Shock

Question 1

Shock caused by a large tension pneumothorax is categorized as

A. Trauma shock

B. Vasodilatory shock

C. Cardiogenic shock

D. Obstructive shock

Answer 1

Answer: D

In 1934, Blalock proposed four categories of shock: hypovolemic, vasogenic, cardiogenic, and neurogenic.

Hypovolemic shock, the most common type, results from loss of circulating blood volume.

This may result from loss of whole blood (hemorrhagic shock), plasma, interstitial fluid (bowel obstruction), or a combination.

Vasogenic shock results from decreased resistance within capacitance vessels, usually seen in sepsis.

Neurogenic shock is a form of vasogenic shock in which spinal cord injury or spinal anesthesia causes vasodilation due to acute loss of sympathetic vascular tone.

Cardiogenic shock results from failure of the heart as a pump, as in arrhythmias or acute myocardial iniarction (MI).

In recent clinical practice, further classification has described six types of shock: hypovolemic, septic (vasodilatory), neurogenic, cardiogenic, obstructive, and traumatic shock.

Obstructive shock is a form of cardiogenic shock that results from mechanical impediment to circulation leading to depressed cardiac output rather than primary cardiac failure. This includes
etiologies such as pulmonary embolism or tension pneumothorax.

In traumatic shock, soft tissue and bony injury lead to the
activation of inflammatory cells and the release of circulating factors, such as cytokines and intracellular molecules that modulate the immune response.

Recent investigations have revealed that the inflammatory mediators released in response to tissue injury (damage-associated molecular patterns [DAMPs]) are recognized by many of the same cellular receptors (pattern recognition receptors [PRRs]) and activate similar signaling pathways as do bacterial products elaborated in sepsis (pathogen-associated molecular patterns [PAMPs]), such as lipo-polysaccharide.

These effects of tissue injury arc combined with the effects of hemorrhage, creating a more complex and amplified deviation from homeostasis.

Question 2

What is true about baroreceptors?

A. Volume receptors can be activated in hemorrhage with
reduction in left atrial pressure.

B. Receptors in the aortic arch and carotid bodies inhibit
the autonomic nervous system (ANS) when stretched.

C. When baroreceptors are stretched, they induced
increased ANS output and produce constriction of
peripheral vessels.

D. None of the above.

Answer 2

Answer: B

Baroreceptors also are an important afferent pathway in initiation of adaptive responses to shock.

Volume receptors, sensitive to changes in both chamber pressure and wall stretch, are
present within the atria of the heart.

They become activated
with low volume hemorrhage or mild reductions in right
atrial pressure.

Receptors in the aortic arch and carotid bodies respond to alterations in pressure or stretch of the arterial wall, responding to larger reductions in intravascular volume or pressure.

These receptors normally inhibit induction of the autonomic nervous system (ANS). When activated, these
baroreceptors diminish their output, thus disinhibiting the
effect of the ANS. The ANS then increases its output, principally via sympathetic activation at the vasomotor centers of the brain stem, producing centrally mediated constriction of peripheral vessels.

(See Schwartz 10th cd., p. 112.)

Question 3

Chemoreceptors in the aorta and carotid bodies do NOT
sense which of the following?

A. Changes in O2 tension

B. H+ ion concentration

C. HCO3- concentration

D. Carbon dioxide (CO2) levels

Answer 3

Answer: C

Chemoreceptors in the aorta and carotid bodies are sensitive to changes in O2, tension, H+ ion concentration, and carbon dioxide (CO2) levels.

Stimulation of the chemoreceptors results in vasodilation of the coronary arteries, slowing of the
heart rate, and vasoconstriction of the splanchnic and skeletal circulation.

In addition, a variety of protein and nonprotein mediators are produced at the site of injury as part of the inflammatory response, and they act as afferent impulses to
induce a host response.

Question 4

Neurogenic shock is characterized by the presence of

A. Cool, moist skin

B. Increased cardiac output

C. Decreased peripheral vascular resistance

D. Decreased blood volume

Answer 4

Answer: C

Neurogenic shock is caused by loss of arteriolar and venular tone in response to paralysis (such as occurs with high spinal anesthesia), acute gastric dilatation, or sudden pain, or unpleasant sights; as such, it is characterized by a decrease in peripheral vascular resistance.

Affected patients usually present with warm, dry skin, a pulse rate that is slower than normal, and hypotension.

A normovolemic state usually exists, and urine output is generally well maintained.

Although blood volume measurements indicate a normal intravascular
volume, because of the greatly increased reservoir capacity of the arterioles and venules, there is a decrease in cardiac output secondary to decreased venous return to the right side of the heart.

Question 5

When a patient with hemorrhagic shock is resuscitated using an intravenous colloid solution rather than lactated Ringer solution, all of the following statements are true EXCEPT

A. Circulating levels of immunoglobulins are decreased.

B. Colloid solutions may bind to the ionized fraction of
serum calcium.

C. Endogenous production of albumin is decreased.

D. Extracellular fluid volume deficit is restored.

Answer 5

Answer: D

Because of higher osmotic pressure, colloid solutions draw extracellular fluid into the vascular space, increasing the extracellular fluid deficit.

In addition, the ionized fraction of serum calcium is decreased, circulating levels of immunoglobulin drop, and reaction to tetanus toxoid given to the patient suffering from major trauma is decreased.

Endogenous production of albumin also decreases. Colloid resuscitation is no more effective than crystalloid resuscitation, and it
is more expensive.

Question 6

In hemorrhage, larger arterioles vasoconstrict in response to the sympathetic nervous system. Which categories of shock are associated with vasodilation of larger arterioles?

A. Septic shock

B. Cardiogenic shock

C. Neurogenic shock

D. A&C

Answer 6

Answer: D

The microvascular circulation plays an integral role in regulating cellular perfusion and is significantly influenced in response to shock.

The microvascular bed is innervated by the sympathetic nervous system and has a profound effect on the larger arterioles.

Following hemorrhage, larger arterioles vasoconstrict; however, in the setting of sepsis or neurogenic
shock, these vessels vasodilate.

Additionally, a host of other vasoactive proteins, including vasopressin, angiotensin II, and endothelin-1, also lead to vasoconstriction to limit organ perfusion to organs such as skin, skeletal muscle, kidneys, and the gastrointestinal (GI) tract to preserve perfusion of the myocardium and central nervous system (CNS).

Question 7

Which of the following is true about antidiuretic hormone
(ADH) production in injured patients?

A. ADH acts as a potent mesenteric vasoconstrictor.

B. ADH levels fall to normal within 2 to 3 days of the initial insult.

C. ADH decreases hepatic gluconeogenesis.

D. ADH secretion is mediated by the renin-angiotensin

Answer 7

Answer: A

The pituitary also releases vasopressin or antidiurctic hormone (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 oi 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.

Question 8

Which of following occur as a result of epinephrine and
norepinephrine?

A. Hepatic glycogenolysis

B. Hypoglycemia

C. Insulin sensitivity

D. Lipogenesis

Answer 8

Answer: A

Epinephrine and norepinephrine have a profound impact on cellular metabolism. Hepatic glycogenolysis, gluconeogenesis, ketogenesis, skeletal muscle protein breakdown, and adipose tissue lipolysis arc increased by catecholamines.

Cortisol, glucagon, and ADH also contribute to the catabolism during shock.

Epinephrine induces further release of glucagon, while
inhibiting the pancreatic ß-cell release of insulin.

The result is a catabolic state with glucose mobilization, hyperglycemia, protein breakdown, negative nitrogen balance, lipolysis, and insulin resistance during shock and injury.

The relative underuse of glucose by peripheral tissues preserves it for the glucose-dependent organs such as the heart and brain.

Question 9

A patient has a blood pressure of 70/50 mm Hg and a serum lactate level of 30 mg/100 mL (normal: 6-16). His cardiac output is 1.9 L/min, and his central venous pressure is 2cm H2O. The most likely diagnosis is

A. Congestive heart failure

B. Cardiac tamponade

C. Hypovolemic shock

D. Septic shock

Answer 9

Answer: C

The findings given in the question are characteristic of
hypovolemic shock, which can be defined as inadequate tissue perfusion secondary to an extracellular fluid loss.

The high lactate level is a result of anaerobic metabolism due to
decreased blood flow to tissues.

The hemodynamic measurements indicate both low blood flow and low venous return.

The total combination is most consistent with a diagnosis of
hypovolemic shock.

Pulmonary embolus, congestive heart failure, and cardiac tamponade are all associated with a high
central venous pressure.

Septic shock, particularly in its early phases, is usually hyperdynamic, and affected patients have a greater-than-normal cardiac output.

Complete hemodynamic
monitoring is vital in hypovolemic shock so that prompt diagnosis and rational therapy can be expeditiously carried out.

Question 10

Which cytokine is anti-inflammatory and increases after shock and trauma?

A. Interleukin (IL)-1

B. IL-2

C. IL-6

D. IL-10

Answer 10

Answer: D

Interleukin (IL)-10 is considered an anti-inflammatory cytokine that may have immunosuppressive properties. Its production is increased after shock and trauma, and it has been associated with depressed immune function clinically, as well as an increased susceptibility to infection.

IL-10 is secreted by T cells, monocytes, and macrophages, and inhibits pro-inflammatory cytokine secretion, O2 radical production by phagocytes, adhesion molecule expression, and lymphocyte activation. Administration of IL-10 depresses cytokine
production and improves some aspects of immune function in
experimental models of shock and sepsis.

Question 11

Tumor necrosis factor-alpha (TNF-a)

A. Can be released as a response to bacteria or
endotoxin

B. Increased more in trauma than septic patients

C. Induces procoagulant activity and peripheral
vasoconstriction

D. Contributes to anemia of chronic illness

Answer 11

Answer: A

Tumor necrosis factor-alpha (TNF-a) 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-a levels peak within 90 minutes of stimulation and return frequently to baseline levels within 4 hours.

Release of TNF-a may be induced by bacteria or endotoxin, and leads
to the development of shock and hypoperfusion, most commonly observed in septic shock.

Production of TNF-a also
may be induced following other insults, such as hemorrhage
and ischemia.

TNF-a levels correlate with mortality in animal models of hemorrhage.

In contrast, the increase in serum TNF-a levels reported in trauma patients is far less than that seen in septic patients.

Once released, TNF-a 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-a
contributes to the muscle protein breakdown and cachexia.

Question 12

A 70-kg male patient presents to ED following a stabwound to the abdomen. He is hypotensive, markedly
tachycardic, land appears confused. What percent of blood volume has he lost?

A. 5%

B. 15%

C. 35%

D. 55%

Answer 12

Answer: D

The clinical signs of shock maybe evidenced by agitation, cool clammy extremities, tachycardia, weak or absent peripheral
pulses, and hypotension.

Such apparent clinical shock results from at least 25 to 30% loss of the blood volume. However, substantial volumes of blood may be lost before the classic
clinical manifestations of shock are evident. Thus, when a patient is significantly tachycardic or hypotensive, this represents both significant blood loss and physiologic decompensation.

The clinical and physiologic response to hemorrhage has been classified according to the magnitude of volume loss.

Loss of up to 15% of the circulating volume (700-750 mL for a 70-kg patient) may produce little in terms of obvious symptoms, while loss of up to 30% of the circulating volume (1.5 L)
may result in mild tachycardia, tachypnea, and anxiety.

Hypotension, marked tachycardia (ie, pulse greater than 110-120
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.

Question 13

Vasodilatory shock

A. Is characterized by failure of vascular smooth muscle to constrict due to low levels of catecholamines

B. Leads to suppression of the renin-angiotensin system

C. Can also be caused by carbon monoxide poisoning

D. Is similar to early cardiogenic shock

Answer 13

Answer: C

In the peripheral circulation, profound vasoconstriction is the
typical physiologic response to the decreased arterial pressure and tissue perfusion with hemorrhage, hypovolemia, or
acute heart failure.

This is not the characteristic response in
vasodilatory shock.

Vasodilatory shock is the result of dysfunction of the endothelium and vasculature secondary to
circulating inflammatory mediators and cells or as a response to prolonged and severe hypoperfusion.

Thus, in vasodilatory
shock, hypotension results from failure of the vascular smooth muscle to constrict appropriately.

Vasodilatory shock is characterized by peripheral vasodilation with resultant hypotension and resistance to treatment with vasopressors.

Despite the hypotension, plasma catecholamine levels are elevated, and the renin-angiotensin system is activated in vasodilatory shock.

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.

Thus, vasodilatory shock seems to represent the final common pathway for profound and prolonged shock of any etiology.

Question 14

A patient in septic shock remains hypotensive despite adequate fluid resuscitation and initiation of norepinephrine.

What is often given to patients with hypotension
refractory to norepinephrine?

A. Dopamine

B. Arginine vasopressin

C. Dobutamine

D. Milrinone

Answer 14

Answer: B

After first-line therapy of the septic patient with antibiotics, IV fluids, and intubation if necessary, vasopressors may be
necessary to treat patients with septic shock.

Catecholamines
are the vasopressors used most often, with norepinephrine being the first-line agent followed by epinephrine.

Occasionally, patients with septic shock will develop arterial resistance to catecholamines.

Arginine vasopressin, a potent vasoconstrictor, is often efficacious in this setting and is often added to norepinephrine.

Question 15

Tight glucose management in critically ill and septic patients

A. Requires insulin to keep serum glucose <140

B. Has no effect on mortality

C. Has no effect on ventilator support

D. Decreases length of antibiotic therapy

Answer 15

Answer: D

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 with 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.

Question 16

Cardiogenic shock

A. Is most commonly caused by exacerbation of congestive heart failure.

B. Cardiogenic shock following an acute myocardial
infarction is typically present on admission.

C. Cardiogenic shock occurs in 5 to 10% of acute MIs.

D. Is characterized by hypotension, reduced cardiac index, and reduced pulmonary artery wedge pressure.

Answer 16

Answer: C

Cardiogenic shock is defined clinically as circulatory pump failure leading to diminished forward flow and subsequent tissue hypoxia, in the setting of adequate intravascular volume.

Hemodynamic criteria include sustained hypotension (ie, systolic blood pressure [SBP] <90 mm Hg for at least 30 minutes), reduced cardiac index (<2.2 L/min per square meter), and elevated pulmonary artery wedge pressure (>15 mm Hg).

Mortality rates for cardiogenic shock are 50 to 80%. Acute, extensive MI is the most common cause of cardiogenic shock; a smaller infarction in a patient with existing left ventricular
dysfunction also may precipitate shock.

Cardiogenic shock
complicates 5 to 10% of acute MIs. Conversely, cardiogenic shock is the most common cause of death in patients hospitalized with acute MI.

Although shock may develop early after MI, it typically is not found on admission.

Seventy-five percent of patients who have cardiogenic shock complicating acute
MIs develop signs of cardiogenic shock within 24 hours after onset of infarction (average 7 hours).

Question 17

All of the following result from the placement of an intraaortic balloon pump in a patient with acute myocardial failure EXCEPT

A. Reduction of systolic afterload

B. Increased cardiac output

C. Increased myocardial O2 demand

D. Increased diastolic perfusion pressure

Answer 17

Answer: C

Intra-aortic balloon pumping increases cardiac output and
improves coronary blood flow by reduction of systolic afterload and augmentation of diastolic perfusion pressure.

Unlike vasopressor agents, these beneficial effects occur without an
increase in myocardial O2 demand.

An intra-aortic balloon
pump can be inserted at the bedside in the ICU via the femoral artery through either a cutdown or using the percutaneous
approach.

Question 18

Which constellation of clinical findings is suggestive of cardiac tamponade?

A. Hypotension, wide pulse pressure, tachycardia

B. Tachycardia, hypotension, jugular venous distension

C. Hypotension, wide pulse pressure, jugular venous distension

D. Hypotension, muffled heart tones, jugular venous distension

Answer 18

Answer: D

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 and cardiac tamponade. Muffled heart tones may be difficult to appreciate in a busy trauma center
and jugular venous distention and central venous pressure maybe diminished by coexistent 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.

Question 19

A 43-year-old man is struck by a motor vehicle while crossing the street; he arrives in the ED hypotensive, bra¬
dycardie, and unable to move his extremities. What is the
most likely cause of his hypotension?

A. Hypovolemic shock

B. Obstructive shock

C. Neurogenic shock

D. Vasodilatory shock

Answer 19

Answer: A

In a subset of patients with spinal 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.

In the multiply injured patient, other causes of hypotension including hemorrhage, tension pneumothorax, and cardiogenic shock must be sought and excluded.

Question 20

Corticosteroids in the treatment of septic shock

A. Improves rates of shock reversal in patients requiring
vasopressors

B. Improves mortality in patients with relative adrenal insufficiency

C. Is contraindicated in patients with positive bacterial blood cultures

D. None of the above

Answer 20

Answer: B

The use of corticosteroids in the treatment of sepsis and septic shock has been controversial for decades.

The observation
that severe sepsis often is associated with adrenal insufficiency or glucocorticoid receptor resistance has generated renewed interest in therapy for septic shock with corticosteroids.

A single IV dose of 50 mg of hydrocortisone improved mean arterial blood pressure response relationships to norepinephrine and phenylephrine in patients with septic shock, and was most notable in patients with relative adrenal insufficiency.

A more recent study evaluated therapy with hydrocortisone (50 mg IV every 6 hours) and fludrocortisone (50 microgram orally once daily) versus placebo for 1 week in patients with septic shock.

As in earlier studies, the authors performed corticotropin tests on these patients to document and stratify patients by relative adrenal insufficiency.

In this study, the 7-day treatment with low doses of hydrocortisone and fludrocortisone significantly and safely lowered the risk of death in patients with septic shock and relative adrenal insufficiency.

In an international, multicenter, randomized trial of corticosteroids
in sepsis, steroids
showed no benefit in intent to treat mortality or shock reversal.

This study suggested that hydrocortisone therapy cannot be recommended as routine adjuvant therapy for septic shock.

However, if SBP remains less than 90 mm Hg despite appropriate fluid and vasopressor therapy, hydrocortisone at 200 mg/day for 7 days in four divided doses or by continuous infusion should be considered.

Question 21

What is FALSE about serum lactate?

A. Generated from pyruvate in the setting of insufficient O2

B. Metabolized by the liver and kidneys.

C. Is an indirect measure of the magnitude and severity
of shock.

D. The time to peak lactate from admission predicts rates of survival.

Answer 21

Answer: D

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 lactate uptake.

Elevated serum lactate is an indirect 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 indicators 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% survivorship if it took longer than 48 hours to normalize the serum lactate.

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.

Question 22

A 68-year-old female is brought into the emergency department by her son for evaluation of altered mental status. The son reports that his mother rarely goes to the doctor, is an alcoholic, and has been a smoker as long
as he can remember. She has occasionally had intermittent bouts of diverticulitis that have been treated with
oral antibiotics. Her most recent bout was 2 weeks ago for which she recently finished a course of antibiotics.

For the past two days she has had frequent stools and increasing abdominal pain over the past 48 hours.

Today she was noted to be somnolent and difficult to arouse by her son.

On exam, her vitals show a temperature of 101.8°F,
with a heart rate of 121. Her blood pressure is 83/54 and respiratory rate of 24,02: 83% on RA. She is lethargic,
lungs are coarse bilaterally; her abdomen is distended, and she grimaces with palpation of her lower abdomen.
Her skin is pale and cool, and she has flat neck veins.

Labs are significant for a white blood cell count (WBC) of 24, creatinine of 32, and lactate of 5.8. An arterial blood gas is obtained that pH of 7.30. pCO2 of 80, and pO2 of 67 with a base deficit of 10. Her central venous
oxygen saturation (ScvO2) is 55%.

The patient is intubated and transfer to the
intensive care unit (ICU) is being arranged. Which
of the following is true regarding the initiation of
goal directed therapy?

A. Antibiotic therapy should be delayed until all cultures are obtained and a causative organism is identified.

B. Normalization of blood lactate is a poor guide for resuscitation.

C. Goals of early goal directed therapy in sepsis are to achieve a central venous pressure (CVP) 8 to 12 mm Hg; urine output >0.5 mL/kg/hr; and ScvO2 of 70% or greater.

D. In intubated patients, a higher CVP (12 to 15 mm Hg) should be considered pathologic.

E. Early initiation of targeted goal directed therapy in sepsis has not been definitively shown to improve survival.

Answer 22

C.

The main principles of sepsis therapy are to begin both treatment and resuscitation immediately upon identification of sepsis or suspected sepsis. Treatment should consist of early initiation of empiric broad spectrum antibiotics and initial antibiotic
administration does not require identification of
the exact causative organism. When sepsis is suspected early initiation of resuscitation with the goal of reversing tissue induced hypoperfusion has been shown to improve patient survival in patients presenting with septic shock.

The goals of resuscitation
should be to achieve: 
a CVP 8-12 mmHg
MAP >65 mm Hg
Urine output >0.5 mL/kg/hr
and ScvO2 of 70% or 
SvO of 65% within 6 hours. 

In mechanically ventilated patients, venous return can be impeded and as a result a higher target for CVP (12 to 15 mm Hg) is recommended.

Note that there is no
arbitrary systolic blood pressure as a primary goal of resuscitation.

Lactate is also a marker of metabolic acidosis and
tissue hypoperfusion, and is seen in a majority of
patients presenting in septic shock. When a patient presents with hypotension and an elevated lactate (>4) they have an increased mortality over elevated
lactate or hypotension alone, if a patient presents with an elevated lactate it can be monitored until it reaches normal levels and can be used along with other markers, to guide resuscitation.

Base deficit is another measure of metabolic acidosis that may be used to gauge the severity of illness and to guide
resuscitation. It is often used as a surrogate for lactate, but there are many other factors that can impact the base deficit (renal failure, alcohol, bicarbonate
losses), making it a less specific measure of tissue
hypoperfusion and acidosis.

In addition to restoring tissue hypoperfusion, a
source of the patients sepsis should be sought and appropriate antibiotics should be administered. Each
hour antibiotics administration is delayed results in a measurable increase in patient mortality.

Ideally, cultures should be obtained prior to giving antibiotics with the goal of administering antibiotics within one-
hour of presenting with sepsis. However if obtaining appropriate cultures would delay the administration of antibiotics beyond one hour, then antibiotics
should be given prior to obtaining cultures.

Question 23

Despite receiving 3 liters of crystalloid, the patient
remains hypotensive with a systolic blood pressure
of 75 and a ScvO2 of 60. Her hematocrit is 41%
Which of the following is the appropriate next
step?

A. Switch to using a hydroxyethyl starch solution as they are considered equivalent to isotonic crystalloid in the resuscitation of septic patients, and are useful in patients in fluid refractory shock.

B. Start a high dose phenylephrine infusion and titrate to a MAP of 65 mm Hg.

C. Initiate a Levophed (norepinephrine) infusion
and if the patient remains hypotensive consider
starting a low dose vasopressin infusion.

D. Start an infusion of intravenous hydrocortisone.

E. Obtain an echocardiogram to determine if the patient is in cardiogenic shock prior to initiating a vasopressor.

Answer 23

C. Many studies have been conducted comparing synthetic starches to isotonic crystalloid based solutions. The results of these studies have varied. Some studies have shown no mortality difference, others have shown increased mortality or increased rates of renal replacement therapy.

None have shown a
benefit, and recent data suggest increased renal failure and mortality with administration of hydroxyethyl starch solutions.

There is also a concern for the potential impact of these solutions on platelet function and coagulation. As a result, starch-based solutions are not recommended for resuscitation.

Vasopressor therapy is recommended for use
in hypotensive septic patients after adequate volume resuscitation to maintain perfusion pressures.

Norepinephrine (Levophed) is currently the initial vasopressor of choice for septic shock, as it provides a balanced pressor and cardiac inotrope effect.

Dopamine is associated with increased short-term
mortality and serious adverse events compared to
norepinephrine.

Pure vasopressors such as phenylephrine should be avoided as the unopposed vasoconstriction can often further worsen the ongoing tissue hypoperfusion and lead to severe extremity or bowel ischemia.

If the patient remains hypotensive after starting norepinephrine then starting a low dose infusion of vasopressin at 0.03 U/min can be used
to decrease the dose of norepinephrine and enhance organ perfusion.

If the patient remains in septic shock despite fluids and appropriate vasopressor therapy then corticosteroid administration can be
considered.

Based on the presentation, there is a high suspicion of septic shock and no clinical or physical exam signs
of cardiogenic shock.

While an echocardiogram may be useful in certain situations, the treatment for septic shock should not be delayed. Delaying treatment of septic shock and can result in increased patient mortality.

Question 24

Initial cultures were sent on admission. Because
of a recent history of antibiotic use and diarrhea, a polymerase chain reaction (PCR) based clostridium difficile toxin test was sent as well.
Despite initiating broad spectrum antibiotics
the patient remain in shock. Twelve hours after admission the labs calls and tells the nurse that the test is positive for clostridium difficile (C. difficile)
toxin. Which of the following statements is true regarding the management of this patient?

A. Repeat the test for C. difficile because PCR based tests have a high false positive rate.

B In addition to broad-spectrum antibiotics, antifungal agents should be routinely started on admission of septic patients.

C. After a patient is asymptomatic, low pro-brain natriuretic peptide can help the decision to discontinue antibiotics.

D. Surgical intervention for this pathology would include a total abdominal colectomy and end ileostomy.

E Once a source of infection is identified, source control should be initiated alter antibiotics have
taken effect and the patient is no longer septic.

Answer 24

D.

This patient has a C. difficile infection and likely toxic megacolon secondary to the infection.

PCR-based C. difficile toxin as well as most current tests for C. difficile are extremely sensitive and specific tor the diagnosis of an active C. difficile infection and repeat
testing is not necessary.

The severity of C. difficile
infections can range from mild to severe. In very
severe cases, patients can present with shock and
sepsis known as fulminant C. difficile colitis or toxic
megacolon. Over the past two decades this diagnosis has become more common, and more and more
patients are requiring surgical intervention.

While we do not know from the description if there is perforation or peritoneal signs, this patient is clearly in shock. Antibiotic therapy should be targeted al the suspected diagnosis and the patient should be immediately evaluated for surgical intervention.

Surgical intervention for toxic megacolon from any cause typically mandates resection of the entire colon (total abdominal colectomy) and placement of an end ileostomy.

Anti-fungal agents should
not be routinely started in septic patients. They
should be used only in patients dial are al risk of or
suspected of having a fungal infection. Patients that are immunocompromised, neutropenic, or live in at
risk areas should be considered for the implementation of anti-fungal agents.

However, there is nothing in this patient’s history that would lead us to suspect
she is at an increased for a fungal infection.

Once a source of infection is identified then antimicrobial therapy should be targeted at the suspected source. If there a specific anatomical source of infection such as an abscess, cholangitis, and so on, that is driving a patient to sepsis, then emergent-targeted therapy should be initialed within 12 hours, not after antibiotics have taken effect. However, if no source of infection is identified and the patient improved with empiric anti-biotic therapy, then procalcitonin levels
(not pro BNP levels) can be used to help a clinician
determine when to stop anti-microbial therapy.

Question 25

Upon arrival to the ICU a chest X-ray is obtained
and it shows bilateral infiltrates. The ventilator is set to assist control mode with a peep of 5. tidal volume of 8 cc/kg, and FiO of 60%. On these settings her most recent PaO2 is 55. You suspect acute respiratory distress syndrome (ARDS).

Which of the following is true regarding ARDS?

A. ARDS requires the presence of a focal and unilateral infiltrate or consolidation on chest X-ray.

B. In patients with ARDS routine corticosteroid
use has been shown to reduce the overall mortality rate compared to placebo.

C. Use of high tidal volumes and low positive end-expiratory pressure (PEEP) is the traditional
ventilator strategy used to ventilate patients with
ARDS.

D. Treatment options for refractory ARDS that has failed conventional ventilation include airway
pressure release ventilation (APRV), high frequency ventilation, and extra-corporeal membrane oxygenation (ECMO).

E Airway pressure release ventilation has been shown to improve mortality in patients with
ARDS.

Answer 25

D.
In 2012, an updated clinical definition of ARDS
(known as the Berlin Definition was published. The presence of bilateral chest opacities is needed to make the diagnosis of ARDS, and either a chest radiograph or a CT scan is an acceptable way to evaluate for this.

A local unilateral infiltrate or consolidation on chest
X-ray would be more consistent with lobar pneumonia than ARDS.

According to the most recent ARDS definition outlined by the ARDS task force the diagnosis of ARDS must be made within one week of a
known clinical insult, and typically the diagnosis is
made within 72 hours.

After the diagnosis is made, the use of low tidal volumes (4 to 6 mL kg> should be initiated as this is the only mode of ventilation shown to improve mortality in randomized controlled trials of patients with ARDS.

As part of this strategy, high PEEP is often utilized to increase alveolar recruitment and improve oxygenation, but has not been shown to improve overall mortality.

Many other strategies are utilized to try and
improve outcomes in patients with refractory ARDS.

One treatment that has been studied is the use of corticosteroids. The ARDSNet trial showed that while corticosteroids reduced then mean number of days on a ventilator and increased the number of shock-
free days, they had no effect on overall survival and were harmful when given more than two weeks after the diagnosis of ARDS was made.

Medun et al. used low dose corticosteroids, and while ICU mortality was significantly reduced, overall mortality was not.

For the patient in ARDS who is refractory to standard mechanical ventilation, salvage or rescue options include switching to APRV, high frequency or “jet” ventilation, and even ECMO. Other rescue therapies include prone positioning, neuromuscular blockade,
and inhaled nitric oxide.

While these treatments are used as rescue therapies in severe ARDS and have been shown to produce improved oxygenation, they have not been shown to improve mortality in controlled trials.

Question 26

In patients treated for septic shock, there are
consequences of a prolonged ICU stay and can include progressive dysfunction and even failure of multiple organ systems. Regarding outcomes of multi-organ dysfunction syndrome (MODS), which of the following b true?

A. For septic patients that develop agitation and delirium, the use of benzodiazepines has been shown to reduce length of ICU stay, making them preferred over other agents.

B. Acute kidney injury is an independent risk factor for death in patients with multiorgan dysfunction syndrome.

C. Because septic patients are hypermetabolic,
parental nutrition has been shown to be beneficial when initiated early.

D. Stress ulcer prophylaxis with proton-pump inhibitors is not associated with any adverse events or complications.

E Critical illness polyneuropathy does not result in difficulty weaning a patient from a ventilator because it results in peripheral nerve dysfunction but preservation of the diaphragm.

Answer 26

B.

There are many challenges that are encountered when managing a critically ill patient, and delirium is a commonly encountered complication in the ICU
setting.

Severely ill and older patients are at particularly high risk for developing delirium, and this has
been shown to adversely impact morbidity and mortality. While benzodiazapenes are effective for delirium acutely, their use has been shown to increase ICU
length of stay and as a result they should be avoided whenever possible.

Rather the primary treatment for agitation and delirium is non-pharmacologic and includes reorientation and maintenance of sleep-wake cycles. If this is ineffective then anti-psychotics such as haloperidol or the newer atypical antipsychotics are preferred to benzodiazepines.

Another area that can challenge the management of septic patients is predicting which patients
are likely to have a worse outcome. There are many
scoring systems that are utilized to predict outcome in these patients, including the well-described APACHE score.

One such system that is specific for multi-organ failure is the Sequential Organ Failure Assessment or SOFA score. This system independently grades the severity of organ dysfunction for 6 different organ systems: respiratory, coagulation,
liver, cardiovascular, central nervous system, and renal. The individual scores are then added to give a total score.

Higher overall SOFA scores directly correlate with a worse outcome (Figure 77-1). Mortality has been shown to directly increase with the number of organ systems that are failing, and approaches 100% when 4 or more organ systems have failed.

Among individual organ systems, one of the strongest predictors of
ICU morbidity and risk of mortality is the development of acute kidney injury and/or renal failure.

Many critically ill patients are at increased risk
of upper gastrointestinal bleeding, and stress ulcer
prophylaxis is indicated tor patients with prolonged
mechanical ventilation (>48 hours) or other risk factors. 

The risk of bleeding from stress ulceration or gastritis in this patient population must be weighed against the risk of treatment with either proton pump inhibitors (PPI) or histamine receptor blockers (H2
blockers).

Multiple studies have shown that patients that receive stress ulcer prophylaxis are at increased risk of adverse events and complications such as C. difficile infections, ventilator associated pneumonia, and thrombocytopenia (H2 blockers).

Although hypermetabolism and a prolonged catabolic state are characteristic of sepsis and MODS, there has been no demonstrated survival benefit of administration of parenteral nutrition.

Multiple series have demonstrated that overall infectious comphcations are lower among patients given enteral nutrition versus total parenteral nutrition, and the gut should be the preferred route for nutritional support whenever possible.

Another important problem that is seen in patients with septic shock is critical illness polyneuropathy. The highly morbid condition is more common in patients with prolonged ICU stay, and among patients who received steroids and/or neuromuscular blocking agents. It can present with muscle atrophy, limb weakness, peripheral
sensory deficits and difficulty weaning patients from mechanical ventilation.

However, cranial nerve function is usually spared.