25: Hypotension

When a patient presents with hypotension, the important question is whether or not the patient is in shock. Shock is present if there is evidence of multisystem organ hypoperfusion. This may manifest itself as tachycardia, tachypnea, diaphoresis, poorly perfused skin and extremities, altered mental status, or decreased urinary output. In addition, it is not necessary for a patient to have overt hypotension to be in shock since a marked reduction in a patient’s usual BP may cause shock (but still be in the low-normal range in previously hypertensive patients). Given the life-threatening nature of shock, hemodynamic stabilization must be prompt and cannot wait for a long series of investigations to be completed.

Therefore, a rational, rapid approach to hypotension is necessary. The 3 main etiologies of shock include distributive (low total peripheral resistance, usually septic), cardiogenic (low cardiac output despite adequate intravascular volume), and hypovolemic (low cardiac output due to low intravascular volume). In terms of epidemiology, septic shock is by far and away the most common. In a trial of over 1600 patients with shock, 62% had septic shock, 16% had hypovolemic shock, and 16% had cardiogenic shock.

Differential Diagnosis of Shock

1. Distributive shock

   1. Septic shock

   2. Hepatic failure

   3. Pancreatitis

   4. Anaphylactic shock

   5. Adrenal insufficiency

   6. Neurogenic shock

   7. Arteriovenous shunts

2. Hypovolemic shock

   1. Hemorrhage

      1. Trauma

      2. Gastrointestinal hemorrhage

      3. Postsurgical, postprocedural bleeding

      4. Intra-abdominal (eg, abdominal aortic aneurysm, ruptured ectopic pregnancy)

   2. Volume depletion

      1. Vomiting

      2. Diarrhea

      3. Excessive diuresis (from diuretics or uncontrolled diabetes)

3. Cardiogenic shock

   1. Poor contractility

      1. Left ventricular (LV) failure

         • (1) Myocardial infarction (MI)

         • (2) Myocarditis

         • (3) Metabolic derangements (eg, profound acidosis, hypophosphatemia, hypocalcemia)

         • (4) Depressant drugs (beta-blockers, calcium-channel blockers)

         • (5) Miscellaneous causes of heart failure (HF) (eg, alcoholic cardiomyopathy, adriamycin-related cardiomyopathy, dilated cardiomyopathy)

      2. Right ventricular (RV) failure

         • (1) MI

         • (2) Pulmonary vascular disease

         • (3) Hypoxic pulmonary vasoconstriction

   2. Outflow obstruction

      1. Aortic stenosis

      2. Hypertrophic cardiomyopathy

      3. Malignant hypertension

      4. Pulmonary embolism (PE)

   3. Arrhythmogenic

      1. Significant bradycardia

      2. Significant tachycardia

   4. Backflow

      1. Acute mitral regurgitation – papillary muscle rupture or dysfunction

      2. Rupture septum or free wall

      3. Acute aortic regurgitation

   5. Reduced filling

      1. Constrictive pericarditis

      2. Tension pneumothorax

      3. Mitral stenosis

The first step in approaching patients with hypotension and shock is recognition. Is there evidence of decreased perfusion? This may be manifest by any 1 or more of the following:

1. Significantly decreased BP

   1. Typically systolic BP < 90 mm Hg

   2. A patient may be in shock with a “normal” BP; comparison to prior BPs is necessary.

   3. BP should be measured with a manual cuff. BPs measured with automatic BP cuffs may be inaccurate at lower BPs, especially the pulse pressure.

   4. The pulse pressure should be calculated: pulse pressure = systolic BP – diastolic BP. Wide pulse pressures suggest high cardiac output, whereas narrow pulse pressures suggest low cardiac output.

2. Tachycardia

3. Increased respiratory rate

4. Alteration of mental status

5. Decreased urinary output

6. Decreased arterial pH

The first diagnostic pivotal step utilizes a combination of the history, physical exam, and laboratory studies to determine if the shock is clearly due to sepsis, hypovolemia or cardiogenic. Hypovolemic shock is often obvious due to a history of hemorrhage or dehydration and patients usually have a history of melena, bright red blood per rectum, vomiting, diarrhea, or poor oral intake. In addition, it is typically associated with signs of low cardiac output including a narrow pulse pressure, cold extremities and poor capillary refill. Anemia or acute kidney injury may be evident on laboratory exam. Distributive shock is most frequently due to sepsis, which is often apparent due to a history of fever, rigors, other infectious symptoms (cough, rash, abdominal pain, urinary urgency, or dysuria) and signs of high cardiac output (warm extremities, bounding pulses, a wide pulse pressure, and brisk capillary refill). However, some patients with advanced sepsis have a poor cardiac output. Laboratory evidence of sepsis often suggests underlying infection, including a leukocytosis, an infiltrate on chest film, pyuria on urinalysis, or diagnostic findings on abdominal CT in patients with abdominal pain. Finally, patients with cardiogenic shock often have a history of CAD or HF or symptoms of acute MI. Their physical exam suggests low cardiac output (poor capillary refill, narrow pulse pressure, and cold extremities) and may also reveal evidence of high filling pressures (jugular venous distention [JVD] or an S₃ gallop). The physical exam, ECG, and echocardiogram can determine whether cardiogenic shock is secondary to poor contractility, outflow obstruction, an arrhythmia, reduced filling, or backflow from valve failure.

The final pivotal step addresses patients in whom the initial evaluation does not delineate a likely etiology of shock. Patients with evidence of a high cardiac output (wide pulse pressure, brisk capillary refill, warm extremities) without an obvious source of sepsis, should be evaluated for unusual causes of systemic inflammatory response syndrome (SIRS) (eg, pancreatitis), occult infections, and other causes of distributive shock (hepatic failure, anaphylaxis, adrenal insufficiency). Patients with evidence of a low cardiac output of unclear etiology (narrow pulse pressure, sluggish capillary refill, cold extremities) should be evaluated for occult massive hemorrhage (eg, intra-abdominal) and less common causes of cardiogenic shock such as PE and pericardial tamponade. Such patients should also be evaluated for septic shock. An echocardiogram can be useful in such patients by revealing unsuspected cardiac etiologies (eg, pericardial tamponade, acute aortic regurgitation due to dissection or right HF suggesting PE).

Finally, it is important to realize that overlapping etiologies are common, especially septic and cardiogenic shock. Figure 25-1 illustrates the diagnostic approach to shock.

Ms. P is clearly hypotensive and the combination of her hypotension, tachycardia, and difficulty staying awake clearly suggest inadequate tissue perfusion and shock. The next pivotal step considers the 3 most common categories of shock: hypovolemic, septic and cardiogenic.

Ms. P clearly has several features suggesting septic shock. Her urinary tract symptoms, fever, and costovertebral angle tenderness point to a possible urinary tract infection. Her leukocytosis is also suggestive. Septic shock is therefore the leading and must not miss hypothesis. Her episode of vomiting suggests some hypovolemia but her hypotension is out of proportion to her 1 episode of emesis. Another possible diagnosis would be hypovolemia due to an osmotic diuresis from severe diabetic hyperosmolar state. Finally, given her diabetes mellitus and prior CAD, cardiogenic shock from an acute MI needs to be considered. Table 25-1 lists the differential diagnosis.

Leading Hypothesis: Septic Shock

Textbook Presentation

Patients with septic shock typically have fever, tachypnea, tachycardia, and hypotension. Whereas patients with cardiogenic or hemorrhagic shock often have cold extremities, patients with septic shock often have warm extremities and bounding pulses after fluid resuscitation. (Pulses are bounding due to a widened pulse pressure.) Mentation may be impaired and urinary output decreased.

Disease Highlights

1. Epidemiology

   1. The annual incidence of sepsis has increased 4-fold since the 1970s, now exceeding 750,000 per year in the United States.

   2. Sepsis is more common among nonwhite compared with white populations in the United States (relative risk 1.90).

   3. Most common sources of infection are the lung, abdomen, urinary tract, and IV catheters. Commonly overlooked sources include sinusitis (associated with nasogastric tubes), acalculous cholecystitis, and Clostridium difficile colitis.

2. Pathophysiology

   1. Sepsis

      1. Occurs when an infection (bacterial, fungal, mycobacterial, or viral) triggers a proinflammatory reaction that is poorly regulated and becomes systemic.

      2. A noninfectious process (eg, acute pancreatitis) may also trigger a similarly dysregulated immune response.

   2. In early stages of sepsis, hyperimmune responses may play a role in the organ dysfunction and cause multiple organ dysfunction syndrome, hypotension, disseminated intravascular coagulation, and death.

   3. In later stages of sepsis, patients may be hypoimmune. Hypoimmunity may also contribute to infection and death.

   4. Mechanisms of hypotension include

      1. Vasodilation (decreased systemic vascular resistance) mediated by elevated nitrous oxide levels, increased prostacyclin levels, and low vasopressin levels, lowers BP.

      2. Cardiac output can be increased or decreased in sepsis.

         • (1) The drop in systemic vascular resistance decreases afterload, which often results in an increase in CO.

         • (2) On the other hand, leakage of fluid out of intravascular space can decrease venous return and thereby decrease CO.

         • (3) In addition, myocardial function can be reduced and also decrease CO.

      3. Typically, the initial hemodynamic response is decreased systemic vascular resistance and increased CO (particularly after fluid resuscitation).

   5. Multiple organ dysfunction syndrome

      1. Lung involvement: acute respiratory distress syndrome secondary to increased permeability with subsequent non-cardiogenic pulmonary edema.

      2. Acute kidney injury secondary to

         • (1) Hypotension

         • (2) Renal vasoconstriction

         • (3) Increased tumor necrosis factor

      3. Disseminated intravascular coagulation: Multiple mediators are involved, including decreased protein C (see Chapter 8, Bleeding Disorders, for details).

   6. Lactic acidosis is common in sepsis and has many causes.

      1. Microcirculatory lesions impair oxygen delivery.

         • (1) Dysregulation of supply and demand

         • (2) Microvascular occlusion

      2. Hypotension impairs oxygen delivery.

      3. Mitochondrial injury impairs oxygen utilization.

      4. Decreased hepatic clearance of lactate contributes to lactic acidosis.

3. The definitions of sepsis, severe sepsis, and septic shock and their associated mortality rates are shown in Table 25-2.

4. There is an increased risk of septic shock in patients with bacteremia (21%), advanced age (≥ 65 years), impaired immune system, community-acquired pneumonia, abdominal infection, and markedly elevated WBC.

5. The mortality rate associated with sepsis ranges from 20% to 50%. Predictors of mortality include

   1. Age > 40 years

   2. Comorbidities: AIDS, hepatic failure, HF, diabetes mellitus, cancer, or immunosuppression.

   3. Temperature < 35.5^°C

   4. Leukopenia < 4000 cells/mcL

   5. Hospital-acquired infection

   6. Candida, Pseudomonas, or Staphylococcus aureus infection.

   7. Inappropriate antibiotics: appropriate antibiotics are associated with a 50% decrease in mortality.

   8. Multiple organ failure

   9. The Mortality in Emergency Department Sepsis (MEDS) Score is a validated scoring index that predicts mortality in patients arriving at emergency departments with suspected infection (Figure 25-2).

Evidence-Based Diagnosis

1. Predictors of bacteremia (Table 25-3)

   1. Fever

      1. In emergency department patients, fever was higher among bacteremic patients (38.8^°C) than nonbacteremic patients (38.1^°C). However, 5% of bacteremic patients are normothermic (temperature < 37.6^°C) and 13% of patients were hypothermic.

      2. The absence of fever was associated with increased mortality.

   2. Chills

      1. Chills can vary from mild to moderate to shaking chills (ie, teeth chattering, bed shaking chills).

      2. Chills of some kind (mild, moderate, or severe) are common in bacteremic patients (sensitivity 88%).

      3. Shaking chills (rigors) are less sensitive but more specific for bacteremia (sensitivity, 45%; specificity, 90%; LR+, 4.7, LR-, 0.61).

         Providers should consider bacteremia in older patients with significant fever or rigors. Patients presenting with rigors should have blood cultures drawn and antibiotics administered.

   3. Rashes: Certain life-threatening infections may produce characteristic rashes (ie, meningococcemia, Rocky Mountain spotted fever, or staphylococcal toxic shock syndrome).

      Patients with fever and a rash should be immediately evaluated for life-threatening diseases including toxic shock syndrome, meningococcemia, or Rocky Mountain spotted fever.

   4. Patients with severe sepsis or septic shock have a high incidence of bacteremia (38% and 69%, respectively)

   5. WBC > 15,000/mcL is only 28% sensitive for bacteremia.

      A normal WBC does not rule out bacteremia.

   6. Catheter site infections

      1. Signs of inflammation at the insertion site are uncommon in patients with central venous catheter infections (sensitivity 27%). Erythema is present in only 3% of patients with catheter-related bloodstream infections.

         Consider central catheter line infection in septic patients even in the absence of erythema or pus.

      2. Certain findings are highly specific for catheter infection, including gross pus at the catheter site.

   7. Injection drug use or an acute abdomen (or both) also increase the risk of bacteremia.

   8. Incidence of bacteremia is low (2%) in patients without any of the following risk factors:

      1. Temperature > 38.3^°C

      2. Shaking chills

      3. Injection drug use

      4. Acute abdomen on exam

      5. Major comorbidity

   9. Procalcitonin is an emerging marker of bacterial infection.

      1. Polypeptide upregulated during bacterial infection in a manner that mirrors the severity of the infection.

      2. Procalcitonin’s release is attenuated by cytokines released during viral infections, particularly interferon-gamma.

      3. Elevated levels suggest bacterial infections whereas normal levels in sepsis suggest a systemic inflammatory response without bacterial infection.

      4. The accuracy is limited (sensitivity, 77%; specificity, 79%; LR+, 3.7; LR–, 0.29) and results must be viewed in context of all of the clinical data.

   10. A lactic acidosis can suggest sepsis. Serum lactate levels are more sensitive for detecting a lactic acidosis from any cause than an increase in the anion gap. An elevated anion gap is only 44-67% sensitive.

2. Cultures from suspected sources (blood, urine, sputum, fluid collection) should be obtained as soon as possible in patients evaluated for sepsis. If central catheters are in place, blood should be obtained peripherally and through the central catheter.

Treatment

1. The treatment of septic shock is complex.

2. The principles of treatment include the following:

   1. Treat the underlying cause.

   2. Prompt volume resuscitation

   3. A variety of other therapies may be critical including vasopressors, inotropes, intubation and mechanical ventilation, blood products and others.

   4. Recommendations evolve frequently. Readers are referred to specialized text for details.

Alternative Diagnosis: Hypovolemic Shock

Typically, a patient with hypovolemic shock will have an obvious source of bleeding, a drop in hematocrit, or recognizable gastrointestinal fluid or renal losses.

Disease Highlights

1. Patients who are hypovolemic have 1 of 2 clinical conditions:

   1. Volume depletion due to vomiting, diarrhea, inadequate oral intake, or excessive diuresis (from diuretics or uncontrolled diabetes)

   2. Hemorrhage (due to trauma, gastrointestinal or intra-abdominal hemorrhage)

2. Hospitalizations related to gastrointestinal hemorrhage are common, 150/100,000 population per year, and have a case fatality rate of 3-10%.

3. Degree of bleeding is often difficult to assess.

   1. Melena can occur with massive hemorrhage or as little as 100 mL of blood loss.

   2. Admission hematocrit correlates poorly with degree of blood loss and mortality.

   Massive hemorrhage may be present in patients despite a normal hematocrit.

4. Hypovolemia secondary to dehydration sufficiently severe to cause hypovolemic shock disproportionately affects the elderly. Common risk factors include:

   1. Female sex

   2. Age > 85

   3. Greater than 4 chronic medical conditions

   4. Taking 4 or more medications

   5. Being confined to bed

Evidence-Based Diagnosis

1. In a review of physical exam findings in hypovolemia, abnormal vital signs are relatively specific but not sensitive (Table 25-4).

   1. Orthostatic vital signs, particularly an increase in pulse are more sensitive than supine vital signs.

      1. When measuring orthostatic vital signs, wait 2 minutes before measuring supine vitals and wait 1 minute after patient stands to measure upright vitals.

      2. Helpful physical findings include:

         • (1) Severe postural dizziness (unable to measure upright vital signs due to dizziness).

         • (2) Postural pulse increment of 30 beats/min or more.

   2. Dry axilla supports hypovolemia in the elderly (sensitivity, 50%; specificity, 82%; LR+ 2.8, LR– 0.61).

   3. Poor skin turgor has no proven diagnostic value in adults.

2. Laboratory evidence is often more revealing.

   1. Hematocrit

      1. Decreased in hemorrhage if bleeding has been ongoing

      2. However, in acute bleeding, isovolemic blood loss prior to hemodilution (from IV or oral fluid repletion) may result in a normal hematocrit.

         A normal hematocrit does not rule out life- threatening acute hemorrhage.

      3. The hematocrit is often elevated in patients with nonhemorrhagic hypovolemia.

   2. Other laboratory findings typically seen in hypovolemic patients include:

      1. An elevated BUN/Cr ratio > 20 (see Chapter 28, Acute Kidney Injury)

      2. A low urine sodium concentration < 30 mEq/L and a Fe_Na < 1%

      3. In patients taking diuretics, the Fe_urea < 35% may be more accurate (see Chapter 28, Acute Kidney Injury)

3. A brisk BP response to a 500 mL bolus given over 10 minutes supports hypovolemia (but may also be seen in sepsis).

Treatment

1. The treatment of hypovolemia is the restoration of an adequate mean pressure by fluid resuscitation.

2. In the case of hemorrhagic hypovolemia, the source of bleeding must be identified and stopped.

3. Vasopressors are not indicated. They can increase BP; however, they may have a detrimental effect on cardiac output and perfusion of vascular beds.

The first step in the evaluation is to recognize shock. Mr. A’s BP is exceptionally low for a 71-year-old man. His BP, combined with his complaint of weakness and cool extremities, makes shock likely. The next pivotal diagnostic step is to evaluate the history, physical exam, and laboratory data to determine if this is likely hypovolemic, septic, or cardiogenic shock. There are no signs or symptoms of sepsis, nor any history to suggest hypovolemia. His cool extremities are consistent with a low cardiac output state (which is often seen in hypovolemic or cardiogenic shock) and his JVD suggests that the low cardiac output is due to cardiogenic, not hypovolemic, shock. Furthermore, his past medical history increases the probability of cardiogenic shock. Possible etiologies of cardiogenic shock include poor contractility (potentially from LV or RV MI or preexistent HF), outflow obstruction (due to, for example, aortic stenosis or PE), backflow (from acute aortic regurgitation or a failed regurgitant mitral valve), or reduced filling (from tamponade or a failed stenotic mitral valve). Given the patient’s history, you consider MI to be most likely. Active alternatives include mitral valve failure or tamponade (given recent cardiac surgery). Table 25-5 lists the differential diagnosis.

Leading Hypothesis: Cardiogenic Shock

Textbook Presentation

Typically, cardiogenic shock presents during or immediately after an MI. The patient presents with chest pain, cool extremities, low BP, and ST elevation myocardial infarction (STEMI).

Disease Highlights

1. Cardiogenic shock is defined as persistent hypotension (systolic BP < 90 mm Hg) or mean arterial pressure 30 mm Hg lower than baseline with severe reduction in cardiac index (< 1.8 L/min/m²) and adequate or elevated filling pressure (LV end-diastolic pressure > 18 mm Hg or RV end-diastolic pressure > 10-15 mm Hg).

2. The majority of cardiogenic shock cases are related to MI.

   1. The incidence of cardiogenic shock appears to be decreasing with increasing use of percutaneous intervention for acute MI.

   2. However, cardiogenic shock still complicates 5-8% of STEMI and 2.5% of non-STEMI.

      1. This translates to 40,000 to 50,000 cases per year in the United States.

      2. Infarction location was anterior in 55% of cases and in multiple locations in 50%.

      3. In the SHOCK trial registry, 53.4% of patients have 3-vessel disease and 15.5% have significant left main disease.

   3. Risk factors for cardiogenic shock include older age, anterior MI, hypertension, diabetes mellitus, multivessel CAD, prior MI or angina, prior diagnosis of HF, STEMI, and left bundle branch block.

   4. The magnitude of LV ejection fraction reduction does not need to be profound for shock to develop. In a large registry of cardiogenic shock, the mean LV ejection fraction was 30%.

   5. Mechanical complications of MI (rupture of the ventricular septum, free wall or papillary muscles) cause 12% of cardiogenic shock cases.

      1. Ventricular septal rupture has a mortality of 87%.

      2. Women and elderly are at increased risk for these complications, particularly elderly individuals who undergo thrombolysis.

3. Any cause of severe RV or LV dysfunction can lead to cardiogenic shock. Other typical etiologies include:

   1. Acute myocarditis

      1. Cardiogenic shock complicates 10-15% of cases.

      2. Patients are younger than those with MI and often present with dyspnea rather than chest pain.

   2. Takotsubo cardiomyopathy

      1. Stress-induced condition that leads to apical ballooning after emotional or respiratory distress.

      2. Leads to cardiogenic shock in 4.2% of cases.

   3. Acute valvular regurgitation

   4. Aortic dissection causing either acute, severe aortic insufficiency or extension of dissection to coronary arteries leading to infarction.

   5. Acute stress in the setting of mitral or aortic stenosis

   6. Cardiac tamponade

   7. PE

   8. Arrhythmia

4. Pathophysiology

   1. In MI effecting the LV, decreased coronary perfusion lowers cardiac output, which further decreases coronary perfusion.

   2. Hypoperfusion causes catecholamine release and activation of the renin-angiotensin system increasing contractility and peripheral blood flow but also increasing myocardial oxygen demand and promotes arrhythmia.

   3. This leads to further ischemia and greater reduction in cardiac output.

   4. Activation of the neurohormonal cascade also leads to salt and water retention and exacerbates pulmonary edema.

   5. Treatment relies on breaking this cycle.

Evidence-Based Diagnosis

The diagnosis of the individual etiologies of cardiogenic shock (eg, MI, PE, etc) is covered elsewhere. The focus of this section will be on the diagnosis of cardiogenic shock itself.

1. Diagnosing cardiogenic shock relies on recognizing signs of decreased cardiac output despite an adequate or elevated filling pressure. However, signs and symptoms have limited accuracy in detecting elevated filling pressures.

   1. JVP ≥ 12 cm H₂0 sensitivity, 65%; specificity, 64%; LR+ 1.8; LR– 0.55

   2. In a single-center study, elevation of the external jugular vein correlated with catheter-measured central venous pressure

      1. External JVP < 5 cm H₂0 predicted a low central venous pressure

         • (1) Senior students and interns: sensitivity, 47%; specificity, 100%; LR+ ∞; LR– 0.5

         • (2) Junior and senior residents: sensitivity, 78%; specificity 92%; LR+ 9.8; LR– 0.2

      2. External JVP > 10 cm H₂0 predicted a high central venous pressure

         • (1) Senior students and interns: sensitivity, 61%; specificity, 75%; LR+ 2.4; LR– 0.5

         • (2) Junior and senior residents: sensitivity, 78%; specificity, 93%; LR+ 11.1; LR– 0.2

   3. 2 pillow orthopnea (86% sensitive, 25% specific, LR+ 1.1, LR– 0.56)

   4. Cold extremities 20% sensitive, 88% specific (LR+ 1.7, LR– 0.9)

   5. The proportional pulse pressure can suggest cardiogenic shock.

      1. Typically, the pulse pressure increases as the systolic BP increases.

      2. A relatively low pulse pressure compared to the systolic BP suggests a low stroke volume.

      3. Proportional pulse pressure (PPP = (systolic BP – diastolic BP)/systolic BP)

      4. A PPP < 25% is 10% sensitive, 96% specific (LR+ 2.5, LR– 0.94) for cardiac index < 2.3 L/(min-m²). This must be measured with manual BP cuff.

2. Once the diagnosis of cardiogenic shock is considered and the need for immediate catheterization for treatment of acute MI (the most common cause) is assessed, echocardiography should be performed early.

3. Bedside portable ultrasound is becoming more prevalent and has been shown to be useful in assessing the cause of cardiogenic shock as well as in undifferentiated shock.

   1. It is especially useful to

      1. Assess for pericardial effusion

      2. Determine global cardiac systolic function

      3. Identify marked LV or RV enlargement

      4. Gauge intravascular volume status by assessing inferior vena cava diameter and respiratory variation.

   2. Preliminary data suggests hand held devices are accurate in residents with limited training (3 hours of didactic training and 5 hours of hands-on training)

      1. LV dysfunction: 88% sensitive, 89% specific, LR+ 8, LR– 0.13

      2. Pericardial effusion: 83% sensitive, 96% specific, LR+ 20.8, LR– 0.18

Treatment

Complete discussion of the treatment of cardiogenic shock is beyond the scope of this chapter. However, when cardiogenic shock is a result of myocardial ischemic, early revascularization (percutaneous coronary intervention or CABG) results in a significant survival benefit and is clearly indicated.

The patient’s clinical picture suggests cardiogenic shock but the etiology remains obscure. Neither the ECG nor troponins suggest an acute MI. You consider the shock is due to one of the less common causes of cardiogenic shock (tamponade, valve failure).

Leading Hypothesis: Cardiac Tamponade

Textbook Presentation

Weakness, hypotension, and tachycardia are typically present. Other classic findings include an elevated jugular venous pressure and muffled heart sounds. However, the signs and symptoms associated with tamponade are quite nonspecific.

Disease Highlights

1. Cardiac tamponade results when fluid accumulation in the pericardial space compresses the heart and causes a reduction in cardiac output. This occurs as a result of pericardial effusion or hemorrhage.

2. As the signs and symptoms associated with it are nonspecific, diagnosing cardiac tamponade relies on understanding the conditions that can lead to pericardial effusion and careful assessment.

3. The incidence of cardiac tamponade and pericardial effusions are not well documented, and there is little data regarding how often pericardial effusions progress to tamponade. However, pericardial effusions are not uncommon; therefore, identifying clinically significant effusions is of great importance.

   1. Common etiologies of pericardial effusions that may lead to tamponade include

      1. Idiopathic pericarditis (20-30%)

      2. Malignancy (13-36%)

      3. Iatrogenic (16%)

      4. Infection (5-21%)

      5. Acute MI (8%)

      6. Collagen vascular disease (5%)

   2. Of these, effusions due to infection (bacterial, fungal, HIV-associated infections) and neoplasm have the greatest incidence of progression to tamponade.

   3. Cardiac tamponade occurs in 1-2% of patients following cardiac surgery and commonly occurs as late as 7 days postoperatively.

   4. Cardiac tamponade was found in almost 19% of patients with a type A aortic dissection. These patients had significantly higher mortality.

4. Tamponade has a wide range of presentations depending on pericardial fluid volume, accumulation rate, and degree of compression. It is typically grouped into 2 main types:

   1. Acute tamponade

      1. Occurs following traumatic injury, rupture of the heart or aorta, or an invasive diagnostic or therapeutic procedure.

      2. Presents with cardiogenic shock (cool extremities, altered mental status, peripheral cyanosis, and JVD)

   2. Subacute tamponade

      1. Occurs in the setting of inflammatory disease or malignancy.

      2. Symptoms often mimic HF (fatigue, dyspnea, chest fullness).

      3. Pericardial effusion may reach as much 2 L before tamponade physiology occurs.

5. Physiology: Tamponade occurs as increasing intrapericardial pressure compresses the cardiac chambers. The key components that determine when tamponade occurs are the rate of fluid accumulation relative to pericardial stretch.

   1. True filling pressure of the heart is the transmural pressure, which is calculated as follows: intracardiac pressure – pericardial pressure.

   2. Rising pericardial pressure offsets intracardiac pressure at some point and leads to competition for the chambers to fill:

      1. During systole, reduced ventricular volume leads to decreased pericardial pressure and atrial filling is preserved.

      2. During diastole, increased ventricular volume leads to increased pericardial pressure, decreased atrial transmural pressure and as tamponade approaches, late diastolic atrial collapse.

      3. As the pericardial effusion continues to increase and pericardial pressure rises, the ventricles compete for limited space. This stress more easily affects the RV and can lead to early diastolic collapse of the RV.

   3. During inspiration, decreased pleural pressure is transmitted to the pericardium and causes increased transmural pressure and increased venous return and right heart filling. In tamponade this RV expansion compresses the LV and results in shift of the interventricular septum and decreased pulmonary venous return and reduced stroke volume.

   4. As cardiac output drops, increases in heart rate, contractility, and peripheral arterial vasoconstriction defend circulation until circulatory collapse occurs.

Evidence-Based Diagnosis

1. Signs and symptoms

   1. Tachypnea and dyspnea nearly always present with cardiac tamponade (87-88%).

   2. Other common findings in patients with cardiac tamponade are tachycardia, elevated jugular venous pressure and pulsus paradoxus with pooled sensitivities of 76-82%.

   3. Chest pain, cough, fever, lethargy, and palpitations are present in 25% or less of patients.

   4. ECG findings associated with tamponade are insensitive with low voltage QRS and electrical alterans having estimated sensitivities of 43% and 16-21%, respectively.

   5. Cardiomegaly on chest film is common with a pooled sensitivity of 89% in 4 studies of 165 patients.

   6. Hypotension and diminished heart sounds are insensitive (28% and 26%, respectively).

2. Pulsus paradoxus

   1. Defined as an exaggerated decrease in BP with the normal inspiration

   2. The paradox comes from decreased systolic BP despite increased venous return during inspiration.

   3. In tamponade, when inspiration increases RV filling, the expansion of the RV within the confined pericardial space pushes the interventricular septum to the left and diminishes left heart filling.

   4. Additionally, inspiratory expansion of the lungs leads to pulmonary venous pooling and even further reduced LV filling.

   5. When the LV diastolic pressures are elevated as in end-stage renal disease, cardiac tamponade does not result in pulsus paradoxus.

   6. Making an accurate measurement of pulsus paradoxus requires a manual sphygmomanometer, a quiet location, and patience.

      1. The sphygmomanometer is fully inflated and slowly deflated, in 1-2 mm Hg steps as the likely pressure is approached listening for the first Korotkoff sounds (which will be heard only with exhalation). Record this pressure.

      2. The cuff is deflated further in 1-2 mm Hg steps until the Korotkoff sounds are heard with inspiration and expiration.

      3. The difference between these pressures is the pulsus paradoxus; a difference > 10 mm Hg suggests cardiac tamponade but may also be seen in severe respiratory distress, massive PE, and other forms of severe hypertension.

3. When cardiac tamponade is suspected, transthoracic echocardiography is the primary diagnostic test to confirm the diagnosis.

4. The main findings on the transthoracic echocardiography include a pericardial effusion associated with the following:

   1. Late diastolic collapse of the right atria

   2. Early to mid diastolic collapse of the RV

   3. Septal shift toward the left during inspiration and toward the right with expiration

   4. Suppression of deep inspiratory collapse of the inferior vena cava

Treatment

1. Once cardiac tamponade is diagnosed, pericardial drainage is required unless tamponade is due to aortic dissection or free wall rupture.

2. Symptomatic management may be used if the patient is hemodynamically stable or in a “pre-tamponade” state. This consists primarily of volume resuscitation with isotonic fluids and supplemental oxygen until drainage can be performed.

3. Pericardiocentesis can be accomplished under ultrasound guidance at the bedside in the ICU if needed emergently. Alternatively, this can be performed under ultrasound or fluoroscopic guidance in the catheterization laboratory.

4. If the effusion is loculated, there is a need for pericardial window, or if the effusion is due to acute traumatic hemopericardium, surgical pericardiotomy is required.

As noted above, the first step in the evaluation of the hypotensive patient is the recognition of shock. The patient’s profound hypotension, particularly at this age, and dizziness suggest symptomatic hypotension and inadequate cerebral perfusion diagnostic of shock. The first pivotal diagnostic step is to consider whether the history and physical exam suggest 1 of 3 leading causes of shock: septic shock, hypovolemic shock, or cardiogenic shock. Her bounding pulses and warm extremities suggest distributive shock, a high output form of shock. As mentioned above, the most common form of distributive shock is septic shock, a must not miss hypothesis. However, her hives and recent use of amoxicillin is a pivotal clue that suggests another cause of distributive shock, anaphylactic shock. This is both the leading and must not miss hypothesis. Table 25-6 lists the differential diagnosis.

Leading Hypothesis: Anaphylactic Shock

Textbook Presentation

Anaphylaxis is an acute systemic reaction caused by IgE-mediated immunologic release of mediators from mast cells and basophils to allergenic triggers like food, insect venom, or medications. Typically, the reaction may affect the patient’s skin, the cardiovascular system, or respiratory system. Anaphylactoid reactions produce the same clinical picture; however, they are not immune-mediated.

Disease Highlights

1. Triggers and mechanisms

   1. Foods are most common triggers in infants, children, and teenagers.

      1. As much as 2% of the US population may have food allergies.

         • (1) Peanut allergies are most common in children.

         • (2) Shellfish allergies are most common in adults.

      2. Each year in the United States there are as many as 100 deaths due to anaphylactic reactions to food.

   2. When the cause of anaphylaxis is identified in adults, the most common culprits are antibiotics or nonsteroidal antiinflammatory drugs, with penicillins responsible for 75% of fatal cases.

2. The patient history is the most important tool to determine whether a patient has had anaphylaxis and the cause of the episode.

   1. Respiratory symptoms may include nasal stuffiness or itching; difficulty in breathing; retrosternal tightness; or pharyngeal, epiglottic, or glottis edema.

   2. Cardiovascular symptoms include dizziness, chest tightness, or overt hypotension.

   3. Skin complaints include itching, warmth, minor swelling, or characteristic urticaria.

   4. Severity, onset, and symptom patterns may vary considerably and results in discrepancies in diagnosis.

3. The estimated lifetime prevalence of anaphylaxis is 0.05-2%. However, even the high-end estimate may be too low as significant evidence points toward underreporting of anaphylaxis.

   1. In Australia, anaphylaxis admissions doubled from 1995 to 2005 to over 10:100,000 population. The increase in incidence is likely more pronounced among young patients, with food the most common trigger.

   2. Deaths related to medicine-induced anaphylaxis have increased 300%. Medicines account for 57% of anaphylaxis-related deaths.

4. Physiology

   1. Interaction of antigen with mast cell IgE or direct drug actions (by histamine, leukotrienes, kinins, prostaglandins or platelet activating factor) cause mast cells to release the mediators of anaphylaxis or anaphylactoid reactions.

   2. These mediators cause vasodilation and the leakage of fluid from capillaries and the post-capillary venules resulting in hypotension.

   3. Several of these substances, in particular leukotrienes, cause respiratory symptoms related to bronchoconstriction and increased mucus production.

   4. When untreated, death may result from hypoxemia due to upper airway angioedema, bronchospasm and mucus plugging and/or shock resulting in multi-organ system failure.

Evidence-Based Diagnosis

1. The sudden onset of skin, cardiovascular, and respiratory symptoms should point toward a diagnosis of anaphylaxis.

   1. However, even if just 2 of these organ systems are involved, or hypotension alone, anaphylaxis should be considered.

   2. Often, these reactions may be self-limited; however, failure to make a diagnosis puts the patient at risk for future life-threatening allergen exposure.

2. Clinical criteria for the diagnosis of anaphylaxis. Essential questions to be asked:

   1. Were there cutaneous manifestations, specifically pruritus, flushing, urticaria, and angioedema?

   2. Was there any sign of airway obstruction involving either the upper airway or the lower airway?

   3. Were syncope or presyncopal symptoms present?

3. According to the National Institute of Allergy and Infectious Disease, the diagnosis of anaphylaxis is highly likely if any the following criteria are met:

   1. Sudden onset of an illness (within minutes to several hours) with involvement of the skin, mucosal tissue, or both and

      1. Respiratory compromise (dyspnea, wheeze-bronchospasm, hypoxemia), or

      2. Reduced BP or associated symptoms of end-organ dysfunction (hypotonia, syncope, or incontinence).

   2. Sudden onset of 2 or more of the following symptoms after exposure to a likely allergen or other trigger for that patient:

      1. Skin or mucosal symptoms (hives, itch-flushing, swollen lips-tongue-uvula)

      2. Respiratory compromise

      3. Reduced BP or associated symptoms

      4. Persistent gastrointestinal symptoms

   3. Reduced BP (systolic BP < 90 mm Hg or greater than 30% decrease from baseline) after exposure to a known allergen for that patient (minutes to hours)

   4. The test characteristics for the criteria are sensitivity, 96.7%; specificity, 82.4%; LR+, 5.5; LR–, 0.04.

4. The sensitivity of individual findings:

   1. Skin/mucosa: 100% skin or mucosal tissue findings, 60.5% generalized hives, 42% pruritus, 44% angioedema, and 30% flushing/diaphoresis.

   2. Respiratory: respiratory compromise 90%, dyspnea 72%, wheezing 24%

   3. Reduced BP or associated end-organ dysfunction, 24%

5. Mature tryptase is released from mast cells when activated. Therefore, measurement of tryptase can be useful to confirm a diagnosis of anaphylaxis.

   1. An increase > 2.0 mcg/L between arrival, 1 hour later and just before discharge was 75% sensitive for severe anaphylaxis.

   2. This test does not have benefit at the time of presentation; however, it may be beneficial to ensure that a diagnosis of anaphylaxis is made when appropriate and minimize the risk for recurrence.

Treatment

1. Initial management of suspected anaphylaxis relies on quick recognition and appropriate supportive care.

   1. Assess patient’s circulation, airway, breathing, mental status, skin, and body weight.

   2. Inject intramuscular epinephrine in the mid-anterolateral aspect of the thigh, 0.01 mg/kg of a 1:1000 (1 mg/mL), maximum 0.5 mg (adult) or 0.3 mg (child). Repeat in 5-15 minutes if needed.

   3. H₁- and H₂- antihistamines as well as corticosteroids are considered second-line agents and are not considered essential medications for the treatment of anaphylaxis. If given, antihistamines may decrease itching, flushing, urticarial, and nasal symptoms but have no effect on airway obstruction or hypotension.

   4. Corticosteroids do not affect the initial symptoms of anaphylaxis but may reduce the likelihood and severity of protracted symptoms. There is no consensus regarding the type of corticosteroid, the route, or the dose that may be beneficial.

   5. Place the patient on their back and elevate lower extremities.

   6. If indicated, provide respiratory support; this may range from supplemental oxygen via nasal cannula to mechanical ventilation.

   7. Establish IV access with wide-bore cannula (16 gauge if possible) and bolus 1-2 L of 0.9 normal saline.

2. Once the patient recovers from the acute episode, steps must be taken to prevent a recurrence.

   1. Provide self-injectable epinephrine from an auto-injector.

   2. Establish an anaphylaxis emergency plan and medical identification of the patient’s allergy (bracelet, wallet card).

   3. Referral to an allergy/immunology specialist to confirm sensitivity to a specific allergen and to discuss long-term risk reduction strategies including immune modulation.