shock.84 At a BD of 0 mmol/L there was an 8% mortality, while there was a 95% mortality at a BD of 26 mmol/L. The LD50 occurred at a BD of 11.8 mmol/L (Fig. 12-3).84 Other clinical parameters such as blood pressure, heart rate, hemoglobin, plasma lactate, and oxygen transport variables were not nearly as accurate as the BD in determining the probability of death in these trauma patients. Neither BD nor serum lactate, however, is as precise at measuring physiologic stress as the oxygen debt. When compared in a model of hemorrhage and resuscitation, the lactate level decreased more slowly and tended to estimate higher residual oxygen debt while the BD decreased more rapidly and tended to estimate lower values of oxygen debt.81 However, the BD appeared to reflect the measured oxygen debt more accurately. As will be discussed more fully later in the chapter (see Section “End Points in Resuscitation of the Trauma Patient”), both lactate and BD are useful in the assessment of trauma patients and in the evaluation of the patient’s response to resuscitation.


FIGURE 12-3 The relation between base deficit (negative base excess) and mortality is depicted for patients who suffered blunt hepatic injury. (Reproduced with permission from Siegel JH, Rivkind AI, Dalal S, et al. Early physiologic predictors of injury severity and death in blunt multiple trauma. Arch Surg. 1990;125:498, Copyright © 1990 American Medical Association. All rights reserved.)


Image General Overview

Shock represents a condition of abnormal tissue perfusion. The manifestations of shock may be dramatic, as in the patient with profound hypotension or obvious external sources of blood loss, or findings may be subtle. As with other trauma-induced injuries, the evaluation, diagnosis, and treatment of the trauma patient in shock begin with the ABCs of the primary survey.85 Advanced shock may produce coma with loss of the ability to maintain and protect the airway, so that endotracheal intubation is necessary. Marked tachypnea may be present as the respiratory system attempts to compensate for metabolic acidosis or in response to generalized anxiety from hypoperfusion of the CNS. In the primary survey, the circulation can be rapidly assessed by evaluation of the presence and location of the pulse (central vs. peripheral), its rate, and its character. Absent peripheral pulses (radial, pedal) associated with weak, rapid central pulses (femoral, carotid) denote a profound circulatory disturbance that requires prompt intervention. Associated findings that may be manifestations of abnormal tissue perfusion include cool clammy skin, altered sensorium (confusion, lethargy, coma), and tachycardia. Low urine output, often used as an indicator of hypovolemia, is unlikely to be a useful tool in the initial assessment of the patient in shock in the trauma resuscitation area. Measurement of blood pressure may be misleading. Compensatory mechanisms to maintain cerebral and coronary perfusion may maintain relatively normal systemic arterial pressure despite hypovolemia and significant underperfusion of splanchnic and peripheral tissues. Up to 30% of the blood volume may be lost before significant changes in blood pressure occur.85 When present, however, hypotension represents a profound circulatory derangement and the failure of compensatory mechanisms and requires immediate attention.

The correction of shock should begin immediately once it is recognized. Treatment generally begins before an etiology for shock is identified. The forms of shock are listed in Table 12-1, but the most common etiology for shock in the trauma patient is hypovolemia from loss of circulating volume (see algorithm, Fig. 12-4). Two large-bore intravenous lines (at least 14- or 16-gauge peripheral or number 7.5–8.5 French resuscitation lines) should be inserted and volume resuscitation instituted. The availability of rapid infusion systems in many trauma centers facilitates rapid volume expansion with the delivery rate limited predominantly by the size and length of the intravenous cannula. Warmers to heat the infusate are essential to prevent hypothermia. For patients in profound shock, immediate blood replacement may be necessary. As soon as possible, fresh frozen plasma (FFP) and platelets should be infused as well, to prevent worsening of the patient’s coagulopathy. As correction of the shock state is underway, the etiology for shock is rapidly sought. Physical examination may indicate potential etiologies (i.e., obvious external hemorrhage, flaccid extremities from spinal cord injury, or penetrating precordial wounds). Rapidly performed radiologic examinations (x-rays of chest and pelvis, diagnostic ultrasound) can provide additional information while the initial resuscitation is being conducted and the response to resuscitation is evaluated. Diagnostic maneuvers that do not directly contribute to the identification and treatment of shock should be deferred until shock has been corrected. Trauma patients can be categorized into three general groups with respect to their response to resuscitative maneuvers (see treatment algorithm, Fig. 12-5). Responders are those patients who rapidly correct their shock state with minimal replacement of intravascular volume. These patients often have an intravascular volume loss that is not ongoing, bleeding that has stopped or been tamponaded (multiple extremity fractures), or an etiology for hypoperfusion other than hypovolemia such as neurogenic shock or obstructive shock. Transient responders represent patients who initially improve with resuscitative efforts, but subsequently deteriorate. This group of patients frequently has intracavitary bleeding that requires surgical control. Nonresponders represent those patients who have persistent manifestations of shock despite vigorous resuscitative efforts. These patients are gravely ill and often present in extremis. These patients typically have high-volume bleeding from injuries to major vessels or severe injuries to solid organs that require immediate operative control. They will rapidly expire from circulatory collapse or develop the progressive spiral of hypothermia, coagulopathy, and irreversible shock unless bleeding is rapidly controlled. Patients who have active, ongoing hemorrhage cannot be successfully resuscitated until hemorrhage has been controlled, and rapid identification of patients who require operative intervention is essential.


FIGURE 12-4 Tissue hypoperfusion algorithm. The most common etiology for shock in the trauma patient is hypovolemia from loss of circulating volume.


FIGURE 12-5 Tissue hypoperfusion algorithm. Trauma patients can be categorized into three general groups with respect to their response to resuscitative maneuvers.

Vascular Access for Patients with Severe Hemorrhage

In the trauma patient presenting with multiple serious injuries and hemorrhagic shock, vascular access is necessary to restore circulatory volume rapidly. The most important factor in considering the procedure and route for vascular access is the anatomical location and magnitude of hemorrhagic injuries and the individual physician’s level of skill and expertise.

Venous access must never be initiated in an injured limb. In patients with injuries below the diaphragm, at least one IV line should be placed in a tributary of the superior vena cava, as there may be vascular disruption of the inferior vena cava. In patients with severe multiple trauma in whom occult thoracoabdominal damage is suspected, it is recommended to have one IV access site above the diaphragm and one below the diaphragm, thus accessing both the superior vena cava and inferior vena cava, respectively. For rapid administration of large amounts of intravenous fluids, short large-bore catheters should be used. Doubling the internal diameter of the venous cannula increases the flow through the catheter 16-fold. When using 8.5 French pulmonary catheter introducers, the side port should be removed, as this increases the resistance roughly 4-fold.

ATLS™ guidelines recommend rapid placement of two large-bore (16-gauge or larger) IV catheters in the patient with serious injuries and hemorrhagic shock.85 The first choice for IV insertion should be a peripheral extremity vein. The most suitable veins are at the wrist, the dorsum of the hand, the antecubital fossa in the arm, and the saphenous in the leg. These sites can be followed by the external jugular and femoral vein. The complication rate of properly placed intravenous catheters is low. Intravascular placement of a large-bore IV should be verified by checking for backflow. An IV site should infuse easily without added pressure. Intravenous fluids can leak into soft tissues when pumped under pressure through an infiltrated IV line, and may create a compartment syndrome. Patient in extremis who lose pulses in the trauma bay need a cut down in the femoral vein.

Subclavian and internal jugular (IJ) catheterization should not be used routinely in hypovolemic trauma patients. The incidence of complications is higher and the rate of success is low due to vascular venous collapse. Rapid peripheral percutaneous IV access may be difficult to achieve in patients with hypovolemia and venous collapse, edema, obesity, scar tissue, history of IV drug abuse, or burns. Under such circumstances, central access with wide-bore catheters may be attempted by percutaneous femoral puncture or cutdown. Subclavian catheterization provides rapid and safe venous access in experienced hands. The most frequent complication of subclavian venipuncture is pneumothorax. Pneumothorax is more likely to occur on the left side because the left pleural dome is anatomically higher. Subclavian and IJ catheters should be inserted on the side of injury in patients with chest wounds, reducing the chances of collapse of the uninjured lung. A simple pneumothorax may result in respiratory compromise in individuals with pulmonary contusions or a pneumothorax in the contralateral hemithorax. It is extremely rare that a subclavian catheterization may be used as a first line of resuscitation in the trauma bay. Regardless of the site of insertion, it is extremely important not to force the wire or the introducer if resistance is encountered. Forcing the introducer could result in perforation of large veins or arteries and bleeding. Venous air embolism is another complication of central line insertion.

Any lines placed during resuscitation of a trauma patient without strict aseptic technique should be removed as soon as the patient’s condition allows for it. Although percutaneous placement of IJ catheters is an excellent means of attaining rapid large-bore catheter access, this is a rather unusual site for intravenous insertion in trauma patients because of the possibility of cervical trauma and the need for cervical collar immobilization. Femoral vein cannulation is another alternative for line placement and is associated with fewer acute complications. Penetration of the hip could result in septic arthritis. Thrombophlebitis occurs more often with femoral than with IJ or subclavian catheters; however, this is most likely with prolonged use.

Venous cutdowns can be performed when rapid, secure, large-bore venous cannulation is desirable, such as in hemodynamic shock and in situations where percutaneous peripheral or central access is either contraindicated or impossible to achieve. Strict aseptic technique should be used. Surgical masks and caps should be worn. Venous cutdown has a low potential for anatomical damage. Cutaneous nerve injury is the most common problem. The infection rate is relatively low when used acutely but increases over time. Therefore, it is recommended that venous cutdown catheters be removed as soon as it is possible to achieve IV access through standard percutaneous IV catheters or a central venous catheter.

Resuscitation Fluids

The type of fluid used for resuscitation is as important as the volume infused. Despite the fact that lactated Ringers continue to be used in most civilian trauma centers, there is an increasing experience being accrued with the use of 6% hetastarch in a balanced salt solution (Hextend) as a fluid of choice for combat casualties. This conduct resulted from the tactical need to provide effective intravascular volume repletion with smaller volumes of fluids. Unfortunately there are little data available at this time to ascertain whether or not clinical outcomes with Hextend are superior when compared to what has been recommended traditionally by the ATLS. There are recent studies indicating that other fluids may have a greater positive impact as first line for resuscitation therapy. These include the use of FFP and lyophilized frozen plasma. A large animal model comparing Hextend to FFP and treatment with an equal ratio of FFP to PRBC showed that Hextend-treated animals displayed a greater coagulopathy, yet it could be rapidly reversed with the administration of blood components. In this study, infusion of FFP, even without any red blood cells, corrected the coagulopathy and resulted in high early survival.86 It is likely that we will see newer and more sophisticated choices available for fluid therapy in shock. A promising alternative is the introduction of lyophilized plasma (LP). In a recent large animal model, the use of LP was found to be safe and effective as FFP for resuscitation after severe trauma.87 LP was analyzed for factor levels and clotting activity before lyophilization and after reconstitution. Animals were subjected to a clinically comparable injury complex including multiple trauma characterized by extremity fracture, hemorrhage, severe liver injury, acidosis, and hypothermia. The authors reported that submitting FFP to lyophilization decreased clotting factor activity by an average of 14%. However, animals treated with LP had similar coagulation profiles, plasma lactate levels, and postinjury blood loss compared with those treated with FFP.

Finally, it is now clear that the role of hypertonic saline as a first-line resuscitative fluid can no longer be recommended. The Resuscitation Outcomes Consortium (ROC) trials for both shock and traumatic brain injury were halted after preliminary data showed no beneficial effect of hypertonic saline for either one of the groups studied in the clinical trials. In both the shock and traumatic brain injury ROC hypertonic saline trials, patients were randomly selected to receive approximately 250 mL of intravenous normal saline, 250 mL of hypertonic saline, or 250 mL of hypertonic saline with dextran thought to prolong the effect of the hypertonic saline. The trauma shock study tested whether hypertonic solutions improve survival by 28 days after injury. Both the hypotensive shock study and the traumatic brain injury study were halted.

Hypotensive Resuscitation

Traditionally, the management of patients in shock has been focused on providing aggressive fluid resuscitation with crystalloid or colloid solutions to rapidly restore circulating blood volume and thus maintaining vital organ perfusion. This approach can potentially increase bleeding by elevating the blood pressure and dislodging established blood clots.88 Other unwanted effects of aggressive fluid resuscitation include worsening coagulopathy and increased tissue edema, which may play a role in the occurrence of abdominal compartment syndrome and multiple organ failure (MOF). Hypotensive resuscitation is not a new concept; in 1918, Cannon et al. described the deleterious effects of injecting fluids before the surgeon could achieve vascular control of the injury.5 Cannon suggested an end point of resuscitation prior to definitive hemorrhage control of a systolic pressure of 70–80 mm Hg, using a crystalloid/colloid mixture as his fluid of choice. In World War II, Cannon’s recommendations were followed by Beecher89 who developed Cannon’s hypotensive resuscitation principals specifically for the care of combat casualties with truncal injuries. This approach was primarily an attempt to minimize transfusion volume and blood loss in the operating room. Bickell et al. in 1994 published a classic prospective analysis comparing immediate and delayed fluid resuscitation in hypotensive adult trauma patients with penetrating torso injuries in the city of Houston.12 In the delayed group, fluid administration was withheld until the time of operative intervention. Improved survival was seen in this study population, with a trend toward fewer complications. These data corroborated the concept that delaying fluid resuscitation until hemorrhage is controlled improves outcome in a selected group of penetrating trauma patients. In subsequent publications following Bickell’s original paper, other investigators have shown that increased prehospital time associated with attempts to place an intravascular access as well as the prehospital use of rapid infusion was correlated with increased mortality.9092 More importantly, the findings reported by Dutton in 2002 were not significantly different when patients were randomized to either a blood pressure of 70 mm Hg or systolic blood pressures of 100 mm Hg.90 This study showed once more that blood pressure is a poor end point of resuscitation in injured patients. Management protocols currently instituted by the military recommend the use of radial pulse and the presence of a normal mental status as the most appropriate indicators of adequate perfusion. Combat casualties found at the scene with a palpable radial pulse and normal mentation are given intravenous access but no intravenous fluids are infused until arriving to a far-forward facility where initial surgical management can be instituted. Preservation of native hemostatic mechanisms is best achieved by allowing for a lower than normal blood pressure and therefore reducing the rate of bleeding. The characteristics of the local environment, the type of injury, and whether fast and adequate hemostasis can be promptly achieved are the current determinants for the use of hypotensive resuscitation during prehospital care.


Image Hypovolemic Shock

Hypovolemic shock occurs when rapid loss of fluids results in inadequate circulating volume and subsequent inadequate perfusion. As previously noted, the most common cause of shock in the trauma patient is loss of circulating volume from hemorrhage. Acute blood loss causes decreased stimulation of baroreceptors (stretch receptors) in the large arteries resulting in decreased inhibition of vasoconstrictor centers in the brainstem, increased stimulation of chemoreceptors in vasomotor centers, and diminished output from atrial stretch receptors. These changes increase vasoconstriction and peripheral arterial resistance. Hypovolemia also induces sympathetic stimulation leading to the release of epinephrine and norepinephrine, activation of the renin–angiotensin cascade, and increased release of vasopressin. Peripheral vasoconstriction is prominent while lack of sympathetic effects on cerebral and coronary vessels and local autoregulation promote maintenance of blood flow to the heart and brain.15


Shock in a trauma patient should be presumed to be due to hemorrhage until proven otherwise. Treatment is instituted as soon as shock is identified, typically before a source of hemorrhage is located.

The clinical and physiologic response to hemorrhage has been classified according to the magnitude of volume loss.85 Loss of up to 15% of the circulating volume (700–750 mL for a 70-kg patient) may produce little in terms of obvious symptoms, while loss of up to 30% of the circulating volume (1.5 L) may result in mild tachycardia, tachypnea, and anxiety. Hypotension, marked tachycardia (pulse >110–120 beats/min), and confusion may not be evident until more than 30% of the blood volume has been lost, while loss of 40% of circulating volume (2 L) is immediately life-threatening. Thus, there is a fine line between the development of mild symptoms of shock and the presence of life-threatening blood loss. Young, healthy patients with vigorous compensatory mechanisms may tolerate larger volumes of blood loss while manifesting fewer clinical signs. These patients may maintain a near-normal blood pressure until a precipitous cardiovascular collapse occurs. Elderly patients may be taking medications that either promote bleeding (warfarin, aspirin) or mask the compensatory response to hypovolemia (β-blockers). In addition, atherosclerotic vascular disease, diminished cardiac compliance with age, inability to elevate heart rate or cardiac contractility in response to hemorrhage, and overall decline in physiologic reserve decrease the ability of the elderly patient to tolerate hemorrhage.93,94

Understanding the mechanism of injury of the patient in shock will help direct the evaluation and management. Identifying the source of blood loss in patients with penetrating wounds is relatively simple since potential bleeding sources will be located along the known or suspected path of the wounding agent. Patients with penetrating injuries who are in shock usually require operative intervention. Occasionally, patients in shock from penetrating injuries may have problems that are readily treated by simple maneuvers outside the operating room. Treatment of a tension pneumothorax with insertion of a thoracostomy tube in the emergency department (ED) is one example. Generally speaking, though, shock from penetrating wounds is typically due to ongoing hemorrhage that mandates operative control.

Patients who suffer multisystem injuries from blunt trauma have multiple sources of potential hemorrhage. There are a limited number of sites, however, that can harbor sufficient extravascular blood volume to induce hypoperfusion or hypotension. Prehospital medical reports may confirm a significant blood loss at the scene of an accident, history of massive blood loss from wounds, visible brisk bleeding, or presence of an open wound in proximity to a major vessel. Injuries to major arteries or veins should be suspected when there is ongoing hemorrhage from an open pelvic fracture. Persistent bleeding from uncontrolled small vessels can, over time, precipitate shock if left untreated. However, attributing profound blood loss to these wounds (i.e., scalp lacerations) should be done only after major intracavitary bleeding has been excluded. When major blood loss is not immediately visible, internal (intracavitary) blood loss should be suspected. Intraperitoneal hemorrhage is probably the most common source of blood loss inducing shock. Its presence may be suspected based on physical examination (distended abdomen, abdominal tenderness, visible abdominal wounds), although the sensitivity of the physical exam for detecting substantial abdominal injuries after blunt trauma is unreliable. A large volume of intraperitoneal blood from abdominal injuries may be present before the physical examination is abnormal. Therefore, ultrasound Focused Assessment Sonography in Trauma (FAST) or diagnostic peritoneal lavage is used frequently in the resuscitation area to rapidly identify intraperitoneal blood. In selected patients, diagnostic laparotomy may be indicated. Each pleural cavity can hold 2–3 L of blood and can, therefore, also be a site of significant blood loss. Diagnostic and therapeutic tube thoracostomy may be indicated in patients based on clinical findings, clinical suspicion, or evidence of a hemopneumothorax on a chest x-ray or pleural FAST. Major retroperitoneal hemorrhage occurring in association with a pelvic fracture can be diagnosed by pelvic radiography in the resuscitation bay. The pattern of the pelvic fracture may provide clues as to the risk of massive blood loss.95


Control of ongoing hemorrhage is a central component of resuscitation of the patient in shock, and is part of the primary survey. Treatment of hemorrhagic shock is instituted concurrently with diagnostic evaluation to identify a source. As mentioned earlier, all trauma patients in shock should be presumed to have hemorrhage until proven otherwise. The method of treatment will depend on the patient’s response to resuscitation, the specific injury or injuries responsible for the blood loss, and consideration of factors such as mechanism of injury, age of the patient, associated injuries, and institutional resources. Patients who fail to respond to initial resuscitative efforts should be assumed to have ongoing active hemorrhage from major vessels (external bleeding, pleural cavity, peritoneal cavity, retroperitoneum, or both thighs) and require prompt operative intervention. Identification of the body cavity harboring active hemorrhage will help focus operative efforts, but since time is of the essence, rapid treatment is essential and diagnostic laparotomy or thoracotomy may be indicated. The actively bleeding patient cannot be resuscitated until control of ongoing hemorrhage is achieved.

Patients who respond to initial resuscitative efforts but then deteriorate hemodynamically frequently have injuries that require operative intervention. The duration of their response will dictate whether diagnostic maneuvers can be performed to identify the site of bleeding. Usually, however, hemodynamic deterioration denotes ongoing bleeding for which some form of intervention (operation, interventional radiology) is required. As noted above, patients who have lost significant intravascular volume with cessation of hemorrhage will often respond to resuscitative efforts if the depth and duration of shock have been limited.

A subset of patients fails to respond to resuscitative efforts despite adequate control of ongoing hemorrhage. These patients present in the following manner: have ongoing fluid requirements despite adequate control of hemorrhage; have persistent hypotension despite restoration of intravascular volume; often require vasopressor support to maintain their systemic blood pressure; and may exhibit a futile cycle of uncorrectable hypothermia, hypoperfusion, acidosis, and coagulopathy that cannot be interrupted despite maximum therapy. These patients have classically been described to be in decompensated or irreversible shock,60 and mortality is inevitable once the patient manifests shock in its terminal stages; however, this is always a diagnosis made in retrospect. Hemodynamic decompensation or the paradoxical peripheral vasodilation that occurs with prolonged hemorrhage has been studied in animal models of shock,13,96 but the mechanisms responsible for its development and the clinical factors that predict its onset in humans with shock have not been elucidated. In patients with hemorrhagic shock, survival is improved if the time between injury and control of bleeding is reduced. Clarke et al. demonstrated that trauma patients with major abdominal injuries requiring emergency laparotomy had an increased probability of death with increasing length of time in the ED.97 This probability increased approximately 1% for every 3 minutes in the ED up to 90 minutes.

The priorities in patients with hemorrhagic shock are (a) secure the airway, (b) support breathing and ventilation, and (c) control the source of hemorrhage and volume resuscitation. In trauma, identifying the body cavity harboring active hemorrhage will help focus the operative effort. Because time is of the essence, simultaneous and rapid evaluation and treatment is essential. Diagnostic laparotomy or thoracotomy may be indicated. The actively bleeding patient cannot be resuscitated until control of ongoing hemorrhage has been achieved. There has been evolution in the management of these patients known as damage control resuscitation.98 This strategy begins in the ED, continues into the operating room, and into the intensive care unit. Initial resuscitation is limited to keep systolic blood pressure around 90 mm Hg. Overly aggressive resuscitation during this phase has been shown to increase bleeding from recently clotted injured vessels. Intravascular volume resuscitation is accomplished with blood products and limited crystalloids. Too little volume infusion with resultant persistent hypotension and hypoperfusion is dangerous, yet overly vigorous resuscitation may be just as deleterious, and results in dilutional coagulopathy, compartment syndromes, acute lung injury, cerebral edema, acid–base and electrolyte disorders, and immune dysfunction. Control of hemorrhage is achieved in the operating room or angiography suite, and efforts to prevent hypothermia and coagulopathy are employed in emergency department (ED), operating room, and intensive care unit.

Cannon made the observation that attempts to increase systolic blood pressure in soldiers with uncontrolled sources of hemorrhage are counterproductive, with increased bleeding and higher mortality.3Several animal studies have confirmed the observation that attempts to restore normal blood pressure with fluids or vasopressors in the setting of active bleeding were rarely achievable and resulted in increased bleeding and higher mortality. A prospective, randomized clinical study compared delayed fluid resuscitation (on arrival in the operating room) with standard fluid resuscitation (with arrival of the paramedics) in hypotensive patients with penetrating torso trauma.12 The authors report that delayed fluid resuscitation resulted in a lower patient mortality. From these and other studies it is reasonable to conclude that in the setting of uncontrolled hemorrhage, any delay in surgical control of bleeding may increase mortality; with uncontrolled hemorrhage, attempting to achieve normal blood pressure may increase mortality, particularly with penetrating injuries and short transport times; a goal of systolic blood pressure of 80–90 mm Hg may be adequate in the patient with penetrating injury; and profound hemodilution should be avoided by early transfusion of red blood cells. For the patient with blunt injury, where the major cause of death is traumatic brain injury, the increase of mortality with hypotension in the setting of brain injury must be avoided. In this setting, a systolic blood pressure of 110 mm Hg would seem to be more appropriate.

Transfusion of packed red blood cells and other blood products is essential in the treatment of the patient in hemorrhagic shock. FFP should also be transfused in patients with massive bleeding or patients with bleeding and associated coagulopathy. Civilian and military trauma data show that the severity of coagulopathy after injury is predictive of mortality.99,100 A number of retrospective studies in military and civilian studies support the early use of FFP in bleeding trauma patients who require massive transfusion. Data collected from a US Army combat support hospital in patients who required massive transfusion of packed red blood cells (defined as the requirement for ≥10 U of packed red blood cells in a 24-hour period) suggest that a high plasma to RBC ratio (1:1.4 U) was independently associated with improved survival.100 A number of retrospective studies in the civilian population support the concept of transfusing FFP, platelets, and packed red blood cells in a 1:1:1 ratio.101,102 While these data are retrospective, a number of civilian trauma centers have adopted this paradigm. A multicenter prospective study of massive transfusion is currently ongoing to address this question.

Image Neurogenic Shock

Neurogenic shock refers to diminished tissue perfusion as a result of loss of vasomotor tone to peripheral arterial beds. Loss of vasoconstrictor impulses results in increased vascular capacitance, decreased venous return, and decreased cardiac output. Neurogenic shock is usually due to injuries to the spinal cord from fractures of the cervical or high thoracic vertebrae that disrupt sympathetic regulation of peripheral vascular tone. Occasionally, an injury such as an epidural hematoma impinging on the spinal cord can produce neurogenic shock without an associated vertebral fracture. Penetrating wounds to the spinal cord can produce neurogenic shock, as well. Sympathetic input to the heart that normally increases heart rate and cardiac contractility and input to the adrenal medulla that increases the release of catecholamines can be disrupted by a high injury to the spinal cord, preventing the typical reflex tachycardia that occurs with the relative hypovolemia from increased venous capacitance and loss of vasomotor tone. Acute spinal cord injury results in activation of multiple secondary injury mechanisms: (a) vascular compromise to the spinal cord with loss of autoregulation, vasospasm, and thrombosis, (b) loss of cellular membrane integrity and impaired energy metabolism, and (c) neurotransmitter accumulation and release of free radicals. Importantly, hypotension contributes to the worsening of acute spinal cord injury as a result of further reduction in blood flow to the injured spinal cord.


The classic description of neurogenic shock consists of decreased blood pressure associated with bradycardia (absence of reflexive tachycardia due to disrupted sympathetic discharge), warm extremities (loss of peripheral vasoconstriction), motor and sensory deficits indicative of an injury to the spinal cord, and radiographic evidence of a fracture in the vertebral column. Determining the presence of neurogenic shock may be difficult, however, since patients with multisystem trauma that includes an injury to the spinal cord often have a traumatic brain injury that may make identification of motor and sensory deficits difficult. Furthermore, associated injuries may cause hypovolemia and complicate the clinical presentation. In a subset of patients with injuries to the spinal cord from penetrating wounds, most patients with hypotension had blood loss as the etiology (74%) and not a neurogenic cause, and few (7%) had all the classic findings of neurogenic shock.103 Hypovolemia should be sought and excluded before the diagnosis of neurogenic shock is made. To assume that the cause of hypotension in a multiply injured patient is due to neurogenic shock without first evaluating and treating potential hemorrhage is often a costly mistake. In patients who have neurogenic shock, the severity of the spinal cord injury seems to correlate with the magnitude of the cardiovascular dysfunction. Patients with complete motor deficits from spinal cord injury are over five times more likely to require vasopressors for neurogenic shock compared to those with incomplete lesions.104


After the airway is secured and ventilation is adequate, fluid resuscitation and restoration of intravascular volume will often improve systemic blood pressure and perfusion in neurogenic shock. Most patients with neurogenic shock will respond to volume resuscitation alone, with adequate improvement in perfusion and resolution of hypotension. Administration of vasoconstrictors can improve peripheral vascular tone, decrease vascular capacitance, and increase venous return, but should only be considered once hypovolemia is excluded and the diagnosis of neurogenic shock established. If the patient’s blood pressure has not responded to appropriate volume resuscitation, continuous infusion of dopamine or a pure α-agonist such as phenylephrine may be used. Specific treatment for the shock state per se is often brief and the need to administer vasoconstrictors typically lasts only 24–48 hours. The duration of the need for vasopressor support for neurogenic shock may correlate with the overall prognosis for improvement in neurologic function.104 Appropriate rapid restoration of blood pressure and circulatory perfusion may also improve perfusion to the spinal cord, prevent progressive ischemia of the spinal cord, and minimize secondary injury to the spinal cord.105 Restoration of normal hemodynamics should precede any operative attempts to stabilize the vertebral fracture. Patients who are hypotensive from spinal cord injury are best monitored in intensive care unit, and carefully followed for evidence of cardiac or respiratory dysfunction.

Image Cardiogenic Shock

Cardiogenic shock refers to a failure of the circulatory pump leading to diminished forward flow and subsequent tissue hypoxia, in the setting of adequate intravascular volume. Hemodynamic criteria for cardiogenic shock include sustained hypotension (i.e., systolic blood pressure ≤90 mm Hg for at least 30 minutes), reduced cardiac index (<2.2 L/(min m2)), and elevated pulmonary artery occlusion pressure (>15 mm Hg).106 Acute myocardial infarction is the most common cause of cardiogenic shock. In this population, mortality for cardiogenic shock ranges between 50% and 80%. In the trauma patient, inadequate cardiac function after blunt thoracic trauma can be due to blunt myocardial injury, cardiac arrhythmia, myocardial infarction, or direct injury to a cardiac valve. As the average age of the population increases, the prevalence of comorbid medical conditions in trauma patients will also increase. Elderly patients with preexisting intrinsic cardiac disease will be more susceptible to suffering an acute myocardial infarction or significant arrhythmia associated with the stress of injury that can also induce cardiac failure and cardiogenic shock. Diminished cardiac output or contractility in the face of adequate intravascular volume (preload) may lead to underperfused vascular beds and reflexive sympathetic discharge. Increased sympathetic stimulation of the heart, either through direct neural input or from circulating catecholamines, increases heart rate, myocardial contraction, and myocardial oxygen consumption. Patients with fixed, flow-limiting stenoses of the coronary arteries may not be able to increase coronary perfusion to meet the increased myocardial oxygen demands and these lesions, therefore, further increase the risk for myocardial damage.15 Diminished cardiac output decreases coronary artery blood flow, resulting in a scenario of increased myocardial oxygen demand at a time when myocardial oxygen supply may be limited. Acute heart failure can also result in fluid accumulation in the pulmonary microcirculatory bed, impairing the diffusion of oxygen from the alveolar space and decreasing myocardial oxygen delivery even further.


Rapid identification of the patient with pump failure and institution of corrective actions are essential in preventing further decreases in cardiac output after such an injury. If increased myocardial oxygen needs cannot be met, there will be progressive and unremitting cardiac dysfunction. Blunt injury to the heart is rarely severe enough to induce pump failure,107 but manifestations of shock in the setting of a patient at risk should raise one’s index of suspicion. Evidence of blunt thoracic injury such as sternal fracture, multiple rib fractures, tenderness or hematomas in the chest wall or precordial area, or a history of a direct precordial impact identifies a patient at increased risk for a blunt cardiac injury. Elderly patients with known preexisting cardiac disease are at increased risk of suffering injury-related cardiac complications including cardiac failure. Furthermore, elderly patients with intrinsic cardiac disease are at risk to suffer a primary cardiac event that induces syncope, a fall, or loss of control of one’s vehicle that then leads to presentation to a trauma center.

Making the diagnosis of cardiogenic shock involves the identification of cardiac dysfunction or acute heart failure in a susceptible patient. Since patients with blunt cardiac injury typically have multisystem trauma,108,109hemorrhagic shock from intra-abdominal bleeding, intrathoracic bleeding, and bleeding from fractures must be excluded. Most instances of blunt cardiac injury are self-limited with no long-term cardiac sequelae. Relatively few patients with blunt cardiac injury will develop dysfunction of the cardiac pump and those who do generally exhibit cardiogenic shock early in their evaluation.107 Therefore, establishing the diagnosis of blunt cardiac injury is secondary to excluding other etiologies for shock and establishing that significant cardiac dysfunction is present. Invasive cardiac hemodynamic monitoring, which generally is not necessary, may be useful in the complex patient with the combination of hemorrhagic shock and cardiogenic shock, or when it is necessary to exclude right ventricular infarction and mechanical cardiac complications, or in the patient with known preexisting myocardial disease. This typically involves continuous monitoring of cardiac output and other hemodynamic variables using the pulmonary artery catheter.110113 Invasive hemodynamic monitoring with a pulmonary artery catheter can reveal diminished cardiac output and elevated pulmonary artery pressures and also may be used to guide the response to therapy. Transesophageal echocardiography (TEE) provides excellent views of the pericardium that are not interfered with by subcutaneous air, bandages covering chest wounds, chest tubes, or unfavorable body habitus that may limit evaluation of cardiac function by transthoracic echocardiography. The rapid evaluation of cardiac function by TEE may be problematic, however, in the presence of severe cervical trauma, maxillofacial trauma, or unstable injuries to the cervical spine that can interfere with placement of the probe. TEE also requires experienced ultrasonographers who may not be rapidly available at all hours. Trauma surgeons are becoming increasingly more experienced in the use of ultrasound as part of the initial resuscitation. While the sensitivity of surgeon-performed ultrasound to diagnose penetrating cardiac wounds may be high,114,115 the ability of surgeons to effectively evaluate cardiac performance as part of the ultrasound examination for trauma has not been established.


Patients with blunt cardiac injury will often have associated injuries that produce hypovolemia, and expansion of intravascular volume as an initial maneuver can improve perfusion significantly. However, hypervolemia can magnify the physiologic derangements produced by cardiac dysfunction and should be avoided. When profound cardiac dysfunction exists, ionotropic support may be indicated to improve cardiac contractility and cardiac performance.116Dobutamine stimulates primarily cardiac β1 receptors to increase cardiac output, but may also vasodilate peripheral vascular beds, lower total peripheral resistance, and lower systemic blood pressure through effects on β2 receptors. Ensuring adequate preload and intravascular volume is, therefore, essential prior to instituting therapy with dobutamine. Dopamine stimulates α receptors (vasoconstriction), β1 receptors (cardiac stimulation), and β2 receptors (vasodilation) with its effects on receptors predominating at low doses. Epinephrine stimulates β receptors and may increase cardiac contractility and heart rate, but can also cause intense peripheral vasoconstriction that can further impair cardiac performance. It is important to balance the beneficial effects of improved cardiac performance versus the potential side effects of excessive reflex tachycardia and peripheral vasoconstriction. This will require serial assessment of tissue perfusion including capillary refill, character of peripheral pulses, adequacy of urine output, or improvement in laboratory parameters of resuscitation such as arterial blood pH, BD, and lactate.

Patients whose cardiac dysfunction is refractory to cardiotonics may require mechanical circulatory support with an intra-aortic balloon pump.116 This can be inserted at the bedside in the intensive care unit via the femoral artery through either a cutdown or percutaneous approach. Aggressive circulatory support of patients with cardiac dysfunction from intrinsic cardiac disease has led to more widespread application of these devices and more familiarity with their operation by both physicians and critical care nurses.

Patients who have suffered an acute myocardial infarction following injury should have preservation of existing myocardium and cardiac function as priorities of therapy. This is accomplished by the following: ensuring adequate systemic oxygen delivery and peripheral tissue oxygenation, maintaining adequate preload with judicious volume restoration, minimizing sympathetic discharge through adequate relief of pain, and correcting electrolyte imbalances. The use of anticoagulation or thrombolytic therapy for the management of acute coronary syndromes will depend on associated injuries and the risk of secondary intracavitary or intracranial bleeding. Patients in cardiac failure from an acute myocardial infarction may benefit from pharmacologic or mechanical circulatory support in a manner similar to that of patients with cardiac failure related to blunt cardiac injury. There are additional pharmacologic tools that are useful in patients with cardiac ischemia from intrinsic coronary artery disease. These include the use of β-blockers to control heart rate and myocardial oxygen consumption, nitrates to promote coronary blood flow through vasodilation, and ACE inhibitors to reduce ACE-mediated vasoconstriction that increases myocardial workload and oxygen consumption.117 Selected patients who do not have significant associated injuries may be candidates for coronary angiography and subsequent procedures to improve coronary blood flow such as transluminal angioplasty, coronary artery stents, or urgent coronary artery bypass grafting.

Image Septic Shock (Vasodilatory Shock)

A multidisciplinary consensus has established some useful definitions for the patient with an inflammatory response and sepsis.118 First, the systemic inflammatory response syndrome (SIRS) occurs as a response to a wide variety of physiologic insults, and is defined as the presence of two or more of the following conditions: temperature >38°C or <36°C, pulse rate >90 beats/min, respiratory rate >20 breaths/min or PaCO2 <32 mm Hg, white blood cell count >12,000/mm3 or <4000/mm3, or >10% immature (band) forms. Sepsis is defined as the systemic inflammatory response to infection. In association with infection, manifestations of sepsis are the same as those previously defined for SIRS. Severe sepsis occurs when sepsis is associated with hypoperfusion and organ dysfunction. Perfusion abnormalities may be manifested by lactic acidosis, oliguria, or an acute alteration in mental status. Septic shock is a subset of severe sepsis and is defined as sepsis-induced hypotension despite adequate fluid resuscitation along with the presence of 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 agents may no longer be hypotensive by the time they manifest hypoperfusion abnormalities or organ dysfunction, yet they would still be considered to have septic shock.119

Septic shock is a clinical syndrome that occurs as part of the body’s immune and inflammatory response to invasive or severe localized infection, typically from bacterial or fungal pathogens. In its attempt to eradicate the pathogens, the reticuloendothelial system elaborates a wide array of protein mediators (cytokines). These mediators enhance effector mechanisms for macrophage and neutrophil killing, increase procoagulant activity and fibroblast activity to localize the invaders, and increase microvascular blood flow to enhance delivery of killing forces to the area of invasion. When this response is overly exuberant or becomes systemic rather than localized, manifestations of sepsis may be evident. These findings include peripheral vasodilation, fever, leukocytosis, and tachycardia.120,121 Sepsis is an uncommon etiology for shock in the acute presentation of a trauma patient unless there has been a substantial delay between injury and presentation to the ED. Typically, invasive infection in the injured patient occurs days to weeks after injury and is prevalent in the severely injured patient who develops a nosocomial infection in the intensive care unit.


Attempts to standardize terminology have led to the establishment of criteria for the diagnosis of sepsis in the hospitalized adult. These criteria include manifestations of the host response to infection (fever, leukocytosis, mental contusion, tachypnea, tachycardia, hypotension, oliguria), as well as identification of an offending organism.118 Septic shock requires the presence of these conditions associated with evidence of tissue hypoperfusion. Recognizing septic shock in the trauma patient begins with defining high-risk groups as follows: critically ill patients in the intensive care unit where nosocomial infection rates are high, patients who have suffered injuries associated with significant contamination (colorectal wounds with fecal spillage, soft tissue wounds embedded with soil or dirt), patients with injuries that may be associated with persistent devitalized tissue (crush injuries), patients whose wounds put them at risk for complications (anastomotic disruption, pancreatic leak), or patients with missed injuries. The clinical manifestations of septic shock should prompt the initiation of treatment before bacteriologic confirmation of an organism or source of active infection is identified. An aggressive search for the source of the infection includes a thorough physical exam, inspection of all wounds, evaluation of intravascular catheters or other foreign bodies, sampling of appropriate body fluids for culture, and adjunctive imaging studies as needed.

The hemodynamic parameters characteristic of septic shock include peripheral vasodilatation with resultant decrease in systemic vascular resistance. Initially, there is a decrease in a cardiac output; however, after volume resuscitation the cardiac output will actually be elevated. Changes in cardiac preload and filling pressures will likewise reflect the volume status of the patient. It is unusual to require placement of a pulmonary arterial catheter to guide therapy in patients with septic shock. Most of these patients can be resuscitated according to central venous pressure, ScvO2, and serum lactate.


Obtunded patients may require intubation to protect their airway while patients whose work of breathing is excessive may require intubation and mechanical ventilation to prevent respiratory collapse. Since vasodilation and a decrease in total peripheral resistance may produce hypotension, restoration of circulatory volume is essential. Since the portal of entry of the offending organism and its identity may not be evident until culture data return or imaging studies are completed, empiric antibiotics that cover the most likely pathogens are chosen. The bacteriologic profile of infectious events in an individual intensive care unit can be obtained from the infection control department and may identify potential responsible organisms. Antibiotics should be tailored to cover the responsible organisms once culture data are available and, if appropriate, the spectrum of coverage narrowed. Long-term empiric use of broad-spectrum antibiotics should be minimized to reduce the development of resistant organisms and avoid the potential complications of fungal overgrowth and antibiotic-associated colitis from Clostridium difficile.122

In the trauma patient, intravenous antibiotics will frequently be insufficient to adequately treat the infection. Source control, that is, drainage of infected fluid collections, removal of infected foreign bodies, and debridement of devitalized tissue are essential to eradicate the infection. This process may require multiple operations. For patients who manifest symptoms of septic shock early in their hospitalization, consideration of the possibility of a missed injury to a hollow viscus should be entertained. Missed abdominal injuries represent a significant source of sepsis and the septic response leading to MODS.123,124Vasopressor therapy may be required as a supportive measure when hypotension is refractory to volume infusion in patients in septic shock. α-Adrenergic agents promote peripheral vasoconstriction, improve systemic blood pressure, and can be titrated by continuous infusion to target an adequate mean arterial pressure. Unfortunately, high doses of α-adrenergic agents can be associated with tachyarrhythmias, ischemia of the midgut, gangrene of the digits, or the development of hyposensitivity requiring increasing doses to achieve the desired goals. As previously noted, vasopressin has been utilized as an adjunct for the treatment of vasodilatory shock in some centers and may be associated with a decreased need for α-adrenergic agents.125 High doses of vasopressin should be avoided so as to decrease adverse gastrointestinal and cardiovascular side effects.

In 2008 the multidisciplinary Surviving Sepsis Campaign published international guidelines for the management of severe sepsis and septic shock.119 These recommendations include the early goal-directed resuscitation of the septic patient during the first 6 hours after recognition, obtaining blood cultures before initiation of antibiotic therapy, prompt performance of imaging to identify the source of infection, the administration of broad-spectrum antibiotic therapy within 1 hour of diagnosis of septic shock, subsequent narrowing antibiotic coverage after microbiologic data are obtained, source control, and administration of crystalloid or colloids for fluid resuscitation. Furthermore, volume resuscitation should be guided by blood pressure, cardiac filling pressures, lactate, and ScvO2. After appropriate filling pressures have been achieved, persistent hypotension should be treated with norepinephrine or dopamine to maintain a target mean arterial pressure ≥65 mm Hg. Inotropic support with dobutamine should be instituted when cardiac output or ScvO2 remains low despite these maneuvers. Stress-dose glucocorticoid therapy should only be given to patients with septic shock if hypotension is poorly responsive to fluid and vasopressor therapy. Treatment with human recombinant activated protein C should be reserved for patients with severe sepsis and high risk of mortality, with caution for its use in surgical patients or other patients at risk for bleeding. In addition, in the absence of active coronary artery disease or acute hemorrhage, a target hemoglobin of 7–9 g/dL is appropriate. Patients with acute lung injury or ARDS should undergo mechanical ventilation with low tidal volumes (6 mL/kg) and maintaining plateau airway pressures ≤30 cm H2O. Much controversy has existed regarding tight glycemic control in the septic patient; the most recent large randomized control trials suggest that the complications of tight glycemic control may outweigh the benefits,126128 and therefore maintaining blood glucose 150 mg/dL appears to be a reasonable target.

Strategies for immune modulation have been developed for the treatment of septic shock. These include the use of anti-endotoxin antibodies, anticytokine antibodies, cytokine receptor antagonists, immune enhancers, anti–nitric oxide compounds, and oxygen radical scavangers.129135 Each of these compounds is designed to alter some aspect of the host immune response to shock. Most of these strategies, however, have failed to demonstrate efficacy in patients despite utility in well-controlled animal experiments. It is unclear whether the failure of these compounds is due to poorly designed clinical trials, inadequate understanding of the interactions of the complex immune response to injury and infection, or animal models of shock that poorly represent human disease. Recent trials have demonstrated the efficacy of activated protein C in improving mortality from sepsis.136 Subgroup analysis of patients with sepsis, but at low risk of death, did, however, document an increased risk of bleeding complications associated with therapy without a substantial improvement in survival.137 Sepsis and nosocomial infections in critically ill patients continue to represent significant sources of morbidity and consume substantial health care resources. Despite advances in critical care, the mortality rate for severe sepsis remains at 30–50%. In United States, 750,000 cases of sepsis occur annually, one third of which are fatal.138

Image Obstructive Shock

Hypoperfusion can be due to mechanical obstruction of the circulation impeding venous return to the heart or preventing cardiac filling. The end result of either of these two events is decreased cardiac output leading to decreased peripheral perfusion. Most commonly, mechanical obstruction is due to the presence of a tension pneumothorax or cardiac tamponade. With either condition, there is decreased cardiac output associated with increased central venous pressure.

Diagnosis and Treatment

The manifestations of a tension pneumothorax are the presence of shock in the context of diminished breath sounds over one hemithorax, hyperresonance to percussion, jugular venous distension, and shift of mediastinal structures to the unaffected side. Unfortunately, not all of the clinical manifestations of tension pneumothorax may be evident on physical examination. Hyperresonance may be difficult to appreciate in a noisy resuscitation area. Jugular venous distension or tracheal deviation may be obscured by a cervical collar in the multiply injured patient and not seen unless specifically sought. Furthermore, hypovolemia from concurrent bleeding may diminish central venous pressure and prevent jugular venous distension even when increased pleural or pericardial pressure restricts flow. For the multiply injured patient with hypotension, the placement of bilateral chest tubes may be both diagnostic and therapeutic in this situation. In these circumstances, a chest x-ray is both unnecessary and potentially a dangerous waste of time. When a chest tube cannot be immediately inserted, such as in the prehospital setting, the pleural space can be decompressed with a large caliber needle inserted in the second interspace at the midclavicular line, or in the fourth or fifth intercostal space at the anterior axillary line. Immediate return of air and rapid resolution of hypotension suggest strongly that a tension pneumothorax was present. Due the immediate threat to life, the diagnosis of tension pneumothorax should be a clinical one. If obtained (which would mean the diagnosis was missed on clinical examination), the typical findings on a chest x-ray include deviation of mediastinal structures, depression of the hemidiaphragm, and hypo-opacification with absent lung markings.

Cardiac tamponade results from the accumulation of blood within the pericardial sac and most commonly occurs from penetrating trauma. While precordial wounds are most likely to injure the heart and produce tamponade, any projectile or wounding agent that passes in proximity to the mediastinum can potentially produce tamponade. Blunt rupture of the heart is fortunately rare, but the diagnosis is aided by the FAST exam that is performed immediately on all patients at risk. The manifestations of cardiac tamponade may be as catastrophic as total circulatory collapse and cardiac arrest or they may be more subtle. A high index of suspicion is warranted to make a rapid diagnosis. Patients who present with circulatory arrest due to cardiac tamponade from a precordial penetrating wound require emergency pericardial decompression through a left anterolateral thoracotomy, and the indications for this maneuver are discussed in Chapter 14. Cardiac tamponade may also be associated with tachycardia, muffled heart tones, jugular venous distension, and elevated central venous pressure. Absence of these clinical findings, however, may not be sufficient to exclude cardiac injury and cardiac tamponade. Muffled heart tones may be difficult to appreciate in a busy trauma center and jugular venous distension and central venous pressure may be diminished by coexistent bleeding and hypovolemia. Therefore, patients at risk for cardiac tamponade whose hemodynamic status permits should undergo additional diagnostic tests.

Invasive hemodynamic monitoring may support the diagnosis of cardiac tamponade if elevated central venous pressure, pulsus paradoxus (decreased systemic arterial pressure with inspiration), or elevated right atrial and right ventricular pressure by pulmonary artery catheter is present. These hemodynamic profiles suffer from lack of specificity, the time required to obtain them, and their inability to exclude cardiac injury in the absence of tamponade. Chest radiographs may provide information on the possible trajectory of a projectile, but are rarely diagnostic since the acutely filled pericardium distends poorly. Pericardial ultrasound as part of a surgeon-performed FAST examination, through either the subxiphoid or transthoracic approach, is practiced routinely at many trauma centers. Excellent results in detecting pericardial fluid have been reported.114,115 The yield in identifying pericardial fluid obviously depends on the skill and experience of the ultrasonographer, body habitus of the patient, and absence of wounds that preclude visualization of the pericardium. Standard two-dimensional transthoracic or TEE to evaluate the pericardium for fluid is typically performed by cardiologists or anesthesiologists skilled at evaluating ventricular function, valvular abnormalities, and integrity of the proximal thoracic aorta. These skilled examiners are usually not immediately available at all hours and waiting for this test may result in inappropriate delays. In addition, while both ultrasound techniques may demonstrate the presence of fluid or characteristic findings of tamponade (large volume of pericardial fluid, right atrial collapse, poor distensibility of the right ventricle), they do not exclude cardiac injury per se,139,140 and their utility will be discussed in greater detail in Chapter 15.

Pericardiocentesis to diagnose pericardial blood and potentially relieve tamponade has a long history in the evaluation of the trauma patient. Its inability to evacuate clotted blood and potential to produce cardiac injury make it a poor alternative in most busy trauma centers. Diagnostic pericardial window represents the most direct method to determine the presence of blood within the pericardium. It can be performed through either the subxiphoid or transdiaphragmatic approach.141,142 Some authors report performing this technique using local infiltrative anesthesia. However, the ability to achieve satisfactory safety and visualization in the trauma victim who may be intoxicated, in pain, or anxious from hypoperfusion usually mandates the use of general anesthesia. Once the pericardium is opened and tamponade relieved, hemodynamics usually improve dramatically and formal pericardial exploration can be performed. Exposure of the heart can be achieved by extending the incision to a formal sternotomy, performing a left anterolateral thoracotomy, or performing bilateral anterior thoracotomies (“clamshell”) as discussed in Chapters 14and 24.

Image Traumatic Shock

Some authors consider traumatic shock a separate clinical entity.60 The term is used to represent a combination of several insults after injury that, by themselves, may be insufficient to induce shock, but produce profound hypoperfusion when combined. Hypoperfusion from relatively modest loss of volume can be magnified by the proinflammatory activation that occurs following injury or shock. The systemic response after trauma, combining the effects of soft tissue injury, long bone fractures, and blood loss, is clearly a different physiologic insult than simple hemorrhagic shock alone. In addition to ischemia or ischemia/reperfusion, simple hemorrhage induces proinflammatory activation and causes many of the cellular changes typically attributed previously only to septic shock.23,27 Examples of traumatic shock might include small-volume hemorrhage accompanied by injury to soft tissue (femur fracture, crush injury) or any combination of hypovolemic, neurogenic, cardiogenic, and obstructive shock that induces rapidly progressive activation of proinflammatory cytokines. MOF, including ARDS, develops relatively often in the blunt trauma patient, but rarely after pure hemorrhagic shock alone. The hypoperfusion deficit in traumatic shock is magnified by the proinflammatory activation that occurs following the induction of shock.

At a cellular level, the pathophysiology of traumatic shock may be attributable to the release of cellular products termed damage-associated molecular patterns (DAMPs, i.e., ribonucleic acid, uric acid, and high mobility group box 1) that activate the same set of cell surface receptors as bacterial products, initiating similar cell signaling.143 The receptors are termed pattern recognition receptors (PRPs) and include the toll-like receptor (TLR) family of proteins. In laboratory models of traumatic shock, the addition of a soft tissue or long bone injury to the hemorrhage produces lethality with significantly less blood loss than when the animals are stressed by hemorrhage alone.

Therapy for this form of shock is focused on correction of the individual elements to diminish the cascade of proinflammatory activation contributing to its existence. Therapeutic maneuvers include prompt control of hemorrhage, adequate volume resuscitation to correct oxygen debt, debridement of nonviable tissue, stabilization of bony injuries, and appropriate treatment of soft tissue wounds.


There is still significant controversy as to how to best determine the effects of the magnitude of shock, specifically, to be able to identify quantitative determinants that are truly indicators of the depth and the duration of shock. If such parameters would be easily measurable, then they would be the ideal end points of resuscitation. Clearly, routinely measured vital signs are not adequate and complex devices used to calculate oxygen delivery are not practical especially early in the resuscitation.

Porter and Ivatury performed an extensive review of the data regarding end points for the resuscitation of trauma patients.144 Most clinicians would agree that heart rate, systemic arterial blood pressure, skin temperature, and urine flow provide relatively little information about the adequacy of oxygen delivery to tissues. Accordingly, reliance on these simple indices of perfusion may result in failure to recognize occult or compensated shock.

Physiologically, shock begins when oxygen delivery (DO2) falls below the tissue oxygen consumption (VO2) requirements. A persistent mismatch between the DO2 and VO2 has been associated with progressive multiple organ dysfunction. Unfortunately, there are several limitations in our ability to assess perfusion status. Due to these limitations, it is necessary to use surrogates of tissue hypoxia. During anaerobic metabolism, large quantities of pyruvate are converted to lactate rather than entering the tricarboxylic acid cycle. Meanwhile, because of the stoichiometry of substrate-level (as contrasted with oxidative) phosphorylation of ADP to ATP, there is a net accumulation of protons.145 Accordingly, increases in arterial BD or blood lactate concentration are evidence of an increase in the rate of anaerobic metabolism. Numerous studies have documented that high blood lactate levels portend an unfavorable outcome in patients with shock,146 but it has not been proven that survival is improved when therapy is titrated using blood lactate concentration as an end point.

BD is the amount of base (in millimoles) required to titrate 1 L of whole blood back to a pH of 7.40 with the sample maintained at 37°C and fully saturated with oxygen and equilibrated with an atmosphere containing carbon dioxide at a PCO2 of 40 mm Hg. In practice, BD is calculated by arterial blood gas analyzers using the nomogram developed by Astrup et al.147 BD has been shown to have prognostic value in patients with shock.148 Although intuitively reasonable, it remains to be proven that titrating therapy to a BD end point improves survival. Until recently, BD was more quickly and easily measured than lactate concentration; however, point-of-care portable lactate assays are now available and used in settings such as during transport in the helicopter or in the prehospital scenario. Preliminary data of prehospital lactate suggest that these values are highly predictive of outcome.149

Few published data have shown that using a monitoring tool to guide resuscitation can improve outcome in critically ill patients.150 Subsequently, Rivers et al. published results from randomized trial of goal-directed therapy for septic shock initiated in the emergency room.151 An algorithm was developed to adjust central venous pressure to 8–12 mm Hg, mean arterial pressure to 65–90 mm Hg, and central venous oxygen saturation to a value greater than 70%. In this study a central venous oximetry catheter was used to titrate resuscitation with the idea of balancing systemic oxygen supply with oxygen demand. The authors found that early institution of goal-directed hemodynamic support prevented cardiovascular collapse in high-risk patients and reduced hospital mortality from 46.5% to 30.5% (P = .009).

Recent reviews suggest that our lack of understanding of the effects of shock and resuscitation stem from a discrepancy between the need to identify effective strategies aimed at restoring normal oxygen delivery and the fact that most resuscitation research is aimed at controlling inflammation and coagulopathy. The degree of activation of the inflammatory mechanisms and coagulation derangements are directly related to the magnitude of the hypoxia-induced tissue injury. It is naïve to believe that simply correcting oxygen delivery or modulating a specific pathway would prevent the ensuing of multiple organ dysfunction.152

Until more practical and quantitative methods are introduced to measure the accumulative effect of the oxygen deficit, it is likely that we will continue to use a combination of surrogates of tissue perfusion. We can estimate the magnitude of the systemic insult by assessing the BD or lactic acid at the time of initiating resuscitation and follow how these parameters respond to our interventions. In addition to theses parameters, we can also use noninvasive methods to quantitatively assess the extent of regional ischemia, and we could build a more complete picture of the patient’s magnitude of injury and response to resuscitation.

Perhaps the most studied method to measure the adequacy of regional tissue perfusion relies on the application of near-infrared spectroscopy (NIRS). The introduction of more quantitative and reproducible methods coupled with reliable and practical devices has generated a plethora of clinical studies demonstrating the use of parameters such as tissue oxygen saturation as well as other parameters measured based on optical determinations.

Image Near-Infrared Spectroscopy


NIRS offers a technique for continuous, noninvasive, bedside monitoring of tissue oxygenation. It measures oxygenation in the tissue’s microvasculature and, thus, not only examines the adequacy of tissue perfusion but also provides a potential window to noninvasively study tissue metabolism. In the clinical setting, NIRS has been used for continuous monitoring of metabolic variables including tissue O2availability,153 tissue O2 consumption, tissue O2saturation (StO2),154 and changes of rate of StO2 decrease due to vascular occlusion,155,156 in diverse populations of patients (trauma,148,157 sepsis,158 and heart failure) with promising results. However, it is early in the history of this “new” technology and many questions remain unanswered.

NIRS-Derived StO2 is Not Pulse Oximetry

NIRS uses the same principles of light transmission and absorption as pulse oximetry to measure StO2. However, StO2 measurements differ in several important ways from the SpO2 measurements provided by pulse oximetry. Importantly, NIRS measurements do not require the arterial pulsatile component on which pulse oximetry relies to derive its estimation. This also means that the saturation of oxygen measured by StO2 belongs not to the arterial compartment as is the pulse oximetry–derived SpO2, but to a different compartment. In fact, the deeper transillumination provided by StO2 allows the assessment of oxygenation in small vascular compartments within the muscle. Given that only 20% of blood volume is stored in the arterial circuit, StO2 is primarily indicative of the venous oxyhemoglobin concentration. Consequently, as opposed to SpO2, StO2 is a measure of the microvasculature, and as such its estimation represents local rather than systemic conditions. Finally, the fact that no oxygen exchange takes place between the thick arterial walls and tissues allows SpO2 to remain fairly constant regardless of whether the measurement is done in the earlobe, fingers, or toes. On the other hand, StO2may vary depending on the site where the probe is placed.

How does it Work?

At physiologic concentrations the molecules that absorb most light are hemoglobin, myoglobin, cytochromes, melanins, carotenes, and bilirubin. These substances can be quantified and measured in intact tissues using simple optical methods. Only three compounds change their spectra when oxygenated: cytochrome aa3, myoglobin, and hemoglobin. Therefore, the assessment of tissue oxygenation by NIRS is based on the specific absorption spectrum of hemoglobin, myoglobin, and cytochrome aa3.

The NIRS sensor consists of an emission probe and a detection probe. The interface between the patient and the NIR spectroscope is only this sensor on the distal tip of the NIRS optical cable. The sensor conducts the optical signal to the patient and back to the monitor.

The spacing between the illumination fibers and detection fibers determines the tissue penetration and thus the type of tissue sampled. The NIRS sensors can be used to monitor tissue oxygenation in different tissues as well as different depths within the same tissue. For this purpose, various types of sensors are available, with the only difference being the distance between emission and detection probes. In clinical setting, measuring oxygenation of the thenar muscle is now the most common use. The thenar eminence is said to be the optimal solution because it is easily accessible, has thin subcutaneous tissue, withholds fairly low amounts of fluid during edematous conditions compared to other sites, and provides consistent results among healthy volunteers.157 Crookes et al.157 studied the StO2 in 707 healthy volunteers, and found a mean StO2 of 86 ± 6%. Fig. 12-6 shows a histogram of the thenar StO2values in 707 healthy human volunteers.


FIGURE 12-6 Histogram of StO2 in healthy volunteers. (Reproduced with permission from Crookes BA, Cohn SM, Bloch S, et al. Can near-infrared spectroscopy identify the severity of shock in trauma patients? J Trauma. 2005;58:806.)

Near-infrared light can propagate through tissues and, at particular wavelengths, is differentially absorbed by the oxygenated and deoxygenated forms of hemoglobin, myoglobin, and cytochrome aa3. They all absorb light at 800 nm, whereas at 760 nm absorption is primarily by the deoxygenated forms. These absorption spectra of oxygenated and deoxygenated hemoglobin provide a means to calculate the ratio of oxygenated hemoglobin to total hemoglobin. When measured in the microcirculation of a volume of tissue, this is expressed as percent tissue oxygen saturation (StO2):


Because Mb, Hb, and cytaa3 absorption spectra overlap, they are indistinguishable with NIRS. In muscle tissue, myoglobin accounts for approximately 10% of the NIRS light absorption signal159 and cytaa3for 2–5%.153 However, the NIRS signal is minimally influenced by myoglobin or cytaa3 oxygen saturation.

Changes in muscle blood flow affect the absorption of 760- to 800-nm light and NIRS has the ability to detect significant fluctuations in localized tissue oxygenation secondary to these flow changes.159Besides that, NIRS rapidly changes in response to progressive oxygen deprivation and correlates with changes in blood flow and oxygen consumption in skeletal muscle.159,160

NIRS in Hemorrhagic Shock

Adequate resuscitation of patients from hemorrhagic shock depends on restoration of oxygen delivery (DO2) to tissues. This process may be monitored in several ways. Traditionally, resuscitation has been monitored indirectly by examination of highly dependent end-organ functions, such as blood pressure, heart rate, urine output, and mental status. Direct measurement of DO2 during shock states requires invasive techniques such as pulmonary artery catheterization. The ideal device for monitoring the adequacy of resuscitation in the trauma patient would have two basic characteristics. It would be noninvasive and it would provide the clinician with an objective parameter that measures oxygenation at the tissue level in end organs.

Changes in StO2 induced by experimental hemorrhagic shock are not as profound as those seen in systemic DO2. However, Beilman et al.161 found that skeletal muscle and gastric StO2 measured by noninvasive NIRS strongly correlates with DO2. Changes in the liver StO2 were less correlated, likely reflecting a protected circulation to the hepatic parenchyma. Rhee et al.162 found similar results, but the decrease in liver was larger.

McKinley et al.163 compared subcutaneous and skeletal muscle StO2 to invasive DO2 measurements. The correlation of the subcutaneous StO2 was different from skeletal muscle StO2. The authors found that skeletal muscle StO2correlates well with systemic oxygen delivery. Subcutaneous tissue, as a tissue with primary functions of energy storage and insulation, had lower O2 consumption requirement and less perfusion per unit than other tissues. The lower O2 consumption resulted in extracting less O2 and maintenance of higher StO2.

Taylor et al.154 evaluated the utility of NIRS for early determination or irreversibility of hemorrhagic shock. They used skeletal muscle StO2 measurements to study this differentiation. NIRS monitoring provided a means for early differentiation between resuscitatable and nonresuscitatable animals after a period of hemorrhagic shock. Recently, Cohn et al.148 did a prospective multicenter study on 383 traumatic shock patients. They compared the sensitivity and specificity of NIRS StO2 measurements in the first hour after arrival at the emergency room in predicting MODS and death to measurements of maximum BDs and minimum blood pressure. When using a cutoff point StO2 of 75% (StO2 minimum <75% in first hour at ER), they found a sensitivity and specificity of 78% and 39% to predict MODS and 91% and 31% to predict death.

Crookes et al.157 studied StO2 in trauma patients. They found that StO2 at admission predicted the development of multiple organ dysfunction and death (Fig. 12-7). They also showed that StO2 absolute values were able to differentiate patients with moderate to severe shock from healthy volunteers. However, StO2 failed to discriminate between healthy volunteers and trauma patients with no shock or with mild shock.



FIGURE 12-7 ROC curves of StO2 for prediction of MODS development and mortality. (From Crookes BA, Cohn SM, Bloch S, et al. Can near-infrared spectroscopy identify the severity of shock in trauma patients? J Trauma. 2005;58:806.)

The use of NIRS measurement of cytochrome aa3 redox state in hemorrhagic shock has also been studied. Cytaa3 is the terminal electron carrier in the mitochondrial electron transport chain, and it is rapidly reduced when local tissue oxygen demand exceeds supply. Therefore, during hypoxemia, cytaa3 would remain in a reduced state, reflecting a cellular shift to anaerobic metabolism. However, the cytaa3contribution to the NIRS light attenuation is very small (about 2–5%).

Controversy exists regarding whether NIRS can be used as a valid tool to measure changes in cytochrome oxidase since the influence of Hb is so dominant. Cairns et al.164 studied cytaa3 redox state in trauma patients and found a direct impairment in mitochondrial oxidative function in severely injured patients who later developed MOF.

Rhee et al.162 compared conventional parameters of resuscitation with NIRS cytaa3 measurements in a hemorrhagic shock model. They found significant correlations between mitochondrial cytaa3 redox state and DO2 throughout shock and resuscitation, but resuscitation did not uniformly restore cellular oxygenation in all tissue beds. Despite the normalization of traditional resuscitation parameters, the postresuscitative NIRS values in the gastric and muscular beds were low. NIRS may be useful in identifying regional areas of dysoxia.

NIRS has also been used to measure pH, by observing spectral changes in the bond energy of the imidazole ring of histidine residue within hemoglobin. Puyana et al.165 examined NIRS measurements of small bowel pH during hemorrhagic shock. NIRS pH represented an accurate measurement of splanchnic mucosal pH.

These findings suggest that NIRS may be useful in measuring not only StO2 but also other important components of tissue metabolism. Furthermore, it may be able to identify at an early stage those patients destined to development of MOF later in their disease. Finally, it may be a useful monitor of differential organ perfusion after resuscitation.

In summary, despite some limitations, StO2 measurement seems to be a useful parameter when determining perfusion status and, probably, in predicting the course of disease. The supporting evidence, although favorable, is still scarce as to fully understand the meaning of its measurements and, thus, to recommend its systematic use. Potentially, additional studies will help clarify its strengths and weaknesses and hopefully will continue to endorse the already suggested utility.

Muscle Oxidative Metabolism Measured with NIRS

The signal obtained by NIRS reflects the state of hemoglobin, myoglobin, and cytaa3 oxygenation, thereby representing the balance between the oxygen supply and consumption. Several groups studied the possibility to dissociate O2consumption from O2 supply by arterial occlusion with a tourniquet, which is called the ischemic challenge.

Hampson and Piantadosi160 were the first to study the skeletal muscle oxygenation in human. They measured the NIRS cytaa3 redox state during forearm tourniquet ischemia in healthy volunteers and reported a significant decrease in muscle oxygenation level in ischemia. By adding exercise at various intensities, these exercise intensities would indicate muscle metabolism. In this way, NIRS-O2 could be a quantitative measure of muscle oxidative metabolism.

Hamaoka et al.166 used these exercise theory and compared the NIRS measurements of muscle O2 consumption to 31P magnetic resonance spectroscopy. Their results confirm that the decline rate in NIRS-O2during arterial occlusion is a quantity of muscle oxidative rate (r = 0.98).

Boushel et al.167 compared values of muscle oxygen saturation and consumption derived from measurements of NIRS, SvO2 with 31P magnetic resonance spectroscopy. Their results showed that the NIRS-O2closely reflected the exercise intensity and correlated highly with the MRS-determined metabolic rate in the muscle.

In the former studies, the flow to the muscle was not monitored. However, a decrease in oxygen delivery in critically ill patients often involves a combination of decreased flow and decreased saturation.

Guery et al.168 used an isolated perfused pig hind limb to produce an experimental model of controlled hypoxemia and ischemia, allowing to detect the influence of flow on NIRS measurements. In both types of hypoxia they found a high correlation of the cytaa3 redox state and DO2 (r2 = 0.90 and 0.87 for, respectively, the ischemic and hypoxic groups). This illustrates that NIRS measurements are well related to DO2 in either ischemic or hypoxic hypoxia.

Gomez et al.169 evaluated the deoxygenation and recovery slopes of StO2 after performing a vascular occlusion test (VOT) in healthy volunteers (Fig. 12-8). This was first done at rest and subsequently during exercise. Presumably, the rate of StO2 decline depends on the specific tissue metabolic rate, the volume of microvasculature screened, redistribution phenomena, and hemoglobin concentration. However, VOT should rapidly stop blood flow fixing the total amount of blood in the tissues during the ischemic phase making vascular blood volume constant while eliminating flow. Ischemia-induced changes in vasomotor tone may account for subtle redistribution within the extremity. Nevertheless, such volume shifts should be small owing to the low blood volume. This suggest that, although the absolute StO2 value reflects a balance between three components (hemoglobin flow, relative weights of vascular beds, and metabolic rate), the deoxygenation slope after VOT must represent only the metabolic rate as flow has ceased and redistribution is minimal.


FIGURE 12-8 Measurement of StO2 during a VOT. Baseline is stable; the forearm cuff is inflated. StO2 is allowed to fall to 40%. The cuff is deflated, and StO2 returns to baseline and overshoots. Deoxygenation and recovery slopes are marked in the figure. (Reproduced from Gomez H, Torres A, Polanco P, et al. Use of non-invasive NIRS during a vascular occlusion test to assess dynamic tissue O-2 saturation response. Intensive Care Med. 2008;34:1600–1607.)

By the same token, the recovery slope after VOT release is a function of the local cardiovascular reserve, defined as the tissue’s ability to reoxygenate. In this case, the slope of recovery is influenced by the ischemic level reached prior to release, arterial oxygen saturation (SaO2), local blood flow (which depends on capillary integrity, local blood volume, and local vasomotor tone), perfusion pressure, and local hemoglobin.169 If the level of ischemia and the perfusion pressure are kept constant between repeated measures, then changes in the recovery slope will be a function of changes in cardiovascular reserve, systemic hemoglobin, and SaO2. Also, changes in microvascular integrity, smooth muscle response, or vasomotor tone will modify the recovery slope. Thus, this parameter is a sensitive, but not specific marker of local cardiovascular reserve.

The results of this study showed that the deoxygenation slope was faster during exercise when compared to rest, whereas the recovery slope did not change. Furthermore, it was identified that unstable trauma patients had a slower recovery slope than healthy volunteers (2.88 ± 1.71 vs. 5.20 ± 1.19, P <.05). Creteur et al.170 had similar findings regarding the recovery slope, but in patients with septic shock. In addition, this group found that the recovery slope had the ability to predict MODS development and mortality.

In summary, the measurement of the redox state of the cytaa3 as well as the estimation of the deoxygenation and recovery slopes has the potential advantage over absolute StO2 measurement, of assessing the oxidative metabolism during ischemia and exercise. This suggests a potential role in noninvasive assessment of metabolism during hypoperfusion states. Nonetheless, there are still questions regarding how these parameters vary according to different resuscitation strategies and also whether it has the potential to guide therapy.


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