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Surgery_Schwartz. 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 manifestations of cardiac tamponade, such as total circula-tory collapse and cardiac arrest, may be catastrophic, or they may be more subtle. A high index of suspicion is warranted to make a rapid diagnosis. Patients who present with circulatory arrest from cardiac tamponade require emergency pericardial decompression, usually through a left thoracotomy. The indi-cations for this maneuver are discussed in Chapter 7. Cardiac tamponade also may be associated with dyspnea, orthopnea, cough, peripheral edema, chest pain, tachycardia, muffled heart tones, jugular venous distention, and elevated central venous pressure. Beck’s triad consists of hypotension, muffled heart tones, and neck vein distention. Unfortunately, absence of these clinical findings may not be sufficient to exclude cardiac injury


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Surgery_Schwartz. venous pressure. Beck’s triad consists of hypotension, muffled heart tones, and neck vein distention. Unfortunately, absence of these clinical findings may not be sufficient to exclude cardiac injury and cardiac tamponade. Muffled heart tones may be difficult to appreciate in a busy trauma center, and jugular venous disten-tion and central venous pressure may be diminished by coexis-tent bleeding. Therefore, patients at risk for cardiac tamponade whose hemodynamic status permits additional diagnostic tests frequently require additional diagnostic maneuvers to confirm cardiac injury or tamponade.Invasive hemodynamic monitoring may support the diag-nosis of cardiac tamponade if elevated central venous pressure, pulsus paradoxus (i.e., decreased systemic arterial pressure with inspiration), or elevated right atrial and right ventricular pres-sure by pulmonary artery catheter are present. These hemody-namic profiles suffer from lack of specificity, the duration of time required to obtain


Surgery_Schwartz

Surgery_Schwartz. or elevated right atrial and right ventricular pres-sure by pulmonary artery catheter are present. These hemody-namic profiles suffer from lack of specificity, the duration of time required to obtain them in critically injured patients, and their inability to exclude cardiac injury in the absence of tam-ponade. Chest radiographs may provide information on the pos-sible trajectory of a projectile, but rarely are diagnostic because Table 5-9Causes of obstructive shockPericardial tamponadePulmonary embolusTension pneumothoraxIVC obstruction Deep venous thrombosis Gravid uterus on IVC NeoplasmIncreased intrathoracic pressure Excess positive end-expiratory pressure NeoplasmIVC = inferior vena cava.Brunicardi_Ch05_p0131-p0156.indd 15029/01/19 11:06 AM 151SHOCKCHAPTER 5the acutely filled pericardium distends poorly. Echocardiogra-phy has become the preferred test for the diagnosis of cardiac tamponade. Good results in detecting pericardial fluid have been reported, but the yield in


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Surgery_Schwartz. pericardium distends poorly. Echocardiogra-phy has become the preferred test for the diagnosis of cardiac tamponade. Good results in detecting pericardial fluid have been reported, but the yield in detecting pericardial fluid depends on the skill and experience of the ultrasonographer, body habitus of the patient, and absence of wounds that preclude visualization of the pericardium. Standard two-dimensional or transesopha-geal echocardiography are sensitive techniques to evaluate the pericardium for fluid, and are typically performed by examiners skilled at evaluating ventricular function, valvular abnormali-ties, and integrity of the proximal thoracic aorta. Unfortunately, these skilled examiners are rarely immediately available at all hours of the night, when many trauma patients present; there-fore, waiting for this test may result in inordinate delays. In addition, although both ultrasound techniques may demonstrate the presence of fluid or characteristic findings of tamponade


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Surgery_Schwartz. there-fore, waiting for this test may result in inordinate delays. In addition, although both ultrasound techniques may demonstrate the presence of fluid or characteristic findings of tamponade (large volume of fluid, right atrial collapse, poor distensibility of the right ventricle), they do not exclude cardiac injury per se. Pericardiocentesis to diagnose pericardial blood and potentially relieve tamponade may be used. Performing pericardiocentesis under ultrasound guidance has made the procedure safer and more reliable. An indwelling catheter may be placed for sev-eral days in patients with chronic pericardial effusions. Needle pericardiocentesis may not evacuate clotted blood and has the potential to produce cardiac injury, making it a poor alternative in busy trauma centers.Diagnostic pericardial window represents the most direct method to determine the presence of blood within the pericar-dium. The procedure is best performed in the operating room under general anesthesia. It


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Surgery_Schwartz. pericardial window represents the most direct method to determine the presence of blood within the pericar-dium. The procedure is best performed in the operating room under general anesthesia. It can be performed through either the subxiphoid or transdiaphragmatic approach. Adequate equip-ment and personnel to rapidly decompress the pericardium, explore the injury, and repair the heart should be present. Once the pericardium is opened and tamponade relieved, hemody-namics usually improve dramatically and formal pericardial exploration can ensue. Exposure of the heart can be achieved by extending the incision to a median sternotomy, performing a left anterior thoracotomy, or performing bilateral anterior tho-racotomies (“clamshell”).Neurogenic ShockNeurogenic shock refers to diminished tissue perfusion as a result of loss of vasomotor tone to peripheral arterial beds. Loss of vasoconstrictor impulses results in increased vascular capacitance, decreased venous return, and decreased


Surgery_Schwartz

Surgery_Schwartz. tissue perfusion as a result of loss of vasomotor tone to peripheral arterial beds. Loss of vasoconstrictor impulses results in increased vascular capacitance, decreased venous return, and decreased cardiac output. Neurogenic shock is usually secondary to spinal cord injuries from vertebral body fractures of the cervical or high thoracic region that disrupt sympathetic regulation of peripheral vascular tone (Table 5-10). Rarely, a spinal cord injury without bony fracture, such as an epidural hematoma impinging on the spinal cord, can produce neurogenic shock. Sympathetic input to the heart, which normally increases heart rate and cardiac contractility, and input to the adrenal medulla, which increases catecholamine release, may also be disrupted, preventing the typical reflex tachycardia that occurs with hypovolemia. Acute spinal cord injury results in activation of multiple secondary injury mechanisms: (a) vascular compromise to the spinal cord with loss of autoregulation, vasospasm,


Surgery_Schwartz

Surgery_Schwartz. occurs with hypovolemia. Acute spinal cord injury results in activation of multiple secondary injury mechanisms: (a) vascular compromise to the spinal cord with loss of autoregulation, vasospasm, and thrombosis; (b) loss of cellular membrane integrity and impaired energy metabo-lism; and (c) neurotransmitter accumulation and release of free radicals. Importantly, hypotension contributes to the worsening of acute spinal cord injury as the result of further reduction in blood flow to the spinal cord. Management of acute spinal cord injury with attention to blood pressure control, oxygenation, and hemodynamics, essentially optimizing perfusion of an already ischemic spinal cord, seems to result in improved neurologic outcome. Patients with hypotension from spinal cord injury are best monitored in an ICU and carefully followed for evidence of cardiac or respiratory dysfunction.Diagnosis. Acute spinal cord injury may result in bradycardia, hypotension, cardiac dysrhythmias, reduced cardiac


Surgery_Schwartz

Surgery_Schwartz. in an ICU and carefully followed for evidence of cardiac or respiratory dysfunction.Diagnosis. Acute spinal cord injury may result in bradycardia, hypotension, cardiac dysrhythmias, reduced cardiac output, and decreased peripheral vascular resistance. The severity of the spi-nal cord injury seems to correlate with the magnitude of cardio-vascular dysfunction. Patients with complete motor injuries are over five times more likely to require vasopressors for neuro-genic shock compared to those with incomplete lesions.114 The classic description of neurogenic shock consists of decreased blood pressure associated with bradycardia (absence of reflex-ive tachycardia due to disrupted sympathetic discharge), warm extremities (loss of peripheral vasoconstriction), motor and sen-sory deficits indicative of a spinal cord injury, and radiographic evidence of a vertebral column fracture. Patients with multisys-tem trauma that includes spinal cord injuries often have head injuries that may make


Surgery_Schwartz

Surgery_Schwartz. of a spinal cord injury, and radiographic evidence of a vertebral column fracture. Patients with multisys-tem trauma that includes spinal cord injuries often have head injuries that may make identification of motor and sensory defi-cits difficult in the initial evaluation. Furthermore, associated injuries may occur that result in hypovolemia, further compli-cating the clinical presentation. In a subset of patients with spi-nal cord injuries from penetrating wounds, most of the patients with hypotension had blood loss as the etiology (74%) rather than neurogenic causes, and few (7%) had the classic findings of neurogenic shock.115 In the multiply injured patient, other causes of hypotension including hemorrhage, tension pneumothorax, and cardiogenic shock, must be sought and excluded.Treatment. After the airway is secured and ventilation is ade-quate, fluid resuscitation and restoration of intravascular volume often will improve perfusion in neurogenic shock. Most patients with


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Surgery_Schwartz. the airway is secured and ventilation is ade-quate, fluid resuscitation and restoration of intravascular volume often will improve perfusion in neurogenic shock. Most patients with neurogenic shock will respond to restoration of intravas-cular volume alone, with satisfactory improvement in perfusion and resolution of hypotension. Administration of vasoconstric-tors will improve peripheral vascular tone, decrease vascular capacitance, and increase venous return, but should only be con-sidered once hypovolemia is excluded as the cause of the hypo-tension and the diagnosis of neurogenic shock is established. If the patient’s blood pressure has not responded to what is felt to be adequate volume resuscitation, dopamine may be used first. A pure α-agonist, such as phenylephrine, may be used primar-ily or in patients unresponsive to dopamine. Specific treatment for the hypotension is often of brief duration, as the need to administer vasoconstrictors typically lasts 24 to 48 hours. On the


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Surgery_Schwartz. or in patients unresponsive to dopamine. Specific treatment for the hypotension is often of brief duration, as the need to administer vasoconstrictors typically lasts 24 to 48 hours. On the other hand, life-threatening cardiac dysrhythmias and hypo-tension may occur up to 14 days after spinal cord injury.The duration of the need for vasopressor support for neurogenic shock may correlate with the overall prognosis or chances of improvement in neurologic function. Appropriate rapid restoration of blood pressure and circulatory perfusion may improve perfusion to the spinal cord, prevent progressive Table 5-10Causes of neurogenic shockSpinal cord traumaSpinal cord neoplasmSpinal/epidural anestheticBrunicardi_Ch05_p0131-p0156.indd 15129/01/19 11:06 AM 152BASIC CONSIDERATIONSPART Ispinal cord ischemia, and minimize secondary cord injury. Res-toration of normal blood pressure and adequate tissue perfusion should precede any operative attempts to stabilize the vertebral fracture.ENDPOINTS


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Surgery_Schwartz. ischemia, and minimize secondary cord injury. Res-toration of normal blood pressure and adequate tissue perfusion should precede any operative attempts to stabilize the vertebral fracture.ENDPOINTS IN RESUSCITATIONShock is defined as inadequate perfusion to maintain normal organ function. With prolonged anaerobic metabolism, tissue acidosis and O2 debt accumulate. Thus, the goal in the treatment of shock is restoration of adequate organ perfusion and tissue oxygenation. Resuscitation is complete when O2 debt is repaid, tissue acidosis is corrected, and aerobic metabo-lism restored. Clinical confirmation of this endpoint remains a challenge.Resuscitation of the patient in shock requires simultaneous evaluation and treatment; the etiology of the shock often is not initially apparent. Hemorrhagic shock, septic shock, and trau-matic shock are the most common types of shock encountered on surgical services. To optimize outcome in bleeding patients, early control of the hemorrhage and


Surgery_Schwartz

Surgery_Schwartz. shock, septic shock, and trau-matic shock are the most common types of shock encountered on surgical services. To optimize outcome in bleeding patients, early control of the hemorrhage and adequate volume resuscita-tion, including both red blood cells and crystalloid solutions, are necessary. Expedient operative resuscitation is mandatory to limit the magnitude of activation of multiple mediator sys-tems and to abort the microcirculatory changes, which may evolve insidiously into the cascade that ends in irreversible hemorrhagic shock. Attempts to stabilize an actively bleeding patient anywhere but in the operating room are inappropriate. Any intervention that delays the patient’s arrival in the operat-ing room for control of hemorrhage increases mortality, thus the important concept of operating room resuscitation of the critically injured patient.Recognition by care providers of the patient who is in the compensated phase of shock is equally important, but more dif-ficult based on


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Surgery_Schwartz. operating room resuscitation of the critically injured patient.Recognition by care providers of the patient who is in the compensated phase of shock is equally important, but more dif-ficult based on clinical criteria. Compensated shock exists when inadequate tissue perfusion persists despite normalization of blood pressure and heart rate. Even with normalization of blood pressure, heart rate, and urine output, 80% to 85% of trauma patients have inadequate tissue perfusion, as evidenced by increased lactate or decreased mixed venous O2 saturation.56,116 Persistent, occult hypoperfusion is frequent in the ICU, with a resultant significant increase in infection rate and mortality in major trauma patients. Patients failing to reverse their lactic acidosis within 12 hours of admission (acidosis that was persis-tent despite normal heart rate, blood pressure, and urine output) developed an infection three times as often as those who normal-ized their lactate levels within 12 hours of


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Surgery_Schwartz. that was persis-tent despite normal heart rate, blood pressure, and urine output) developed an infection three times as often as those who normal-ized their lactate levels within 12 hours of admission. In addi-tion, mortality was fourfold higher in patients who developed infections. Both injury severity score and occult hypotension (lactic acidosis) longer than 12 hours were independent predic-tors of infection.117 Thus, recognition of subclinical hypoperfu-sion requires information beyond vital signs and urinary output.Endpoints in resuscitation can be divided into systemic or global parameters, tissue-specific parameters, and cellu-lar parameters. Global endpoints include vital signs, cardiac output, pulmonary artery wedge pressure, O2 delivery and con-sumption, lactate, and base deficit (Table 5-11).Assessment of Endpoints in ResuscitationInability to repay O2 debt is a predictor of mortality and organ failure; the probability of death has been directly cor-related to the


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Surgery_Schwartz. deficit (Table 5-11).Assessment of Endpoints in ResuscitationInability to repay O2 debt is a predictor of mortality and organ failure; the probability of death has been directly cor-related to the calculated O2 debt in hemorrhagic shock. Direct measurement of the O2 debt in the resuscitation of patients is difficult. The easily obtainable parameters of arterial blood pressure, heart rate, urine output, central venous pressure, and pulmonary artery occlusion pressure are poor indicators of the adequacy of tissue perfusion. Therefore, surrogate parameters have been sought to estimate the O2 debt; serum lactate and base deficit have been shown to correlate with O2 debt.Lactate. Lactate is generated by conversion of pyruvate to lactate by lactate dehydrogenase in the setting of insufficient O2. Lactate is released into the circulation and is predominantly taken up and metabolized by the liver and kidneys. The liver accounts for approximately 50% and the kidney for about 30% of whole body


Surgery_Schwartz

Surgery_Schwartz. Lactate is released into the circulation and is predominantly taken up and metabolized by the liver and kidneys. The liver accounts for approximately 50% and the kidney for about 30% of whole body lactate uptake. Elevated serum lactate is an indi-rect measure of the O2 debt, and therefore an approximation of the magnitude and duration of the severity of shock. The admission lactate level, highest lactate level, and time interval to normalize the serum lactate are important prognostic indi-cators for survival. For example, in a study of 76 consecutive patients, 100% survival was observed among the patients with normalization of lactate within 24 hours, 78% survival when lactate normalized between 24 and 48 hours, and only 14% sur-vivorship if it took longer than 48 hours to normalize the serum lactate.56 In contrast, individual variability of lactate may be too great to permit accurate prediction of outcome in any individual case. Base deficit and volume of blood transfusion required


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Surgery_Schwartz. serum lactate.56 In contrast, individual variability of lactate may be too great to permit accurate prediction of outcome in any individual case. Base deficit and volume of blood transfusion required in the first 24 hours of resuscitation may be better predictors of mortality than the plasma lactate alone.Base Deficit. Base deficit is the amount of base in millimoles that is required to titrate 1 L of whole blood to a pH of 7.40 with the sample fully saturated with O2 at 37°C (98.6°F) and a partial pressure of CO2 of 40 mmHg. It usually is measured by arterial blood gas analysis in clinical practice as it is readily and quickly available. The mortality of trauma patients can be stratified according to the magnitude of base deficit measured in the first 24 hours after admission.60 In a retrospective study of over 3000 trauma admissions, patients with a base deficit worse than 15 mmol/L had a mortality of 70%. Base deficit can be stratified into mild (3 to 5 mmol/L), moderate (6 to 14


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Surgery_Schwartz. study of over 3000 trauma admissions, patients with a base deficit worse than 15 mmol/L had a mortality of 70%. Base deficit can be stratified into mild (3 to 5 mmol/L), moderate (6 to 14 mmol/L), and severe (15 mmol/L) categories, with a trend toward higher mortality with worsening base deficit in patients with trauma. Both the magnitude of the perfusion deficit as indicated by the base deficit and the time required to correct it are major factors determining outcome in shock.Indeed, when elevated base deficit persists (or lactic acidosis) in the trauma patient, ongoing bleeding is often the 7Table 5-11Endpoints in resuscitationSystemic/global Lactate Base deficit Cardiac output Oxygen delivery and consumptionTissue specific Gastric tonometry Tissue pH, oxygen, carbon dioxide levels Near infrared spectroscopyCellular Membrane potential Adenosine triphosphateBrunicardi_Ch05_p0131-p0156.indd 15229/01/19 11:06 AM 153SHOCKCHAPTER 5etiology. Trauma patients admitted with a base


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Surgery_Schwartz. infrared spectroscopyCellular Membrane potential Adenosine triphosphateBrunicardi_Ch05_p0131-p0156.indd 15229/01/19 11:06 AM 153SHOCKCHAPTER 5etiology. Trauma patients admitted with a base deficit greater than 15 mmol/L required twice the volume of fluid infusion and six times more blood transfusion in the first 24 hours com-pared to patients with mild acidosis. Transfusion requirements increased as base deficit worsened and ICU and hospital lengths of stay increased. Mortality increased as base deficit worsened; the frequency of organ failure increased with greater base deficit.57 The probability of trauma patients developing ARDS has been reported to correlate with severity of admission base deficit and lowest base deficit within the first 24 hours postinjury.59 Persistently high base deficit is associated with abnormal O2 utilization and higher mortality. Monitoring base deficit in the resuscitation of trauma patients assists in assess-ment of O2 transport and efficacy of


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Surgery_Schwartz. base deficit is associated with abnormal O2 utilization and higher mortality. Monitoring base deficit in the resuscitation of trauma patients assists in assess-ment of O2 transport and efficacy of resuscitation.58Factors that may compromise the utility of the base defi-cit in estimating O2 debt are the administration of bicarbonate, hypothermia, hypocapnia (overventilation), heparin, ethanol, and ketoacidosis. However, the base deficit remains one of the most widely used estimates of O2 debt for its clinical relevance, accuracy, and availability.Near Infrared Spectroscopy. Near infrared (NIR) spectros-copy can measure tissue oxygenation and redox state of cyto-chrome a,a3 on a continuous, noninvasive basis. The NIR probe emits multiple wavelengths of light in the NIR spectrum (650 to 1100 nm). Photons are then either absorbed by the tissue or reflected back to the probe. Maximal exercise in laboratory stud-ies resulted in reduction of cytochrome a,a3; this correlated with tissue


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Surgery_Schwartz. 1100 nm). Photons are then either absorbed by the tissue or reflected back to the probe. Maximal exercise in laboratory stud-ies resulted in reduction of cytochrome a,a3; this correlated with tissue lactate elevation. NIR spectroscopy can be used to com-pare tissue oxyhemoglobin levels (indicating tissue O2 supply to cytochrome a,a3 with mitochondrial O2 consumption), thus demonstrating flow-independent mitochondrial oxidative dys-function and the need for further resuscitation. Trauma patients with decoupled oxyhemoglobin and cytochrome a,a3 have redox dysfunction and have been shown to have a higher incidence of organ failure (89 vs. 13%).121,122Tissue PH, Oxygen, and Carbon Dioxide Concentration. Tissue probes with optical sensors have been used to measure tissue pH and partial pressure of O2 and CO2 in subcutaneous sites, muscle, and the bladder. These probes may use transcuta-neous methodology with Clark electrodes or direct percutaneous probes.123,124 The percutaneous probes


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Surgery_Schwartz. of O2 and CO2 in subcutaneous sites, muscle, and the bladder. These probes may use transcuta-neous methodology with Clark electrodes or direct percutaneous probes.123,124 The percutaneous probes can be inserted through an 18-gauge catheter and hold promise as continuous monitors of tissue perfusion.Right Ventricular End-Diastolic Volume Index. Right ven-tricular end-diastolic volume index (RVEDVI) seems to more accurately predict preload for cardiac index than does pulmonary artery wedge pressure.125 Chang and colleagues reported that 50% of trauma patients had persistent splanchnic ischemia that was reversed by increasing RVEDVI. RVEDVI is a parameter that seems to correlate with preload-related increases in cardiac output. More recently, these authors have described left ven-tricular power output as an endpoint (LVP >320 mmHg·L/min per square meter), which is associated with improved clearance of base deficit and a lower rate of organ dysfunction following


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Surgery_Schwartz. left ven-tricular power output as an endpoint (LVP >320 mmHg·L/min per square meter), which is associated with improved clearance of base deficit and a lower rate of organ dysfunction following injury.126REFERENCESEntries highlighted in bright blue are key references. 1. Gross S. A System of Surgery: Pathologic, Diagnsotic, Thera-peutic and Operative. Philadelphia: Lea and Febiger; 1872. 2. Bernard C. Lecons sur les Phenomenes de la Via Communs aux Animaux et aux Vegetaux. Paris: JB Ballieve; 1879. 3. Cannon W. Traumatic Shock. New York: Appleton and Co.; 1923. 4. Blalock A. Principles of Surgical Care, Shock and Other Prob-lems. St. Louis: CV Mosby; 1940. 5. 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 paren-chymal cells. J Leukoc Biol. 2008;83(1):80-88. 6. Wiggers C. Experimental Hemorrhagic Shock. Physiology of Shock. New York: Commonwealth;


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Surgery_Schwartz. TLR4 signaling in both bone marrow-derived cells and paren-chymal cells. J Leukoc Biol. 2008;83(1):80-88. 6. Wiggers C. Experimental Hemorrhagic Shock. Physiology of Shock. New York: Commonwealth; 1950. 7. Peitzman AB, Corbett WA, Shires GT, 3rd, Illner H, Shires GT, Inamdar R. Cellular function in liver and muscle dur-ing hemorrhagic shock in primates. Surg Gynecol Obstet. 1985;161(5):419-424. 8. Carrico CJ, Canizaro PC, Shires GT. Fluid resuscitation fol-lowing injury: rationale for the use of balanced salt solutions. Crit Care Med. 1976;4(2):46-54. 9. Shaftan GW, Chiu CJ, Dennis C, Harris B. Fundamen-tals of physiologic control of arterial hemorrhage. Surgery. 1965;58(5):851-856. 10. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med. 2017;45(3):486-552. 11. Shah NS, Kelly E, Billiar TR, et al. Utility of clinical param-eters of tissue oxygenation in a quantitative model of


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Surgery_Schwartz. of sepsis and septic shock: 2016. Crit Care Med. 2017;45(3):486-552. 11. Shah NS, Kelly E, Billiar TR, et al. Utility of clinical param-eters of tissue oxygenation in a quantitative model of irrevers-ible hemorrhagic shock. Shock. 1998;10(5):343-346. 12. Dunser MW, Wenzel V, Mayr AJ, Hasibeder WR. Management of vasodilatory shock: defining the role of arginine vasopres-sin. Drugs. 2003;63(3):237-256. 13. Argenziano M, Chen JM, Choudhri AF, et al. Management of vasodilatory shock after cardiac surgery: identification of predisposing factors and use of a novel pressor agent. J Thorac Cardiovasc Surg. 1998;116(6):973-980. 14. Barroso-Aranda J, Schmid-Schonbein GW, Zweifach BW, Engler RL. Granulocytes and no-reflow phenomenon in irre-versible hemorrhagic shock. Circ Res. 1988;63(2):437-447. 15. Ince C, Sinaasappel M. Microcirculatory oxygenation and shunting in sepsis and shock. Crit Care Med. 1999; 27(7):1369-1377. 16. Singer M, De Santis V, Vitale D, Jeffcoate W. Multiorgan failure is


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Surgery_Schwartz. C, Sinaasappel M. Microcirculatory oxygenation and shunting in sepsis and shock. Crit Care Med. 1999; 27(7):1369-1377. 16. Singer M, De Santis V, Vitale D, Jeffcoate W. Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet. 2004;364(9433):545-548. 17. Shires T, Coln D, Carrico J, Lightfoot S. Fluid therapy in hem-orrhagic shock. Arch Surg. 1964;88:688-693. 18. Robin ED. Of men and mitochondria: coping with hypoxic dysoxia. The 1980 J. Burns Amberson Lecture. Am Rev Respir Dis. 1980;122(4):517-531. 19. Stacpoole PW. Lactic acidosis and other mitochondrial disor-ders. Metabolism. 1997;46(3):306-321. 20. Crowell JW, Smith EE. Oxygen deficit and irreversible hemor-rhagic shock. Am J Physiol. 1964;206:313-316. 21. Nathan C. Points of control in inflammation. Nature. 2002; 420(6917):846-852. 22. Sauaia A, Moore FA, Moore EE, Haenel JB, Read RA, Lezotte DC. Early predictors of postinjury multiple organ fail-ure. Arch Surg.


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Surgery_Schwartz. of control in inflammation. Nature. 2002; 420(6917):846-852. 22. Sauaia A, Moore FA, Moore EE, Haenel JB, Read RA, Lezotte DC. Early predictors of postinjury multiple organ fail-ure. Arch Surg. 1994;129(1):39-45. 23. Matzinger P. The danger model: a renewed sense of self. Science. 2002;296(5566):301-305. 24. Jiang J, Bahrami S, Leichtfried G, Redl H, Ohlinger W, Schlag G. Kinetics of endotoxin and tumor necrosis factor appearance in portal and systemic circulation after hemorrhagic shock in rats. Ann Surg. 1995;221(1):100-106. 25. Endo S, Inada K, Yamada Y, et al. Plasma endotoxin and cyto-kine concentrations in patients with hemorrhagic shock. Crit Care Med. 1994;22(6):949-955.Brunicardi_Ch05_p0131-p0156.indd 15329/01/19 11:06 AM 154BASIC CONSIDERATIONSPART I 26. Puyana JC, Pellegrini JD, De AK, Kodys K, Silva WE, Miller CL. Both T-helper-1and T-helper-2-type lymphokines are depressed in posttrauma anergy. J Trauma. 1998;44(6): 1037-1045; discussion 1045-1036. 27. Faist E,


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Surgery_Schwartz. JD, De AK, Kodys K, Silva WE, Miller CL. Both T-helper-1and T-helper-2-type lymphokines are depressed in posttrauma anergy. J Trauma. 1998;44(6): 1037-1045; discussion 1045-1036. 27. Faist E, Schinkel C, Zimmer S, Kremer JP, Von Donnersmarck GH, Schildberg FW. Inadequate interleukin-2 synthesis and interleukin-2 messenger expression following thermal and mechanical trauma in humans is caused by defective trans-membrane signalling. J Trauma. 1993;34(6):846-853; discus-sion 853-844. 28. Meng ZH, Dyer K, Billiar TR, Tweardy DJ. Essential role for IL-6 in postresuscitation inflammation in hemorrhagic shock. Am J Physiol Cell Physiol. 2001;280(2):C343-351. 29. Meng ZH, Dyer K, Billiar TR, Tweardy DJ. Distinct effects of systemic infusion of G-CSF vs. IL-6 on lung and liver inflammation and injury in hemorrhagic shock. Shock. 2000;14(1):41-48. 30. Neidhardt R, Keel M, Steckholzer U, et al. Relationship of interleukin-10 plasma levels to severity of injury and clinical outcome in injured


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Surgery_Schwartz. injury in hemorrhagic shock. Shock. 2000;14(1):41-48. 30. Neidhardt R, Keel M, Steckholzer U, et al. Relationship of interleukin-10 plasma levels to severity of injury and clinical outcome in injured patients. J Trauma. 1997;42(5):863-870; discussion 870-861. 31. Kasai T, Inada K, Takakuwa T, et al. Anti-inflammatory cyto-kine levels in patients with septic shock. Res Commun Mol Pathol Pharmacol. 1997;98(1):34-42. 32. Kahlke V, Dohm C, Mees T, Brotzmann K, Schreiber S, Schroder J. Early interleukin-10 treatment improves survival and enhances immune function only in males after hemor-rhage and subsequent sepsis. Shock. 2002;18(1):24-28. 33. Karakozis S, Hinds M, Cook JW, Kim D, Provido H, Kirkpatrick JR. The effects of interleukin-10 in hemorrhagic shock. J Surg Res. 2000;90(2):109-112. 34. Comerford I, McColl SR. Mini-review series: focus on chemo-kines. Immunol Cell Biol. 2011;89(2):183-184. 35. Younger JG, Sasaki N, Waite MD, et al. Detrimental effects of complement activation in


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Surgery_Schwartz. I, McColl SR. Mini-review series: focus on chemo-kines. Immunol Cell Biol. 2011;89(2):183-184. 35. Younger JG, Sasaki N, Waite MD, et al. Detrimental effects of complement activation in hemorrhagic shock. J Appl Physiol. 2001;90(2):441-446. 36. Moore EE, Moore FA, Franciose RJ, Kim FJ, Biffl WL, Banerjee A. The postischemic gut serves as a priming bed for circulating neutrophils that provoke multiple organ failure. J Trauma. 1994;37(6):881-887. 37. Adams JM, Hauser CJ, Livingston DH, Lavery RF, Fekete Z, Deitch EA. Early trauma polymorphonuclear neutrophil responses to chemokines are associated with development of sepsis, pneumonia, and organ failure. J Trauma. 2001;51(3): 452-456; discussion 456-457. 38. Lau YT, Hwang TL, Chen MF, Liu MS. Calcium transport by rat liver plasma membranes during sepsis. Circ Shock. 1992;38(4):238-244. 39. Somogyi R, Zhao M, Stucki JW. Modulation of cytosolic-[Ca2+] oscillations in hepatocytes results from cross-talk among second messengers. The


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Surgery_Schwartz. during sepsis. Circ Shock. 1992;38(4):238-244. 39. Somogyi R, Zhao M, Stucki JW. Modulation of cytosolic-[Ca2+] oscillations in hepatocytes results from cross-talk among second messengers. The synergism between the alpha 1adrenergic response, glucagon and cyclic AMP, and their antagonism by insulin and diacylglycerol manifest themselves in the control of the cytosolic-[Ca2+] oscillations. Biochem J. 1992;286 (Pt 3):869-877. 40. Trump BF, Berezesky IK. Calcium-mediated cell injury and cell death. FASEB J. 1995;9(2):219-228. 41. Powers KA, Szaszi K, Khadaroo RG, et al. Oxidative stress generated by hemorrhagic shock recruits Toll-like recep-tor 4 to the plasma membrane in macrophages. J Exp Med. 2006;203(8):1951-1961. 42. Suzuki YJ, Forman HJ, Sevanian A. Oxidants as stimu-lators of signal transduction. Free Radic Biol Med. 1997;22(1-2):269-285. 43. Mollen KP, McCloskey CA, Tanaka H, et al. Hypoxia activates c-Jun N-terminal kinase via Rac1-dependent reactive oxygen species production


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Surgery_Schwartz. transduction. Free Radic Biol Med. 1997;22(1-2):269-285. 43. Mollen KP, McCloskey CA, Tanaka H, et al. Hypoxia activates c-Jun N-terminal kinase via Rac1-dependent reactive oxygen species production in hepatocytes. Shock. 2007;28(3):270-277. 44. Bertges DJ, Fink MP, Delude RL. Hypoxic signal transduction in critical illness. Crit Care Med. 2000;28(4 Suppl):N78-86. 45. Guillemin K, Krasnow MA. The hypoxic response: huffing and HIFing. Cell. 1997;89(1):9-12. 46. Buchman TG, Cabin DE, Vickers S, et al. Molecular biology of circulatory shock. Part II. Expression of four groups of hepatic genes is enhanced after resuscitation from cardiogenic shock. Surgery. 1990;108(3):559-566. 47. Cobb JP, O’Keefe GE. Injury research in the genomic era. Lancet. 2004;363(9426):2076-2083. 48. Cobb JP, Laramie JM, Stormo GD, et al. Sepsis gene expres-sion profiling: murine splenic compared with hepatic responses determined by using complementary DNA microarrays. Crit Care Med.


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Surgery_Schwartz. JP, Laramie JM, Stormo GD, et al. Sepsis gene expres-sion profiling: murine splenic compared with hepatic responses determined by using complementary DNA microarrays. Crit Care Med. 2002;30(12):2711-2721. 49. Wiegand G, Selleng K, Grundling M, Jack RS. Gene expres-sion pattern in human monocytes as a surrogate marker for systemic inflammatory response syndrome (SIRS). Mol Med. 1999;5(3):192-202. 50. Gray IC, Campbell DA, Spurr NK. Single nucleotide poly-morphisms as tools in human genetics. Hum Mol Genet. 2000;9(16):2403-2408. 51. Mira JP, Cariou A, Grall F, et al. Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study. JAMA. 1999;282(6):561-568. 52. Xiao W, Mindrinos MN, Seok J, et al. A genomic storm in critically injured humans. J Exp Med. 2011;208(13): 2581-2590. 53. Eastridge BJ, Salinas J, McManus JG, et al. Hypotension begins at 110 mmHg: redefining “hypotension” with data. J Trauma. 2007;63(2):291-297;


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Surgery_Schwartz. injured humans. J Exp Med. 2011;208(13): 2581-2590. 53. Eastridge BJ, Salinas J, McManus JG, et al. Hypotension begins at 110 mmHg: redefining “hypotension” with data. J Trauma. 2007;63(2):291-297; discussion 297-299. 54. Luna GK, Eddy AC, Copass M. The sensitivity of vital signs in identifying major thoracoabdominal hemorrhage. Am J Surg. 1989;157(5):512-515. 55. Victorino GP, Battistella FD, Wisner DH. Does tachycardia correlate with hypotension after trauma? J Am Coll Surg. 2003;196(5):679-684. 56. Abramson D, Scalea TM, Hitchcock R, Trooskin SZ, Henry SM, Greenspan J. Lactate clearance and survival following injury. J Trauma. 1993;35(4):584-588; discussion 588-589. 57. Davis JW, Parks SN, Kaups KL, Gladen HE, O’Donnell-Nicol S. Admission base deficit predicts transfusion requirements and risk of complications. J Trauma. 1996;41(5):769-774. 58. Kincaid EH, Miller PR, Meredith JW, Rahman N, Chang MC. Elevated arterial base deficit in trauma patients: a marker of impaired oxygen


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Surgery_Schwartz. and risk of complications. J Trauma. 1996;41(5):769-774. 58. Kincaid EH, Miller PR, Meredith JW, Rahman N, Chang MC. Elevated arterial base deficit in trauma patients: a marker of impaired oxygen utilization. J Am Coll Surg. 1998;187(4): 384-392. 59. Rixen D, Raum M, Bouillon B, Lefering R, Neugebauer E. Base deficit development and its prognostic significance in posttrauma critical illness: an analysis by the trauma regis-try of the Deutsche Gesellschaft fur unfallchirurgie. Shock. 2001;15(2):83-89. 60. Rutherford EJ, Morris JA, Jr., Reed GW, Hall KS. Base defi-cit stratifies mortality and determines therapy. J Trauma. 1992;33(3):417-423. 61. Thorson CM, Van Haren RM, Ryan ML, et al. Admission hematocrit and transfusion requirements after trauma. J Am Coll Surg. 2013;216(1):65-73. 62. Jacobs LM, Burns KJ, Pons PT, Gestring ML. Initial steps in training the public about bleeding control: surgeon participa-tion and evaluation. J Am Coll Surg. 2017;224(6):1084-1090. 63. Jacobs LM, Joint


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Surgery_Schwartz. LM, Burns KJ, Pons PT, Gestring ML. Initial steps in training the public about bleeding control: surgeon participa-tion and evaluation. J Am Coll Surg. 2017;224(6):1084-1090. 63. Jacobs LM, Joint committee to create a national policy to enhance survivability from intentional mass C, active shooter E. The Hartford Consensus IV: a call for increased national resil-ience. Bull Am Coll Surg. 2016;101(3):17-24. 64. Clarke JR, Trooskin SZ, Doshi PJ, Greenwald L, Mode CJ. Time to laparotomy for intra-abdominal bleeding from trauma Brunicardi_Ch05_p0131-p0156.indd 15429/01/19 11:06 AM 155SHOCKCHAPTER 5does affect survival for delays up to 90 minutes. J Trauma. 2002;52(3):420-425. 65. Holcomb JB, Jenkins D, Rhee P, et al. Damage control resuscitation: directly addressing the early coagulopathy of trauma. J Trauma. 2007;62(2):307-310. 66. Marshall HP, Jr., Capone A, Courcoulas AP, et al. Effects of hemodilution on long-term survival in an uncontrolled hemor-rhagic shock model in rats. J


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Surgery_Schwartz. of trauma. J Trauma. 2007;62(2):307-310. 66. Marshall HP, Jr., Capone A, Courcoulas AP, et al. Effects of hemodilution on long-term survival in an uncontrolled hemor-rhagic shock model in rats. J Trauma. 1997;43(4):673-679. 67. Bickell WH, Wall MJ, Jr., Pepe PE, et al. Immediate versus delayed fluid resuscitation for hypotensive patients with pene-trating torso injuries. N Engl J Med. 1994;331(17):1105-1109. 68. Human albumin administration in critically ill patients: system-atic review of randomised controlled trials. Cochrane Injuries Group Albumin Reviewers. BMJ. 1998;317(7153):235-240. 69. Mann DV, Robinson MK, Rounds JD, et al. Superiority of blood over saline resuscitation from hemorrhagic shock: a 31P magnetic resonance spectroscopy study. Ann Surg. 1997;226(5):653-661. 70. Vassar MJ, Fischer RP, O’Brien PE, et al. A multicenter trial for resuscitation of injured patients with 7.5% sodium chlo-ride. The effect of added dextran 70. The Multicenter Group for the Study of


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Surgery_Schwartz. MJ, Fischer RP, O’Brien PE, et al. A multicenter trial for resuscitation of injured patients with 7.5% sodium chlo-ride. The effect of added dextran 70. The Multicenter Group for the Study of Hypertonic Saline in Trauma Patients. Arch Surg. 1993;128(9):1003-1011; discussion 1011-1003. 71. Hebert PC, Yetisir E, Martin C, et al. Is a low transfusion threshold safe in critically ill patients with cardiovascular dis-eases? Crit Care Med. 2001;29(2):227-234. 72. Hebert PC, Wells G, Blajchman MA, et al. A multicenter, ran-domized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340(6):409-417. 73. Holcomb JB, Del Junco DJ, Fox EE, et al. The Prospec-tive, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) study: comparative effectiveness of a timevarying treatment with competing risks. Arch Surg. 2012:1-10. 74. Gonzalez EA, Moore FA, Holcomb


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Surgery_Schwartz. Multicenter, Major Trauma Transfusion (PROMMTT) study: comparative effectiveness of a timevarying treatment with competing risks. Arch Surg. 2012:1-10. 74. Gonzalez EA, Moore FA, Holcomb JB, et al. Fresh frozen plasma should be given earlier to patients requiring massive transfusion. J Trauma. 2007;62(1):112-119. 75. Borgman MA, Spinella PC, Perkins JG, et al. The ratio of blood products transfused affects mortality in patients receiv-ing massive transfusions at a combat support hospital. J Trauma. 2007;63(4):805-813. 76. Stansbury LG, Dutton RP, Stein DM, Bochicchio GV, Scalea TM, Hess JR. Controversy in trauma resuscitation: do ratios of plasma to red blood cells matter? Transfus Med Rev. 2009;23(4):255-265. 77. Holcomb JB, Tilley BC, Baraniuk S, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR ran-domized clinical trial. JAMA. 2015;313(5):471-482. 78. Hess JR, Lindell AL, Stansbury LG,


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Surgery_Schwartz. and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR ran-domized clinical trial. JAMA. 2015;313(5):471-482. 78. Hess JR, Lindell AL, Stansbury LG, Dutton RP, Scalea TM. The prevalence of abnormal results of conventional coagu-lation tests on admission to a trauma center. Transfusion. 2009;49(1):34-39. 79. Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M, Burch JM, Galloway B. Predicting life-threatening coagulopa-thy in the massively transfused trauma patient: hypothermia and acidoses revisited. J Trauma. 1997;42(5):857-861; discus-sion 861-852. 80. Holcomb JB, Wade CE, Michalek JE, et al. Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. Ann Surg. 2008;248(3):447-458. 81. Brasel KJ, Vercruysse G, Spinella PC, et al. The association of blood component use ratios with the survival of massively transfused trauma patients with and without severe brain injury. J


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Surgery_Schwartz. KJ, Vercruysse G, Spinella PC, et al. The association of blood component use ratios with the survival of massively transfused trauma patients with and without severe brain injury. J Trauma. 2011;71(2 suppl 3):S343-352. 82. 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;377(9771): 1096-1101, 1101 e1091-1092. 83. Niles SE, McLaughlin DF, Perkins JG, et al. Increased mortal-ity associated with the early coagulopathy of trauma in com-bat casualties. J Trauma. 2008;64(6):1459-1463; discussion 1463-1455. 84. Holcomb JB, Minei KM, Scerbo ML, et al. Admission rapid thrombelastography can replace conventional coagulation tests in the emergency department: experience with 1974 consecu-tive trauma patients. Ann Surg. 2012;256(3):476-486. 85. Roumen RM, Redl H, Schlag G, et al. Inflammatory media-tors in relation to the development of


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Surgery_Schwartz. department: experience with 1974 consecu-tive trauma patients. Ann Surg. 2012;256(3):476-486. 85. Roumen RM, Redl H, Schlag G, et al. Inflammatory media-tors in relation to the development of multiple organ fail-ure in patients after severe blunt trauma. Crit Care Med. 1995;23(3):474-480. 86. Leone M, Boutiere B, Camoin-Jau L, et al. Systemic endo-thelial activation is greater in septic than in traumatichemorrhagic shock but does not correlate with endothelial acti-vation in skin biopsies. Crit Care Med. 2002;30(4):808-814. 87. Mollen KP, Anand RJ, Tsung A, Prince JM, Levy RM, Billiar TR. Emerging paradigm: toll-like receptor 4-sentinel for the detection of tissue damage. Shock. 2006;26(5):430-437. 88. Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med. 2001;345(8):588-595. 89. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of


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Surgery_Schwartz. DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303-1310. 90. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165-228. 91. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36(1):296-327. 92. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-810. 93. Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle: 2018 update. Intensive Care Med. 2018. 94. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sep-sis


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Surgery_Schwartz. The Surviving Sepsis Campaign Bundle: 2018 update. Intensive Care Med. 2018. 94. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sep-sis and septic shock: 2016. Intensive Care Med. 2017;43(3): 304-377. 95. Myburgh JA, Finfer S, Billot L. Hydroxyethyl starch or saline in intensive care. N Engl J Med. 2013;368(8):775. 96. Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis. N Engl J Med. 2012;367(2):124-134. 97. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-1377. 98. Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372(14):1301-1311. 99. Angus DC, Barnato AE, Bell D, et al. A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe


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Surgery_Schwartz. N Engl J Med. 2015;372(14):1301-1311. 99. Angus DC, Barnato AE, Bell D, et al. A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators. Intensive Care Med. 2015;41(9):1549-1560. 100. van den Berghe G, Wouters P, Weekers F, et al. Inten-sive insulin therapy in critically ill patients. N Engl J Med. 2001;345(19):1359-1367. 101. Ventilation with lower tidal volumes as compared with tra-ditional tidal volumes for acute lung injury and the acute Brunicardi_Ch05_p0131-p0156.indd 15529/01/19 11:06 AM 156BASIC CONSIDERATIONSPART Irespiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342(18):1301-1308. 102. Beitler JR, Shaefi S, Montesi SB, et al. Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis. Intensive Care Med. 2014;40(3):332-341. 103. Annane D, Sebille V, Charpentier C, et al. Effect of


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Surgery_Schwartz. mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis. Intensive Care Med. 2014;40(3):332-341. 103. Annane D, Sebille V, Charpentier C, et al. Effect of treat-ment with low doses of hydrocortisone and fludrocorti-sone on mortality in patients with septic shock. JAMA. 2002;288(7):862-871. 104. Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008;358(2):111-124. 105. Hollenberg SM, Kavinsky CJ, Parrillo JE. Cardiogenic shock. Ann Intern Med. 1999;131(1):47-59. 106. Webb JG, Lowe AM, Sanborn TA, et al. Percutaneous coro-nary intervention for cardiogenic shock in the SHOCK trial. J Am Coll Cardiol. 2003;42(8):1380-1386. 107. Edens JW, Chung KK, Pamplin JC, et al. Predictors of early acute lung injury at a combat support hospital: a prospective observational study. J Trauma. 2010;69 Suppl 1:S81-86. 108. Aji J, Hollenberg S. Cardiogenic shock: giving the heart a break. Crit Care Med.


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Surgery_Schwartz. lung injury at a combat support hospital: a prospective observational study. J Trauma. 2010;69 Suppl 1:S81-86. 108. Aji J, Hollenberg S. Cardiogenic shock: giving the heart a break. Crit Care Med. 2006;34(4):1248-1249. 109. Alonso DR, Scheidt S, Post M, Killip T. Pathophysiology of cardiogenic shock. Quantification of myocardial necrosis, clinical, pathologic and electrocardiographic correlations. Circulation. 1973;48(3):588-596. 110. Goldstein DJ, Oz MC. Mechanical support for postcardi-otomy cardiogenic shock. Semin Thorac Cardiovasc Surg. 2000;12(3):220-228. 111. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60(16):1581-1598. 112. Gibbons RJ, Smith SC, Jr., Antman E. American College of Cardiology/American Heart Association clinical practice guidelines: part II: evolutionary changes in a continuous quality improvement project. Circulation. 2003;107(24):3101-3107. 113. Menon V, Hochman JS. Management of


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Surgery_Schwartz. Heart Association clinical practice guidelines: part II: evolutionary changes in a continuous quality improvement project. Circulation. 2003;107(24):3101-3107. 113. Menon V, Hochman JS. Management of cardiogenic shock complicating acute myocardial infarction. Heart. 2002;88(5): 531-537. 114. Levi L, Wolf A, Belzberg H. Hemodynamic parameters in patients with acute cervical cord trauma: description, intervention, and prediction of outcome. Neurosurgery. 1993;33(6):1007-1016; discussion 1016-1007. 115. Zipnick RI, Scalea TM, Trooskin SZ, et al. Hemodynamic responses to penetrating spinal cord injuries. J Trauma. 1993;35(4):578-582; discussion 582-573. 116. Abou-Khalil B, Scalea TM, Trooskin SZ, Henry SM, Hitchcock R. Hemodynamic responses to shock in young trauma patients: need for invasive monitoring. Crit Care Med. 1994;22(4):633-639. 117. Claridge JA, Crabtree TD, Pelletier SJ, Butler K, Sawyer RG, Young JS. Persistent occult hypoperfusion is associated with a significant increase


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Surgery_Schwartz. monitoring. Crit Care Med. 1994;22(4):633-639. 117. Claridge JA, Crabtree TD, Pelletier SJ, Butler K, Sawyer RG, Young JS. Persistent occult hypoperfusion is associated with a significant increase in infection rate and mortality in major trauma patients. J Trauma. 2000;48(1):8-14; discussion 14-15. 118. Ivatury RR, Simon RJ, Havriliak D, Garcia C, Greenbarg J, Stahl WM. Gastric mucosal pH and oxygen delivery and oxygen consumption indices in the assessment of adequacy of resuscitation after trauma: a prospective, randomized study. J Trauma. 1995;39(1):128-134; discussion 134-136. 119. Maynard N, Beale R, Smithies M, Bihari D. Gastric intramu-cosal pH in critically ill patients. Lancet. 1992;339(8792): 550-551. 120. Gomersall CD, Joynt GM, Freebairn RC, Hung V, Buckley TA, Oh TE. Resuscitation of critically ill patients based on the results of gastric tonometry: a prospective, randomized, controlled trial. Crit Care Med. 2000;28(3):607-614. 121. Cairns CB, Moore FA, Haenel JB, et


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Surgery_Schwartz. of critically ill patients based on the results of gastric tonometry: a prospective, randomized, controlled trial. Crit Care Med. 2000;28(3):607-614. 121. Cairns CB, Moore FA, Haenel JB, et al. Evidence for early supply independent mitochondrial dysfunction in patients developing multiple organ failure after trauma. J Trauma. 1997;42(3):532-536. 122. Cohn SM, Crookes BA, Proctor KG. Near-infrared spectros-copy in resuscitation. J Trauma. 2003;54(5 Suppl):S199-202. 123. Knudson MM, Bermudez KM, Doyle CA, Mackersie RC, Hopf HW, Morabito D. Use of tissue oxygen tension measure-ments during resuscitation from hemorrhagic shock. J Trauma. 1997;42(4):608-614; discussion 614-616. 124. McKinley BA, Marvin RG, Cocanour CS, Moore FA. Tissue hemoglobin O2 saturation during resuscitation of traumatic shock monitored using near infrared spectrometry. J Trauma. 2000;48(4):637-642. 125. Cheatham ML, Nelson LD, Chang MC, Safcsak K. Right ven-tricular end-diastolic volume index as a predictor of


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Surgery_Schwartz. shock monitored using near infrared spectrometry. J Trauma. 2000;48(4):637-642. 125. Cheatham ML, Nelson LD, Chang MC, Safcsak K. Right ven-tricular end-diastolic volume index as a predictor of preload status in patients on positive end-expiratory pressure. Crit Care Med. 1998;26(11):1801-1806. 126. Chang MC, Meredith JW, Kincaid EH, Miller PR. Maintain-ing survivors’ values of left ventricular power output dur-ing shock resuscitation: a prospective pilot study. J Trauma. 2000;49(1):26-33; discussion 34-37.Brunicardi_Ch05_p0131-p0156.indd 15629/01/19 11:06 AM


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Surgery_Schwartz. Surgical InfectionsRobert E. Bulander, David L. Dunn, and Greg J. Beilman 6chapterHISTORICAL BACKGROUNDAlthough treatment of infection has long been an integral part of the surgeon’s practice, the body of knowledge that led to the present field of surgical infectious disease was derived from the evolution of germ theory and antisepsis. Application of the latter to clinical practice, concurrent with the development of anesthe-sia, was pivotal in allowing surgeons to expand their repertoire to encompass complex procedures that previously were associ-ated with extremely high rates of morbidity and mortality due to postoperative infections. However, until recently the occurrence of infection related to the surgical wound was the rule rather than the exception. In fact, the development of modalities to effectively prevent and treat infection has occurred only within the last several decades.A number of observations by 19th century physicians and investigators were critical to our current


Surgery_Schwartz

Surgery_Schwartz. to effectively prevent and treat infection has occurred only within the last several decades.A number of observations by 19th century physicians and investigators were critical to our current understanding of the pathogenesis, prevention, and treatment of surgical infections. In 1846, Ignaz Semmelweis, a Magyar physician, took a post at the Allgemein Krankenhaus in Vienna. He noticed that the mortality rate from puerperal (“childbed”) fever was nearly three times higher in the teaching ward than in the ward where patients were delivered by midwives. He also made the observa-tion that women who delivered prior to arrival on the teaching ward had a negligible mortality rate. When a colleague died from overwhelming infection resulting from a knife scratch received during an autopsy of a woman who had died of puer-peral fever, Semmelweis observed that pathologic changes in his friend were identical to those of women dying from this postpartum disease. He hypothesized that puerperal fever


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Surgery_Schwartz. who had died of puer-peral fever, Semmelweis observed that pathologic changes in his friend were identical to those of women dying from this postpartum disease. He hypothesized that puerperal fever was caused by putrid material carried on the examining fingers of medical students and physicians who cared for women dying of the disease, and who often went from the autopsy room to the wards. The low mortality rate in the midwives’ ward, Sem-melweis realized, was because midwives did not participate in autopsies. Fired with the zeal of his revelation, he posted a notice on the door to the ward requiring all caregivers to rinse their hands thoroughly in chlorine water prior to entering the area. This simple intervention reduced the mortality rate from puerperal fever on the teaching ward to 1.5%, surpassing the record of the midwives. In 1861, he published his classic work on childbed fever based on records from his practice. Unfor-tunately, Semmelweis’ ideas were not well accepted by the


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Surgery_Schwartz. surpassing the record of the midwives. In 1861, he published his classic work on childbed fever based on records from his practice. Unfor-tunately, Semmelweis’ ideas were not well accepted by the authorities of the time.1 Increasingly frustrated by the indiffer-ence of the medical profession, he began writing open letters to well-known obstetricians in Europe and was committed to an asylum due to concerns that he was losing his mind. He died shortly thereafter. His achievements were only recognized after Pasteur’s description of the germ theory of disease.Louis Pasteur performed a body of work during the lat-ter part of the 19th century that provided the underpinnings of modern microbiology, at the time known as germ theory. His work in humans followed experiments identifying infectious agents in silkworms. He was able to elucidate the principle that contagious diseases are caused by specific microbes and that these microbes are foreign to the infected organism. Using this principle,


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Surgery_Schwartz. in silkworms. He was able to elucidate the principle that contagious diseases are caused by specific microbes and that these microbes are foreign to the infected organism. Using this principle, he developed techniques of sterilization criti-cal to oenology and identified several bacteria responsible for human illnesses, including Staphylococcus and Streptococcus pneumoniae (pneumococcus).Joseph Lister, the son of a wine merchant, was appointed professor of surgery at the Glasgow Royal Infirmary in 1859. In his early practice, he noted that more than half of his patients undergoing amputation died because of postoperative infection. After hearing of Pasteur’s work, Lister experimented with the use of a solution of carbolic acid, which he knew was being used to treat sewage. He first reported his findings to the British Medical Association in 1867 using dressings saturated with car-bolic acid on 12 patients with compound fractures; 10 recovered Historical Background 157Pathogenesis of


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Surgery_Schwartz. his findings to the British Medical Association in 1867 using dressings saturated with car-bolic acid on 12 patients with compound fractures; 10 recovered Historical Background 157Pathogenesis of Infection 159Host Defenses / 159Definitions / 160Microbiology of Infectious Agents 161Bacteria / 161Fungi / 162Viruses / 162Prevention and Treatment of Surgical Infections 163General Principles / 163Source Control / 163Appropriate Use of Antimicrobial Agents / 164Infections of Significance in Surgical Patients 169Surgical Site Infections / 169Intra-Abdominal Infections / 171Organ-Specific Infections / 172Infections of the Skin and Soft Tissue / 173Postoperative Nosocomial Infections / 174Sepsis / 175Resistant Organisms / 177Blood-Borne Pathogens / 177Biologic Warfare Agents 178Bacillus anthracis (Anthrax) / 178Yersinia pestis (Plague) / 178Smallpox / 178Francisella tularensis (Tularemia) / 179Brunicardi_Ch06_p0157-p0182.indd 15701/03/19 4:46 PM 158without amputation, one survived


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Surgery_Schwartz. (Anthrax) / 178Yersinia pestis (Plague) / 178Smallpox / 178Francisella tularensis (Tularemia) / 179Brunicardi_Ch06_p0157-p0182.indd 15701/03/19 4:46 PM 158without amputation, one survived with amputation, and one died of causes unrelated to the wound. In spite of initial resistance, his methods were quickly adopted throughout much of Europe.From 1878 until 1880, Robert Koch was the district medi-cal officer for Wollstein, an area in Prussia where anthrax was endemic. Performing experiments in his home, without the ben-efit of scientific equipment and academic contact, Koch devel-oped techniques for culture of Bacillus anthracis and proved the ability of this organism to cause anthrax in healthy animals. He developed the following four postulates to identify the asso-ciation of organisms with specific diseases: (a) the suspected pathogenic organism should be present in all cases of the disease and absent from healthy animals, (b) the suspected pathogen should be isolated from a


Surgery_Schwartz

Surgery_Schwartz. with specific diseases: (a) the suspected pathogenic organism should be present in all cases of the disease and absent from healthy animals, (b) the suspected pathogen should be isolated from a diseased host and grown in a pure culture in vitro, (c) cells from a pure culture of the suspected organism should cause disease in a healthy animal, and (d) the organism should be reisolated from the newly diseased animal and shown to be the same as the original. He used these same techniques to identify the organisms responsible for cholera and tuberculosis. During the next century, Koch’s postulates, as they came to be called, became critical to the understanding of surgi-cal infections.2The first intra-abdominal operation to treat infection via “source control” (i.e., surgical intervention to eliminate the source of infection) was appendectomy. This operation was pioneered by Charles McBurney at the New York College of Physicians and Surgeons, among others.3 McBurney’s classic report on


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Surgery_Schwartz. eliminate the source of infection) was appendectomy. This operation was pioneered by Charles McBurney at the New York College of Physicians and Surgeons, among others.3 McBurney’s classic report on early operative intervention for appendicitis was pre-sented before the New York Surgical Society in 1889. Appen-dectomy for the treatment of appendicitis, previously an often fatal disease, was popularized after the 1902 coronation of King Edward VII of England was delayed due to his falling ill with appendicitis. Edward insisted on carrying out his sched-ule, despite worsening abdominal pain. Sir Frederick Treves, a prominent London surgeon, was among the consultants in atten-dance upon Edward. As the prince’s condition deteriorated, and as he continued to insist that he would go to Westminster Abbey to be crowned, Treves told him, “Then Sire, you will go as a corpse.” Edward relented, Treves drained a large periappendi-ceal abscess, and the king lived.4During the 20th century the


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Surgery_Schwartz. Abbey to be crowned, Treves told him, “Then Sire, you will go as a corpse.” Edward relented, Treves drained a large periappendi-ceal abscess, and the king lived.4During the 20th century the development of effective anti-microbials added a new dimension to modern surgical practice. Sir Alexander Fleming, after serving in the British Army Medical Corps during World War I, continued his work on the natural antibacterial action of the blood and antiseptics. In 1928, while studying influenza virus, he noted a zone of inhibition around a mold colony (Penicillium notatum) that serendipitously grew on a plate of Staphylococcus, and he named the active substance penicillin. Penicillin, along with the sulfonamide antibiotics, were among the first of hundreds of potent antimicrobials that became a critical component of the armamentarium to prevent and treat aggressive, lethal surgical infections.5Concurrent with the development of antimicrobial agents were advances in the field of clinical


Surgery_Schwartz

Surgery_Schwartz. a critical component of the armamentarium to prevent and treat aggressive, lethal surgical infections.5Concurrent with the development of antimicrobial agents were advances in the field of clinical microbiology. Many new microbes were identified, including numerous anaerobes. The autochthonous microflora of the skin, gastrointestinal tract, and other parts of the body that the surgeon encountered in the pro-cess of an operation were characterized in great detail. However, it remained unclear whether these organisms were commensals or pathogens. Subsequently, the initial clinical observations of surgeons such as Frank Meleney, William Altemeier, and others provided the key when they observed that aerobic and anaerobic host flora could synergize to cause serious soft tissue and severe intra-abdominal infection.6,7 Thus, the concepts that resident Key Points1 Sepsis is a life-threatening syndrome reflecting both an infection and the systemic host response to it. It has a broad variety of


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Surgery_Schwartz. infection.6,7 Thus, the concepts that resident Key Points1 Sepsis is a life-threatening syndrome reflecting both an infection and the systemic host response to it. It has a broad variety of presentations and manifestations that hold in com-mon some form of organ dysfunction. Outcomes in patients with sepsis are improved with an organized approach to therapy that addresses rapid resuscitation, antibiotics, and source control.2 Source control is a key concept in the treatment of most surgically relevant infections. Infected or necrotic material must be drained or removed as part of the treatment plan in this setting. Delays in adequate source control are associated with worsened outcomes.3 Principles relevant to appropriate antibiotic prophylaxis for surgery: (a) select an agent with activity against organisms commonly found at the site of surgery, (b) administer the ini-tial dose of the antibiotic within 30 minutes prior to incision, (c) redose the antibiotic during long operations


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Surgery_Schwartz. against organisms commonly found at the site of surgery, (b) administer the ini-tial dose of the antibiotic within 30 minutes prior to incision, (c) redose the antibiotic during long operations based upon the half-life of the agent to ensure adequate tissue levels, and (d) limit the antibiotic regimen to no more than 24 hours after surgery for routine prophylaxis.4 When using antimicrobial agents for therapy of serious infection, several principles should be followed: (a) identify likely sources of infection, (b) select an agent (or agents) that will have efficacy against likely organisms for these sources, (c) begin therapy rapidly with broad coverage, as inadequate or delayed antibiotic therapy results in increased mortality, (d) when possible, obtain cultures early and use results to refine therapy, (e) if no infection is identified after 3 days, strongly consider discontinuation of antibiotics, based upon the patient’s clinical course, and (f) discontinue antibiotics after an


Surgery_Schwartz

Surgery_Schwartz. to refine therapy, (e) if no infection is identified after 3 days, strongly consider discontinuation of antibiotics, based upon the patient’s clinical course, and (f) discontinue antibiotics after an appropriate course of therapy.5 The incidence of surgical site infections can be reduced by appropriate patient preparation, timely perioperative antibi-otic administration, maintenance of perioperative normo-thermia and normoglycemia, and appropriate wound management.6 The keys to good outcomes in patients with necrotizing soft tissue infection are early recognition and appropriate debridement of infected tissue with repeated debridement until no further signs of infection are present.7 Transmission of HIV and other infections spread by blood and body fluids from patient to healthcare worker can be minimized by practicing universal precautions, which include routine use of barriers when anticipating contact with blood or body fluids, washing of hands and other skin surfaces immediately


Surgery_Schwartz

Surgery_Schwartz. can be minimized by practicing universal precautions, which include routine use of barriers when anticipating contact with blood or body fluids, washing of hands and other skin surfaces immediately after contact with blood or body fluids, and careful handling and disposal of sharp instruments dur-ing and after use.Brunicardi_Ch06_p0157-p0182.indd 15801/03/19 4:46 PM 159SURGICAL INFECTIONSCHAPTER 6microbes were nonpathogenic until they entered a sterile body cavity at the time of surgery, and that many, if not most, surgical infections were polymicrobial in nature, became critical ideas.8,9 These tenets became firmly established after microbiology lab-oratories demonstrated the invariable presence of aerobes and anaerobes in peritoneal cultures obtained at the time of surgery for intra-abdominal infection due to perforated viscus or gangre-nous appendicitis. Clinical trials provided ample evidence that optimal therapy for these infections required effective source control and the


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Surgery_Schwartz. infection due to perforated viscus or gangre-nous appendicitis. Clinical trials provided ample evidence that optimal therapy for these infections required effective source control and the administration of antimicrobial agents directed against both types of pathogens.William Osler made an observation in 1904 in his treatise The Evolution of Modern Medicine that was to have profound implications for the future of treatment of infection: “Except on few occasions, the patient appears to die from the body’s response to infection rather than from it.”10 The discovery of cytokines began to allow insight into the human organism’s response to infection, and led to an explosion in our understand-ing of the host inflammatory response. Expanding knowledge of the multiple pathways activated during the response to invasion by infectious organisms has permitted the design of new thera-pies targeted at modifying the inflammatory response to infec-tion, which seems to cause much of the organ


Surgery_Schwartz

Surgery_Schwartz. the response to invasion by infectious organisms has permitted the design of new thera-pies targeted at modifying the inflammatory response to infec-tion, which seems to cause much of the organ dysfunction and failure. Preventing and treating this process of multiple organ failure during infection is one of the major challenges of modern critical care and surgical infectious disease.PATHOGENESIS OF INFECTIONHost DefensesThe mammalian host possesses several layers of endogenous defense mechanisms that serve to prevent microbial invasion, limit proliferation of microbes within the host, and contain or eradicate invading microbes. These defenses are integrated and redundant so that the various components function as a com-plex, highly regulated system that is extremely effective in cop-ing with microbial invaders. They include site-specific defenses that function at the tissue level, as well as components that freely circulate throughout the body in both blood and lymph. Systemic host


Surgery_Schwartz

Surgery_Schwartz. with microbial invaders. They include site-specific defenses that function at the tissue level, as well as components that freely circulate throughout the body in both blood and lymph. Systemic host defenses invariably are recruited to a site of infec-tion, a process that begins immediately upon introduction of microbes into a sterile area of the body. Perturbation of one or more components of these defenses (e.g., via immunosuppres-sants, foreign body, chronic illness, or burns) may have substan-tial negative impact on resistance to infection.Entry of microbes into the mammalian host is precluded by a number of barriers that possess either an epithelial (integu-ment) or mucosal (respiratory, gut, and urogenital) surface. Barrier function, however, is not solely limited to physical characteristics. Host barrier cells may secrete substances that limit microbial proliferation or prevent invasion. Also, resident or commensal microbes adherent to the physical surface and to each other may


Surgery_Schwartz

Surgery_Schwartz. Host barrier cells may secrete substances that limit microbial proliferation or prevent invasion. Also, resident or commensal microbes adherent to the physical surface and to each other may preclude invasion, particularly of virulent organ-isms; this is termed colonization resistance.11The most extensive physical barrier is the integument or skin. In addition to the physical barrier posed by the epithelial surface, the skin harbors its own resident microflora that may block the attachment and invasion of noncommensal microbes. Microbes also are held in check by chemicals secreted by seba-ceous glands and by the constant shedding of epithelial cells. The endogenous microflora of the integument primarily com-prises gram-positive aerobic microbes belonging to the genera Staphylococcus and Streptococcus, as well as Corynebacterium and Propionibacterium species. These organisms plus Entero-coccus faecalis and faecium, Escherichia coli and other Entero-bacteriaceae, and yeast such as


Surgery_Schwartz

Surgery_Schwartz. and Streptococcus, as well as Corynebacterium and Propionibacterium species. These organisms plus Entero-coccus faecalis and faecium, Escherichia coli and other Entero-bacteriaceae, and yeast such as Candida albicans can be isolated from the infraumbilical regions of the body. Diseases of the skin (e.g., eczema and dermatitis) are associated with overgrowth of skin commensal organisms, and barrier breaches invariably lead to the introduction of these microbes.The respiratory tract possesses several host defense mech-anisms that facilitate the maintenance of sterility in the distal bronchi and alveoli. In the upper respiratory tract, respiratory mucus traps larger particles, including microbes. This mucus is then passed into the upper airways and oropharynx by cili-ated epithelial cells, where the mucus is cleared via coughing. Smaller particles arriving in the lower respiratory tract are cleared via phagocytosis by pulmonary alveolar macrophages. Any process that diminishes these host


Surgery_Schwartz

Surgery_Schwartz. the mucus is cleared via coughing. Smaller particles arriving in the lower respiratory tract are cleared via phagocytosis by pulmonary alveolar macrophages. Any process that diminishes these host defenses can lead to development of bronchitis or pneumonia.The urogenital, biliary, pancreatic ductal, and distal respi-ratory tracts do not possess resident microflora in healthy indi-viduals, although microbes may be present if these barriers are affected by disease (e.g., malignancy, inflammation, calculi, or foreign body), or if microorganisms are introduced from an external source (e.g., urinary catheter or pulmonary aspiration). In contrast, significant numbers of microbes are encountered in many portions of the gastrointestinal tract, with vast numbers being found within the oropharynx and distal colon or rectum, although the specific organisms differ.One would suppose that the entire gastrointestinal tract would be populated via those microbes found in the oropharynx, but this is not


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Surgery_Schwartz. distal colon or rectum, although the specific organisms differ.One would suppose that the entire gastrointestinal tract would be populated via those microbes found in the oropharynx, but this is not the case.11 This is because after ingestion these organisms routinely are killed in the highly acidic, low-motility environment of the stomach during the initial phases of diges-tion. Thus, only small numbers of microbes populate the gas-tric mucosa (∼102 to 103 colony-forming units [CFU]/mL). This population expands in the presence of drugs or disease states that diminish gastric acidity. Microbes that are not destroyed within the stomach enter the small intestine, in which a certain amount of microbial proliferation takes place, such that approxi-mately 105 to 108 CFU/mL are present in the terminal ileum.The relatively low-oxygen, static environment of the colon is accompanied by the exponential growth of microbes that com-prise the most extensive host endogenous microflora. Anaerobic


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Surgery_Schwartz. terminal ileum.The relatively low-oxygen, static environment of the colon is accompanied by the exponential growth of microbes that com-prise the most extensive host endogenous microflora. Anaerobic microbes outnumber aerobic species approximately 100:1 in the distal colon, and approximately 1011 to 1012 CFU/g are pres-ent in feces. Large numbers of facultative and strict anaerobes (Bacteroides fragilis, distasonis, and thetaiotaomicron, Bifido-bacterium, Clostridium, Eubacterium, Fusobacterium, Lactoba-cillus, and Peptostreptococcus species) as well as several orders of magnitude fewer aerobic microbes (E coli and other Entero-bacteriaceae, E faecalis and faecium, C albicans and other Candida spp.) are present. Intriguingly, although colonization resistance on the part of this extensive, well-characterized host microflora effectively prevents invasion of enteric pathogens such as Salmonella, Shigella, Vibrio, and other enteropathogenic bacterial species, these same organisms provide


Surgery_Schwartz

Surgery_Schwartz. well-characterized host microflora effectively prevents invasion of enteric pathogens such as Salmonella, Shigella, Vibrio, and other enteropathogenic bacterial species, these same organisms provide the initial inoc-ulum for infection should perforation of the gastrointestinal tract occur. It is of great interest that only some of these microbial species predominate in established intra-abdominal infections.Once microbes enter a sterile body compartment (e.g., the pleural or peritoneal cavity) or tissue, additional host defenses act to limit and/or eliminate these pathogens. Initially, several Brunicardi_Ch06_p0157-p0182.indd 15901/03/19 4:46 PM 160BASIC CONSIDERATIONSPART Iprimitive and relatively nonspecific host defenses act to con-tain the nidus of infection, which may include microbes as well as debris, devitalized tissue, and foreign bodies, depending on the nature of the injury. These defenses include the physi-cal barrier of the tissue itself, as well as the capacity of


Surgery_Schwartz

Surgery_Schwartz. as well as debris, devitalized tissue, and foreign bodies, depending on the nature of the injury. These defenses include the physi-cal barrier of the tissue itself, as well as the capacity of pro-teins such as lactoferrin and transferrin to sequester the critical microbial growth factor iron, thereby limiting microbial growth. In addition, fibrinogen within the inflammatory fluid has the ability to trap large numbers of microbes during the process in which it polymerizes into fibrin. Within the peritoneal cavity, unique host defenses exist, including a diaphragmatic pump-ing mechanism whereby particles—including microbes—within peritoneal fluid are expunged from the abdominal cavity via specialized structures (stomata) on the undersurface of the dia-phragm that lead to thoracic lymphatic channels. Concurrently, containment by the omentum and intestinal ileus serve to wall off infections. However, the latter processes and fibrin trapping have a high likelihood of contributing to the


Surgery_Schwartz

Surgery_Schwartz. channels. Concurrently, containment by the omentum and intestinal ileus serve to wall off infections. However, the latter processes and fibrin trapping have a high likelihood of contributing to the formation of an intra-abdominal abscess.Microbes also immediately encounter a series of host defense mechanisms that reside within the vast majority of tissues of the body. These include resident macrophages and low levels of complement (C) proteins and immunoglobulins (e.g., antibodies).12 The response in macrophages is initiated by genome-encoded pattern recognition receptors that respond to invading microbes. With exposure to a foreign organism, these receptors recognize microbial pathogen-associated molecular patterns (PAMPs) and endogenous danger-associated molecular patterns (DAMPs). Toll-like receptors (TLRs) are a well-defined example of a PAMP that plays an important role in pathogen signaling.13 Resident macrophages secrete a wide array of sub-stances in response to the


Surgery_Schwartz

Surgery_Schwartz. Toll-like receptors (TLRs) are a well-defined example of a PAMP that plays an important role in pathogen signaling.13 Resident macrophages secrete a wide array of sub-stances in response to the aforementioned processes, some of which appear to regulate the cellular components of the host defense response. This results in recruitment and proliferation of inflammatory cells. Macrophage cytokine synthesis is upreg-ulated. Secretion of tumor necrosis factor-alpha (TNF-α), of interleukins (IL)-1β, 6, and 8; and of gamma interferon (IFN-γ) occurs within the tissue milieu, and depending on the magnitude of the host defense response, the systemic circulation.14 Concur-rently, a counterregulatory response is initiated consisting of binding protein (TNF-BP), cytokine receptor antagonists (e.g., IL-1ra), and anti-inflammatory cytokines (IL-4 and IL-10).The interaction of microbes with these first-line host defenses leads to microbial opsonization (C1q, C3bi, and IgFc), phagocytosis, and both


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Surgery_Schwartz. IL-1ra), and anti-inflammatory cytokines (IL-4 and IL-10).The interaction of microbes with these first-line host defenses leads to microbial opsonization (C1q, C3bi, and IgFc), phagocytosis, and both extracellular (C5b6-9 membrane attack complex) and intracellular microbial destruction (via cellular ingestion into phagocytic vacuoles). Concurrently, the classical and alternate complement pathways are activated both via direct contact with and via IgM and IgG binding to microbes, leading to the release of a number of different biologically active com-plement protein fragments (C3a, C4a, C5a), acting to markedly enhance vascular permeability. Bacterial cell wall components and a variety of enzymes expelled from leukocyte phagocytic vacuoles during microbial phagocytosis and killing act in this capacity as well.Simultaneously, the release of substances to which poly-morphonuclear leukocytes (PMNs) in the bloodstream are attracted takes place. These consist of C5a, microbial cell wall


Surgery_Schwartz

Surgery_Schwartz. this capacity as well.Simultaneously, the release of substances to which poly-morphonuclear leukocytes (PMNs) in the bloodstream are attracted takes place. These consist of C5a, microbial cell wall peptides containing N-formyl-methionine, and macrophage secretion of cytokines such as IL-8. This process of host defense recruitment leads to further influx of inflammatory fluid into the area of incipient infection and is accompanied by diapedesis of large numbers of PMNs, a process that begins within several minutes and may peak within hours or days. The magnitude of the response and eventual outcome is generally related to several factors: (a) the initial number of microbes, (b) the rate of microbial proliferation in relation to containment and killing by host defenses, (c) microbial virulence, and (d) the potency of host defenses. In regard to the latter, drugs or disease states that diminish any or multiple components of host defenses are asso-ciated with higher rates and potentially


Surgery_Schwartz

Surgery_Schwartz. and (d) the potency of host defenses. In regard to the latter, drugs or disease states that diminish any or multiple components of host defenses are asso-ciated with higher rates and potentially more grave infections.DefinitionsSeveral possible outcomes can occur subsequent to microbial invasion and the interaction of microbes with resident and recruited host defenses: (a) eradication; (b) containment, often leading to the presence of purulence, the hallmark of chronic infections (e.g., a furuncle in the skin and soft tissue or abscess within the parenchyma of an organ or potential space); (c) locoregional infection (cellulitis, lymphangitis, and aggressive soft tissue infection) with or without distant spread of infec-tion (metastatic abscess); or (d) systemic infection (bactere-mia or fungemia). Obviously, the latter represents the failure of resident and recruited host defenses at the local level, and is associated with significant morbidity and mortality. Disease progression


Surgery_Schwartz

Surgery_Schwartz. or fungemia). Obviously, the latter represents the failure of resident and recruited host defenses at the local level, and is associated with significant morbidity and mortality. Disease progression commonly occurs such that serious locoregional infection is associated with concurrent systemic infection. A chronic abscess also may intermittently drain and/or be associ-ated with bacteremia.Infection is defined by the presence of microorganisms in host tissue or the bloodstream. The classic findings of rubor, calor, and dolor in areas such as the skin or subcutaneous tis-sue are common at the site of infection. Most infections in nor-mal individuals with intact host defenses are associated with these local manifestations, plus systemic manifestations such as elevated temperature, elevated white blood cell (WBC) count, tachycardia, or tachypnea. The systemic manifestations noted previously comprise what has been termed the systemic inflammatory response syndrome (SIRS). SIRS reflects a


Surgery_Schwartz

Surgery_Schwartz. white blood cell (WBC) count, tachycardia, or tachypnea. The systemic manifestations noted previously comprise what has been termed the systemic inflammatory response syndrome (SIRS). SIRS reflects a pro-inflammatory state in response to a variety of disease processes, including infection, pancreatitis, polytrauma, malignancy, and burns. There are a variety of systemic manifestations of infec-tion, with the classic factors of fever, tachycardia, and tachypnea broadened to include a variety of other variables (Table 6-1).15The definition of sepsis is evolving. Earlier models described sepsis as SIRS caused by infection. This was based upon the idea that sepsis is mediated by the production of a cascade of proinflammatory mediators produced in response to exposure to microbial products. These products include lipo-polysaccharide (endotoxin, LPS) derived from gram-negative organisms; peptidoglycans and teichoic acids from grampositive organisms; many different microbial cell wall


Surgery_Schwartz

Surgery_Schwartz. These products include lipo-polysaccharide (endotoxin, LPS) derived from gram-negative organisms; peptidoglycans and teichoic acids from grampositive organisms; many different microbial cell wall compo-nents, such as mannan from yeast and fungi; and many others.There are several issues, however, with basing a sepsis diagnosis on the presence of SIRS. One problem is that it is insufficiently specific. Patients can exhibit SIRS criteria without the presence of the more whole-body dysregulation consistent with sepsis, and conversely can suffer from sepsis without meet-ing SIRS criteria. Patients with SIRS do not necessarily prog-ress to sepsis and do not necessarily have worsened outcomes because of the SIRS diagnosis; in other words, SIRS is not inher-ently life-threatening. Another issue is that the SIRS criteria can vary and are inconsistently applied. Numerous definitions exist, specifying differing physiologic and laboratory criteria for the Brunicardi_Ch06_p0157-p0182.indd


Surgery_Schwartz

Surgery_Schwartz. is that the SIRS criteria can vary and are inconsistently applied. Numerous definitions exist, specifying differing physiologic and laboratory criteria for the Brunicardi_Ch06_p0157-p0182.indd 16001/03/19 4:46 PM 161SURGICAL INFECTIONSCHAPTER 6diagnosis. This creates difficulty in clinical, epidemiological, and research settings. Further, sepsis is not a purely inflamma-tory phenomenon, as both proand anti-inflammatory cascades have been shown to be activated in septic patients. Basing a diagnosis upon inflammatory markers alone disregards nonin-flammatory organ dysfunction, which may not manifest as SIRS but can contribute to mortality. A final concern is that defining sepsis using SIRS criteria implies that SIRS, sepsis, severe sep-sis, and septic shock exist upon a continuum, and while SIRS and sepsis have common features, the former does not necessar-ily lead to the latter. This being said, SIRS criteria have utility in that they point toward an organism experiencing


Surgery_Schwartz

Surgery_Schwartz. and while SIRS and sepsis have common features, the former does not necessar-ily lead to the latter. This being said, SIRS criteria have utility in that they point toward an organism experiencing physiological stress. The presence of SIRS warrants further investigation by the clinician.16An international consensus panel proposed new defini-tions of sepsis and septic shock in 2016. What is known as the Sepsis-3 model defines sepsis as life-threatening organ dysfunc-tion caused by a dysregulated host response to infection. Organ dysfunction is quantified by an increase of ≥2 points on the Sequential Organ Failure Assessment (SOFA). The SOFA score looks at PaO2/FiO2 ratio, bilirubin, platelet count, mean arterial pressure (MAP), Glasgow Coma Scale (GCS) score, creatinine level, and urine output (Table 6-2). An increase in SOFA score of 2 or more is correlated with a 10% in-hospital mortality risk, which is suggestive of the life-threatening nature of sepsis. An abbreviated version of the


Surgery_Schwartz

Surgery_Schwartz. (Table 6-2). An increase in SOFA score of 2 or more is correlated with a 10% in-hospital mortality risk, which is suggestive of the life-threatening nature of sepsis. An abbreviated version of the scoring system, the quick SOFA (qSOFA) is recommended as a screening and mon-itoring tool for patients with suspected sepsis. The qSOFA sug-gests potentially life-threatening sepsis when at least two of the following parameters are met: altered mental status, systolic blood pressure of 100 mmHg or less, and respiratory rate greater than 22 breaths/minute. The qSOFA can readily identify patients at risk of poor outcome from sepsis without reliance upon labo-ratory or imaging data.16Under the older nomenclature, severe sepsis was char-acterized as sepsis combined with the presence of new-onset organ failure. The Sepsis-3 definitions consider the term “severe sepsis” to be redundant, as by this definition all sepsis involves organ dysfunction. Under the Sepsis-3 guidelines, septic shock is a


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Surgery_Schwartz. failure. The Sepsis-3 definitions consider the term “severe sepsis” to be redundant, as by this definition all sepsis involves organ dysfunction. Under the Sepsis-3 guidelines, septic shock is a subset of sepsis in which circulatory and cellular metabolic derangements are profound enough to significantly increase the risk of death. Sepsis is the most common cause of death in non-coronary critical care units and the 11th most common cause of death overall in the United States, with a mortality rate of 10.3 cases per 100,000 population in 2010.17 Septic shock is the most severe manifestation of infection, with an attendant mortality rate in excess of 40%. It can be identified by persistent arterial hypo-tension requiring vasopressors to maintain mean arterial pressure (MAP) ≥65, and by serum lactate >2 mmol/L (18 mg/dL) despite adequate volume resuscitation.16,18,19MICROBIOLOGY OF INFECTIOUS AGENTSA partial list of common pathogens that cause infections in sur-gical patients is provided


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Surgery_Schwartz. lactate >2 mmol/L (18 mg/dL) despite adequate volume resuscitation.16,18,19MICROBIOLOGY OF INFECTIOUS AGENTSA partial list of common pathogens that cause infections in sur-gical patients is provided in Table 6-3.BacteriaBacteria are responsible for the majority of surgical infections. Specific species are identified using Gram stain and growth characteristics on specific media. The Gram stain is an important evaluation that allows rapid classification of bacteria by color. This color is related to the staining characteristics of the bacterial cell wall: gram-positive bacteria stain blue and gram-negative bacteria stain red. Bacteria are classified based upon a num-ber of additional characteristics, including morphology (cocci and bacilli), the pattern of division (single organisms, groups of organisms in pairs [diplococci], clusters [staphylococci], and chains [streptococci]), and the presence and location of spores.Gram-positive bacteria that frequently cause infections in surgical


Surgery_Schwartz

Surgery_Schwartz. of organisms in pairs [diplococci], clusters [staphylococci], and chains [streptococci]), and the presence and location of spores.Gram-positive bacteria that frequently cause infections in surgical patients include aerobic skin commensals (Staphylo-coccus aureus and epidermidis and Streptococcus pyogenes) and enteric organisms such as E faecalis and faecium. Aerobic skin commensals cause a large percentage of surgical site infec-tions (SSIs), either alone or in conjunction with other patho-gens; enterococci can cause nosocomial infections (urinary tract infections [UTIs] and bacteremia) in immunocompromised or chronically ill patients, but are of relatively low virulence in healthy individuals.There are many pathogenic gram-negative bacterial spe-cies that are capable of causing infection in surgical patients. Most gram-negative organisms of interest to the surgeon are bacilli belonging to the family Enterobacteriaceae, including Escherichia coli, Klebsiella pneumoniae, Serratia


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Surgery_Schwartz. in surgical patients. Most gram-negative organisms of interest to the surgeon are bacilli belonging to the family Enterobacteriaceae, including Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Enterobacter, Citrobacter, and Acinetobacter species. Other gram-negative bacilli of note include Pseudomonas, including P aeruginosa and fluorescens, and Stenotrophomonas species.1Table 6-1Criteria for systemic inflammatory response syndrome (SIRS)General variables Fever (core temp >38.3°C) Hypothermia (core temp <36°C) Heart rate >90 bpm Tachypnea Altered mental status Significant edema or positive fluid balance (>20 mL/kg over 24 hours) Hyperglycemia in the absence of diabetesInflammatory variables Leukocytosis (WBC >12,000) Leukopenia (WBC <4,000) Bandemia (>10% band forms) Plasma C-reactive protein >2 s.d. above normal value Plasma procalcitonin >2 s.d. above normal valueHemodynamic variables Arterial hypotension (SBP <90 mmHg, MAP <70, or SBP decrease >40 mmHg)Organ


Surgery_Schwartz

Surgery_Schwartz. C-reactive protein >2 s.d. above normal value Plasma procalcitonin >2 s.d. above normal valueHemodynamic variables Arterial hypotension (SBP <90 mmHg, MAP <70, or SBP decrease >40 mmHg)Organ dysfunction variables Arterial hypoxemia Acute oliguria Creatinine increase Coagulation abnormalities Ileus Thrombocytopenia HyperbilirubinemiaTissue perfusion variables Hyperlactatemia Decreased capillary fillingbpm = beats per minute; MAP = mean arterial pressure; SBP = systolic blood pressure; s.d. = standard deviations; SvO2 = venous oxygen saturation; WBC = white blood cell count.Brunicardi_Ch06_p0157-p0182.indd 16101/03/19 4:46 PM 162BASIC CONSIDERATIONSPART IAnaerobic organisms divide poorly or are unable to grow in air, as most do not possess the enzyme catalase, which allows for metabolism of reactive oxygen species. Anaerobes are the predominant indigenous flora in many areas of the human body, with the particular species being dependent on the site. For example, Propionibacterium


Surgery_Schwartz

Surgery_Schwartz. of reactive oxygen species. Anaerobes are the predominant indigenous flora in many areas of the human body, with the particular species being dependent on the site. For example, Propionibacterium acnes and other species are a major component of the skin microflora and cause the infectious mani-festation of acne. As noted previously, large numbers of anaer-obes contribute to the microflora of the oropharynx and colon.Infection due to Mycobacterium tuberculosis was once one of the most common causes of death in Europe, causing one in four deaths in the 17th and 18th centuries. In the 19th and 20th centuries, thoracic surgical intervention was often required for severe pulmonary disease, now an increasingly uncommon occur-rence in developed countries. This organism and other related organisms (M avium-intracellulare and M leprae) are known as acid-fast bacilli. Other acid-fast bacilli include Nocardia. These organisms typically are slow growing, sometimes necessitating observation in


Surgery_Schwartz

Surgery_Schwartz. (M avium-intracellulare and M leprae) are known as acid-fast bacilli. Other acid-fast bacilli include Nocardia. These organisms typically are slow growing, sometimes necessitating observation in culture for weeks to months prior to final identi-fication, although deoxyribonucleic acid (DNA)-based analysis is increasingly available to provide a means for preliminary, rapid detection.FungiFungi are typically identified by use of special stains (e.g., potas-sium hydroxide, India ink, methenamine silver, or Giemsa). Initial identification is assisted by observation of the form of branching and septation in stained specimens or in culture. Final identification is based on growth characteristics in special media, similar to bacteria, as well as on the capacity for growth at a different temperature (25°C vs. 37°C). Fungi of relevance to surgeons include those that cause nosocomial infections in surgical patients as part of polymicrobial infections or fungemia (e.g., C albicans and related


Surgery_Schwartz

Surgery_Schwartz. (25°C vs. 37°C). Fungi of relevance to surgeons include those that cause nosocomial infections in surgical patients as part of polymicrobial infections or fungemia (e.g., C albicans and related species), rare causes of aggressive soft tissue infections (e.g., Mucor, Rhizopus, and Absidia spp.), and opportunistic pathogens that cause infection in the immuno-compromised host (e.g., Aspergillus fumigatus, niger, terreus, and other spp., Blastomyces dermatitidis, Coccidioides immitis, and Cryptococcus neoformans). Agents currently available for antifungal therapy are described in Table 6-4.VirusesDue to their small size and necessity for growth within cells, viruses are difficult to culture, requiring a longer time than is typically optimal for clinical decision making. Previously, viral infection was identified by indirect means (i.e., the host anti-body response); more modern techniques identify the presence of viral DNA or ribonucleic acid (RNA) using methods such as polymerase chain