Principles of surgery

PART I
Basic Considerations

CHAPTER 5
Shock

BASIC SCIENCE QUESTIONS

1. The initiating event in shock is

A. Hypotension

B. Decreased cardiac output

C. Decreased oxygen delivery

D. Cellular energy deficit

Answer: D

Regardless of etiology, the initial physiologic responses in shock are driven by tissue hypoperfusion and the developing cellular energy deficit. This imbalance between cellular supply and demand leads to neuroendocrine and inflammatory responses, the magnitude of which is usually proportional to the degree and duration of shock. (See Schwartz 9th ed., p. 91, and Fig. 5-1.)

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FIG. 5-1. Pathways leading to decreased tissue perfusion and shock. Decreased tissue perfusion can result directly from hemorrhage/hypovolemia, cardiac failure, or neurologic injury. Decreased tissue perfusion and cellular injury can then result in immune and inflammatory responses. Alternatively, elaboration of microbial products during infection or release of endogenous cellular products from tissue injury can result in cellular activation to subsequently influence tissue perfusion and the development of shock. HMGB1 = high mobility group box 1; LPS = lipopolysaccharide; RAGE = receptor for advanced glycation end products.

2. Which of the following can initiate afferent impulses to the CNS which triggers the neuroendocrine response of shock?

A. Severe alkalosis

B. Hypothermia

C. Hyperthermia

D. Hyperglycemia

Answer: B

Afferent impulses transmitted from the periphery are processed within the central nervous system (CNS) and activate the reflexive effector responses or efferent impulses. These effector responses are designed to expand plasma volume, maintain peripheral perfusion and tissue O2 delivery, and restore homeostasis. The afferent impulses that initiate the body’s intrinsic adaptive responses and converge in the CNS originate from a variety of sources. The initial inciting event usually is loss of circulating blood volume. Other stimuli that can produce the neuroendocrine response include pain, hypoxemia, hypercarbia, acidosis, infection, change in temperature, emotional arousal, or hypoglycemia. The sensation of pain from injured tissue is transmitted via the spinothalamic tracts, resulting in activation of the hypothalamic-pituitary-adrenal axis, as well as activation of the autonomic nervous system (ANS) to induce direct sympathetic stimulation of the adrenal medulla to release catecholamines. (See Schwartz 9th ed., p. 93.)

3. Vasoconstriction is one of the initial physiologic responses to hypovolemic shock. This is mediated by

A. Activation of alpha adrenergic receptors on the arterioles

B. Downregulation of alpha adrenergic receptors on the arterioles

C. Activation of beta adrenergic receptors on the arterioles

D. Downregulation of beta adrenergic receptors on the arterioles

Answer: A

Direct sympathetic stimulation of the peripheral circulation via the activation of alpha1-adrenergic receptors on arterioles induces vasoconstriction and causes a compensatory increase in systemic vascular resistance and blood pressure. (See Schwartz 9th ed., p. 93.)

4. Anti-diuretic hormone (ADH) is secreted in response to shock and remains elevated for approximately 1 week. Which of the following is seen as a result of this increased level of ADH?

A. Decreased water permeability in the distal tubule

B. Increased sodium loss in the distal tubule

C. Mesenteric vasoconstriction

D. Mesenteric vasodilation

Answer: C

The pituitary also releases vasopressin or ADH in response to hypovolemia, changes in circulating blood volume sensed by baroreceptors and left atrial stretch receptors, and increased plasma osmolality detected by hypothalamic osmoreceptors. Epinephrine, angiotensin II, pain, and hyperglycemia increase production of ADH. ADH levels remain elevated for about 1 week after the initial insult, depending on the severity and persistence of the hemodynamic abnormalities. ADH acts on the distal tubule and collecting duct of the nephron to increase water permeability, decrease water and sodium losses, and preserve intravascular volume. Also known as arginine vasopressin, ADH acts as a potent mesenteric vasoconstrictor, shunting circulating blood away from the splanchnic organs during hypovolemia. This may contribute to intestinal ischemia and predispose to intestinal mucosal barrier dysfunction in shock states. Vasopressin also increases hepatic gluconeogenesis and increases hepatic glycolysis. (See Schwartz 9th ed., p. 94.)

5. Hypoxia at the cellular level decreases ATP production (also called dysoxia). This results in

A. Changes in intracellular calcium signaling

B. Increased cell membrane potential

C. Increased intracellular pH

D. Increased number of mitochondria

Answer: A

The majority of ATP is generated in our bodies through aerobic metabolism in the process of oxidative phosphorylation in the mitochondria. This process is dependent on the availability of O2 as a final electron acceptor in the electron transport chain. As O2 tension within a cell decreases, there is a decrease in oxidative phosphorylation, and the generation of ATP slows. When O2 delivery is so severely impaired such that oxidative phosphorylation cannot be sustained, the state is termed dysoxia. When oxidative phosphorylation is insufficient, the cells shift to anaerobic metabolism and glycolysis to generate ATP. This occurs via the breakdown of cellular glycogen stores to pyruvate. Although glycolysis is a rapid process, it is not efficient, allowing for the production of only 2 mol of ATP from 1 mol of glucose. This is compared to complete oxidation of 1 mol of glucose that produces 38 mol of ATP. Additionally, under hypoxic conditions in anaerobic metabolism, pyruvate is converted into lactate, leading to an intracellular metabolic acidosis. There are numerous consequences secondary to these metabolic changes. The depletion of ATP potentially influences all ATP dependent cellular processes. This includes maintenance of cellular membrane potential, synthesis of enzymes and proteins, cell signaling, and DNA repair mechanisms. Decreased intracellular pH also influences vital cellular functions such as normal enzyme activity, cell membrane ion exchange, and cellular metabolic signaling. These changes also will lead to changes in gene expression within the cell. Furthermore, acidosis leads to changes in calcium metabolism and calcium signaling. Compounded, these changes may lead to irreversible cell injury and death. (See Schwartz 9th ed., p. 95.)

6. Toll-like receptors play a role in the “danger signaling” pathway which modulates the immune response to injury. Stimulation of these receptors is by molecules released from

A. The pituitary

B. The adrenal medulla

C. Macrophages

D. Damaged cells

Answer: D

Only recently has it been realized that the release of intracellular products from damaged and injured cells can have paracrine and endocrine-like effects on distant tissues to activate the inflammatory and immune responses. This hypothesis, which was first proposed by Matzinger, is known as danger signaling. Under this novel paradigm of immune function, endogenous molecules are capable of signaling the presence of danger to surrounding cells and tissues. These molecules that are released from cells are known as damage associated molecular patterns (DAMPs, Table 5-1). DAMPs are recognized by cell surface receptors to effect intracellular signaling that primes and amplifies the immune response. These receptors are known as pattern recognition receptors (PRRs) and include the Toll-like receptors (TLRs) and the receptor for advanced glycation end products. Interestingly, TLRs and PRRs were first recognized for their role in signaling as part of the immune response to the entry of microbes and their secreted products into a normally sterile environment. (See Schwartz 9th ed., p. 95.)

TABLE 5-1 Endogenous damage associated molecular pattern molecules


Hyaluronan oligomers

Heparan sulfate

Extra domain A of fibronectin

Heat shock proteins 60, 70, Gp96

Surfactant Protein A

b-Defensin 2

Fibrinogen

Biglycan

High mobility group box 1

Uric acid

Interleukin-1a

S-100s

Nucleolin


7. Which of the following cytokines is released immediately after major injury?

A. IL-10

B. IL-2

C. TNF-alpha

D. TNF-beta

Answer: C

Tumor necrosis factor alpha (TNF-α) was one of the first cytokines to be described, and is one of the earliest cytokines released in response to injurious stimuli. Monocytes, macrophages, and T cells release this potent proinflammatory cytokine. TNF-α levels peak within 90 minutes of stimulation and return frequently to baseline levels within 4 hours. Release of TNF-α may be induced by bacteria or endotoxin, and leads to the development of shock and hypoperfusion, most commonly observed in septic shock. Production of TNF-α also may be induced following other insults, such as hemorrhage and ischemia. TNF-α levels correlate with mortality in animal models of hemorrhage. In contrast, the increase in serum TNF-α levels reported in trauma patients is far less than that seen in septic patients. Once released, TNF-α can produce peripheral vasodilation, activate the release of other cytokines, induce procoagulant activity, and stimulate a wide array of cellular metabolic changes. During the stress response, TNF-α contributes to the muscle protein breakdown and cachexia. (See Schwartz 9th ed., p. 96.)

8. Which of the following is an anti-inflammatory cytokine?

A. IL-1

B. IL-6

C. IL-8

D. IL-10

Answer: D

IL-10 is an anti-inflammatory cytokine. IL-1, 6, and 8 are proinflammatory cytokines. (See Schwartz 9th ed., p. 96, and Table 5-2.)

TABLE 5-2 Inflammatory mediators of shock

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9. Which of the following best describes the hemodynamic response to neurogenic shock?

A. Increased cardiac index, unchanged venous capacitance

B. Increased cardiac index, decreased venous capacitance

C. Variable change in cardiac index (can increase or decrease), increased venous capacitance

D. Variable change in cardiac index (can increase or decrease), decreased venous capacitance

Answer: A

(See Schwartz 9th ed., p. 93, and Table 5-3.)

• Increased cardiac index, unchanged venous capacitance is seen in neurogenic shock

• Increased cardiac index, decreased venous capacitance is most most commonly associated with in septic shock

• Variable change in cardiac index (can increase or decrease), increased venous capacitance is most likely seen in cardiogenic shock

• Variable change in cardiac index (can increase or decrease), decreased venous capacitance = septic shock

TABLE 5-3 Hemodynamic responses to different types of shock

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10. What percentage of the blood volume is normally in the splanchnic circulation?

A. 10%

B. 20%

C. 30%

D. 40%

Answer: B

Most alterations in cardiac output in the normal heart are related to changes in preload. Increases in sympathetic tone have a minor effect on skeletal muscle beds but produce a dramatic reduction in splanchnic blood volume, which normally holds 20% of the blood volume. (See Schwartz 9th ed., p. 94.)

CLINICAL QUESTIONS

1. Which of the following can be used to indirectly estimate the oxygen debt incurred during shock?

A. Arterial pH

B. Arteriolar-alveolar O2 gradient

C. Base deficit

D. Serum bicarbonate

Answer: C

Hypoperfused cells and tissues experience what has been termed oxygen debt, a concept first proposed by Crowell in 1961. The O2 debt is the deficit in tissue oxygenation over time that occurs during shock. When O2 delivery is limited, O2 consumption can be inadequate to match the metabolic needs of cellular respiration, creating a deficit in O2 requirements at the cellular level. The measurement of O2 deficit uses calculation of the difference between the estimated O2 demand and the actual value obtained for O2 consumption. Under normal circumstances, cells can “repay” the O2 debt during reperfusion. The magnitude of the O2 debt correlates with the severity and duration of hypoperfusion. Surrogate values for measuring O2 debt include base deficit and lactate levels. (See Schwartz 9th ed., p. 95.)

2. A 70-kg -man with a laceration to the brachial artery loses a total of 800 mL of blood. What ACS (American College of Surgeons) class of hemorrhage would this represent?

A. Class I hemorrhage

B. Class II hemorrhage

C. Class III hemorrhage

D. Class IV hemorrhage

Answer: B

Blood volume in an adult can roughly be calculated as 70 ml per kg. Therefore, this patient would have a blood volume of 4900 ml (hence the estimate that an adult male has a blood volume of approximately 5 liters). 800 mL is 16.3% of the estimated total blood volume, which would make this a Class II hemorrhage.

Loss of up to 15% of the circulating volume (700 to 750 mL for a 70-kg patient) may produce little in terms of obvious symptoms, while loss of up to 30% of the circulating volume (1.5 L) may result in mild tachycardia, tachypnea, and anxiety. Hypotension, marked tachycardia [i.e., pulse greater than 110 to 120 beats per minute (bpm)], and confusion may not be evident until more than 30% of the blood volume has been lost; loss of 40% of circulating volume (2 L) is immediately life threatening, and generally requires operative control of bleeding (Table 5-4). (See Schwartz 9th ed., p. 99.)

TABLE 5-4 Classification of hemorrhage

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3. A patient arrives in the ER following a motor vehicle accident with multiple injuries. Hypotension in this patient is defined as systolic blood pressure less than

A. 110

B. 90

C. 70

D. 50

Answer: A

Recent data in trauma patients suggest that a systolic blood pressure (SBP) of less than 110 mmHg is a clinically relevant definition of hypotension and hypoperfusion based upon an increasing rate of mortality below this pressure (Fig. 5-2). (See Schwartz 9th ed., p. 99.)

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FIG. 5-2. The relationship between systolic blood pressure and mortality in trauma patients with hemorrhage. These data suggest that a systolic blood pressure of less than 110 mmHg is a clinically relevant definition of hypotension and hypoperfusion based upon an increasing rate of mortality below this pressure. Base deficit (BD) is also shown on this graph. ED = emergency department. (Reproduced with permission from Eastridge BJ, Salinas J, McManus JG, et al: Hypotension begins at 110 mmHg: Redefining “hypotension” with data. J Trauma 63:291; discussion 297, 2007.)

4. 2 hours following major surgery with significant blood loss, a patient has a base deficit of –6. This would be classified as

A. Mild base deficit

B. Moderate base deficit

C. Severe base deficit

D. Extremely severe base deficit

Answer: B

Davis and colleagues stratified the extent of base deficit into mild (–3 to –5 mmol/L), moderate (–6 to –9 mmol/L), and severe (less than –10 mmol/L), and from this established a correlation between base deficit upon admission with transfusion requirements, the development of multiple organ failure, and death. (See Schwartz 9th ed., p. 99.)

5. The probability of death for a patient with a base deficit of –6 is approximately

A. 5%

B. 15%

C. 25%

D. 35%

Answer: C

The probability of death after blunt trauma can be estimated based on logistic regression analysis as described by Siegel. (Arch Surg 125:498, 1990). The LD50 for base deficit is approximately –11.8. The predicted mortality for a patient with a base deficit of –6 is approximately 25%. (See Schwartz 9th ed., p. 100.)

6. In a patient with ongoing hemorrhage, the risk of death increases 1%

A. Every 3 minutes in the ER

B. Every 10 minutes in the ER

C. Every 30 minutes in the ER

D. Every 60 minutes in the ER

Answer: A

Control of ongoing hemorrhage is an essential component of the resuscitation of the patient in shock…. Patients who fail to respond to initial resuscitative efforts should be assumed to have ongoing active hemorrhage from large vessels and require prompt operative intervention. Based on trauma literature, patients with ongoing hemorrhage demonstrate increased survival if the elapsed time between the injury and control of bleeding is decreased. Although there are no randomized controlled trials, retrospective studies provide compelling evidence in this regard. To this end, Clarke and colleagues demonstrated that trauma patients with major injuries isolated to the abdomen requiring emergency laparotomy had an increased probability of death with increasing length of time in the emergency department than patients who were in the emergency department for 90 minutes or less. This probability increased approximately 1% for each 3 minutes in the emergency department. (See Schwartz 9thed., p. 100.)

7. A 24-year-old arrives at the emergency department (ED) with multiple stab wounds to the abdomen, severe blunt trauma to the head (GCS 10), and a systolic blood pressure of 80 mm Hg. An appropriate goal for resuscitation in the ED would be a systolic blood pressure of

A. 80–90 mm Hg

B. 90–100 mm Hg

C. 100–110 mm Hg

D. 110–120 mm Hg

Answer: A

Reasonable conclusions in the setting of uncontrolled hemorrhage include: Any delay in surgery for control of hemorrhage increases mortality; with uncontrolled hemorrhage attempting to achieve normal blood pressure may increase mortality, particularly with penetrating injuries and short transport times; a goal of SBP of 80 to 90 mmHg may be adequate in the patient with penetrating injury; and profound hemodilution should be avoided by early transfusion of red blood cells. For the patient with blunt injury, where the major cause of death is a closed head injury, the increase in mortality with hypotension in the setting of brain injury must be avoided. In this setting, a SBP of 110 mmHg would seem to be more appropriate. (See Schwartz 9th ed., p. 101.)

8. An INR of 1.5 on arrival to the intensive care unit (ICU) is associated with what probability of death?

A. INR is not predictive of outcome

B. 10%

C. 20%

D. 30%

Answer: C

Fresh frozen plasma (FFP) should also be transfused in patients with massive bleeding or bleeding with increases in prothrombin or activated partial thromboplastin 1.5 times greater than control. Civilian trauma data show that severity of coagulopathy early after ICU admission is predictive of mortality (Fig. 5-3). (See Schwartz 9th ed., p. 101.)

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FIG. 5-3. The relationship between coagulopathy and mortality in trauma patients. Civilian trauma data show that severity of coagulopathy as determined by an increasing International Normalized Ratio (INR) early after intensive care unit (ICU) admission is predictive of mortality. (Reproduced with permission from Gonzalez EA, Moore FA, Holcomb JB, et al: Fresh frozen plasma should be given earlier to patients requiring massive transfusion. J Trauma 62:112, 2007.)

9. In a patient requiring massive transfusion, 1 unit of FFP (fresh frozen plasma) should be given for every

A. 1.5 units of PRBCs (1 to 1.5 ratio FFP:PRBC)

B. 3 units of PRBCs (1 to 3 ratio FFP:PRBC)

C. 6 units of PRBCs (1 to 6 ratio FFP:PRBC)

D. 8 units of PRBCs (1 to 8 ratio FFP:PRBC)

Answer: A

Evolving data suggest, more liberal transfusion of FFP in bleeding patients, but the clinical efficacy of FFP requires further investigation. Recent data collected from a U.S. Army combat support hospital in patients who received massive transfusion of packed red blood cells (>10 units in 24 hours) suggest, that a high plasma to RBC ratio (1:1.4 units) was independently associated with improved survival (Fig. 5-4). (See Schwartz 9th ed., p. 101.)

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FIG. 5-4. Increasing ratio of transfusion of fresh frozen plasma to red blood cells improves outcome of trauma patients receiving massive transfusions. RBC = red blood cell. (Reproduced with permission from Borgman MA, Spinella PC, Perkins JG, et al: The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma63:805, 2007.)

10. Shock following severe carbon monoxide poisoning is most commonly

A. Hypovolemic shock

B. Neurogenic shock

C. Cardiogenic shock

D. Vasodilatory shock

Answer: D

The most frequently encountered form of vasodilatory shock is septic shock. Other causes of vasodilatory shock include hypoxic lactic acidosis, carbon monoxide poisoning, decompensated and irreversible hemorrhagic shock, terminal cardiogenic shock, and postcardiotomy shock (Table 5-5). Thus, vasodilatory shock seems to represent the final common pathway for profound and prolonged shock of any etiology. (See Schwartz 9th ed., p. 102.)

TABLE 5-5 Causes of septic and vasodilatory shock


Systemic response to infection

Noninfectious systemic inflammation

Pancreatitis

Burns

Anaphylaxis

Acute adrenal insufficiency

Prolonged, severe hypotension

Hemorrhagic shock

Cardiogenic shock

Cardiopulmonary bypass

Metabolic

Hypoxic lactic acidosis

Carbon monoxide poisoning


11. Insulin drips should be used to maintain serum glucose in nondiabetic, critically ill patients at levels between

A. 80 and 110 mg/dL

B. 100 and 150 mg/dL

C. 120 and 200 mg/dL

D. 150 and 250 mg/dL

Answer: A

Hyperglycemia and insulin resistance are typical in critically ill and septic patients, including patients without underlying diabetes mellitus. A recent study reported significant positive impact of tight glucose management on outcome in critically ill patients. The two treatment groups in this randomized, prospective study were assigned to receive intensive insulin therapy (maintenance of blood glucose between 80 and 110 mg/dL) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg/dL, with a goal between 180 and 200 mg/dL). The mean morning glucose level was significantly higher in the conventional treatment as compared to the intensive insulin therapy group (153 vs. 103 mg/dL). Mortality in the intensive insulin treatment group (4.6%) was significantly lower than in the conventional treatment group (8.0%), representing a 42% reduction in mortality. This reduction in mortality was most notable in the patients requiring longer than 5 days in the ICU. Furthermore, intensive insulin therapy reduced episodes of septicemia by 46%, reduced duration of antibiotic therapy, and decreased the need for prolonged ventilatory support and renal replacement therapy. (See Schwartz 9th ed., p. 103.)

12. A 62-year-old man is involved in a moving vehicle accident. He suffered significant blunt trauma to the sternum during the accident. He has a systolic blood pressure of 95 on arrival to the ER. His CVP is 15 and his CXR is normal. Which of the following is the most likely cause of his hypotension?

A. Cardiac contusion

B. Spinal cord injury

C. Myocardial infarction

D. Intra-abdominal hemorrhage

Answer: C

Relatively few patients with blunt cardiac injury will develop cardiac pump dysfunction. Those who do generally exhibit cardiogenic shock early in their evaluation. Therefore, establishing the diagnosis of blunt cardiac injury is secondary to excluding other etiologies for shock and establishing that cardiac dysfunction is present.

Both spinal cord injury and hemorrhage would result in a low CVP. (See Schwartz 9th ed., p. 106.)

13. A patient unresponsive to catecholamines after an acute myocardial infarction is placed on amrinone. Which of the following is a common side effect of amrinone?

A. Neutropenia

B. Anemia

C. Thrombocytopenia

D. Bone marrow failure

Answer: C

The phosphodiesterase inhibitors amrinone and milrinone may be required on occasion in patients with resistant cardiogenic shock. These agents have long half-lives and induce thrombocytopenia and hypotension, and use is reserved for patients unresponsive to other treatment. (See Schwartz 9th ed., p. 106.)

14. A 72-year-old woman suffered an acute MI and, 12 hours later, is in cardiogenic shock. Which of the following is the best treatment for this patient?

A. Inotropic support until stabilized then PTCA (percutaneous transluminal coronary angiography)

B. Immediate PTCA with stenting, if feasible

C. Immediate PTCA to define anatomy followed by coronary artery bypass

D. None of the above

Answer: B

Current guidelines of the American Heart Association recommend percutaneous transluminal coronary angiography for patients with cardiogenic shock, ST elevation, left bundle-branch block, and age less than 75 years. Early definition of coronary anatomy and revascularization is the pivotal step in treatment of patients with cardiogenic shock from acute MI. When feasible, percutaneous transluminal coronary angioplasty (generally with stent placement) is the treatment of choice. Coronary artery bypass grafting seems to be more appropriate for patients with multiple vessel disease or left main coronary artery disease. (See Schwartz 9th ed., p. 106.)

15. An unconscious patient with a systolic BP of 80 and a HR of 80 most likely has

A. Cardiogenic shock

B. Hemorrhagic shock

C. Neurogenic shock

D. Obstructive shock

Answer: A

Sympathetic input to the heart, which normally increases heart rate and cardiac contractility, and input to the adrenal medulla, which in-creases catecholamine release, may also be disrupted [with spinal cord injury], preventing the typical reflex tachycardia that occurs with hypovolemia.

The classic description of neurogenic shock consists of decreased blood pressure associated with bradycardia (absence of reflexive tachycardia due to disrupted sympathetic discharge), warm extremities (loss of peripheral vasoconstriction), motor and sensory deficits indicative of a spinal cord injury, and radiographic evidence of a vertebral column fracture. (See Schwartz 9th ed., pp. 107-108.)