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Surgery_Schwartz. environment. These bacterial products, including lipo-polysaccharide, are known as pathogen-associated molecular patterns. The salutary consequences of PRR activation most likely relate to the initiation of the repair process and the mobi-lization of antimicrobial defenses at the site of tissue disruption. However, in the setting of excessive tissue damage, the inflam-mation itself may lead to further tissue damage, amplifying the response both at the local and systemic level.21 PRR activation leads to intracellular signaling and release of cellular products, including cytokines (Fig. 5-4).Before the recruitment of leukocytes into sites of injury, tissue-based macrophages or mast cells act as sentinel respond-ers, releasing histamines, eicosanoids, tryptases, and cytokines (Fig. 5-5). Together these signals amplify the immune response by further activation of neurons and mast cells, as well as increasing the expression of adhesion molecules on the endothe-lium. Furthermore, these


Surgery_Schwartz

Surgery_Schwartz. Together these signals amplify the immune response by further activation of neurons and mast cells, as well as increasing the expression of adhesion molecules on the endothe-lium. Furthermore, these mediators cause leukocytes to release platelet-activating factor, further increasing the stickiness of the endothelium. Additionally, the coagulation and kinin cascades impact the interaction of endothelium and leukocytes.Cytokines/ChemokinesThe immune response to shock encompasses the elaboration of mediators with both proinflammatory and anti-inflammatory properties (Table 5-4). Furthermore, new mediators, new rela-tionships between mediators, and new functions of known mediators are continually being identified. As new pathways are uncovered, understanding of the immune response to injury and the potential for therapeutic intervention by manipulating the immune response following shock will expand. What seems clear at present, however, is that the innate immune response can help restore


Surgery_Schwartz

Surgery_Schwartz. the potential for therapeutic intervention by manipulating the immune response following shock will expand. What seems clear at present, however, is that the innate immune response can help restore homeostasis, or if it is excessive, promote cel-lular and organ dysfunction.Multiple mediators have been implicated in the host immune response to shock. It is likely that some of the most important mediators have yet to be discovered and the roles of many known mediators have not been defined. A compre-hensive description of all of the mediators and their complex interactions is beyond the scope of this chapter. For a general overview, a brief description of the more extensively studied mediators, as well as some of the known effects of these sub-stances, see the following discussion. A more comprehensive review can be found in Chapter 2, “Systemic Response to Injury and Metabolic Support.”Tumor necrosis factor alpha (TNF-a) was one of the first cytokines to be described, and it is one of


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Surgery_Schwartz. review can be found in Chapter 2, “Systemic Response to Injury and Metabolic Support.”Tumor necrosis factor alpha (TNF-a) was one of the first cytokines to be described, and it is one of the earliest cytokines released in response to injurious stimuli. Monocytes, macro-phages, and T cells release this potent proinflammatory cyto-kine. TNF-a levels peak within 90 minutes of stimulation and return frequently to baseline levels within 4 hours. Release of TNF-a may be induced by bacteria or endotoxin and leads to the development of shock and hypoperfusion, most commonly observed in septic shock. Production of TNF-a also may be induced following other insults, such as hemorrhage and isch-emia. TNF-a levels correlate with mortality in animal models of hemorrhage.24 In contrast, the increase in serum TNF-a levels reported in trauma patients is far less than that seen in septic patients.25 Once released, TNF-a can produce peripheral vaso-dilation, activate the release of other cytokines,


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Surgery_Schwartz. in serum TNF-a levels reported in trauma patients is far less than that seen in septic patients.25 Once released, TNF-a can produce peripheral vaso-dilation, activate the release of other cytokines, induce proco-agulant activity, and stimulate a wide array of cellular metabolic changes. During the stress response, TNF-a contributes to the muscle protein breakdown and cachexia.Interleukin-1 (IL-1) has actions similar to those of TNF-a. IL-1 has a very short half-life (6 minutes) and primarily acts in a paracrine fashion to modulate local cellular responses. Sys-temically, IL-1 produces a febrile response to injury by activat-ing prostaglandins in the posterior hypothalamus, and causes anorexia by activating the satiety center. This cytokine also aug-ments the secretion of ACTH, glucorticoids, and β-endorphins. In conjunction with TNF-a, IL-1 can stimulate the release of other cytokines such as IL-2, IL-4, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor, and


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Surgery_Schwartz. glucorticoids, and β-endorphins. In conjunction with TNF-a, IL-1 can stimulate the release of other cytokines such as IL-2, IL-4, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor, and interferon-g.IL-2 is produced by activated T cells in response to a vari-ety of stimuli and activates other lymphocyte subpopulations and natural killer cells. The lack of clarity regarding the role of IL-2 in the response to shock is intimately associated with that of understanding immune function after injury. Some investigators have postulated that increased IL-2 secretion promotes shock-induced tissue injury and the development of shock. Others have demonstrated that depressed IL-2 production is associated with, Table 5-3Endogenous damage-associated molecular pattern moleculesMitochondrial DNAHyaluronan oligomersHeparan sulfateExtra domain A of fibronectinHeat shock proteins 60, 70, Gp96Surfactant Protein Aβ-Defensin 2FibrinogenBiglycanHigh mobility group box 1Uric


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Surgery_Schwartz. DNAHyaluronan oligomersHeparan sulfateExtra domain A of fibronectinHeat shock proteins 60, 70, Gp96Surfactant Protein Aβ-Defensin 2FibrinogenBiglycanHigh mobility group box 1Uric acidInterleukin-1αS-100sNucleolinNeuropeptidesTissue-based macrophages/mast cells Histamines,leukotrienes,chemokines,TNF TraumaDAMPs (HMGB1,heparan sulfate,uric acid)Macrophages Bacteria andbacterialproductsComplementNeutrophilsDegranulationChemokines,TNFDefensinsTNF,Interferon-LymphocytesAntigenStimulation/activationProductionFigure 5-4. A schema of information flow between immune cells in early inflammation following tissue injury and infection. Cells require multiple inputs and stimuli before activation of a full response. DAMPs = damage associated molecular patterns; HMGB1 = high mobility group box 1; TNF = tumor necrosis factor.Brunicardi_Ch05_p0131-p0156.indd 13829/01/19 11:06 AM 139SHOCKCHAPTER 5and perhaps contributes to, the depression in immune func-tion after hemorrhage that may increase


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Surgery_Schwartz. = tumor necrosis factor.Brunicardi_Ch05_p0131-p0156.indd 13829/01/19 11:06 AM 139SHOCKCHAPTER 5and perhaps contributes to, the depression in immune func-tion after hemorrhage that may increase the susceptibility of patients who develop shock to suffer infections.26,27 It has been postulated that overly exuberant proinflammatory activation promotes tissue injury, organ dysfunction, and the subsequent immune dysfunction/suppression that may be evident later.22 Emphasizing the importance of temporal changes in the produc-tion of mediators, both the initial excessive production of IL-2 and later depressed IL-2 production are probably important in the progression of shock.MKK3p 38MKK 7JNKDAMPLPS signalingHemorrhagic shockIschemia/reperfusionTissue traumaToxic exposureDanger signalingInjuryNecrosisCD14HMGB-1HMGB-1LPSActivatedTLR4TRAMTRIFIRF 3MyD88-dependentpathwayMyD88-independentpathwayNuclear membraneOtherco-receptorsSecretion fromstressed cellsBreakdownof matrixMyD88MALIRAK 4IRAK


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Surgery_Schwartz. 3MyD88-dependentpathwayMyD88-independentpathwayNuclear membraneOtherco-receptorsSecretion fromstressed cellsBreakdownof matrixMyD88MALIRAK 4IRAK 1TRAF 6TAK 1IKK 1IKK 2IRF 3MD-2NEMOI˜Bp 50p 65NF-˜Bp 50p 65TBK 1Cell membraneCell membraneTLR4TLR4TLR4MD-2LBPFigure 5-5. Signaling via the pattern recognition receptor TLR4. LPS signaling via TLR4 requires the cofactors LPS binding protein (LBP), MD-2, and CD14. Endogenous danger signals released from a variety of sources also signal in a TLR4-dependent fashion, although it is as yet unknown what cofactors may be required for this activity. Once TLR4 is activated, an intracellular signaling cascade is initiated that involves both a MyD88-dependent and independent pathway. DAMP = damage associated molecular pattern; LPS = lipopolysaccharide; MD-2 = myeloid differentiation factor-2; MyD88 = myeloid differentiation primary response gene 88; NF-kB = nuclear factor kB; TLR4 = Toll-like receptor-4. (Reproduced with permission from Mollen KP, Levy


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Surgery_Schwartz. = myeloid differentiation factor-2; MyD88 = myeloid differentiation primary response gene 88; NF-kB = nuclear factor kB; TLR4 = Toll-like receptor-4. (Reproduced with permission from Mollen KP, Levy RM, Prince JM, et al. Systemic inflammation and end organ damage following trauma involves functional TLR4 signaling in both bone marrow-derived cells and parenchymal cells, J Leukoc Biol. 2008 Jan;83(1):80-88.)Brunicardi_Ch05_p0131-p0156.indd 13929/01/19 11:06 AM 140BASIC CONSIDERATIONSPART IIL-6 is elevated in response to hemorrhagic shock, major operative procedures, or trauma. Elevated IL-6 levels correlate with mortality in shock states. IL-6 contributes to lung, liver, and gut injury after hemorrhagic shock.28 Thus, IL-6 may play a role in the development of diffuse alveolar damage and ARDS. IL-6 and IL-1 are mediators of the hepatic acute phase response to injury, and enhance the expression and activity of comple-ment, C-reactive protein, fibrinogen, haptoglobin, amyloid A, and


Surgery_Schwartz

Surgery_Schwartz. ARDS. IL-6 and IL-1 are mediators of the hepatic acute phase response to injury, and enhance the expression and activity of comple-ment, C-reactive protein, fibrinogen, haptoglobin, amyloid A, and alpha1-antitrypsin, and promote neutrophil activation.29IL-10 is considered an anti-inflammatory cytokine that may have immunosuppressive properties. Its production is increased after shock and trauma, and it has been associated with depressed immune function clinically, as well as an increased susceptibility to infection.30 IL-10 is secreted by T cells, mono-cytes, and macrophages, and inhibits proinflammatory cytokine secretion, O2 radical production by phagocytes, adhesion mol-ecule expression, and lymphocyte activation.30,31 Administra-tion of IL-10 depresses cytokine production and improves some aspects of immune function in experimental models of shock and sepsis.32,33Recent studies point to the importance of chemokines, a specific set of cytokines, that have the ability to induce


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Surgery_Schwartz. some aspects of immune function in experimental models of shock and sepsis.32,33Recent studies point to the importance of chemokines, a specific set of cytokines, that have the ability to induce che-motaxis of leukocytes. Chemokines bind to specific chemokine receptors and transduce chemotactic signals to leukocytes. The significance of this large family of chemoattractant cytokines in immunology is difficult to understate, as almost every facet of the immune system is influenced by chemokines, including immune system development, immune surveillance, immune priming, effector responses, and immune regulation.34ComplementThe complement cascade can be activated by injury, shock, and severe infection, and contributes to host defense and pro-inflammatory activation. Significant complement consumption occurs after hemorrhagic shock.35 In trauma patients, the degree of complement activation is proportional to the magnitude of injury and may serve as a marker for severity of injury. Patients


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Surgery_Schwartz. occurs after hemorrhagic shock.35 In trauma patients, the degree of complement activation is proportional to the magnitude of injury and may serve as a marker for severity of injury. Patients in septic shock also demonstrate activation of the complement pathway, with elevations of the activated complement proteins C3a and C5a. Activation of the complement cascade can con-tribute to the development of organ dysfunction. Activated complement factors C3a, C4a, and C5a are potent mediators of increased vascular permeability, smooth muscle cell contraction, histamine and arachidonic acid by-product release, and adher-ence of neutrophils to vascular endothelium. Activated comple-ment acts synergistically with endotoxin to induce the release of TNF-a and IL-1. The development of ARDS and MODS in trauma patients correlates with the intensity of complement activation.36 Complement and neutrophil activation may corre-late with mortality in multiply injured patients.NeutrophilsNeutrophil


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Surgery_Schwartz. in trauma patients correlates with the intensity of complement activation.36 Complement and neutrophil activation may corre-late with mortality in multiply injured patients.NeutrophilsNeutrophil activation is an early event in the upregulation of the inflammatory response; neutrophils are the first cells to be recruited to the site of injury. Polymorphonuclear leuko-cytes (PMNs) remove infectious agents, foreign substances that have penetrated host barrier defenses, and nonviable tis-sue through phagocytosis. However, activated PMNs and their products may also produce cell injury and organ dysfunction. Activated PMNs generate and release a number of substances that may induce cell or tissue injury, such as reactive O2 spe-cies, lipid-peroxidation products, proteolytic enzymes (elastase, cathepsin G), and vasoactive mediators (leukotrienes, eico-sanoids, and platelet-activating factor). Oxygen-free radicals, such as superoxide anion, hydrogen peroxide, and hydroxyl radical, are


Surgery_Schwartz

Surgery_Schwartz. cathepsin G), and vasoactive mediators (leukotrienes, eico-sanoids, and platelet-activating factor). Oxygen-free radicals, such as superoxide anion, hydrogen peroxide, and hydroxyl radical, are released and induce lipid peroxidation, inactivate enzymes, and consume antioxidants (such as glutathione and tocopherol). Ischemia-reperfusion activates PMNs and causes PMN-induced organ injury. In animal models of hemorrhagic shock, activation of PMNs correlates with irreversibility of shock and mortality, and neutrophil depletion prevents the pathophysiologic sequelae of hemorrhagic and septic shock. Human data corroborate the activation of neutrophils in trauma and shock and suggest a role in the development of MODS.37 Plasma markers of PMN activation, such as elastase, correlate with severity of injury in humans.Interactions between endothelial cells and leukocytes are important in the inflammatory process. The vascular endothe-lium contributes to regulation of blood flow, leukocyte


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Surgery_Schwartz. of injury in humans.Interactions between endothelial cells and leukocytes are important in the inflammatory process. The vascular endothe-lium contributes to regulation of blood flow, leukocyte adher-ence, and the coagulation cascade. Extracellular ligands such as intercellular adhesion molecules, vascular cell adhesion mol-ecules, and the selectins (E-selectin, P-selectin) are expressed on the surface of endothelial cells, and are responsible for leuko-cyte adhesion to the endothelium. This interaction allows acti-vated neutrophils to migrate into the tissues to combat infection, but also can lead to PMN-mediated cytotoxicity and microvas-cular and tissue injury.Cell SignalingA host of cellular changes occur following shock. Although many of the intracellular and intercellular pathways that are important in shock are being elucidated, undoubtedly there are many more that have yet to be identified. Many of the media-tors produced during shock interact with cell surface receptors on


Surgery_Schwartz

Surgery_Schwartz. that are important in shock are being elucidated, undoubtedly there are many more that have yet to be identified. Many of the media-tors produced during shock interact with cell surface receptors on target cells to alter target cell metabolism. These signaling pathways may be altered by changes in cellular oxygenation, redox state, high-energy phosphate concentration, gene expres-sion, or intracellular electrolyte concentration induced by shock. Cells communicate with their external environment through the use of cell surface membrane receptors, which, once bound by a ligand, transmit their information to the interior of the cell through a variety of signaling cascades. These signaling path-ways may subsequently alter the activity of specific enzymes, the expression or breakdown of important proteins, or affect intracellular energy metabolism. Intracellular calcium (Ca2+) homeostasis and regulation represents one such pathway. Intra-cellular Ca2+ concentrations regulate many aspects


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Surgery_Schwartz. proteins, or affect intracellular energy metabolism. Intracellular calcium (Ca2+) homeostasis and regulation represents one such pathway. Intra-cellular Ca2+ concentrations regulate many aspects of cellular metabolism; many important enzyme systems require Ca2+ for Table 5-4Inflammatory mediators of shockPROINFLAMMATORYANTI-INFLAMMATORYInterleukin-1α/βInterleukin-4Interleukin-2Interleukin-10Interleukin-6Interleukin-13Interleukin-8Prostaglandin E2InterferonTGFβTNF PAF PAF = platelet activating factor; TGFβ = transforming growth factor β; TNF = tumor necrosis factor.Brunicardi_Ch05_p0131-p0156.indd 14029/01/19 11:06 AM 141SHOCKCHAPTER 5full activity. Profound changes in intracellular Ca2+ levels and Ca2+ transport are seen in models of shock.38 Alterations in Ca2+ regulation may lead to direct cell injury, changes in transcription factor activation, alterations in the expression of genes impor-tant in homeostasis, and the modulation of the activation of cells by other shock-induced


Surgery_Schwartz

Surgery_Schwartz. direct cell injury, changes in transcription factor activation, alterations in the expression of genes impor-tant in homeostasis, and the modulation of the activation of cells by other shock-induced hormones or mediators.39,40A proximal portion of the intracellular signaling cascade consists of a series of kinases that transmit and amplify the sig-nal through the phosphorylation of target proteins. The O2 radi-cals produced during shock and the intracellular redox state are known to influence the activity of components of this cascade, such as protein tyrosine kinases, mitogen activated kinases, and protein kinase C.41-43 Either through changes in these sig-naling pathways, changes in the activation of enzyme systems through Ca2+-mediated events, or direct conformational changes to oxygen-sensitive proteins, O2 radicals also regulate the activ-ity of a number of transcription factors that are important in gene expression, such as nuclear factor kB, APETALA1, and hypoxia-inducible


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Surgery_Schwartz. proteins, O2 radicals also regulate the activ-ity of a number of transcription factors that are important in gene expression, such as nuclear factor kB, APETALA1, and hypoxia-inducible factor 1.44,45 It is therefore becoming increas-ingly clear that oxidant-mediated direct cell injury is merely one consequence of the production of O2 radicals during shock.The study of the effects of shock on the regulation of gene expression as an important biologic effect was stimulated by the work of Buchman and colleagues.46 The effects of shock on the expression and regulation of numerous genes and gene products has been studied in both experimental animal models and human patients. These studies include investigations into single genes of interest as well as large-scale genomic and proteomic analysis.47-49 Changes in gene expression are critical for adaptive and survival cell signaling. Polymorphisms in gene promoters that lead to a differential level of expression of gene products are also


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Surgery_Schwartz. Changes in gene expression are critical for adaptive and survival cell signaling. Polymorphisms in gene promoters that lead to a differential level of expression of gene products are also likely to contribute significantly to varied responses to similar insults.50,51 In a recent study, the genetic responses to traumatic injury in humans or endotoxin delivery to healthy human volunteers demonstrated that severe stresses produce a global reprioritiza-tion affecting >80% of the cellular functions and pathways.52 The similarities in genomic responses among different injuries revealed a fundamental human response to stressors involving dysregulated immune responses (Fig. 5-6). Furthermore, in trau-matic injury patients, complications like nosocomial infections and organ failure were not associated with any genomic evi-dence of a second hit and differed only in the magnitude and duration of this genomic reprioritization.FORMS OF SHOCKHypovolemic/HemorrhagicThe most common cause of shock in


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Surgery_Schwartz. with any genomic evi-dence of a second hit and differed only in the magnitude and duration of this genomic reprioritization.FORMS OF SHOCKHypovolemic/HemorrhagicThe most common cause of shock in the surgical or trauma patient is loss of circulating volume from hemorrhage. Acute blood loss results in reflexive decreased baroreceptor stimu-lation from stretch receptors in the large arteries, resulting in decreased inhibition of vasoconstrictor centers in the brain stem, increased chemoreceptor stimulation of vasomotor centers, and diminished output from atrial stretch receptors. These changes increase vasoconstriction and peripheral arterial resistance. Hypovolemia also induces sympathetic stimulation, leading to epinephrine and norepinephrine release, activation of the renin-angiotensin cascade, and increased vasopressin release. Periph-eral vasoconstriction is prominent, while lack of sympathetic effects on cerebral and coronary vessels and local autoregula-tion promote maintenance of


Surgery_Schwartz

Surgery_Schwartz. and increased vasopressin release. Periph-eral vasoconstriction is prominent, while lack of sympathetic effects on cerebral and coronary vessels and local autoregula-tion promote maintenance of cardiac and CNS blood flow.Diagnosis. Treatment of shock is initially empiric. A secure airway must be confirmed or established in obtunded patients. The priority is the initiation of volume infusion while the search for the cause of the hypotension is pursued. Shock in a trauma patient or postoperative patient should be presumed to be due to hemorrhage until proven otherwise. The clinical signs of shock may be evidenced by agitation, cool clammy extremities, tachy-cardia, weak or absent peripheral pulses, and hypotension. Such apparent clinical shock results from at least 25% to 30% loss of the blood volume. However, substantial volumes of blood may be lost before the classic clinical manifestations of shock are evident. Thus, when a patient is significantly tachycardic or hypotensive, this


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Surgery_Schwartz. blood volume. However, substantial volumes of blood may be lost before the classic clinical manifestations of shock are evident. Thus, when a patient is significantly tachycardic or hypotensive, this represents both significant blood loss and physiologic decompensation. The clinical and physiologic response to hemorrhage has been classified according to the magnitude of volume loss. Loss of up to 15% of the circulat-ing volume (700 to 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 tachycar-dia, tachypnea, and anxiety. Hypotension, marked tachycardia (i.e., pulse greater than 110 to 120 bpm), and confusion may not be evident until more than 30% of the blood volume has been lost; loss of 40% of circulating volume (2 L) is immedi-ately life threatening and generally requires operative control of bleeding (Table 5-5). Young healthy patients with vigor-ous compensatory mechanisms may


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Surgery_Schwartz. of 40% of circulating volume (2 L) is immedi-ately life threatening and generally requires operative control of bleeding (Table 5-5). Young healthy patients with vigor-ous compensatory mechanisms may tolerate larger volumes of blood loss while manifesting fewer clinical signs despite the presence of significant peripheral hypoperfusion. These patients may maintain a near-normal blood pressure until a precipitous cardiovascular collapse occurs. Elderly patients may be tak-ing medications that either promote bleeding (e.g., warfarin or aspirin), or mask the compensatory responses to bleeding (e.g., β-blockers). In addition, atherosclerotic vascular disease, diminishing cardiac compliance with age, inability to elevate heart rate or cardiac contractility in response to hemorrhage, and overall decline in physiologic reserve decrease the elderly Dysregulated adaptive immune responseMagnitude of responseMagnitude of responseUncomplicated outcomeComplicated outcomeDysregulated innate immune


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Surgery_Schwartz. decline in physiologic reserve decrease the elderly Dysregulated adaptive immune responseMagnitude of responseMagnitude of responseUncomplicated outcomeComplicated outcomeDysregulated innate immune responseFigure 5-6. The concurrent dysregulated innate immune responses that promote inflammation and dysregulated adaptive immune responses that result in immunosuppression occur in patients follow-ing traumatic injury. However, these genetic responses can result in complicated outcomes in trauma patients if the magnitude or dura-tion of these responses are pronounced. (Reproduced with permission from Xiao W, Mindrinos MN, Seok J, et al. A genomic storm in criti-cally injured humans, J Exp Med. 2011 Dec 19;208(13):2581-2590.)Brunicardi_Ch05_p0131-p0156.indd 14129/01/19 11:06 AM 142BASIC CONSIDERATIONSPART Ipatient’s ability to tolerate hemorrhage. Recent data in trauma patients suggest that a systolic blood pressure (SBP) of less than 110 mmHg is a clinically relevant definition of


Surgery_Schwartz

Surgery_Schwartz. CONSIDERATIONSPART Ipatient’s ability to tolerate hemorrhage. Recent data in trauma patients suggest that a systolic blood pressure (SBP) of less than 110 mmHg is a clinically relevant definition of hypotension and hypoperfusion based upon an increasing rate of mortality below this pressure (Fig. 5-7).53In addressing the sensitivity of vital signs and identifying major thoracoabdominal hemorrhage, a study retrospectively identified patients with injury to the trunk and an abbreviated injury score of 3 or greater who required immediate surgical intervention and transfusion of at least 5 units of blood within the first 24 hours. Ninety-five percent of patients had a heart rate greater than 80 bpm at some point during their postinjury course. However, only 59% of patients achieved a heart rate greater than 120 bpm. Ninety-nine percent of all patients had a recorded blood pressure of less than 120 mmHg at some point. Ninety-three percent of all patients had a recorded SBP of less than 100


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Surgery_Schwartz. greater than 120 bpm. Ninety-nine percent of all patients had a recorded blood pressure of less than 120 mmHg at some point. Ninety-three percent of all patients had a recorded SBP of less than 100 mmHg.54 A more recent study corroborated that tachy-cardia was not a reliable sign of hemorrhage following trauma and was present in only 65% of hypotensive patients.55Serum lactate and base deficit are measurements that are helpful to both estimate and monitor the extent of bleeding and shock. The amount of lactate that is produced by anaerobic res-piration is an indirect marker of tissue hypoperfusion, cellular O2 debt, and the severity of hemorrhagic shock. Several stud-ies have demonstrated that the initial serum lactate and serial lactate levels are reliable predictors of morbidity and mortality with hemorrhage following trauma (Fig. 5-8).56 Similarly, base deficit values derived from arterial blood gas analysis provide clinicians with an indirect estimation of tissue acidosis from


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Surgery_Schwartz. mortality with hemorrhage following trauma (Fig. 5-8).56 Similarly, base deficit values derived from arterial blood gas analysis provide clinicians with an indirect estimation of tissue acidosis from hypoperfusion. Davis and colleagues stratified the extent of base deficit into mild (–3 to –5 mmol/L), moderate (–6 to –9 mmol/L), and severe (less than –10 mmol/L), and from this established a correlation between base deficit upon admission with transfu-sion requirements, the development of multiple organ failure, and death (Fig. 5-9).57 Both base deficit and lactate correlate with the extent of shock and patient outcome, but interestingly do not firmly correlate with each other.58-60 Evaluation of both values may be useful in trauma patients with hemorrhage.Although hematocrit changes may not rapidly reflect the total volume of blood loss, admission hematocrit has been shown to be associated with 24 hour fluid and transfusion requirements and more strongly associated with PRBC


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Surgery_Schwartz. may not rapidly reflect the total volume of blood loss, admission hematocrit has been shown to be associated with 24 hour fluid and transfusion requirements and more strongly associated with PRBC transfu-sion than either tachycardia, hypotension, or acidosis.61 It must be noted that lack of a depression in the initial hematocrit does not rule out substantial blood loss or ongoing bleeding.In management of trauma patients, understanding the pat-terns of injury of the patient in shock will help direct the evalu-ation and management. Identifying the sources of blood loss in patients with penetrating wounds is relatively simple because potential bleeding sources will be located along the known or suspected path of the wounding object. Patients with penetrating injuries who are in shock usually require operative intervention. Patients who suffer multisystem injuries from blunt trauma have multiple sources of potential hemorrhage. Blood loss sufficient to cause shock is generally of a large


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Surgery_Schwartz. require operative intervention. Patients who suffer multisystem injuries from blunt trauma have multiple sources of potential hemorrhage. Blood loss sufficient to cause shock is generally of a large volume, and there are a limited number of sites that can harbor sufficient extravascular blood volume to induce hypotension (e.g., external, intratho-racic, intra-abdominal, retroperitoneal, and long bone fractures). In the nontrauma patient, the GI tract must always be considered as a site for blood loss. Substantial blood loss externally may be suspected from prehospital medical reports documenting a sub-stantial blood loss at the scene of an accident, history of massive Table 5-5Classification of hemorrhage CLASSPARAMETERIIIIIIIVBlood loss (mL)<750750–15001500–2000>2000Blood loss (%)<1515–3030–40>40Heart rate (bpm)<100>100>120>140Blood pressureNormalOrthostaticHypotensionSevere hypotensionCNS symptomsNormalAnxiousConfusedObtundedbpm = beats per minute; CNS = central nervous


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Surgery_Schwartz. (%)<1515–3030–40>40Heart rate (bpm)<100>100>120>140Blood pressureNormalOrthostaticHypotensionSevere hypotensionCNS symptomsNormalAnxiousConfusedObtundedbpm = beats per minute; CNS = central nervous system.3025201510506065707580859095100105Systolic BP in the ED110115120125130135140145150155160121086420% MortalityBase deficit% MortalityBDFigure 5-7. The relationship between systolic blood pressure and mortality in trauma patients with hemorrhage. These data suggest that a systolic blood pressure of less than 110 mmHg is a clinically relevant definition of hypotension and hypoperfusion based upon an increasing rate of mortal-ity below this pressure. Base deficit (BD) is also shown on this graph. ED = emergency department. (Reproduced with permission from Eastridge BJ, Salinas J, McManus JG, et al. Hypotension begins at 110 mm Hg: redefining “hypotension” with data, J Trauma. 2007 Aug;63(2):291-297.)Brunicardi_Ch05_p0131-p0156.indd 14229/01/19 11:06 AM 143SHOCKCHAPTER 5blood loss from


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Surgery_Schwartz. al. Hypotension begins at 110 mm Hg: redefining “hypotension” with data, J Trauma. 2007 Aug;63(2):291-297.)Brunicardi_Ch05_p0131-p0156.indd 14229/01/19 11:06 AM 143SHOCKCHAPTER 5blood loss from wounds, visible brisk bleeding, or presence of a large hematoma adjacent to an open wound. Injuries to major arteries or veins with associated open wounds may cause massive blood loss rapidly. Direct pressure must be applied and sustained to minimize ongoing blood loss. Tourniquets should be used for extremity bleeding stopped by direct pressure and applied in the prehospital setting as needed.62,63 Persistent bleeding from uncontrolled smaller vessels can, over time, precipitate shock if inadequately treated.When major blood loss is not immediately visible in the setting of trauma, internal (intracavitary) blood loss should be suspected. Each pleural cavity can hold 2 to 3 L of blood and can therefore be a site of significant blood loss. Diagnostic and therapeutic tube thoracostomy may be


Surgery_Schwartz

Surgery_Schwartz. blood loss should be suspected. Each pleural cavity can hold 2 to 3 L of blood and can therefore be a site of significant blood loss. Diagnostic and therapeutic tube thoracostomy may be indicated in unstable patients based on clinical findings and clinical suspicion. In a more stable patient, a chest radiograph may be obtained to look for evidence of hemothorax. Major retroperitoneal hem-orrhage typically occurs in association with pelvic fractures, which is confirmed by pelvic radiography in the resuscitation bay. Intraperitoneal hemorrhage is probably the most common source of blood loss that induces shock. The physical exam for detection of substantial blood loss or injury is insensitive and unreliable; large volumes of intraperitoneal blood may be present before physical examination findings are apparent. Findings with intra-abdominal hemorrhage include abdominal distension, abdominal tenderness, or visible abdominal wounds. Hemodynamic abnormalities generally stimulate a search


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Surgery_Schwartz. findings are apparent. Findings with intra-abdominal hemorrhage include abdominal distension, abdominal tenderness, or visible abdominal wounds. Hemodynamic abnormalities generally stimulate a search for blood loss before the appearance of obvious abdominal findings. Adjunctive tests are essential in the diagnosis of intraperitoneal bleeding; intraperitoneal blood may be rapidly identified by diagnostic ultrasound or diagnostic peritoneal lavage. Further-more, patients that have sustained high-energy blunt trauma that are hemodynamically stable or that have normalized their vital signs in response to initial volume resuscitation should undergo computed tomography scans to assess for head, chest, and/or abdominal bleeding.Treatment. Control of ongoing hemorrhage is an essential component of the resuscitation of the patient in shock. As mentioned in the previous “Diagnosis” section, treatment of hemorrhagic shock is instituted concurrently with diagnostic evaluation to identify a


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Surgery_Schwartz. of the resuscitation of the patient in shock. As mentioned in the previous “Diagnosis” section, treatment of hemorrhagic shock is instituted concurrently with diagnostic evaluation to identify a source. Patients who fail to respond to initial resuscitative efforts should be assumed to have ongo-ing active hemorrhage from large vessels and require prompt operative intervention. Based on trauma literature, patients with ongoing hemorrhage demonstrate increased survival if the elapsed time between the injury and control of bleeding is decreased. Although there are no randomized controlled trials, retrospective studies provide compelling evidence in this regard. To this end, Clarke and colleagues64 demonstrated that trauma Serum lactateMuscle lactateLiver lactateTime (hours)Serum lactate (mg/100 ml)Tissue lactate (M/gm tissue)012345510152025306090120150Figure 5-8. Progressive increases in serum lactate, muscle lactate, and liver lactate in a baboon model of hemorrhagic shock. (Repro-duced


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Surgery_Schwartz. ml)Tissue lactate (M/gm tissue)012345510152025306090120150Figure 5-8. Progressive increases in serum lactate, muscle lactate, and liver lactate in a baboon model of hemorrhagic shock. (Repro-duced with permission from Peitzman AB, Corbett WA, Shires GT, et al: Cellular function in liver and muscle during hemorrhagic shock in primates, Surg Gynecol Obstet. 1985 Nov;161(5):419-424.)Extracellular BEA, mmol/L10059590858075706560555045403530252015100102–6–14–22–38% MortalityBase excess = –11.8LD50% Mortality = e˜1 + e˜x 10010090807060504030201001020% Predicted death on the basis of linear logistic model from BEAECF% Observed death0–0.19–0.17–4.5–7.4–9.7–11.8–14–16.4–19.2–23.530405060708090100Figure 5-9. The relationship between base deficit (negative base excess) and mortality in trauma patients. BEA = base excess arterial; ECF = extracellular fluid. (Reproduced with permission from Siegel JH, Rivkind AI, Dalal S, et al: Early physiologic predictors of injury severity and death in blunt


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Surgery_Schwartz. BEA = base excess arterial; ECF = extracellular fluid. (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 Apr;125(4):498-508.)Brunicardi_Ch05_p0131-p0156.indd 14329/01/19 11:06 AM 144BASIC CONSIDERATIONSPART Ipatients with major injuries isolated to the abdomen requiring emergency laparotomy had an increased probability of death with increasing length of time in the emergency department for patients who were in the emergency department for 90 minutes or less. This probability increased approximately 1% for each 3 minutes in the emergency department.The appropriate priorities in these patients are as follows: (a) control the source of blood loss, (b) perform IV volume resuscitation with blood products in the hypotensive patient, and (c) secure the airway. In trauma, identifying the body cavity har-boring active hemorrhage will help focus operative efforts;


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Surgery_Schwartz. volume resuscitation with blood products in the hypotensive patient, and (c) secure the airway. In trauma, identifying the body cavity har-boring active hemorrhage will help focus operative efforts; how-ever, because 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. Our current understanding has led to the management strategy known as damage control resuscitation.65 This strategy begins in the emergency depart-ment, continues into the operating room, and into the intensive care unit (ICU). Initial resuscitation is limited to keep SBP around 80 to 90 mmHg. This prevents renewed bleeding from recently clotted vessels. Resuscitation and intravascular volume resuscitation is accomplished with blood products and lim-ited crystalloids, which is addressed further later in this section. Too little volume allowing persistent


Surgery_Schwartz

Surgery_Schwartz. and intravascular volume resuscitation is accomplished with blood products and lim-ited crystalloids, which is addressed further later in this section. Too little volume allowing persistent severe hypoten-sion and hypoperfusion is dangerous, yet too vigorous of a vol-ume resuscitation may be just as deleterious. Control of hemorrhage is achieved in the operating room (or angiography suite once surgical causes of hemorrhage have been ruled out), and efforts to warm patients and to prevent coagulopathy using multiple blood products and pharmacologic agents are used in both the operating room and ICU.Cannon and colleagues first made the observation that attempts to increase blood pressure in soldiers with uncontrolled sources of hemorrhage is counterproductive, with increased bleeding and higher mortality.3 This work was the foundation for the “hypotensive resuscitation” strategies. Several laboratory studies confirmed the observation that attempts to restore normal blood pressure with


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Surgery_Schwartz. mortality.3 This work was the foundation for the “hypotensive resuscitation” strategies. Several laboratory studies confirmed the observation that attempts to restore normal blood pressure with fluid infusion or vasopressors was rarely achievable and resulted in more bleeding and higher mortality.66 A prospective, randomized clinical study compared delayed fluid resuscitation (upon arrival in the operating room) with standard fluid resuscitation (with arrival by the paramedics) in hypotensive patients with penetrating torso injury.67 The authors reported that delayed fluid resuscitation resulted in lower patient mortality. Further laboratory studies demonstrated that fluid restriction in the setting of profound hypotension resulted in early deaths from severe hypoperfusion. These studies also showed that aggressive crystalloid resuscitation attempting to normalize blood pressure resulted in marked hemodilution, with hematocrits of 5%.66 Reasonable conclusions in the setting of


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Surgery_Schwartz. also showed that aggressive crystalloid resuscitation attempting to normalize blood pressure resulted in marked hemodilution, with hematocrits of 5%.66 Reasonable conclusions in the setting of uncontrolled hemorrhage include (a) any delay in surgery for control of hemorrhage increases mortality; (b) with uncontrolled hemorrhage, attempting to achieve normal blood pressure may increase mortality, particularly with penetrating injuries and short transport times; (c) a goal of SBP of 80 to 90 mmHg may be adequate in the patient with penetrating injury; and (d) 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 a closed head injury, the increase in mortality with hypotension in the setting of brain injury must be avoided. In this setting, a SBP of 110 mmHg would seem to be more appropriate.Patients who respond to initial resuscitative effort but then deteriorate hemodynamically frequently


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Surgery_Schwartz. brain injury must be avoided. In this setting, a SBP of 110 mmHg would seem to be more appropriate.Patients who respond to initial resuscitative effort but then deteriorate hemodynamically frequently have injuries that require operative intervention. The magnitude and duration of their response will dictate whether diagnostic maneuvers can be performed to identify the site of bleeding. However, hemo-dynamic deterioration generally denotes ongoing bleeding for which some form of intervention (i.e., operation or interven-tional radiology) is required. Patients who have lost significant intravascular volume, but whose hemorrhage is controlled or has abated, often will respond to resuscitative efforts if the depth and duration of shock have been limited.A subset of patients exists who fail to respond to resuscita-tive efforts despite adequate control of ongoing hemorrhage. These patients have ongoing fluid requirements despite ade-quate control of hemorrhage, have persistent hypotension


Surgery_Schwartz

Surgery_Schwartz. respond to resuscita-tive efforts despite adequate control of ongoing hemorrhage. These patients have ongoing fluid requirements despite ade-quate control of hemorrhage, have persistent hypotension despite restoration of intravascular volume necessitating vasopressor support, and may exhibit a futile cycle of uncorrectable hypothermia, hypoperfusion, acidosis, and coagulopathy that cannot be interrupted despite maximum ther-apy. These patients have deteriorated to decompensated or irre-versible shock with peripheral vasodilation and resistance to vasopressor infusion. Mortality is almost inevitable once the patient manifests shock in its terminal stages. Unfortunately, this is often diagnosed in retrospect.Fluid resuscitation is a major adjunct to physically con-trolling hemorrhage in patients with shock. The ideal type of fluid to be used continues to be debated; however, crystalloids continue to be the mainstay fluid of choice. Several studies have demonstrated increased risk of


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Surgery_Schwartz. patients with shock. The ideal type of fluid to be used continues to be debated; however, crystalloids continue to be the mainstay fluid of choice. Several studies have demonstrated increased risk of death in bleeding trauma patients treated with colloid compared to patients treated with crystalloid.68 In patients with severe hemorrhage, restoration of intravascular volume should be achieved with blood products.69Ongoing studies continue to evaluate the use of hypertonic saline as a resuscitative adjunct in bleeding patients.70 The ben-efit of hypertonic saline solutions may be immunomodulatory. Specifically, these effects have been attributed to pharmacologic effects resulting in decreased reperfusion-mediated injury with decreased O2 radical formation, less impairment of immune function compared to standard crystalloid solution, and less brain swelling in the multi-injured patient. The reduction of total volume used for resuscitation makes this approach appealing as a resuscitation


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Surgery_Schwartz. compared to standard crystalloid solution, and less brain swelling in the multi-injured patient. The reduction of total volume used for resuscitation makes this approach appealing as a resuscitation agent for combat injuries and may contribute to a decrease in the incidence of ARDS and multiple organ failure.Transfusion of packed red blood cells and other blood products is essential in the treatment of patients in hemorrhagic shock. Current recommendations in stable ICU patients aim for a target hemoglobin of 7 to 9 g/dL71,72; however, no prospective randomized trials have compared restrictive and liberal transfu-sion regimens in trauma patients with hemorrhagic shock. The current standard in severely injured patients is termed dam-age control resuscitation and consists of transfusion with red blood cells, fresh frozen plasma (FFP), and platelet units given in equal number.73 Civilian and military trauma data show that the development of coagulopathy of trauma is predictive of


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Surgery_Schwartz. with red blood cells, fresh frozen plasma (FFP), and platelet units given in equal number.73 Civilian and military trauma data show that the development of coagulopathy of trauma is predictive of mortality.74 Data collected from a U.S. Army combat support hospital helped to propagate this practice, showing in patients that received massive transfusion of packed red blood cells (>10 units in 24 hours) that a high plasma to RBC ratio (1:1.4 units) was independently associated with improved survival.75 A number of civilian studies have demonstrated similar results.76 Similarly, platelet transfusion is important. The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) 45Brunicardi_Ch05_p0131-p0156.indd 14429/01/19 11:06 AM 145SHOCKCHAPTER 5trial has demonstrated that damage-control resuscitation, a massive transfusion strategy targeting a balanced delivery of plasma-platelet-red blood cell in a ratio of 1:1:1, results in improved survival at 3 hours and a reduction in


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Surgery_Schwartz. resuscitation, a massive transfusion strategy targeting a balanced delivery of plasma-platelet-red blood cell in a ratio of 1:1:1, results in improved survival at 3 hours and a reduction in deaths caused by exsanguination in the first 24 hours.77 Studies have demon-strated that low platelet counts in trauma patients was associ-ated with increased mortality78 and that increased platelet use appears to improve outcome.79,80 The benefit of platelet trans-fusion may be most pronounced in trauma patients with brain injury.81 It has been suggested that platelets should be transfused in the bleeding patient to maintain counts above 50 × 109/L. In addition, transfusion of whole blood is gaining in popularity, and ongoing studies are evaluating the benefit of this approach.There is a potential role for other coagulation factor based products, such as fibrinogen concentrates and prothrombin complex concentrates. Use of these agents may be guided by a drop in fibrinogen levels to less than 1


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Surgery_Schwartz. role for other coagulation factor based products, such as fibrinogen concentrates and prothrombin complex concentrates. Use of these agents may be guided by a drop in fibrinogen levels to less than 1 g/L, or less specifically by thromboelastogram findings to suggest hyperfibrinolysis. Data also support the use of antifibrinolytic agents in bleeding trauma patients, specifically tranexamic acid (a synthetic lysine analogues that acts as a competitive inhibitor of plasmin and plasminogen). The multinational Clinical Randomization of an Antifibrinolytic in Significant Haemorrhage 2 (CRASH-2) trial suggested that early use of tranexamic acid limits rebleeding and reduces mortality82 (Fig 5-10). In the past, coagulopathy associated with the bleeding patient was presumed to be due solely to dilution and depletion of clotting factors and plate-lets. We now understand that an acute coagulopathy of trauma occurs as an immediate consequence of injury, with abnormal admission coagulation as a


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Surgery_Schwartz. and depletion of clotting factors and plate-lets. We now understand that an acute coagulopathy of trauma occurs as an immediate consequence of injury, with abnormal admission coagulation as a predictor of high mortality.83 Tradi-tional measurement of platelets, INR, and PTT may not reflect the coagulopathy of trauma or response to therapy effectively. Recently, viscoelastic functional testing such as thromboelas-tography (TEG) has been utilized as a quicker, more compre-hensive determination of coagulopathy and fibrinolysis in the injured patient. Holcomb et al recently reported that TEG pre-dicted patients with substantial bleeding and red cell transfusion better than conventional coagulopathy tests, and it also predicted the need for platelet transfusion better than platelet count and the need for plasma transfusion better than fibrinogen levels.84OR (95% CI) of tranexamic acidTime to treatment (h)0.58765432101.01.52.02.53.0Figure 5-10. Early treatment (within 3 hours) of trauma


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Surgery_Schwartz. the need for plasma transfusion better than fibrinogen levels.84OR (95% CI) of tranexamic acidTime to treatment (h)0.58765432101.01.52.02.53.0Figure 5-10. Early treatment (within 3 hours) of trauma patients with tranexamic acid reduces mortality. However, later treatment exacerbated outcome. (Reproduced with permission from Roberts I, Shakur H, Afolabi A, et al. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial, Lancet. 2011 Mar 26;377(9771):1096-1101.)Additional resuscitative adjuncts in patients with hemor-rhagic shock include minimization of heat loss and maintaining normothermia. The development of hypothermia in the bleeding patient is associated with acidosis, hypotension, and coagulopa-thy. Hypothermia in bleeding trauma patients is an independent risk factor for bleeding and death. This likely is secondary to impaired platelet function and impairments in the coagulation


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Surgery_Schwartz. coagulopa-thy. Hypothermia in bleeding trauma patients is an independent risk factor for bleeding and death. This likely is secondary to impaired platelet function and impairments in the coagulation cascade. Several studies have investigated the induction of con-trolled hypothermia in patients with severe shock based on the hypothesis of limiting metabolic activity and energy require-ments, creating a state of “suspended animation.” These studies are promising and continue to be evaluated in large trials.Traumatic ShockThe 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. Multiple organ failure, including acute respiratory distress syn-drome (ARDS), develops relatively often in the blunt trauma patient, but rarely after pure hemorrhagic shock (such as a GI bleed). The hypoperfusion deficit in traumatic shock is magnified by the proinflammatory


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Surgery_Schwartz. develops relatively often in the blunt trauma patient, but rarely after pure hemorrhagic shock (such as a GI bleed). The hypoperfusion deficit in traumatic shock is magnified by the proinflammatory activation that occurs following the induc-tion of shock. In addition to ischemia or ischemia-reperfusion, accumulating evidence demonstrates that even simple hemor-rhage induces proinflammatory activation that results in many of the cellular changes typically ascribed only to septic shock.85,86 At the cellular level, this may be attributable to the release of cellular products termed damage associated molecu-lar patterns (DAMPs, i.e., riboxynucleic 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.5,87 These receptors are termed pattern recognition receptors (PRRs) and include the TLR family of proteins. Examples of traumatic shock include small volume hemorrhage accompanied by soft


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Surgery_Schwartz. signaling.5,87 These receptors are termed pattern recognition receptors (PRRs) and include the TLR family of proteins. Examples of traumatic shock include small volume hemorrhage accompanied by soft tissue injury (femur fracture, crush injury), or any combination of hypovolemic, neurogenic, cardiogenic, and obstructive shock that precipitate rapidly progressive proin-flammatory activation. In laboratory models of traumatic shock, the addition of a soft tissue or long bone injury to hemorrhage produces lethality with significantly less blood loss when the animals are stressed by hemorrhage. Treatment of traumatic shock is focused on correction of the individual elements to diminish the cascade of proinflammatory activation, and includes prompt control of hemorrhage, adequate volume resus-citation to correct O2 debt, debridement of nonviable tissue, stabilization of bony injuries, and appropriate treatment of soft tissue injuries.Septic Shock (Vasodilatory Shock)In the peripheral


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Surgery_Schwartz. to correct O2 debt, debridement of nonviable tissue, stabilization of bony injuries, and appropriate treatment of soft tissue injuries.Septic Shock (Vasodilatory Shock)In the peripheral circulation, profound vasoconstriction is the typical physiologic response to the decreased arterial pressure and tissue perfusion with hemorrhage, hypovolemia, or acute heart failure. This is not the characteristic response in vasodila-tory shock. Vasodilatory shock is the result of dysfunction of the endothelium and vasculature secondary to circulating inflam-matory mediators and cells or as a response to prolonged and severe hypoperfusion. Thus, in vasodilatory shock, hypotension results from failure of the vascular smooth muscle to constrict appropriately. Vasodilatory shock is characterized by peripheral vasodilation with resultant hypotension and resistance to treat-ment with vasopressors. Despite the hypotension, plasma cate-cholamine levels are elevated, and the renin-angiotensin system


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Surgery_Schwartz. peripheral vasodilation with resultant hypotension and resistance to treat-ment with vasopressors. Despite the hypotension, plasma cate-cholamine levels are elevated, and the renin-angiotensin system 6Brunicardi_Ch05_p0131-p0156.indd 14529/01/19 11:06 AM 146BASIC CONSIDERATIONSPART Iis activated in vasodilatory shock. The most frequently encoun-tered form of vasodilatory shock is septic shock. Other causes of vasodilatory shock include hypoxic lactic acidosis, carbon monoxide poisoning, decompensated and irreversible hemor-rhagic shock, terminal cardiogenic shock, and postcardiotomy shock (Table 5-6). Thus, vasodilatory shock seems to represent the final common pathway for profound and prolonged shock of any etiology.88Despite advances in intensive care, the mortality rate for severe sepsis remains at 30% to 50%. In the United States, 750,000 cases of sepsis occur annually, one-third of which are fatal.89 Sepsis accounts for 9.3% of deaths in the United States, as many yearly as


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Surgery_Schwartz. sepsis remains at 30% to 50%. In the United States, 750,000 cases of sepsis occur annually, one-third of which are fatal.89 Sepsis accounts for 9.3% of deaths in the United States, as many yearly as MI. Septic shock is a by-product of the body’s response to disruption of the host-microbe equilibrium, result-ing in invasive or severe localized infection.In the attempt to eradicate the pathogens, the immune and other cell types (e.g., endothelial cells) elaborate soluble medi-ators that enhance macrophage and neutrophil killing effec-tor mechanisms, 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 enhanced cardiac output, peripheral vasodilation, fever, leukocytosis, hyperglycemia, and tachycardia. In septic


Surgery_Schwartz

Surgery_Schwartz. rather than localized, manifestations of sepsis may be evident. These findings include enhanced cardiac output, peripheral vasodilation, fever, leukocytosis, hyperglycemia, and tachycardia. In septic shock, the vasodilatory effects are due, in part, to the upregulation of the inducible isoform of nitric oxide synthase (iNOS or NOS 2) in the vessel wall. iNOS produces large quantities of nitric oxide for sustained periods of time. This potent vasodilator suppresses vascular tone and renders the vasculature resistant to the effects of vasoconstricting agents. Additionally, endothelial activation or injury likely contributes to some degree of vascular dysfunction.Diagnosis. 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 in addition to identification of an offending organism. The terms sepsis and septic shock are used to quantify the


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Surgery_Schwartz. adult. These criteria include manifestations of the host response to infection in addition to identification of an offending organism. The terms sepsis and septic shock are used to quantify the magnitude of the systemic inflammatory reac-tion. Patients with sepsis have evidence of an infection, as well as systemic signs of inflammation (e.g., fever, leukocytosis, and tachycardia). Hypoperfusion with signs of organ dysfunction is termed severe sepsis. Septic shock requires the presence of the aforementioned signs, associated with more significant evidence of tissue hypoperfusion and systemic hypotension. Beyond the hypotension, maldistribution of blood flow and shunting in the microcirculation further compromise delivery of nutrients to the tissue beds.90,91 The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) have refined the defi-nitions and utilize a Sequential (Sepsis-related) Organ Failure Assessment (SOFA) score to help determine signs of organ


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Surgery_Schwartz. Definitions for Sepsis and Septic Shock (Sepsis-3) have refined the defi-nitions and utilize a Sequential (Sepsis-related) Organ Failure Assessment (SOFA) score to help determine signs of organ dys-function and to guide management.92Recognizing septic shock begins with defining the patient at risk. The clinical manifestations of septic shock will usually become evident and prompt the initiation of treatment before bacteriologic confirmation of an organism or the source of an organism is identified. In addition to fever, tachycardia, and tachypnea, signs of hypoperfusion such as confusion, malaise, oliguria, or hypotension may be present. These should prompt an aggressive search for infection, including a thorough physical examination, inspection of all wounds, evaluation of intravas-cular catheters or other foreign bodies, obtaining appropriate cultures, and adjunctive imaging studies, as needed.Treatment. Evaluation of the patient in septic shock begins with an assessment of the


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Surgery_Schwartz. catheters or other foreign bodies, obtaining appropriate cultures, and adjunctive imaging studies, as needed.Treatment. Evaluation of the patient in septic shock begins with an assessment of the adequacy of their airway and ven-tilation. Severely obtunded patients and patients whose work of breathing is excessive require intubation and ventilation to prevent respiratory collapse. Because vasodilation and decrease in total peripheral resistance may produce hypotension, fluid resuscitation and restoration of circulatory volume with bal-anced salt solutions is essential. The Surviving Sepsis Campaign has updated treatment recommendations and care bundles with a most recent goal for care within the first hour93,94 (Table 5-7). Serum lactate should be measured as a marker of shock. Fluid resuscitation should begin within the first hour and should be at least 30 mL/kg for hypotensive patients. Incremental fluid boluses should be continued based upon endpoint of resuscita-tion, including


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Surgery_Schwartz. should begin within the first hour and should be at least 30 mL/kg for hypotensive patients. Incremental fluid boluses should be continued based upon endpoint of resuscita-tion, including clearance of lactate. Starch-based colloid solu-tions should be avoided as recent evidence suggests that these fluids may be deleterious in the setting of sepsis.90,95,96 Blood cultures should be obtained. Empiric antibiotics must be chosen carefully based on the most likely pathogens (gram-negative rods, gram-positive cocci, and anaerobes) because the portal of entry of the offending organism and its identity may not be evi-dent until culture data return or imaging studies are completed. Knowledge of the bacteriologic profile of infections in an indi-vidual unit can be obtained from most hospital infection control departments and will suggest potential responsible organisms. Antibiotics should be tailored to cover the responsible organ-isms once culture data are available, and if appropriate, the


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Surgery_Schwartz. control departments and will suggest potential responsible organisms. Antibiotics should be tailored to cover the responsible organ-isms once culture data are available, and if appropriate, the Table 5-6Causes of septic and vasodilatory shockSystemic response to infectionNoninfectious systemic inflammation Pancreatitis BurnsAnaphylaxisAcute adrenal insufficiencyProlonged, severe hypotension Hemorrhagic shock Cardiogenic shock Cardiopulmonary bypassMetabolic Hypoxic lactic acidosis Carbon monoxide poisoningTable 5-7Surviving Sepsis Campaign bundles of care to be initiated within the first hour after presentation in the patient with sepsis93,94Measure serum lactate level. Remeasure if the initial lactate is >2 mmol/LObtain blood culture prior to administration of antibioticsAdminister broad spectrum antibioticsRapid administration of 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/LUse vasopressors if the patient is hypotensive during or after fluid resuscitation to maintain a


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Surgery_Schwartz. spectrum antibioticsRapid administration of 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/LUse vasopressors if the patient is hypotensive during or after fluid resuscitation to maintain a mean arterial pressure ≥65 mmHgBrunicardi_Ch05_p0131-p0156.indd 14629/01/19 11:06 AM 147SHOCKCHAPTER 5spectrum of coverage narrowed. Long-term, empiric, broad-spectrum antibiotic use should be minimized to reduce the development of resistant organisms and to avoid the potential complications of fungal overgrowth and antibiotic-associated colitis from overgrowth of Clostridium difficile. IV antibiotics will be insufficient to adequately treat the infectious episode in the settings of infected fluid collections, infected foreign bodies, and devitalized tissue. These situations require source control and involve percutaneous drainage and operative management to target a focus of infection. These situations may require mul-tiple operations to ensure proper wound hygiene and healing.After


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Surgery_Schwartz. control and involve percutaneous drainage and operative management to target a focus of infection. These situations may require mul-tiple operations to ensure proper wound hygiene and healing.After first-line therapy of the septic patient with antibiot-ics, IV fluids, and intubation if necessary, vasopressors may be necessary to treat patients with septic shock. Catecholamines are the vasopressors used most often, with norepinephrine being the first-line agent followed by epinephrine. Occasionally, patients with septic shock will develop arterial resistance to catechol-amines. Arginine vasopressin, a potent vasoconstrictor, is often efficacious in this setting and is often added to norepinephrine.The majority of septic patients have hyperdynamic physi-ology with supranormal cardiac output and low systemic vas-cular resistance. On occasion, septic patients may have low cardiac output despite volume resuscitation and even vasopres-sor support. Dobutamine therapy is recommended for


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Surgery_Schwartz. and low systemic vas-cular resistance. On occasion, septic patients may have low cardiac output despite volume resuscitation and even vasopres-sor support. Dobutamine therapy is recommended for patients with cardiac dysfunction as evidenced by high filling pres-sures and low cardiac output or clinical signs of hypoperfusion after achievement of restoration of blood pressure following fluid resuscitation. Mortality in this group is high. Despite the increasing incidence of septic shock over the past several decades, the overall mortality rates have changed little. Stud-ies of interventions, including immunotherapy, resuscitation to pulmonary artery endpoints with hemodynamic optimization (cardiac output and O2 delivery, even to supranormal values), and optimization of mixed venous O2 measurements up to 72 hours after admission to the ICU, have not changed mortality.The advances made in the treatment of patients with sep-sis and septic shock and collaborative groups such as the


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Surgery_Schwartz. measurements up to 72 hours after admission to the ICU, have not changed mortality.The advances made in the treatment of patients with sep-sis and septic shock and collaborative groups such as the Sur-viving Sepsis Campaign continue to evaluate, modify, and put forth recommendations based upon data. Negative results from previous studies have led to the suggestion that earlier inter-ventions directed at improving global tissue oxygenation may be of benefit. To this end, Rivers and colleagues reported that goal-directed therapy of septic shock and severe sepsis initiated in the emergency department and continued for 6 hours signifi-cantly improved outcome.97 This approach involved adjustment of cardiac preload, afterload, and contractility to balance O2 delivery with O2 demand. They found that goal-directed therapy during the first 6 hours of hospital stay (initiated in the emer-gency department) had significant effects, such as higher mean venous O2 saturation, lower lactate levels,


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Surgery_Schwartz. that goal-directed therapy during the first 6 hours of hospital stay (initiated in the emer-gency department) had significant effects, such as higher mean venous O2 saturation, lower lactate levels, lower base deficit, higher pH, and decreased 28-day mortality (49.2% vs. 33.3%) compared to the standard therapy group. The frequency of sud-den cardiovascular collapse was also significantly less in the group managed with goal-directed therapy (21.0% vs. 10.3%). Interestingly, the goal-directed therapy group received more IV fluids during the initial 6 hours, but the standard therapy group required more IV fluids by 72 hours. The authors emphasize that continued cellular and tissue decompensation is subclinical and often irreversible when obvious clinically. Goal-directed therapy allowed identification and treatment of these patients with insidious illness (global tissue hypoxia in the setting of normal vital signs).Several multicenter trials have been performed to further refine these


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Surgery_Schwartz. and treatment of these patients with insidious illness (global tissue hypoxia in the setting of normal vital signs).Several multicenter trials have been performed to further refine these finding. In the Protocolized Care for Early Septic Shock (ProCESS) trial, a multicenter, randomized trial in which patients were identified early in the emergency department as having septic shock and received antibiotics and other nonre-suscitation aspects of care promptly, the investigators found no significant advantage, with respect to mortality or morbid-ity, of protocol-based resuscitation over bedside care that was provided according to the treating physician’s judgment. They also found no significant benefit of the mandated use of central venous catheterization and central hemodynamic monitoring in all patients. This last finding was recapitulated in the Pro-tocolised Management in Sepsis (ProMISe) trial.98,99 Failure of these more recent trials to show a benefit of early goal-directed


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Surgery_Schwartz. in all patients. This last finding was recapitulated in the Pro-tocolised Management in Sepsis (ProMISe) trial.98,99 Failure of these more recent trials to show a benefit of early goal-directed protocols vs. standard of care may be secondary to the gener-alized improvement in early recognition of sepsis and institu-tion of protocolized care by efforts such as the Surviving Sepsis Campaign.Hyperglycemia and insulin resistance are typical in criti-cally ill and septic patients, including patients without underly-ing diabetes mellitus. A recent study reported significant positive impact of tight glucose management on outcome in critically ill patients.100 The two treatment groups in this randomized, pro-spective study were assigned to receive intensive insulin therapy (maintenance of blood glucose between 80 and 110 mg/dL) or conventional treatment (infusion of insulin only if the blood glu-cose level exceeded 215 mg/dL, with a goal between 180 and 200 mg/dL). The mean morning glucose


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Surgery_Schwartz. glucose between 80 and 110 mg/dL) or conventional treatment (infusion of insulin only if the blood glu-cose level exceeded 215 mg/dL, with a goal between 180 and 200 mg/dL). The mean morning glucose level was significantly higher in the conventional treatment as compared to the inten-sive insulin therapy group (153 vs. 103 mg/dL). Mortality in the intensive insulin treatment group (4.6%) was significantly lower than in the conventional treatment group (8.0%), representing a 42% reduction in mortality. This reduction in mortality was most notable in the patients requiring longer than 5 days in the ICU. Furthermore, intensive insulin therapy reduced episodes of septicemia by 46%, reduced duration of antibiotic therapy, and decreased the need for prolonged ventilatory support and renal replacement therapy.Another treatment protocol that has been demonstrated to increase survival in patients with ARDS investigated the use of lower ventilatory tidal volumes compared to traditional tidal


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Surgery_Schwartz. therapy.Another treatment protocol that has been demonstrated to increase survival in patients with ARDS investigated the use of lower ventilatory tidal volumes compared to traditional tidal volumes.101 The majority of the patients enrolled in this multicenter, randomized trial developed ARDS secondary to pneumonia or sepsis. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 mL/kg of predicted body weight, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 mL/kg of predicted body weight. The trial was stopped after the enroll-ment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0% vs. 39.8%, P = .007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean ± SD, 12 ± 11 vs. 10 ± 11; P = .007). The investigators concluded that in


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Surgery_Schwartz. and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean ± SD, 12 ± 11 vs. 10 ± 11; P = .007). The investigators concluded that in patients with acute lung injury and ARDS, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use. Additional strategies in ARDS manage-ment include higher levels of positive end expiratory pressure (PEEP), alveolar recruitment maneuvers, and prone position-ing. Prone positioning has become part of many standardized protocols. This is supported by several studies, including a Brunicardi_Ch05_p0131-p0156.indd 14729/01/19 11:06 AM 148BASIC CONSIDERATIONSPART Imeta-analysis demonstrating that prone positioning is associ-ated with significantly reduced mortality from ARDS in the low tidal volume era.102The use of corticosteroids in the treatment of sepsis and septic shock has been


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Surgery_Schwartz. that prone positioning is associ-ated with significantly reduced mortality from ARDS in the low tidal volume era.102The use of corticosteroids in the treatment of sepsis and septic shock has been controversial for decades. The observa-tion that severe sepsis often is associated with adrenal insuf-ficiency or glucocorticoid receptor resistance has generated renewed interest in therapy for septic shock with corticosteroids. A single IV dose of 50 mg of hydrocortisone improved mean arterial blood pressure response relationships to norepinephrine and phenylephrine in patients with septic shock and was most notable in patients with relative adrenal insufficiency. A study evaluated therapy with hydrocortisone (50 mg IV every 6 hours) and fludrocortisone (50 µg orally once daily) vs. placebo for 1 week in patients with septic shock.103 As in earlier studies, the authors performed corticotropin tests on these patients to document and stratify patients by relative adrenal insufficiency. In


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Surgery_Schwartz. 1 week in patients with septic shock.103 As in earlier studies, the authors performed corticotropin tests on these patients to document and stratify patients by relative adrenal insufficiency. In this study, 7-day treatment with low doses of hydrocortisone and fludrocortisone significantly and safely lowered the risk of death in patients with septic shock and relative adrenal insuf-ficiency. In an international, multicenter, randomized trial of corticosteroids in sepsis (CORTICUS study; 499 analyzable patients), steroids showed no benefit in intent to treat mortality or shock reversal.104 This study suggested that hydrocortisone therapy cannot be recommended as routine adjuvant therapy for septic shock. However, if SBP remains less than 90 mmHg despite appropriate fluid and vasopressor therapy, hydrocorti-sone at 200 mg/day for 7 days in four divided doses or by con-tinuous infusion should be considered.Additional adjunctive immune modulation strategies have been developed for the


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Surgery_Schwartz. therapy, hydrocorti-sone at 200 mg/day for 7 days in four divided doses or by con-tinuous infusion should be considered.Additional adjunctive immune modulation strategies have been developed for the treatment of septic shock. These include the use of antiendotoxin antibodies, anticytokine anti-bodies, cytokine receptor antagonists, immune enhancers, a non– isoform-specific nitric oxide synthase inhibitor, and O2 radical scavengers. These compounds are each designed to alter some aspect of the host immune response to shock that is hypothesized to play a key role in its pathophysiology. However, most of these strategies have failed to demonstrate efficacy in human 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 host immune response to injury and infection, or animal models of shock that poorly represent the human


Surgery_Schwartz

Surgery_Schwartz. to poorly designed clinical trials, inadequate understanding of the interactions of the complex host immune response to injury and infection, or animal models of shock that poorly represent the human disease.Cardiogenic ShockCardiogenic shock is defined clinically as circulatory pump failure leading to diminished forward flow and subsequent tis-sue hypoxia, in the setting of adequate intravascular volume. Hemodynamic criteria include sustained hypotension (i.e., SBP <90 mmHg for at least 30 minutes), reduced cardiac index (<2.2 L/min per square meter), and elevated pulmonary artery wedge pressure (>15 mmHg).105 Mortality rates for cardiogenic shock are 50% to 80%. Acute, extensive MI is the most common cause of cardiogenic shock; a smaller infarction in a patient with existing left ventricular dysfunction also may precipitate shock. Cardiogenic shock complicates 5% to 10% of acute MIs. Con-versely, cardiogenic shock is the most common cause of death in patients hospitalized with


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Surgery_Schwartz. dysfunction also may precipitate shock. Cardiogenic shock complicates 5% to 10% of acute MIs. Con-versely, cardiogenic shock is the most common cause of death in patients hospitalized with acute MI. Although shock may develop early after MI, it typically is not found on admission. Seventy-five percent of patients who have cardiogenic shock complicating acute MIs develop signs of cardiogenic shock within 24 hours after onset of infarction (average 7 hours).Recognition of the patient with occult hypoperfusion is critical to prevent progression to obvious cardiogenic shock with its high mortality rate; early initiation of therapy to maintain blood pressure and cardiac output is vital. Rapid assessment, adequate resuscitation, and reversal of the myocardial ischemia are essential in optimizing outcome in patients with acute MI. Prevention of infarct extension is a critical component. Large segments of nonfunctional but viable myocardium contribute to the development of cardiogenic shock


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Surgery_Schwartz. outcome in patients with acute MI. Prevention of infarct extension is a critical component. Large segments of nonfunctional but viable myocardium contribute to the development of cardiogenic shock after MI. In the setting of acute MI, expeditious restoration of cardiac output is mandatory to minimize mortality; the extent of myocardial salvage possible decreases exponentially with increased time to restoration of coronary blood flow. The degree of coronary flow after percuta-neous transluminal coronary angioplasty correlates with inhos-pital mortality (i.e., 33% mortality with complete reperfusion, 50% mortality with incomplete reperfusion, and 85% mortality with absent reperfusion).106 Inadequate cardiac function can be a direct result of cardiac injury, including profound myocardial contusion, blunt cardiac valvular injury, or direct myocardial damage (Table 5-8).105-108 The pathophysiology of cardiogenic shock involves a vicious cycle of myocardial ischemia that causes myocardial


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Surgery_Schwartz. blunt cardiac valvular injury, or direct myocardial damage (Table 5-8).105-108 The pathophysiology of cardiogenic shock involves a vicious cycle of myocardial ischemia that causes myocardial dysfunction, which results in more myocar-dial ischemia. When sufficient mass of the left ventricular wall is necrotic or ischemic and fails to pump, the stroke volume decreases. An autopsy series of patients dying from cardiogenic shock have found damage to 40% of the left ventricle.109 Isch-emia distant from the infarct zone may contribute to the systolic dysfunction in patients with cardiogenic shock. The majority of these patients have multivessel disease, with limited vasodila-tor reserve and pressure-dependent coronary flow in multiple areas of the heart. Myocardial diastolic function is impaired in cardiogenic shock as well. Decreased compliance results from myocardial ischemia, and compensatory increases in left ven-tricular filling pressures progressively occur.Diminished cardiac output


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Surgery_Schwartz. in cardiogenic shock as well. Decreased compliance results from myocardial ischemia, and compensatory increases in left ven-tricular filling pressures progressively occur.Diminished cardiac output or contractility in the face of adequate intravascular volume (preload) may lead to under-perfused vascular beds and reflexive sympathetic discharge. Table 5-8Causes of cardiogenic shockAcute myocardial infarctionPump failureMechanical complications Acute mitral regurgitation Acute ventricular septal defect Free wall rupture Pericardial tamponadeArrhythmiaEnd-stage cardiomyopathyMyocarditisSevere myocardial contusionLeft ventricular outflow obstruction Aortic stenosis Hypertrophic obstructive cardiomyopathyObstruction to left ventricular filling Mitral stenosis Left atrial myxomaAcute mitral regurgitationAcute aortic insufficiencyMetabolicDrug reactionsBrunicardi_Ch05_p0131-p0156.indd 14829/01/19 11:06 AM 149SHOCKCHAPTER 5Increased sympathetic stimulation of the heart, either through


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Surgery_Schwartz. regurgitationAcute aortic insufficiencyMetabolicDrug reactionsBrunicardi_Ch05_p0131-p0156.indd 14829/01/19 11:06 AM 149SHOCKCHAPTER 5Increased sympathetic stimulation of the heart, either through direct neural input or from circulating catecholamines, increases heart rate, myocardial contraction, and myocardial O2 consump-tion, which may not be relieved by increases in coronary artery blood flow in patients with fixed stenoses of the coronary arter-ies. Diminished cardiac output may also decrease coronary artery blood flow, resulting in a scenario of increased myocar-dial O2 demand at a time when myocardial O2 supply may be limited. Acute heart failure may also result in fluid accumula-tion in the pulmonary microcirculatory bed, decreasing myocar-dial O2 delivery even further.Diagnosis. Rapid identification of the patient with pump failure and institution of corrective action are essential in pre-venting the ongoing spiral of decreased cardiac output from injury causing increased


Surgery_Schwartz

Surgery_Schwartz. identification of the patient with pump failure and institution of corrective action are essential in pre-venting the ongoing spiral of decreased cardiac output from injury causing increased myocardial O2 needs that cannot be met, leading to progressive and unremitting cardiac dysfunc-tion. In evaluation of possible cardiogenic shock, other causes of hypotension must be excluded, including hemorrhage, sepsis, pulmonary embolism, and aortic dissection. Signs of circulatory shock include hypotension, cool and mottled skin, depressed mental status, tachycardia, and diminished pulses. Cardiac exam may include dysrhythmia, precordial heave, or distal heart tones. Confirmation of a cardiac source for the shock requires electrocardiogram and urgent echocardiography. Other useful diagnostic tests include chest radiograph, arterial blood gases, electrolytes, complete blood count, and cardiac enzymes. Inva-sive cardiac monitoring, which generally is not necessary, can be useful to exclude right


Surgery_Schwartz

Surgery_Schwartz. include chest radiograph, arterial blood gases, electrolytes, complete blood count, and cardiac enzymes. Inva-sive cardiac monitoring, which generally is not necessary, can be useful to exclude right ventricular infarction, hypovolemia, and possible mechanical complications.Making the diagnosis of cardiogenic shock involves the identification of cardiac dysfunction or acute heart failure in a susceptible patient. In the setting of blunt traumatic injury, hemorrhagic shock from intra-abdominal bleeding, intrathoracic bleeding, and bleeding from fractures must be excluded, before implicating cardiogenic shock from blunt cardiac injury. Rela-tively few patients with blunt cardiac injury will develop cardiac pump dysfunction. Those who do generally exhibit cardiogenic shock early in their evaluation. Therefore, establishing the diag-nosis of blunt cardiac injury is secondary to excluding other etiologies for shock and establishing that cardiac dysfunction is present. Invasive hemodynamic


Surgery_Schwartz

Surgery_Schwartz. Therefore, establishing the diag-nosis of blunt cardiac injury is secondary to excluding other etiologies for shock and establishing that cardiac dysfunction is present. Invasive hemodynamic monitoring with a pulmonary artery catheter may uncover evidence of diminished cardiac out-put and elevated pulmonary artery pressure.Treatment. After ensuring that an adequate airway is present and ventilation is sufficient, attention should be focused on sup-port of the circulation. Intubation and mechanical ventilation often are required, if only to decrease work of breathing and facilitate sedation of the patient. Rapidly excluding hypovolemia and establishing the presence of cardiac dysfunction are essen-tial. Treatment of cardiac dysfunction includes maintenance of adequate oxygenation to ensure adequate myocardial O2 deliv-ery and judicious fluid administration to avoid fluid overload and development of cardiogenic pulmonary edema. Electrolyte abnormalities, commonly hypokalemia and


Surgery_Schwartz

Surgery_Schwartz. ensure adequate myocardial O2 deliv-ery and judicious fluid administration to avoid fluid overload and development of cardiogenic pulmonary edema. Electrolyte abnormalities, commonly hypokalemia and hypomagnesemia, should be corrected. Pain is treated with IV morphine sulfate or fentanyl. Significant dysrhythmias and heart block must be treated with antiarrhythmic drugs, pacing, or cardioversion, if necessary. Early consultation with cardiology is essential in current management of cardiogenic shock, particularly in the setting of acute MI.105When profound cardiac dysfunction exists, inotropic support may be indicated to improve cardiac contractility and cardiac output. Dobutamine primarily stimulates 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


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Surgery_Schwartz. 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 receptors (vasoconstriction), β1-receptors (cardiac stimulation), and β2-receptors (vasodilation), with its effects on β-receptors predominating at lower doses. Dopamine may be preferable to dobutamine in treatment of cardiac dysfunction in hypotensive patients. Tachycardia and increased peripheral resistance from dopamine infusion may worsen myocardial ischemia. Titration of both dopamine and dobutamine infusions may be required in some patients.Epinephrine stimulates αand β-receptors and may increase cardiac contractility and heart rate; however, it also may have intense peripheral vasoconstrictor effects that impair further cardiac performance. Catecholamine infusions must be carefully controlled to maximize coronary perfusion,


Surgery_Schwartz

Surgery_Schwartz. however, it also may have intense peripheral vasoconstrictor effects that impair further cardiac performance. Catecholamine infusions must be carefully controlled to maximize coronary perfusion, while minimizing myocardial O2 demand. Balancing the beneficial effects of impaired cardiac performance with the potential side effects of excessive reflex tachycardia and peripheral vasocon-striction requires serial assessment of tissue perfusion using indices such as capillary refill, character of peripheral pulses, adequacy of urine output, or improvement in laboratory param-eters of resuscitation such as pH, base deficit, and lactate. Inva-sive monitoring generally is necessary in these unstable patients. The phosphodiesterase inhibitors amrinone and milrinone may be required on occasion in patients with resistant cardiogenic shock. These agents have long half-lives and induce thrombocy-topenia and hypotension, and use is reserved for patients unre-sponsive to other treatment.Patients


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Surgery_Schwartz. patients with resistant cardiogenic shock. These agents have long half-lives and induce thrombocy-topenia and hypotension, and use is reserved for patients unre-sponsive to other treatment.Patients whose cardiac dysfunction is refractory to car-diotonics may require mechanical circulatory support with an intra-aortic balloon pump.110 Intra-aortic balloon pumping increases cardiac output and improves coronary blood flow by reduction of systolic afterload and augmentation of diastolic perfusion pressure. Unlike vasopressor agents, these beneficial effects occur without an increase in myocardial O2 demand. An intra-aortic balloon pump can be inserted at the bedside in the ICU via the femoral artery through either a cutdown or using the 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


Surgery_Schwartz

Surgery_Schwartz. 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.Preservation of existing myocardium and preservation of cardiac function are priorities of therapy for patients who have suffered an acute MI. Ensuring adequate oxygenation and O2 delivery, maintaining adequate preload with judicious volume restoration, minimizing sympathetic discharge through adequate relief of pain, and correcting electrolyte imbalances are all straightforward nonspecific maneuvers that may improve exist-ing cardiac function or prevent future cardiac complications. Anticoagulation and aspirin are given for acute MI. Although thrombolytic therapy reduces mortality in patients with acute MI, its role in cardiogenic shock is less clear. Patients in car-diac failure from an acute MI may benefit from pharmaco-logic or mechanical circulatory support in a manner similar


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Surgery_Schwartz. with acute MI, its role in cardiogenic shock is less clear. Patients in car-diac failure from an acute MI may benefit from pharmaco-logic or mechanical circulatory support in a manner similar to that of patients with cardiac failure related to blunt cardiac Brunicardi_Ch05_p0131-p0156.indd 14929/01/19 11:06 AM 150BASIC CONSIDERATIONSPART Iinjury. Additional pharmacologic tools may include the use of β-blockers to control heart rate and myocardial O2 consumption, nitrates to promote coronary blood flow through vasodilation, and ACE inhibitors to reduce ACE-mediated vasoconstrictive effects that increase myocardial workload and myocardial O2 consumption.Current guidelines of the American Heart Association recommend percutaneous transluminal coronary angiography for patients with cardiogenic shock, ST elevation, left bundle-branch block, and age less than 75 years.111,112 Early definition of coronary anatomy and revascularization is the pivotal step in treatment of patients with


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Surgery_Schwartz. shock, ST elevation, left bundle-branch block, and age less than 75 years.111,112 Early definition of coronary anatomy and revascularization is the pivotal step in treatment of patients with cardiogenic shock from acute MI.113 When feasible, percutaneous transluminal coronary angioplasty (generally with stent placement) is the treatment of choice. Coronary artery bypass grafting seems to be more appropriate for patients with multiple vessel disease or left main coronary artery disease.Obstructive ShockAlthough obstructive shock can be caused by a number of dif-ferent etiologies that result in mechanical obstruction of venous return (Table 5-9), in trauma patients this is most commonly due to the presence of tension pneumothorax. Cardiac tamponade occurs when sufficient fluid has accumulated in the pericardial sac to obstruct blood flow to the ventricles. The hemodynamic abnormalities in pericardial tamponade are due to elevation of intracardiac pressures with limitation of ventricular


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Surgery_Schwartz. in the pericardial sac to obstruct blood flow to the ventricles. The hemodynamic abnormalities in pericardial tamponade are due to elevation of intracardiac pressures with limitation of ventricular filling in diastole with resultant decrease in cardiac output. Acutely, the pericardium does not distend; thus small volumes of blood may produce cardiac tamponade. If the effusion accumulates slowly (e.g., in the setting of uremia, heart failure, or malignant effusion), the quantity of fluid producing cardiac tamponade may reach 2000 mL. The major determinant of the degree of hypotension is the pericardial pressure. With either cardiac tamponade or tension pneumothorax, reduced filling of the right side of the heart from either increased intrapleural pressure secondary to air accumulation (tension pneumothorax) or increased intra-pericardial pressure precluding atrial filling secondary to blood accumulation (cardiac tamponade) results in decreased cardiac output associated with increased


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Surgery_Schwartz. pneumothorax) or increased intra-pericardial pressure precluding atrial filling secondary to blood accumulation (cardiac tamponade) results in decreased cardiac output associated with increased central venous pressure.Diagnosis and Treatment. The diagnosis of tension pneu-mothorax should be made on clinical examination. The classic findings include respiratory distress (in an awake patient), hypo-tension, diminished breath sounds over one hemithorax, hyper-resonance to percussion, jugular venous distention, and shift of mediastinal structures to the unaffected side with tracheal deviation. In most instances, empiric treatment with pleural decompression is indicated rather than delaying to wait for radiographic confirmation. When a chest tube cannot be imme-diately inserted, such as in the prehospital setting, the pleural space can be decompressed with a large caliber needle. Immedi-ate return of air should be encountered with rapid resolution of hypotension. Unfortunately, not all of


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Surgery_Schwartz. prehospital setting, the pleural space can be decompressed with a large caliber needle. Immedi-ate return of air should be encountered with rapid resolution of hypotension. Unfortunately, not all of the clinical manifestations of tension pneumothorax may be evident on physical examina-tion. Hyperresonance may be difficult to appreciate in a noisy resuscitation area. Jugular venous distention may be absent in a hypovolemic patient. Tracheal deviation is a late finding and often is not apparent on clinical examination. Practically, three findings are sufficient to make the diagnosis of tension pneu-mothorax: respiratory distress or hypotension, decreased lung sounds, and hypertympany to percussion. Chest X-ray findings that may be visualized include deviation of mediastinal struc-tures, depression of the hemidiaphragm, and hypo-opacification with absent lung markings. As discussed previously, definitive treatment of a tension pneumothorax is immediate tube thora-costomy. The chest tube


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Surgery_Schwartz. of the hemidiaphragm, and hypo-opacification with absent lung markings. As discussed previously, definitive treatment of a tension pneumothorax is immediate tube thora-costomy. The chest tube should be inserted rapidly, but care-fully, and should be large enough to evacuate any blood that may be present in the pleural space. Most recommend place-ment is in the fourth intercostal space (nipple level) at the ante-rior axillary line.Cardiac tamponade results from the accumulation of blood within the pericardial sac, usually from penetrating trauma or chronic medical conditions such as heart failure or uremia. Although 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 cardiac rupture, a rare event in trauma vic-tims who survive long enough to reach the hospital, can produce refractory shock and tamponade in the multiply-injured patient. The