Decisive Management of Undifferentiated Shock

Emerg Med 40(7):7, 2008

By Kaushal Shah, MD, and Oscar Rago, MD

The causes of undifferentiated shock are elusive, but hypotensive patients need immediate attention. The
authors present a systematic approach to assessing and managing the type of shock that defies
categorization.

Dr. Shah is the director of trauma and assistant residency director and Dr. Rago is a senior resident in the
department of emergency medicine at St. Luke’s-Roosevelt Hospital in New York City.

When a patient presents with hives from a bee sting or with major trauma, the emergency physician
knows exactly how to manage the situation. Not so with undifferentiated shock. The definition of shock is
inadequate tissue perfusion causing a mismatch between oxygen supply and demand and resulting in
global tissue hypoxia. Defining it is easy, but making the diagnosis and quickly identifying the etiology can
be difficult, because patients may have nonspecific complaints, signs, and symptoms.

Rapidly identifying the type of shock can be especially challenging. The term “undifferentiated shock” is
used to describe shock that does not fit into any obvious category. No clear guidelines exist on how to
manage patients with undifferentiated shock, but all patients in shock need immediate attention, so early
diagnosis and therapy are critical. Sustained hypotension is the strongest independent predictor of
adverse hospital outcome.

What makes shock so hard to diagnose? One problem is that, although shock has specific clinical features
(see box above), the patient’s vital signs may be deceptively normal. No single vital sign is completely
diagnostic of shock. Several studies have shown that blood pressure and heart rate are poor predictors of
shock because of the body’s ability to compensate. Waiting for abnormal vital signs before initiating
treatment may increase morbidity and mortality. One study demonstrated that a systolic blood pressure of
less than 80 mm Hg in the emergency department was associated with a 50% mortality rate and that
nontrauma patients transported by ambulance with a systolic blood pressure below 100 mm Hg had a
26% in-hospital mortality rate. The need to determine and treat the underlying problem is of utmost
importance.

This article presents a systematic approach to the assessment and management of patients with
undifferentiated shock.

DETERMINING THE ETIOLOGY

Once shock is identified, the management plan will depend largely on the type of shock occurring. The box
below lists all the major types of shock and their common etiologies, including an “unclassified” category
listing causes that are often overlooked.
Therapeutic options range from intravenous fluids (critical in septic shock but detrimental in cardiogenic
shock) to epinephrine (critical in anaphylactic shock but detrimental in cardiac tamponade). Because one
treatment may help the patient and another may hurt him, it is imperative to understand the etiology and
pathophysiology of the hypoperfusion.

With undifferentiated shock, our approach is simple:

• Perform a thorough history and physical examination.

• Do focused diagnostic studies (ECG, chest films, pregnancy test, bedside ultrasonography, and blood
glucose test).
• Obtain additional tests, including lactate, D-dimer, and brain natriuretic peptide (BNP).
• Reconsider obstructive and unclassified shock.
• Treat with intravenous fluids (if appropriate), calcium, steroids, and antibiotics.

All the while, the physician should be considering an extensive differential diagnosis (especially obstructive
and unclassified causes of shock) and eliminating each possibility with the various history and physical
examination findings and test results.

OFTEN OVERLOOKED CAUSES

There is no substitute for a thorough history and physical examination. However, a targeted approach can
also yield very accurate results. You are more likely to find something if you know what you are looking
for. Maintaining a high index of suspicion for less common etiologies is crucial. The following causes of
shock, for example, are often overlooked:
New medication or overdose. Consider anaphylactic shock if the patient is on a new medication. These
patients can present with altered mental status and diffuse swelling without classic hives. Patients can also
accidentally or intentionally take an overdose of their own medications or those of family members. Empty
the patient’s pockets and speak to available friends and family. A history of depression is a red flag for
toxicologic causes of hypotension.

Dark, sticky/tarry stool. Patients don’t always realize that dark, sticky/tarry stool contains blood. They
will tell you immediately if they have rectal bleeding with bright red blood, but they may think dark stools
are a transient abnormal bowel movement or were caused by something they ate. Do a rectal
examination. The classic appearance and odor of melena is unmistakable.

Jugular vein distension (JVD). This is probably the single most important physical examination finding
in patients with unexplained hypotension. It leads to an array of life-threatening diagnoses very quickly
(see box below).

A hypotensive patient will not have distended jugular veins unless a serious obstructive or cardiogenic
problem is present. A patient with unilateral decreased breath sounds, shortness of breath, or a deviated
trachea has a tension pneumothorax and needs needle decompression immediately. A chest film is not
necessary to treat this diagnosis. Although the Beck triad of JVD, hypotension, and muffled heart sounds
suggests cardiac tamponade, we recommend a bedside ultrasound study to identify a pericardial effusion.
If this is present, consider pericardiocentesis in the emergency department or in the catheterization
laboratory in consultation with the cardiology service.

A regular ECG may reveal signs of right ventricular myocardial infarction (ST-segment
depression/elevation in the inferior/lateral leads and a tall R wave in lead V1). A right-sided ECG will
confirm a right-sided infarct, with more than 1 mm of ST elevation in lead V4R being the most sensitive
ECG sign.

For a pulmonary embolus to cause JVD, it is likely a large clot. If the patient is too unstable for computed
tomography (CT) angiography or a ventilation-perfusion scan, consider bedside echocardiography to
identify right atrial enlargement suggestive of pulmonary embolus or even empiric thrombolytic therapy in
the deteriorating patient.

Congestive heart failure (CHF) can usually be diagnosed clinically. Are there bilateral rales on the
respiratory exam? Is bilateral lower-extremity edema present? Congestive heart failure generally presents
with hypertension. A patient with signs of CHF and hypotension is in cardiogenic shock due to either a new
myocardial infarct that reduces the ejection fraction, acute failure of a cardiac valve, rupture of a papillary
muscle (a new murmur is likely and the patient may not have cardiomegaly), or end-stage CHF (patients
should have a history of CHF and cardiomegaly).

New murmur. A new murmur is a red flag for valvular disease—including endocarditis—or papillary
muscle rupture. Patients with CHF should be scheduled for valve repair or replacement surgery as soon as
possible. If the patient is febrile with a new murmur, strongly consider endocarditis as the cause of septic
shock.

Decreased lung sounds. Unequal breath sounds and hypotension can signal a tension pneumothorax.
Sometimes this occurs after the patient is placed on a ventilator; the positive pressure converts the small
pneumothorax (easily missed on chest films) to a tension pneumothorax. Although this diagnosis is rare, it
is critical to consider so that needle decompression can be performed in a timely manner.
Cullen sign. The Cullen sign is found in many abdominal causes of hypotension, including hemorrhagic
pancreatitis, leaking abdominal aortic aneurysm (AAA), or ruptured spleen or liver. Although patients with
this sign may not have the classic acute abdomen, it should prompt an immediate general surgery
consultation. However, a bedside ultrasound study demonstrating free fluid in the Morrison pouch or a
large aorta would be more definitive evidence for prompt emergent surgical intervention. Bedside
ultrasound studies in the emergency department have been shown to reliably diagnose AAA and hasten
trips to the operating room for definitive repair.

FOCUSED DIAGNOSTIC STUDIES

In a true emergency, such as undifferentiated hypotension, the physician should maximize point-of-care
testing by collecting all available data while the evaluation is being performed. All women of child-bearing
age should be tested for pregnancy. In this age of increased in vitro fertilization, ectopic pregnancies are
being seen more frequently; currently, the overall incidence ranges from 3.3% to 5.8% of all pregnancies.

Bedside blood glucose measurements will help facilitate the diagnosis of hypoglycemia or diabetic
ketoacidosis as an etiology of hypotension. Quick, low-cost, low-risk tests such as an ECG and chest films
should also be obtained as soon as possible.

Electrocardiogram. In cases of hypotension, an accurate ECG interpretation may be very revealing. The
box below lists ECG findings that may be present in patients with hypotension. Remember to obtain a
right-sided ECG to diagnose a right ventricular infarction.

Elevation in the ST segment in two contiguous leads or anterior ST-segment depression that suggests a
posterior infarct requires a cardiology consultation for cardiac catheterization. Patients who are
hypotensive may need inotropic drugs or emergency placement of an intra-aortic balloon pump. Although
vasopressors may be necessary to maintain perfusion, use them with caution because they will increase
myocardial oxygen consumption and potentially increase the infarct size. Hypotension with a right
ventricular infarct is common, especially after the administration of sublingual nitroglycerin. The treatment
is increasing the preload with intravenous fluids and, if necessary, mild inotropic support with dopamine.

Tachyarrhythmias and bradyarrhythmias are generally not difficult to diagnose on presentation because
vital signs are easily and immediately available. However, heart blocks can be very subtle, with P waves
hidden in the most inconspicuous places. Look closely for second-degree type II and third-degree heart
blocks in all bradycardic patients. Temporary transcutaneous pacing or more definitive intravenous pacing
before permanent pacemaker placement is the short-term treatment.

Electrical alternans and low voltage on the ECG suggests pericardial effusion or cardiac tamponade.
Hypotension in this scenario is treated temporarily with increased preload using intravenous fluids or,
more definitively, with pericardiocentesis.

Hyperkalemia typically has very classic ECG findings: peaked T waves, depressed P waves, and widened
QRS rhythms that finally progress to a sinusoidal wave pattern. However, in severe cases, the ECG may
look like an odd wide-complex rhythm (sinusoidal) or severe bradycardia without the classic findings. The
foremost concern with wide QRS rhythms (non-bundle branch pattern) that are not tachycardic is
hyperkalemia. However, antidepressant overdoses from tricyclic antidepressants and third-degree heart
blocks should also be considered when wide QRS rhythms occur.

Chest films. The box below lists the critical findings on chest films that may help the emergency
physician determine the etiology of the hypotension. A pulmonary infiltrate is generally considered
consistent with pneumonia; however, consider the possibility of pulmonary embolus as well. If the clinical
picture is consistent with pulmonary infection, the likely etiology of hypotension is septic shock. There are
approximately 750,000 cases of sepsis every year, and a significant number progress to severe sepsis and
septic shock with mortality in the 30% to 50% range. For this reason, emergency physicians must
aggressively treat patients with intravenous fluids and antibiotics and also start early, goal-directed
therapy, which is known to significantly reduce mortality.

A widened mediastinum is seen in up to 59% of patients with thoracic aortic dissection. Although most of
these patients present with hypertension, one study of more than 1000 aortic dissection patients revealed
that 29% had hypotension. The study found that these patients were more likely to have a type A
dissection (in the ascending aorta), aortic regurgitation requiring valve repair, and ST deviations. The
diagnosis of aortic dissection can be made with a CT scan of the chest or transesophageal
echocardiography. The treatment of type A dissections is surgical repair of the aortic root.

Pulmonary embolus is a difficult diagnosis (see July 2008 cover article). The chest film is abnormal in
more than 80% of patients. However, patients with pulmonary embolus can occasionally present with a
normal chest film, a pulmonary infiltrate or atelectasis, and, rarely, with the Hampton hump (pleural
wedge-based density) or Westermark sign (abrupt cutoff of a dilated proximal pulmonary artery). The
sensitivities of the Westermark sign and Hampton hump are 14% and 22%, respectively.

A hemothorax or large pleural effusion should prompt investigation of a possible traumatic event. Trauma
is often not considered in patients with altered mental status, especially the demented elderly, but it can
be the underlying problem. When the etiology of shock is unclear, start considering the unlikely
possibilities.

Congestive heart failure is often clear on chest films, which show increased pulmonary vasculature
markings, cephalization, cardiomegaly, Kerley B lines, and pleural effusion. When the patient is
hypotensive, remember to consider valve malfunction and a ruptured papillary muscle in addition to a
progressive worsening ejection fraction as the etiology. If the chest film is consistent with CHF but no
cardiomegaly is present, consider adult respiratory distress syndrome.

When the heart appears large on chest films, remember that the patient may have cardiomegaly or a
normal-sized heart surrounded by a pericardial effusion. For this reason, unless you know the patient has
cardiomegaly, you should describe the chest film as an enlarged cardiac silhouette and always consider
the possibility of a pericardial effusion. The distinction can be made easily with a bedside ultrasound study
of the heart to assess for pericardial fluid.

Bedside ultrasonography. The bedside ultrasonography study is a diagnostic tool that has become
increasingly available to emergency physicians. The portability and ease of use of the ultrasound machine
make it ideal for assessing unstable patients. When properly trained, emergency physicians can become
proficient in performing limited, goal-directed ultrasonography. The ability to identify signs of life-
threatening processes, such as pericardial effusion, free fluid in the abdomen, AAA, and ectopic and
intrauterine pregnancies, has made ultrasonography essential in the complete evaluation of the
undifferentiated shock patient.

Rose developed the Undifferentiated Hypotensive Patient (UHP) ultrasound protocol for rapid and
systematic evaluation of reversible causes of hypotension. The protocol contains three basic components:
abdominal free fluid evaluation, qualitative cardiac evaluation, and abdominal aorta evaluation. The UHP
protocol recommends a single view of the hepatorenal interface, a subxiphoid view of the heart, and a
sweeping transverse view of the aorta from the substernal position down to the bifurcation of the aorta.

A single hepatorenal view of the Morrison pouch to detect intraperitoneal fluid in nontrauma hypotensive
patients can be very helpful. If fluid is present, it raises the suspicion of ruptured ectopic pregnancy or
cyst, ruptured AAA, or occult trauma that was not initially suspected. Bedside right-upper-quadrant
ultrasound in cases of ruptured ectopic pregnancy has been shown to reduce time to diagnosis and
treatment. Additional views as performed in the FAST (focused assessment with sonography for trauma)
examination can also be performed to increase the sensitivity for detection of intraperitoneal fluid in the
abdomen. These views are not useful for identifying intra-abdominal organ injury. From our experience
with trauma, we know a patient can have intraperitoneal fluid and a negative bedside ultrasound. It is
important to remember that an ultrasound study cannot detect free fluid in the abdomen unless more
than 600 ml is present.

A subxiphoid view of the heart can quickly detect a pericardial effusion, which may suggest cardiac
tamponade (another treatable cause of life-threatening hypotension) in the right setting.

Detection of an AAA (aortic diameter greater than 3 cm on ultrasound) at the bedside of a hypotensive
patient can be lifesaving. It avoids delays due to CT scan imaging and the risks related to transporting an
unstable patient. There is evidence that emergency ultrasound decreases time to diagnosis of a ruptured
AAA; in addition, it facilitates vascular surgery consultation and definitive treatment in the operating
room.

Only one randomized controlled trial has studied the value of bedside ultrasound for nontraumatic
hypotensive patients in the emergency department. Jones studied early versus delayed goal-directed
ultrasonography to determine the etiology of nontraumatic, undifferentiated hypotension. The following
seven views were obtained: subcostal view of the heart, inferior vena cava, parasternal long cardiac,
apical four-chamber cardiac, hepatorenal recess, pelvis and retrovesical area, and abdominal aorta.
Although there was no difference in mortality between the early and delayed groups, the use of goal-
directed ultrasonography led to narrower differential diagnoses and more accurate physician impression of
the final diagnosis. With the aide of ultrasound, the early group selected the correct diagnosis in 80% of
cases, whereas the group that did not have the help of ultrasound for the initial 15 minutes of the
resuscitation selected the correct diagnosis in only 50% of cases.

Additional advanced uses of bedside ultrasonography include identifying right atrial collapse (a sign of
pericardial effusion progressing to cardiac tamponade), right atrial and ventricular dilatation (a sign of a
significant pulmonary embolus that may require thrombolysis), appearance of inferior vena cava or
internal jugular view to determine volume status, and estimation of left ventricular ejection fraction.

Additional laboratory tests. When the etiology of hypotension is unclear, it is worth obtaining three
extra blood tests: lactate, D-dimer, and BNP. An elevated lactate level correlates with a poor short-term
prognosis in critically ill patients seen in the emergency department. In one study, a single lactate level
greater then 4 mmol/L carried a 28% mortality for patients presenting with an infection. Elevated lactate
is not specific for infection but is clearly a marker for hypoperfusion. A persistently elevated lactate level
in the setting of trauma has also been shown to predict morbidity and mortality. Aggressive management
should include monitoring lactate clearance. Ideally, lactate levels should decrease by 50% after the onset
of resuscitation. When using lactate levels as endpoints, the goal level should be less than 2 mmol/L. In
general, an elevated lactate in cases of undifferentiated shock often signals ongoing sepsis or mesenteric
ischemia.

Another important measurement is a D-dimer value. D-dimer is particularly useful as an adjunct in

attempting to exclude aortic dissection or pulmonary embolism. A few studies have demonstrated that a
positive D-dimer is present in virtually all aortic dissections (highly sensitive statistically), and that the D-
dimer concentration correlates with the prognosis. With respect to pulmonary emboli, although the D-
dimer is a nonspecific test and the sensitivity is only high among low-risk patients, a positive D-dimer
should prompt physicians to at least consider a pulmonary embolus. In cases of undifferentiated shock, a
negative test can help narrow the differential diagnosis by excluding aortic dissection and pulmonary
embolus, thereby allowing the physician to refocus efforts on other diagnoses. One fact is clear: If a high
suspicion exists for either aortic dissection or pulmonary embolus, do not use the D-dimer. Get a
confirmatory test.

Brain natriuretic peptide measurement is a useful adjunct when attempting to exclude pulmonary edema.
The negative predictive value of a BNP level less than 50 pg/ml is 96%. In clinical practice, physicians
essentially exclude CHF as a diagnosis if the BNP is less than 100 pg/ml. However, an elevated BNP level
is not as useful because many conditions, such as renal failure and cirrhosis, can increase BNP levels. A
BNP value greater than 480 pg/ml has a sensitivity of 68% and a specificity of 88% for CHF.

TREATMENT DECISIONS

Regardless of the etiology of the patient’s hypotension, the emergency physician needs to perform a quick
primary survey that includes assessment of the airway, work of breathing, and hemodynamic status. After
this, the patient should be undressed and a thorough secondary survey should be performed, starting with
the head and neck and moving down to the lower extremities. Although the patient may exhibit a set of
physical signs consistent with shock, such as tachypnea, tachycardia, and hypotension, these are usually
late findings. For every hypotensive patient, physicians should assess airway, breathing, and circulation
and then establish intravenous access with two large-bore catheters or a central venous line.

If the type of shock is easily identified, treat it accordingly. For example, anaphylactic shock requires
epinephrine, intravenous fluids, antihistamines, steroids, nebulized beta2 agonists, and possibly
intubation. If the etiology is unclear, follow steps two through five in the box above. If the underlying
cause is still not immediately clear and all diagnostic studies have been done, reconsider obstructive
causes. Look specifically for a tension pneumothorax on the chest films. Could it have developed after the
post-intubation chest film? Have D-dimer and BNP results been reported by the laboratory? Review the
unclassified category of shock: toxicologic etiologies (overdose of tricyclic antidepressants, iron, or
antihypertensives), metabolic etiologies (hyperkalemia), and endocrine etiologies (addisonian crisis,
thyroid storm, and myxedema coma).

When the diagnosis remains elusive, empiric management is often necessary. A crystalloid isotonic
solution is the fluid of choice because most patients have a volume deficit. With the exception of patients
in CHF or cardiogenic shock, a 20 ml/kg bolus of normal saline solution is an appropriate start.
Reassessment of the patient is necessary after each fluid bolus, because some patients can require up to
six liters to replete their intravascular volume. Vasopressors should be initiated if the patient is
hypotensive despite fluids; however, they are not very effective in intravascularly depleted patients. The
goal is a mean arterial pressure greater than 60 mm Hg for adequate perfusion. Maximize oxygen delivery
by maintaining a high PO2, intubate if necessary, and give packed red blood cells for hemoglobin levels of
less than 10 mg/dl.
Finally, remember that the most common cause of undifferentiated shock is sepsis. If you assume sepsis
is present in your nontraumatic, undifferentiated hypotensive patient, you’ll be correct 75% of the time.
After blood and urine cultures have been obtained, administer broad-spectrum antibiotics.

Consider empiric treatment with calcium because hyperkalemia and antihypertensive medication
overdoses (beta blockers or calcium channel blockers) can cause hypotension without fitting any of the
classic shock presentations. Hyperkalemia typically causes peaked T waves and widened QRS complexes.
However, it can also cause bradycardia and junctional rhythms with hypotension. Calcium works almost
immediately to protect the myocardium from the cardiotoxic effects of hyperkalemia. The only patients
that should not be given calcium empirically are those on digoxin.

Also consider empiric treatment with steroids, specifically hydrocortisone. Although controversial, multiple
studies have used low-dose hydrocortisone for septic shock with improved outcomes and decreased need
for vasopressors.

SYSTEMATIC APPROACH

Patients in shock need immediate attention, and emergency department physicians are in the unique
position of seeing shock in its very early stages. In cases of undifferentiated shock, when the etiology is
unclear, a systematic approach can lead to an early diagnosis and prompt treatment that are critical to the
patient’s recovery.