Chapter 4 Shock

Principles of Surgery Companion Handbook


Circulatory Homeostasis
Pathophysiology of Hypovolemic Shock
 Compensatory Responses
 Pulmonary Derangements in Shock
Therapy for Shock
 Hypovolemic Shock
 Cardiogenic Shock
 Neurogenic Shock
 Septic Shock

Shock is a pathophysiologic condition clinically recognized as a state of inadequate tissue perfusion. There are four distinct categories: hematogenic, neurogenic, vasogenic, and cardiogenic. It is clear that shock is a systemic disorder that disrupts vital organ function as the eventual result of a variety of causes. Whereas hemorrhagic or traumatic shock is characterized by global hypoperfusion, septic shock may be associated with hyperdynamic circulation resulting in a maldistribution of regional or intraorgan blood flow.


Preload Most of the blood volume at rest is contained within the venous system. The effect of the return of this venous blood to the heart produces ventricular end-diastolic wall tension, a major determinant of cardiac output. Gravitational shifts in blood volume distribution are rapidly compensated for by active and passive alterations in venous capacity. In the normal heart, most changes in cardiac output are a reflection of alterations in preload. Changes in position, intrathoracic pressure, intrapericardial pressure, and circulating blood volume produce major changes in cardiac output.

The normal circulating blood volume is maintained within narrow limits by balancing salt and water intake with external losses by the kidney's ability to respond to alterations in hemodynamics and the hormonal effects of renin, angiotensin, and antidiuretic hormone. In the acute setting, the changes in the venous tone, systemic vascular resistance, and intrathoracic pressure come into use. In addition, the net effect of preload on the ventricle also responds to the cardiac determinants of ventricular function, including coordinated atrial contraction, which augments ventricular diastolic filling, and tachycardia, which drops the effect of preload on the ventricle by compromising diastolic filling time.

Ventricular Contraction The Frank-Starling curve describes the varying force of ventricular contraction as a function of its preload. A number of disease states, including myocardial injury, valve dysfunction, and cardiac hypertrophy, may alter the mechanical performance of the heart. Septic, hemorrhagic, and traumatic shock deteriorate intrinsic cardiac function. While the mechanisms of these alterations in myocardial performance are unclear, their effect on the evaluation and management of global perfusion in clinical shock may be assessed by Swan-Ganz catheterization that measures preload indirectly as end-diastolic pressure, thermodilution cardiac output, and estimations of calculated vascular resistance.

Afterload Afterload is the force acting to resist myocardial work during contraction. Arterial pressure is the major component of afterload that influences the ejection fraction. The decreased effective circulating volume in shock states prevents this compensatory maintenance of cardiac output.


Hypovolemic shock results from a decrease in the circulating or effective intravascular volume. As intravascular volume is lost, an increase in peripheral vascular resistance occurs to defend the blood pressure in compensation for falling cardiac output. Differential increases in peripheral resistance in regional arteriolar beds, particularly in the skin, gut, and kidney, further defend pressure at the cost of further decreasing organ flow. The pale, cool skin noted on examination and the blanching of the bowel with decreased pulses in the mesentery are gross signs seen at the bedside and at laparotomy. A decrease in circulating blood volume also results in tachycardia in response to decreased stroke volume from inadequate preload. Orthostatic testing may unmask cardiovascular instability.

Compensatory Responses

The following compensatory responses occur during hypodemic shock:

  1. Increased vascular tone, which elevates peripheral vascular resistance and results in a redistribution of blood flow among the organ systems of the body
  2. Increased sympathetic activity, greater myocardial contractility, and enhanced venous return
  3. Decreased capillary hydrostatic pressure and mobilization of the interstitial fluid pool into the intravascular space
  4. Tissue extraction of oxygen, which is enhanced in hemorrhagic shock by the presence of acidosis and elevated levels of erythrocyte 2,3-diphosphoglycerate (2,3-DPG)
  5. Arteriolar constriction and loss of circulating volume, which diminish renal blood flow
  6. Release of epinephrine and norepinephrine, which produce vasoconstriction and tachycardia, resulting in increased cardiac output and blood pressure
  7. Stimulation of adrenocorticotropic hormone (ACTH) release
  8. Decreased insulin secretion, which augments the mobilization of glucose, amino acids, and fat stores
  9. Increased antidiuretic hormone (ADH) secretion, which increases water permeability and passive sodium transport, allowing increased water resorption and splanchnic vasoconstriction

Activation of the renin-angiotensin system occurs. Angiotensin II is a powerful arterial and arteriolar vasoconstrictor that stimulates renal prostaglandin production as well as the release of aldosterone and ACTH.

Increased aldosterone secretion occurs. This represents the principal mechanism by which the kidney may excrete the accumulated by-products of anaerobic metabolism and cellular damage.

Prostaglandins, particularly prostaglandin E2 (PGE2), and kallikreins, produced in the kidney, function locally to dilate renal vessels and increase renal blood flow. Thromboxane A2 results in splanchnic and cutaneous vasoconstriction and may promote cardiovascular dysfunction. The leukotrienes, produced by activated mast cells, also are potent vasoconstrictors that promote muscle catabolism and amino acid release.

Pulmonary Derangements in Shock

Accompanying successful fluid resuscitation is the emergence of pulmonary dysfunction in 1–2 percent of the survivors of shock. This occurs in some patients without lung injury per se. Acute respiratory distress syndrome (ARDS) is characterized by hypoxia (despite oxygen therapy), decreased pulmonary compliance, diffuse or patchy infiltrates on chest x-ray, and noncardiac pulmonary edema.

Etiology A number of injuries can trigger a final common pathway, resulting in the symptom complex known as ARDS. These include direct pulmonary injury, as seen in aspiration, inhalation injury, pulmonary contusion, and near drowning, and seemingly unrelated disorders, as seen in multiple transfusions and trauma such as fractures. Common to all these disorders is the initiation of inflammatory mediators. These result in increases in microvascular permeability and subsequent proteinaceous fluid deposition in the alveolar epithelial and pulmonary capillary endothelial interface. Resulting from this disruption are abnormal ventilation and perfusion relationships and hypoxia. Diuretics and fluid restriction have no impact on this pathophysiology and are not useful. Colloid administration also has not been shown to effectively decrease extravascular lung water because the normal barrier is disrupted and is permeable to large molecules such as albumin (Fig. 4-1).


Diagnosis The diagnosis of ARDS begins with clinical suspicion and is based on documentation of hypoxia, an abnormal chest x-ray, and a measured decreased lung compliance.

Therapy for ARDS The therapeutic goal is to maintain tissue oxygenation. Supplemental oxygen is supplied to maintain a PaO2 of 65 mmHg or more. Hemoglobin concentration should be maintained at 12 g/dL or higher, with buffering of pH to allow optimal oxygen transport. A pulmonary artery catheter is desirable to monitor central volumes and mixed venous saturations. Standard pulmonary management includes the use of a volume ventilator in the mandatory mode with tidal volume and rate set to allow adequate carbon dioxide exchange. This usually can be accomplished with rates of 10–12 breaths per minute and tidal volumes of 10–12 mL/kg of dry weight. Positive end-expiratory pressure (PEEP) is initiated at 5 cmH2O to approximate glottic pressure. PEEP is used to maintain oxygenation at nontoxic levels (50 percent or less) of oxygen. In managing the patient with ARDS, the ventilator is set at 100 percent oxygen, and the optimal level of PEEP is identified. This level is found by increasing PEEP by increments of 2.5 cmH2O, allowing at least 30 min for equilibration and measuring arterial and mixed venous blood gases, pulmonary capillary wedge pressure, and cardiac output. PEEP is increased to as much as 20 cmH2O, and optimal settings (highest oxygenation without compromise of cardiac output) are identified. PEEP is then set at this level, and oxygen is decreased incrementally to maintain a PaO2 of 65 mmHg, with a goal of 50 percent inspired oxygen or less. PEEP can then be decreased, if oxygenation is maintained, by increments of 2.5 cmH2O every 12 h.

Volume loading to ensure adequate filling pressures before PEEP is applied is beneficial in interpreting changes in wedge pressure and cardiac output that may occur after use of PEEP. Increased intrathoracic pressure and decreased venous return can cause depression of cardiac output. Lowering of PEEP is necessary if cardiac output becomes compromised. Pneumothorax can occur at high pressures (>20 cmH2O) and can be catastrophic. Peak airway pressures should be monitored carefully.

Trials of early application of PEEP in patients at high risk for ARDS failed to show any benefit in overall mortality or complications. The course of ARDS has been relatively unaffected in trials of anti-inflammatory drugs such as ibuprofen and sepsis trials using anticytokine therapy.


Hypovolemic Shock

Initial care of the injured patient should follow the guidelines from the advanced trauma life support procedures of the American College of Surgeons Committee on Trauma. Therapy for shock is aimed at replacement of preexisting deficits through the rapid infusion of isotonic fluid solutions and blood. Initial therapy should be with lactated Ringer's solution run through two large-bore intravenous (IV) lines. If shock persists, blood should be infused while a source for the hemorrhage is defined. The development of acidosis during resuscitation from shock merely indicates inadequate resuscitation and should be treated with additional fluids, not bicarbonate. There appears to be no advantage to the use of “colloid” solutions such as albumin over that of crystalloid. Hypotension is treated through continued fluid replacement. Vasopressors do not have a role in the therapy of hypovolemic shock because they serve only to further constrict an already highly vasoconstricted state and further worsen peripheral perfusion. There appeared to be early support for the use of vasodilators to improve peripheral perfusion during shock, but their clinical usefulness in patients has not been proved. Although early studies suggested that there is adrenocorticoid depletion in hemorrhagic shock, in the normal patient, steroids have no place during resuscitation.


Lactated Ringer's Solution This equilibrates rapidly throughout the extracellular compartment, restoring the extracellular fluid deficit associated with blood loss. Concern that the lactate content of Ringer's solution might aggravate the lactic acidosis coexisting with hemorrhagic shock is unwarranted.

Colloid Solutions Colloidal substances such as albumin raise the intravascular colloidal pressure, leading to intravascular influx of interstitial fluid. Because colloids remain briefly in the intravascular space, a lower total volume of resuscitative fluid is required to attain hemodynamic stability than when crystalloid solutions are used. Colloid solutions are more expensive and may bind and decrease the ionized fraction of serum calcium, decrease circulating levels of immunoglobulins, decrease the immune reaction to tetanus toxoid, and decrease endogenous production of albumin. A meta-analysis of colloid versus crystalloid fluid resuscitation concluded that crystalloid is superior to colloid for resuscitation after trauma in human beings, with a 12 percent reduction in mortality after crystalloid infusion.

Hypertonic Saline A small volume of hypertonic saline can be an effective initial resuscitative solution. Hypertonic saline resuscitation results in a lower water load than equivalent resuscitation with balanced salt solutions. In view of the need for electrolyte monitoring and lack of definition of the volumes appropriate for infusion, long-term benefits have not been established.

Hetastarch Hydroxyethyl starch (hetastarch) is an artificial colloid derived from amylopectin that has colloidal properties similar to those of albumin. It is less expensive than albumin, and because of its larger molecular weight and need for enzymatic degradation, it has a longer plasma half-life than albumin. As with any colloidal solution, hetastarch restores intravascular volume at the further expense of the already compromised interstitial space when used in resuscitation during shock. Mild and transient coagulopathies have been noted in patients resuscitated with hetastarch.

Dextran Dextran, in 40- and 70-kD solutions, also has been used as a plasma expander. Although dextran has a shorter half-life than hetastarch, it also approximates the colloidal activity of albumin when given by intravenous infusion. Dextran use is associated with a greater risk of anaphylaxis than is hetastarch or albumin and has produced coagulation defects and immunoglobulin depression.

Blood Substitutes Stroma-free hemoglobin (SFH) has been used to provide oxygen-carrying capacity, but problems with the use of SFH for resuscitation remain. Perfluorochemical compounds have enhanced abilities to dissolve gases, particularly oxygen and carbon dioxide. Potential adverse effects include acute pulmonary edema, activation of complement and the coagulation cascade, acute respiratory failure, and depression of the reticuloendothelial system.


Vasopressors Treatment with vasopressors during shock may elevate blood pressure but at the expense of further increased peripheral resistance and diminished tissue perfusion. Vasopressor therapy also may worsen the plasma volume deficit associated with hemorrhage, and the use of such agents in place of adequate fluid resuscitation is inadvisable.

Positioning Elevating both legs while maintaining the head, trunk, and arms in the supine position is the preferred position for the treatment of hypovolemic shock.

MAST Garment When applied to the extremities with modest pressures, the MAST garment functions well as a splint and may control some venous bleeding. When applied at high pressures, the resulting increase in total peripheral resistance may elevate the systemic pressure while decreasing cardiac output and peripheral perfusion. Additionally, inflation of the abdominal bolster may compress the inferior vena cava, impairing venous return to the heart by further increasing the venous resistance. The MAST garment may be of value when used occasionally as specific treatment of bleeding pelvic fractures. Its use must not delay the immediate repletion of intravascular and extravascular volume or rapid transport of the injured patient.

Pulmonary Support Breathing high oxygen concentrations probably is of little value during a period of hypotension. Nevertheless, in the small but significant group of patients in hypovolemic shock in whom the oxygen saturation is not normal, the initial use of increased oxygen concentrations may be extremely important. This can occur in patients with preexisting defects, such as chronic obstructive pulmonary disease. Although oxygen is not administered routinely to patients in shock, if any doubt exists as to the adequacy of oxygenation of arterial blood, the initial administration of oxygen until the injuries to the patient have been diligently assessed is certainly justified.

Antibiotics The use of broad-spectrum antibiotics is advisable as a preventive measure in the severely injured patient. Cefoxitin 2 g IV has proved to be a safe and effective single agent in multiorgan abdominal injuries.

Analgesics Treatment of pain in the patient with hypovolemic shock is rarely a problem. However, if the causative injury produces severe pain, e.g., fracture, peritonitis, or injury to the chest wall, control of pain becomes mandatory. Small doses of narcotics should be given intravenously for the management of pain in patients with shock.

Steroids Steroid depletion with hypovolemic shock may occur in the elderly patient or in patients with specific adrenocortical diseases, such as incipient Addison's disease, postadrenalectomy patients, or patients who have had adrenal suppression with exogenous adrenocortical steroids. In these specific instances, the IV administration of hydrocortisone is desirable. In the trauma patient with hypovolemic shock, administration of adrenocorticoids is not indicated.

Monitoring Continuous bedside monitoring of circulatory efficacy, including assessment of the heart rate, arterial blood pressure, urinary output, and peripheral perfusion, remains the cornerstone for resuscitation. Adequate resuscitation is indicated when adequate cerebral function and urinary output are restored. In the patient with multiple injuries, central venous pressure (CVP) monitoring is useful. The use of a balloon-tipped Swan-Ganz catheter allows measurement of pulmonary artery and pulmonary wedge pressures as well as thermodilution cardiac output determinations. Early use of the Swan-Ganz catheter rarely is necessary in the initial emergency department treatment for hemorrhagic shock.

Cardiogenic Shock

Cardiogenic shock occurs when the heart is unable to generate sufficient cardiac output to maintain adequate tissue perfusion. Cardiogenic shock is manifested by hypotension in the face of adequate intravascular volume.

Pathophysiology Myocardial failure may result from a variety of diseases, including valvular heart disease, cardiomyopathy, and direct myocardial contusion. Acute myocardial infarction is the most frequent cause of cardiogenic shock, which is often fatal when 40 percent of the left ventricular mass has been lost. Papillary muscle dysfunction, ischemic ventricular septal defects, massive left ventricular infarction, and arrhythmias are complications of acute myocardial infarction that may lead to cardiogenic shock.

The initial compensatory response to diminished myocardial contraction is tachycardia, in an attempt to maintain cardiac output, despite a decreased left ventricular ejection fraction, at the expense of increasing myocardial oxygen consumption. As the cardiac index falls below 2 L/min/m2, hypotension produces reflex sympathetic vasoconstriction. An increase in afterload further impairs left ventricular function and increases myocardial work. The combination of increased myocardial oxygen demand, hypotension, and shortened diastole amplifies the mismatch between coronary arterial oxygen delivery and myocardial oxygen demand, extending the zone of infarction in the patient who does not receive prompt intervention.

Treatment Although the goal of medical management of cardiogenic shock has been to enhance ventricular performance and improve global perfusion, the traditional management with fluids and inotropic drugs continues to yield a mortality of 80–90 percent. Initial therapy includes optimizing ventricular preload by manipulating filling pressure, decreasing afterload in the patient with adequate systolic pressure, correcting arrhythmias, and improving contractility to sustain vital organ perfusion.

Monitoring and Volume Management Supplemental oxygen, pain relief and sedation, and continuous electrocardiographic (ECG) monitoring should be initiated early. A Foley catheter is inserted for monitoring urine output. Cutaneous oximetry and automated arterial blood pressure cuff measurements can be used in place of an intraarterial catheter for continuous arterial pressure monitoring and blood gas determinations. Placement of a Swan-Ganz catheter for measurement of cardiac output and pulmonary artery wedge pressure is crucial to therapeutic decision-making in these critically ill patients. If any pulmonary complications evolve, early intubation and mechanical ventilation will decrease the myocardial oxygen demand as a consequence of the increased work of breathing.

Inotropic Agents The beta1-adrenergic receptors of the myocardium respond to exogenous sympathomimetic drugs by increasing contractility and improving cardiac output. These effects are obtained at the cost of increasing myocardial oxygen demand in the setting of already compromised myocardial perfusion, but IV infusion of dopamine may promptly reverse life-threatening hypotension and restore mean arterial pressure to about 80 mmHg. The dopaminergic effects of splanchnic, coronary, and renal vasodilatation at low doses (2–5 µg/kg/min) are augmented by adrenergic-mediated increases in contractility and heart rate as dosages rise to 5–8 µg/kg/min. At higher doses, alpha-adrenergic receptor effects predominate, and central arterial pressure can increase while coronary artery constriction further decreases coronary blood flow. Dopamine also causes a variable increase in heart rate and can precipitate other arrhythmias, which underscores the need to titrate the lowest acceptable dose. Dobutamine, a synthetic catecholamine with predominantly inotropic effect, appears to be less arrhythmogenic and may redistribute cardiac output to the coronary circulation. Studies appear to favor dobutamine over dopamine for treating cardiogenic shock after cardiopulmonary bypass or myocardial infarction.

Vasodilator Agents Some patients with low cardiac output and high filling pressures have near-normal arterial blood pressure in the setting of profoundly decreased perfusion by clinical assessment. In these circumstances, systolic ventricular wall stress is high, and reducing afterload should increase cardiac output and decrease myocardial work. An agent such as sodium nitroprusside should be used with extreme caution in hypotensive patients because redistribution of an already depressed cardiac output away from the coronary and cerebral circulation can occur, and any decrease in systemic diastolic pressure would further depress coronary perfusion pressures.

Mechanical Support Despite significant associated morbidity, successful mechanical cardiac support will maintain organ perfusion while decreasing myocardial oxygen demand by unloading the left ventricle and reducing myocardial work. The intraaortic balloon counterpulsation device has been used most widely. It can be inserted at the bedside and fulfills the criteria of elevating diastolic blood pressure, which increases pulmonary perfusion, while decreasing myocardial work, by increasing cardiac output distal to the ventricle.

Arrhythmias Rapid ventricular rates can depress cardiac output to shock levels. Cardiac output falls because stroke volume cannot be compensated for by the rapid heart rate. Digoxin is the drug of choice for atrial fibrillation or atrial flutter, but electrical cardioversion should be undertaken promptly for tachycardia that produces hypotension and hypoperfusion. Resistant sinus tachycardia, while well tolerated by the normal heart, may produce a low-flow state in the diseased heart. Verapamil has been useful in treating tachyarrhythmias of atrial origin, and propranolol slows sinus tachycardia. Beta blockade can further decrease cardiac output in this setting. Immediate nonsynchronized direct-current electric shock is mandatory treatment for ventricular fibrillation or ventricular flutter that has caused cardiogenic shock with loss of consciousness. In the patient with acute myocardial injury, premature ventricular complexes may lead to ventricular tachyarrhythmias. IV lidocaine usually is the initial treatment and also is given after cardioversion to prevent recurrent ventricular fibrillation. Bretylium tosylate has been useful in treating life-threatening ventricular tachyarrhythmias that are unresponsive to lidocaine or class Ia agents, such as procainamide.

Low cardiac output with ventricular rates less than 70 beats/min may occur in patients with impaired cardiac performance. Stroke volume cannot increase to compensate for the pathologic bradycardia. Electrical pacing of the heart at a rate of 80–100 beats/min can restore sufficient cardiac output whether the underlying mechanism is sinus bradycardia, atrial fibrillation with slow ventricular rate, or atrioventricular dissociation.

Neurogenic Shock

Neurogenic shock is the form of shock that occurs after serious interference with the balance of vasodilator and vasoconstrictor influences to the arterioles and venules. This is the shock that is seen with clinical syncope. Neurogenic shock often is observed with serious paralysis of vasomotor influences, as in high spinal anesthesia or injury to the spinal cord. The reflex interruption of nerve impulses also occurs with acute gastric dilatation.

The clinical picture of neurogenic shock is quite different from that classically seen in hypovolemic shock. While the blood pressure may be extremely low, the pulse rate usually is slower than normal and is accompanied by dry, warm, and even flushed skin. Measurements made during neurogenic shock indicate a reduction in cardiac output, but this is accompanied by a decrease in resistance of arteriolar vessels and a decrease in venous tone. There appears to be a normovolemic state with a greatly increased reservoir capacity in the arterioles and venules, thereby inducing a decreased venous return to the right side of the heart and hence a reduction in cardiac output.

Treatment Treatment of neurogenic shock usually is obvious. Gastric dilatation can be treated rapidly with nasogastric suction. Shock due to high spinal anesthesia can be treated effectively with administration of fluids and a vasopressor such as ephedrine or phenylephrine (Neo-Synephrine). With the milder forms of neurogenic shock, such as fainting, simply removing the patient from the stimulus, relieving the pain, and elevating the legs is adequate therapy while the vasoconstrictor nerves regain the ability to maintain normal arteriolar and venous resistance. In uncomplicated neurogenic shock, central venous pressure should be slightly low, with a near-normal cardiac output. Fluid administration without vasopressors in this form of hypotension may produce a gradually rising arterial pressure and cardiac output without elevation of central venous pressure by gradually “filling” the expanded vascular pool. Slight volume overextension is much less deleterious than excessive vasopressor administration. Balance is best obtained by maintaining a normal central venous pressure that rises slightly with rapid fluid administration (ensuring adequate volume) and using a vasopressor such as phenylephrine judiciously to support arterial pressure.

Septic Shock

Although any agent capable of producing infection, including viruses, parasites, and fungi, may generate septic shock, the most frequent causative organisms in the antibiotic era are gram-negative bacteria and, occasionally, gram-positive bacteria. The initial infectious process appears to be only a stimulus for a series of host responses that may culminate in death, even in the absence of infection at the time of death. Overall mortality exceeds 30 percent, with mortalities over 80 percent in complicated cases with associated multiple organ system failure.

The most common source of gram-negative infection is the genitourinary system. The second most frequent site of origin is the respiratory system, followed by the alimentary system, including the biliary tract. Increasing and prolonged use of indwelling catheters for monitoring and hyperalimentation is responsible for many bloodstream infections.

Clinical Manifestations Gram-negative infections frequently are heralded by the onset of chills and temperature elevations above 38°C. The patient may rapidly progress to evidence of altered organ function, most often renal and pulmonary in nature. Unlike most other forms of shock, the patient who is normovolemic has hypotension despite an increased cardiac output and a reasonable filling pressure. The peripheral resistance is low and produces the paradoxical “warm shock” with pink, dry extremities. The high cardiac output often is associated with a decrease in oxygen use and a narrowed arteriovenous oxygen difference.

In a patient who is initially hypovolemic or persists in the shock state, a hypodynamic pattern emerges that is characterized by a falling cardiac output, low central pressures, and increased peripheral resistance with more typical cold, pale extremities consistent with global hypoperfusion. Early volume replacement frequently increases cardiac output and produces a hyperdynamic circulation, while the patient later in shock is unresponsive to volume replacement and has a low cardiac output with increasing metabolic acidosis.

Concomitant laboratory tests usually show an elevation in the white blood cell count, but leukopenia may be present in immunosuppressed and debilitated patients or those with overwhelming white cell consumption from sepsis. Thrombocytopenia may be an early indicator of gram-negative sepsis, particularly in pediatric and burn patients. Mild hypoxia with compensatory hyperventilation and respiratory alkalosis are common early findings, despite clinical or radiologic evidence of intrinsic pulmonary disease.

Pathophysiology At the organ level, cardiovascular response to systemic infection, in the absence of hypovolemia, is the development of a hyperdynamic state. A number of vasoregulatory mediators combine to produce a net decrease in systemic vascular resistance. Despite an increased cardiac index and decreased oxygen extraction, no direct evidence for cellular hypoxia has been detected. Myocardial depressant factor, although poorly characterized biochemically, appears to be a reasonable explanation for documented decreases in left ventricular ejection fraction despite acceptable filling pressures.

Interleukin-1 (IL-1) is an endogenous mediator of infection. Cellular dysfunction accompanying acute hemorrhagic shock is associated with a reduction in the transcellular membrane potential. Tumor necrosis factor-alpha (TNF-a) is capable of inducing membrane depolarization and decreasing skeletal muscle membrane potential and extremity lactate efflux, similar to that seen in sepsis. TNF-a is an important mediator of septic shock.

TNF-a induces the synthesis and secretion of a variety of secondary mediators, including other cytokines, prostaglandins, leukotrienes, platelet-activating factor, complement components, and activation of the clotting cascade, that possess toxic properties capable of causing widespread tissue damage if liberated systemically. In addition, lipopolysaccharide (LPS) may synergize with TNF-a to induce many of the toxic effects mediated by TNF-a. The TNF-a–induced release of these factors may be responsible for pathologic changes seen in the lungs, liver, bowel, and kidneys in response to sepsis and septic shock.

Therapy The control of infection by antibiotic treatment and early surgical debridement or radiologically guided drainage represent definitive therapy. Other recommended measures include fluid therapy and the use of vasoactive drugs. It is essential that a prompt search for the source of infection be made as soon as infection becomes evident. If the infectious process requires drainage, operation should be performed as soon as possible after the patient has been stabilized, because some conditions, such as septic shock secondary to ascending cholangitis, will respond only briefly to adjunctive measures.

Antibiotic treatment should be based on the results of cultures and sensitivity tests when possible, but in the absence of these data, broad-spectrum antibiotics should be started, including coverage for anaerobic organisms such as Bacteroides species or fungi, if clinically indicated. Antibiotic therapy should be adjusted when culture and sensitivity reports become available.

Correction of preexisting fluid deficits is essential using pulmonary capillary wedge pressure and cardiac output as a guide. Monitoring is essential, because fluid requirements may be massive in these patients. Resuscitation requirements in excess of 10 L of lactated Ringer's solution are common. The only indications for steroid treatment in patients with septic shock are hypoadrenalism and for stress coverage in patients taking steroids (or who recently completed a course of steroids) for immunosuppression or anti-inflammatory purposes.

Future clinical use of anti-TNF antibodies, protein C, or other antimediator treatment regimens probably will depend on early recognition of the sepsis syndrome for success unless used prophylactically in a population of patients at high risk.

Pharmacologic Support Dopamine is the initial inotropic agent used. Dobutamine often increases cardiac input with less tachycardia and arrhythmia than dopamine. The use of vasodilators in septic shock is limited by low systemic pressure or decreased cardiac filling pressures. More potent vasopressors, despite their obvious detrimental effect on peripheral perfusion, may be transiently unavoidable in patients who have persistent life-threatening hypotension despite optimal fluid and dopamine infusions. Norepinephrine is a potent alpha-receptor agonist that usually is effective in raising pressure in patients for whom the measures described earlier have failed. Epinephrine, a catecholamine with potent alpha- and beta-adrenergic activity, may support the blood pressure in patients who do not respond to norepinephrine.

Manipulations of Humoral Responses Given the obviously complex and ill-defined interactions among a large number of mediators, therapy directed at any single agent is probably ineffective. Carefully tailored multidrug or serial antimediator therapy eventually may allow modulation of the deleterious systemic effects of the necessary host responses to injury and infection. Initial trials of steroids, fibronectin, and naloxone were disappointing. Treatment with HA-1A improved survival and organ function in the presence of gram-negative bacteremia with or without shock. The E5 trial was beneficial in patients with gram-negative bacteremia only in the absence of shock. None of the antibodies directed at lipid A or other epitopes of the core lipopolysaccharide are established therapeutic modalities.

The naturally occurring IL-1 receptor antagonist has been manufactured by recombinant technology. IL-1ra failed to show efficacy in human sepsis. Monoclonal antibodies to TNF also are available and appear promising in patients with septic shock. The use of anticoagulants such as anti–thrombin III in the treatment of sepsis that is unassociated with shock is under investigation.

For a more detailed discussion, see Barber A, Shires GT III, and Shires GT: Shock, chap. 4 in Principles of Surgery, 7th ed.

Copyright © 1998 McGraw-Hill
Seymour I. Schwartz
Principles of Surgery Companion Handbook

Principles of Surgery, Companion Handbook
Principles of Surgery, Companion Handbook
ISBN: 0070580855
EAN: 2147483647
Year: 1998
Pages: 277
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