Shock

Introduction
Shock is a clinically diagnosed condition that results from many varied etiologies. It accounts for
more morbidity and mortality in children worldwide than any other diagnosis; dehydration and
hypovolemic shock alone result in 6-20 million deaths annually in infants and children worldwide.
Shock can damage any and all tissues and organ systems in the body. Delay in recognizing and
quickly treating a state of shock results in a progression from compensated reversible shock to
widespread multiple system organ failure to death. Morbidity may be widespread and can include
renal failure, brain damage, gut ischemia, hepatic failure, metabolic derangements, diffuse
intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), cardiac failure, and
death.
Pediatric practitioners treating acutely ill children from neonates to young adults are faced with
different degrees and causes of shock on a regular basis, making shock in infants and children
one of the most common, and often life-threatening, conditions encountered.
This article reviews the common physiologic foundations of shock that underpin all patients with
this condition. The different pathophysiologic classifications of shock are defined along with their
etiologies. The defining clinical findings of shock are described, and current diagnostic and
therapeutic strategies are presented to help guide the most effective and appropriate treatment
for resuscitating the child in shock.
For excellent patient education resources, visit eMedicine's Shock Center. Also, see eMedicine's
patient education article Shock.

Physiology
Shock is defined physiologically as inadequate delivery of substrates and oxygen to meet the
metabolic needs of the tissues. As cells are starved of oxygen and substrate, they can no longer
sustain efficient aerobic oxygen production. Aerobic metabolism generates 36 ATP molecules per
glucose molecule. As oxygen delivery (DO 2 ) is impaired, the cell must switch to the much less
efficient anaerobic metabolic pathway, which generates only 2 ATP molecules per molecule of
glucose, with resulting production and accumulation of lactic acid.
Eventually, cellular metabolism is no longer able to generate enough energy to power the
components of cellular homeostasis, leading to the disruption of cell membrane ionic pumps,
accumulation of intracellular sodium with an efflux of potassium, and accumulation of cytosolic
calcium. The cell swells, the cell membrane breaks down, and cell death ensues. Widespread
cellular death results in multiple system organ failure and, if irreversible, death.
This metabolic disruption may occur from either an absolute deficiency of DO 2 , defined as
hypoxic shock, or a combination of hypoxia and deficient substrate delivery, predominantly of
glucose, defined as ischemic shock. Most often they develop in combination, which results
clinically in hypoxic-ischemic injury. Because DO 2 is critical in either hypoxic or ischemic shock,
considering DO 2 when defining shock physiologically is useful.

DO2 is defined as the amount of oxygen delivered to the tissues of the body per minute.
DO2 depends on the amount of blood pumped per minute, or cardiac output (CO), and the arterial
oxygen content of that blood (CaO2). Thus, DO 2 may be defined by the following equation:
DO2 (mL O2/min) = CaO2 (mL O2/L blood) X CO (L/min)
The CaO2 depends on how much oxygen-carrying capacity is available in terms of hemoglobin
(Hb) content and depends on how much oxygen the patient's Hb contains, defined as the arterial
oxygen saturation (SaO2). A small, but clinically irrelevant, amount of oxygen is directly dissolved
in the blood that is not bound to Hb. Therefore, CaO2 may be defined by the following formula:
CaO2 (mL/100 mL) = Hb (g/100 mL) X SaO2 X 1.34 mL O2/g + (0.003 X PaO 2 )
A state of clinical shock may occur when CaO2 is impaired either by hypoxia, which decreases
SaO2, or by anemia, which reduces the amount of Hb and, hence, reduces the body's total
oxygen-carrying capacity.
CO depends on the amount of blood pumped with each heartbeat, known as stroke volume (SV),
and the heart rate (HR). SV depends on the ventricular end-diastolic filling volume (commonly
referred to as ventricular preload), the state of myocardial contractility, and the afterload on the
heart. Each of these variables, which affect CO, can be impaired in clinical shock states. Thus,
the following relationship is observed:
CO = HR (beats/min) X SV (mL/beat)
SV depends on (1) preload, (2) afterload, and (3) contractility.
The recognition and treatment of pediatric shock depends on an understanding of these
physiologic principles and definitions. Once understood, the different clinical presentations and
causes of shock, as well as their most appropriate treatment strategies, are easily appreciated.

Etiology
Several etiologic classifications of shock are recognized. In each of these classifications, one or
more of the physiologic principles defined above are disturbed. The major categories are as
follows:

Hypovolemic
Distributive
Cardiogenic
Septic
Obstructive
Miscellaneous

Hypovolemic Shock
Hypovolemic shock results from an absolute deficiency of intravascular blood volume. It is a
leading cause of pediatric mortality in the United States and worldwide, although the specific
causative agents may be different around the world. Gastroenteritis results in 6-20 million deaths
in infants and children annually worldwide. Children with gastroenteritis may lose 10-20% of their

circulating volume within 1-2 hours.1 Rehydration is often impeded by concurrent vomiting, and
deterioration may be rapid. Common infectious etiologies include bacterial causes of
gastroenteritis, such as Salmonella, Shigella, and Campylobacter species and Escherichia
coli, and viral causes, such as rotaviruses, adenoviruses, norovirus, and enteroviruses.
Worldwide, infectious amebiasis and cholera are also important causes.
Physiologically, rapid loss of intravascular volume reduces ventricular preload, resulting in
decreased stroke volume and CO and, thus, decreased DO 2 . In addition, a hemorrhagic
component or dysentery may reduce Hb content, resulting in decreased CaO2.
In the United States, the leading cause of death in children older than 1 year is trauma. Trauma
kills more children than all other causes of death combined. 2 A major component of traumatic
death is hemorrhage. Hemorrhagic shock reduces both CaO 2 and preload, resulting in decreased
DO2 to the tissues.
Other causes of hypovolemia include capillary leak and tissue third spacing, which results in
leakage of fluid out of the intravascular space into the interstitial tissues. Etiologies include burns,
sepsis, and other systemic inflammatory diseases. Patients with such etiologies may appear
"puffy" and total-body fluid overloaded; however, they are actually significantly intravascularly
depleted, with inadequate preload, and are in significant shock. By understanding the physiologic
disturbance affecting intravascular volume and preload, such patients need even more fluid
administration, despite their overall edematous appearance, in order to improve DO 2 and prevent
or correct a state of shock.
Therapy is discussed more in detail below (see Treatment of Shock and Pharmacologic Therapy).
Causes of hypovolemic shock

Intravascular volume loss

o Gastroenteritis
o Burns
o Diabetes insipidus
o Heat stroke
Hemorrhage
o Trauma
o Surgery
o GI bleeding
Interstitial loss
o Burns
o Sepsis
o Nephrotic syndrome
o Intestinal obstruction
o Ascites

Distributive Shock
In certain clinical states, normal peripheral vascular tone becomes inappropriately relaxed.
Common causes include anaphylaxis, neurologic injury, sepsis, and drug-related causes.
Vasodilation results in increased venous capacitance, causing a relative hypovolemia even if the

patient has not actually lost any net fluid. However, the common physiologic disturbance that
affects DO2 in all forms of distributive shock is a decrease in preload that results from inadequate
effective intravascular volume as a result of massive vasodilation.
Reference range blood pressure in children
In neonates, the 10th to 90th percentile ranges are used. 3 In children, the 50th to 90th percentile
ranges are indicated.4 The following is modified from Hazinski's 1992 discussion in Nursing Care
of the Critically Ill Child.5

Birth (12 h, <1000 g) - Systolic pressure, 39-59 mm Hg; diastolic pressure, 16-36 mm Hg
Birth (12 h, 3 kg) - Systolic pressure, 50-70 mm Hg; diastolic pressure, 25-45 mm Hg
Neonate (9 h) - Systolic pressure, 60-90 mm Hg; diastolic pressure, 20-60 mm Hg
Infant (6 mo) - Systolic pressure, 87-105 mm Hg; diastolic pressure, 53-66 mm Hg
Toddler (2 y) - Systolic pressure, 95-105 mm Hg; diastolic pressure, 53-66 mm Hg
School aged child (7 y) - Systolic pressure, 97-112 mm Hg; diastolic pressure, 57-71 mm
Hg
Adolescent (15 y) - Systolic pressure, 112-128 mm Hg; diastolic pressure, 66-80 mm Hg

Common causes of distributive shock

Anaphylaxis
o Medications (eg, antibiotics, vaccines, other drugs)
o Blood products
o Envenomation
o Foods
o Latex
Neurologic causes
o Head injury
o Spinal shock
Drugs
Sepsis

Anaphylaxis results in mast cell degranulation with resultant histamine release and vasodilation.
Neurologic injury can interrupt sympathetic input to vasomotor neurons, resulting in vasodilation.
Spinal shock may result from cervical cord injuries above T-1, which interrupt the sympathetic
chain, allowing for unopposed parasympathetic stimulation. Such patients may present with the
clinical picture of hemodynamic instability and hypotension accompanied by bradycardia because
they may lose sympathetic vascular tone (resulting in vasodilation) while unable to mount an
appropriate sympathetic-mediated tachycardic response. Drugs may also cause vasodilation.
Finally, sepsis results in the release of many vasoactive mediators that may cause profound
vasodilation resulting in an aspect of distributive shock. Sepsis is discussed more in detail below
(see Sepsis).

Cardiogenic Shock
Impairment of cardiac contractility defines cardiogenic shock. A decreased contractile state
results in decreased SV and CO and, therefore, in decreased DO 2. Causes include congestive

heart failure, ischemic heart disease (common in adults, rare in children), cardiomyopathy,
cardiac tamponade, sepsis, and drugs.

Obstructive Shock
Certain physical causes of shock must be considered in pediatric patients, especially in neonates
within the first few weeks of life, who may be born with obstructive congenital heart disease.
Examples include coarctation of the aorta, interrupted aortic arch, and severe aortic valvular
stenosis.
In addition, acquired heart disease from diseases such as rheumatic fever or subacute bacterial
endocarditis, as well as hypertrophic cardiomyopathy, can lead to direct obstruction of
CO. Although ultimate treatment of such obstructive causes of CO that result in clinical shock
clearly depends on surgical correction or palliation of the physical obstruction, temporizing
measures in neonates may require maintaining patency of the ductus arteriosus in order to
bypass the obstruction until more definitive surgery can be performed. The discussion of surgical
correction of obstructive congenital heart lesions is beyond the scope of this article.

Sepsis
Sepsis may be defined as a systemic inflammatory response triggered by the presence of
infectious agents or their toxins. The presence of infectious agents such as endotoxin or grampositive bacterial cell wall components together with the resultant release of inflammatory
mediators and cytokines such as tumor necrosis factor (TNF)alpha; interleukins (IL) such as IL1, IL-2, and IL-6; products of the coagulation cascade; complement activation; and bradykinins
may lead to disturbances of virtually every variable in the DO 2 equation.
Sepsis can induce activity of the enzyme nitric oxide synthase, resulting in production of the
potent direct vasodilator nitric oxide, leading to inappropriate and often massive regional and
systemic vasodilation. This distributive effect reduces effective preload and impairs CO and DO 2.
Sepsis may disrupt capillary integrity, resulting in intravascular fluid leak into tissue third spaces,
causing hypovolemia.
Many different circulating toxins and inflammatory mediators can depress myocardial function and
reduce cardiac contractility, adding a cardiogenic component to impaired CO. Over-activation of
the clotting cascade can result in DIC, which can directly plug and block critical tissue capillary
beds, resulting in microvascular obstructive shock, as well as hemorrhage further depleting
intravascular volume and decreasing critical oxygen carrying capacity by reducing Hb.
Finally, multiple system organ failure, including respiratory failure, may result in hypoxia,
complicating efforts at optimizing systemic DO2. Septic shock may disturb many, if not all, of the
physiologic variables that determine systemic DO2.

Diagnosis
Shock is a clinical physiologic diagnosis. The diagnosis of shock involves the clinical recognition
that the body's tissues and cells are not receiving adequate delivery of oxygen and metabolic
substrate. Symptoms and clinical findings are an extension of organs not getting what they need
to function. A lack of kidney perfusion results in decreased urine output. If the brain's needs are

not met, mental status changes occur. The lack of delivery of metabolic needs results in changes
to gut and liver function.
The diagnosis of shock in infants and children can be difficult. Frank hypotensive shock with weak
or absent pulses; cold, blue extremities; and a gray or mottled appearance are generally easily
recognized. However, compensated shock, in which the central blood pressure is preserved at
the expense of peripheral end-organ perfusion, is often much more difficult to appreciate. Infants
and children have a remarkable ability to preserve their central blood pressure, attempting to
protect their heart and brain in many forms of shock while critically reducing perfusion to the
extremities, gut, kidneys, and other end organs.

Clinical History
The clinical history of patients who present in shock varies depending on the etiology of the
individual patient's condition. A child with vomiting, profuse diarrhea, or both is at risk for
hypovolemic shock. A child who has experienced blunt or penetrating trauma is at risk for
bleeding that may result in hemorrhagic shock. Fever may herald an infection that could result in
septic shock. This concern is heightened in an immunocompromised patient who presents with
fever, such as a child receiving chemotherapy or a neonate. A neonate who presents within the
first weeks of life with a large liver or cardiac murmur may have a congenital obstructive ductaldependent heart lesion that presents in shock as the ductus arteriosus closes.
Other general nonspecific symptoms may manifest in the child in shock. Lethargy, weakness, a
sense of malaise, decreased urine output, fussiness, and poor feeding are all nonspecific
symptoms that may accompany shock. However, the approach to any patient who presents
acutely ill, regardless of the differential diagnosis, must begin with an initial evaluation of the
patient's ABCs. If the patient's circulation is compromised, that patient is said to be in shock, and
therapy must be immediately initiated while further evaluation is performed.

Clinical Evaluation
Compensated versus decompensated shock
To begin to categorize and prioritize the management of a child in shock, first determine the
central blood pressure. Blood pressure measurements determine the central driving pressure
responsible for perfusing the most critical organs, namely the brain and the heart. Minimum blood
pressure requirements can be determined by establishing the fifth percentile for normal systolic
blood pressure in a healthy, well-perfused child. The American Heart Association, in the course on
pediatric advanced life support (PALS), defines infants with fifthpercentile systolic blood
pressure as follows:6

Newborn - 60 mm Hg
Infant (1 mo to 1 y) - 70 mm Hg
Child (>1 y) - 70 + 2 X age (in y)

Thus, children with poor perfusion and blood pressure below the parameters listed above may be
said to have decompensated shock. Such children, if not quickly and aggressively resuscitated,
experience additional organ damage and may progress to irreversible shock and death. Children
with an adequate systolic blood pressure may still be in shock but may be in a state of

compensated shock. Thus, although central perfusion to the brain and heart are still considered
adequate, other vital organ systems may be hypoperfused and may sustain damage that, if not
reversed, progresses to decompensated shock. Therefore, in order to determine if a patient is in
shock, many different indicators of tissue organ perfusion must be examined.
Heart rate
Because CO depends on both SV and HR, the body typically tries to maintain CO when SV
decreases by increasing the HR. Unless the HR cannot increase for some reason (eg,
pharmacologic blockade; neurologic damage, such as cervical cord injury; operative insults that
may be sustained during open-heart surgery), a patient in the early stages of shock is typically
tachycardic. However, such a sign is certainly not very sensitive in children because children may
be tachycardic from a wide variety of stimuli, including fever, pain, and agitation. Nevertheless,
with the exceptions mentioned above, tachycardia is generally a fairly early and specific finding in
both compensated and decompensated shock.
Skin perfusion
The skin may be considered a nonvital end organ. As such, a patient who has the ability to
compensate for decreased DO2 by diverting blood away from end organs that are not immediately
vital (ie, other than the heart and brain) manifests signs of decreased skin perfusion. Distal pulses
are diminished, the skin appears cool, and capillary refill is prolonged (ie, >5 s). Capillary refill is
best determined by pressing on a distal extremity, preferably a finger or toe, for 5 seconds and
releasing pressure. The time taken to refill is noted. At normal room temperature, the distal
capillary bed normally refills within 2-3 seconds. Refill time longer than 5 seconds is considered
prolonged.7
However, patients with inappropriate vasodilation from a distributive mechanism of shock may be
unable to vasoconstrict their end-organ and skin microvasculature. Therefore, in the early phases
of distributive shock, such as in anaphylaxis or certain forms of sepsis, the skin may appear very
briskly perfused with warm extremities, bounding pulses, and brisk capillary refill (<1-2 s). When
distributive mechanisms of shock are possible, the skin perfusion may not be reliably reassuring.
Hypotension, tachycardia, or other evidence of metabolic disturbances, such as the presence of a
persistent lactic acidosis, may reinforce the recognition that tissue DO 2 is impaired.
Other organ system function
Renal perfusion may be reflected by absolute urine output. Typically, in the absence of renal
damage, a well-perfused kidney can produce 1-2 mL urine/kg/h or more. However, renal damage
may result from early hypoxic-ischemic injury, resulting in renal tubular damage due to acute
tubular necrosis (ATN) that renders urine output unreliable as an indicator of adequate
intravascular volume and perfusion.
Mental status may reflect central perfusion to the brain. Altered mental status may coincide with
profound central shock. Normal mental status may be preserved in a patient in shock if central
blood pressure is adequate despite peripheral organ compromise (compensated shock).
Cardiac versus noncardiogenic shock

From a treatment standpoint, the most critical determination to make may be whether the cause
of shock is the result of direct cardiac failure or of some other etiology. Cardiogenic shock outside
the neonatal period or known congenital heart disease is relatively rare in the general pediatric
population. However, patients with cardiogenic shock make up a significant proportion of patients
in shock in tertiary care pediatric intensive care units because many patients with intrinsic
congenital heart disease are cared for in many of these institutions.
When considering cardiogenic shock in children, remember that children are not just small adults.
Anatomically, infants and small children have larger heads, shorter and fatter necks, and
relatively little abdominal fat compared with adults. As a result, checking infants and children for
hepatomegaly is more reliable than measuring jugular venous distention, which is often difficult to
appreciate.
Findings in cardiogenic shock tachycardia include the following:
Tachycardia
Hepatomegaly
Cardiac gallop
Cardiac murmurs
Precordial heave
Cardiomegaly on chest radiography
Cardiac hypertrophy on cardiac echocardiography
Jugular venous distention
ECG abnormalities

Objective Data
Although the overall clinical appearance, including assessment of skin color, temperature, pulses,
capillary refill, HR, blood pressure, urine output, and mental status, is critically important in
determining the presence or absence of shock, certain objective signs may help solidify or better
define the diagnosis. These include the patient's acid-base status, arterial oxygen tension and
mixed venous oxygen saturation, central venous pressure (CVP) and/or pulmonary capillary
wedge pressure (PCWP), and CO or cardiac index (CI).
Acid-base status
A patient in shock produces lactic acid that results in metabolic acidosis, which is typically
detected by a decrease in serum bicarbonate. Diarrhea also leads to direct bicarbonate loss,
which may exacerbate metabolic acidosis in a patient with shock due to dehydration from
diarrhea. Measurement of serum lactate levels may help distinguish bicarbonate loss from lactic
acidosis due to shock.
Mixed venous oxygen saturation
A blood sample from the right atrium through a central venous catheter or blood from a pulmonary
oxygen catheter (Swan-Ganz catheter) sampled from the port placed in the right atrium is mixed
venous blood returning to the heart. Mixed venous blood gas can be determined with the venous
Hb oxygen saturation directly measured by co-oximetry. By comparing the mixed venous oxygen
saturation (SvO2) with the SaO2, a determination of the arteriovenous oxygen saturation
difference can be noted. In a patient with a relatively normal SaO 2 (90-100%), the normal SvO2 is

70-80%. The tissues typically extract 28-33% of oxygen delivered to them. If the oxygen
extraction difference is greater than 33%, perfusion to the tissue capillary beds may be
inadequate, reflecting a state of shock.
Alternatively, if the oxygen extraction difference is less than 25%, oxygenated blood may be
shunting past tissue capillary beds as a result of inappropriate distribution of blood flow (ie,
distributive shock with arteriovenous shunts resulting from vasodilation). 8 Sepsis can also inhibit
the metabolic machinery of a cell, decreasing oxygen extraction and leading to an increase in
venous saturation.
Near-infrared spectroscopy
A new technology currently under investigation in select pediatric intensive care units is nearinfrared spectroscopy (NIRS).9, 10 A probe placed over a patient's skin, such as the forehead over
the brain, the flank over the kidneys, or the abdomen, sends an infrared signal through the skin
and reports pooled-tissue oxygen saturation. Because most of the blood in any given region is
predominantly venous, the oxygen saturation is close to that of the tissue venous oxygen
saturation in that region.
Arterial blood makes a certain contribution to the value reported by the NIRS unit; thus, the value
reported is slightly higher than that of venous oxygen saturation. However, the reported values
have been shown to correlate with venous oxygen saturations, allowing for a noninvasive
measurement and an observation of the trend of increased or decreased tissue oxygen saturation
to be followed in critical tissue beds such as the brain, kidneys, or mesenteric region. Such
information may help identify adequate or inadequate DO 2 analogous in determining a venous
oxygen saturation described above and may help guide evaluation and response to therapy.
Central venous pressure and pulmonary capillary wedge pressure
A catheter in a central vein wedged in a pulmonary vein may transduce the pressure generated
by the blood in that vessel. Low CVP or PCWP may reflect inadequate intravascular volume.
Care must be taken in entirely relying on such measurements. The cardiac filling pressure
measured by these catheters reflects ventricular function and compliance, not necessarily
intravascular volume alone. Volume expansion by as much as 30% has been shown not to
change measurements of right atrial pressure and the CVP.11 Alternatively, changes in ventricular
afterload or compliance lead to changes in PCWP or CVP without altering preload. Nevertheless,
such values, taken in context together with the clinical examination findings, may help determine
clinical status.
A normal CVP in a normal compliant heart is typically 1-3 cm H 2 O. Pressures much higher than
10 cm H2 O may reflect volume overload or poor right-sided heart compliance or function. The
same may be said for the relationship between PCWP and left atrial compliance. Volume
administration is generally thought to be maximal at PCWP measurements of 12-18 cm H 2 O in
patients with adequate left-sided heart function.
Cardiac index
A pulmonary artery catheter may be useful in determining a measurement of CO. The CO divided
by body surface area (BSA) yields the CI. Normal CI is 3.5-5.5 L/min/m 2K.8 Monitoring changes in

CI together with changes in intravascular volume administration or cardiotropic infusions may

help guide and optimize administration of these therapies.

Treatment of Shock
Initial Treatment
Regardless of the cause of shock, the ABCs must be immediately evaluated and stabilized. Do
not delay this initial stabilization for further workup and imaging studies. The patient's airway must
be patent, and the patient must be adequately oxygenated and ventilated. Initially, administer
100% supplemental oxygen at a high flow rate. If the patient is in respiratory distress, consider
intubating and providing mechanical ventilation. Stabilizing the airway and providing mechanical
ventilation may relieve the patient's metabolic work of breathing and may facilitate elimination of
carbon dioxide, helping to compensate the coexistent metabolic acidosis. Place the patient on
appropriate noninvasive monitors such as a pulse oximeter and cardiorespiratory monitor, and
obtain a simple bedside glucose measurement.
Once the airway has been stabilized, if necessary, and adequate ventilation and administration of
oxygen have been ensured, immediately place attention on improving circulation and systemic
DO2. Circulatory improvement is achieved via volume expansion and, if necessary,
pharmacologic therapy with vasopressors and cardiac inotropic agents, as indicated in
Pharmacologic Therapy.
If sepsis is a concern, initial coverage with empiric antibiotics is essential in order to eliminate the
precipitating cause of shock. Such empiric coverage may vary depending on the age of the
patient and previous antibiotic exposure. Neonates are often started on a combination of
ampicillin and gentamicin. Older infants and children may be covered with a third-generation
cephalosporin, possibly along with expanded gram-positive organism coverage with vancomycin
initially. Management of significant septic shock should be multidisciplinary and should involve the
resources of infectious disease specialists when available.

Additional Workup
Although stabilization of the airway and breathing and an aggressive response to improving the
circulation of any patient who presents clinically in shock takes precedence over any other
workup that might delay resuscitation, additional studies may ultimately help identify an etiology
and may help guide ultimate therapy of the patient in shock.
CBC count
Include a CBC count with differential in blood work. Pay particular attention to the Hb content,
which determines the blood's oxygen-carrying capacity. Consider transfusing a patient
with anemia who presents in severe shock as soon as possible. A significantly elevated or
depressed white cell count, along with a white cell differential suggestive of infection, could
support the diagnosis of septic shock. Similarly, thrombocytopenia may herald a bleeding disorder
that could result in internal hemorrhage or diffuse intravascular coagulation that might accompany
septic shock.
Complete metabolic panel

A complete metabolic panel (CMP) may contain a wealth of information about the patient in
shock. Hypernatremia suggests intravascular volume contraction consistent with hypovolemic
shock. A decreased serum carbon dioxide suggests a metabolic acidosis that may reflect a
significant lactic acidosis from anaerobic metabolism associated with shock. Hypovolemia may
result in an elevated BUN and creatine levels. Other abnormalities may reflect hypoxic-ischemic
damage to other organ systems in the body, such as the liver, which may result in elevated liver
function enzymes such as aspartate transaminase (AST) and alanine transaminase (ALT).
Chest radiography
Again, never delay resuscitation of the patient in shock in order to perform chest radiography or
other radiography. However, evaluation of the cardiac silhouette on a chest radiograph may help
delineate cardiogenic shock (see Media file 1) from hypovolemic shock, in which the heart size
appears small. Furthermore, respiratory distress in a patient in shock may result from ARDS that
may develop in any patient in shock or from pneumonia and sepsis.
Blood gas
An ABG test helps to determine the arterial oxygen tension/pressure (PaO 2) of the blood,
assisting in titration of supplemental oxygen delivery to the patient in shock. In addition, ABG
findings help to determine the patient's acid-base status, which reflects the degree of systemic
shock and the patient's response to therapy.
Volume expansion
The major physiologic abnormality in most forms of pediatric shock is either an absolute or a
relative intravascular hypovolemia. Dehydration, hemorrhage, sepsis, and other distributive
etiologies all cause intravascular hypovolemia with a reduction in cardiac ventricular filling volume
(preload). Studies in children have confirmed that children with hypovolemic shock who receive
appropriate aggressive fluid resuscitation within the first hour of resuscitation have the most
optimal chance of survival and recovery. Unlike adults, children do not have an apparent increase
in fluid-related complications such as pulmonary edema. Therefore, the therapy of choice is rapid
and aggressive fluid resuscitation.
If possible, place 2 large-bore free-flowing intravenous (IV) catheters. If vascular access is not
easily and readily achieved, then an intraosseous (IO) needle may be placed into the bone
marrow for rapid fluid administration. Such an IO line can be considered as good as an IV line for
the purpose of any fluid or medication administration necessary for the acute resuscitation of a
compromised infant or child in shock.
Administer 20 mL/kg of an isotonic crystalloid infusion, such as 0.9% isotonic sodium chloride or
lactated Ringer solution, over 5 minutes or less. Immediately reevaluate and administer additional
20 mL/kg infusions of isotonic crystalloid or colloid as indicated by further evaluation of signs of
perfusion. If the volume infusion is administered through an IO line, the resistance may be higher
than in an IV line, and the volume may need to be pushed manually with a syringe. So long as the
volume is infusing without evidence of local swelling at the IO insertion site or in the tissue
posterior to the IO, the fluid is passing into the marrow cavity and hence into the intravascular
space.

As soon as the initial 20-mL/kg volume of fluid has been infused, reevaluate the patient. If the
patient retains the clinical appearance of shock, immediately infuse another 20 mL/kg and repeat
the cycle. If more than two to three 20-mL/kg volumes of crystalloid have been infused into a
patient at risk for hemorrhage (eg, from trauma), administer blood or packed RBCs (PRBCs). A
child with severe hypovolemia or sepsis may require more than 60 mL/kg of volume in the first
hour of resuscitation, often within the first 15 minutes.
In one study of survival in children with septic shock, children who received on average 65 mL/kg
of volume in the first hour had a statistically increased chance of survival compared with other
groups who received less than 40 mL/kg in the first hour.12 Simply put, children who receive
appropriate yet aggressive fluid resuscitation early have the best chance of surviving severe
septic shock or shock and dehydration.
The only exception to repetitive volume resuscitation in a child with shock is the child who
presents with cardiogenic shock. Even so, such a child may be mildly dehydrated and could
benefit from an initial 20 mL/kg of isotonic crystalloid volume expansion. During the infusion of
such a volume, the child can be evaluated for the possibility of cardiogenic shock (see Findings in
cardiogenic shock tachycardia). Because myocardial failure is the root cause of such a patient's
poor CO, cardiotropic medications would be indicated in a patient with cardiogenic shock.

Pharmacologic Therapy
Inotropic agents increase myocardial contractility and have variable effects on peripheral vascular
resistance. Some inotropic agents may be vasoconstrictors (eg, epinephrine, norepinephrine),
whereas others are vasodilators (eg, dobutamine, milrinone). Which inotropic agents are
indicated and are effective in patients with any given etiology of shock depends on the clinical
volume and contractile state of the patient's cardiovascular system. Indications for the use of such
cardiotropic medications include cardiogenic shock that requires pharmacologic improvement of
contractile function or decompensated shock refractory to volume expansion alone.
However, the use of vasoconstrictors and inotropic agents may have potentially adverse
consequences. Inotropic agents increase myocardial oxygen demand, which may be detrimental
in a marginally perfused heart, resulting in increased myocardial ischemia. Vasoconstrictors may
further microvascular ischemia, which worsens perfusion to peripheral end-organ tissue capillary
beds such as the renal or splanchnic vasculature. Nevertheless, if the patient has refractory
central hypotension compromising perfusion to the brain and the heart muscle, these agents must
be used, or irreversible shock and death may ensue. Sometimes, the risk of compromising endorgan perfusion must be assumed in order to restore perfusion to the most critical organs (ie,
brain, heart) first, and the consequences of renal, hepatic, and skin ischemia must be treated
later.
Dopamine
Dopamine (Intropin) is often used either alone or in combination with other inotropic agents. It is
recommended as the first inotrope of choice for fluid-refractory septic shock (clinical signs of
shock after a total of 60 mL/kg of crystalloid or colloid administered over the first 15 min) by the
American College of Critical Care Medicine Task Force.13Dopamine is generally useful for its
mixed and vasodilatory effect on end-organ perfusion such as renal and splanchnic vasculature

at a low dose (ie, 2-5 mcg/kg/min IV). At an intermediate dose (ie, 5-10 mcg/kg/min IV), the
beta1-agonist effect assists by improving myocardial contractility, CO, and enhancing conduction
(ie, increasing SA rate) in the heart. At a higher dose (ie, 10-20 mcg/kg/min IV or more), the
alpha-agonist effect increases and may increase peripheral vasoconstriction and central blood
pressure.
Epinephrine
Epinephrine (Adrenalin) is recommended for fluid refractory dopamine resistant nonvasodilatory
shock. Epinephrine stimulates both alpha- and beta-receptors so that both increased myocardial
contractility and increased peripheral vasoconstriction occur. The peripheral vasoconstriction
brings blood back into the central circulation but at the expense of peripheral end-organ
perfusion. Ventricular dysrhythmias may be precipitated. At high enough doses, extremities
become ischemic and even turn dark and potentially necrotic. A typical dose is 0.1 mcg/kg/min IV
and are titrated upward according to effect and adverse effects. In severe cases, patients may
receive doses of 2-3 mcg/kg/min IV or even higher.
Dobutamine
Dobutamine (Dobutrex) is almost a pure inotropic agent, with primarily beta1-agonist effects, that
increases cardiac contractility. It also provides some relatively weak beta2-mediated peripheral
vasodilation that might reduce systemic vascular resistance and afterload and improve tissue
perfusion. Minimal alpha-agonist effect occurs. Therefore, dobutamine is an appropriate drug to
provide to a patient with cardiogenic shock in order to help augment myocardial contractility.
Dobutamine is less likely to precipitate ventricular dysrhythmias than epinephrine. A typical dose
begin with 5 mcg/kg/min IV and is gradually increased to 20 mcg/kg/min IV.
Norepinephrine
Norepinephrine (Levophed) is predominantly an alpha-agonist that results in increased peripheral
vasoconstriction and, thus, increased peripheral vascular resistance. It is recommended for use in
fluid-refractory, dopamine-resistant vasodilatory ("warm") shock. Some beta1-agonistic effects
occur in inotropy. Its predominant role is as a pressor agent to increase blood pressure in the
setting of shock that persists after adequate fluid replacement. Some practitioners provide the
alpha-mediated vasoconstrictive effect with norepinephrine and titrate improvement in myocardial
contractility with dobutamine. Others rely on epinephrine. Typical doses of norepinephrine are
similar to epinephrine and begin at 0.1 mcg/kg/min IV and are titrated upward according to effect
and adverse effects.
Phosphodiesterase inhibitors
Inamrinone (formerly amrinone [Inocor]) and milrinone are phosphodiesterase inhibitors that work
via a different mechanism than the catecholamines. They produce an increase in intracellular
cyclic adenosine monophosphate (cAMP), which raises intracellular calcium levels, improving
cardiac inotropy as well as peripheral vasodilation. They may be useful for the treatment of shock
in patients who have adequate intravascular volume but need increased cardiac contractility and
better peripheral perfusion. Phosphodiesterase inhibitors may be used together with
catecholamines to further increase myocardial contractility while reducing systemic vascular
resistance and afterload. They are often a useful adjunct after heart surgery in patients who have

myocardial impairment. They may also be useful in improving perfusion in patients who remain in
compensated shock with poor peripheral perfusion but a normal central blood pressure and
adequate intravascular volume.
Typical doses of inamrinone in children are a loading dose of 0.75 mg/kg IV over 2-3 minutes
followed by a continuous IV infusion of 5-10 mcg/kg/min. Most pediatric dosing recommendations
for milrinone are derived from adult data. Milrinone may be initiated with a loading dose of 25-50
mcg/kg over 10 minutes, followed by a continuous IV infusion of 0.375-0.75 mcg/kg/min. Adverse
effects of both inamrinone and milrinone may include arrhythmias as well as
thrombocytopenia.14 Care must be given when choosing to start phosphodiesterase inhibitors
because of their vasodilator effects and long half-life; at times, forgoing the loading dose and only
initiating an infusion may be appropriate and allows for a more controlled gradual effect on the
patients physiology.
Dextrose
Neonates and infants have limited glycogen stores that may become rapidly depleted during
shock, resulting in hypoglycemia. Alternatively, high levels of endogenous and exogenous
catecholamines may result in a relative insulin-resistant state that can cause serum
hyperglycemia. Because glucose is the major metabolic substrate, perform a rapid bedside
glucose test on all patients who present in shock. If the glucose level is low, provide replacement
therapy with IV dextrose. The dose of dextrose is 0.5-1 g/kg IV. Dextrose is best provided as a
continuous IV infusion.
Calcium
Calcium mediates excitation-contraction coupling in muscle cells, including cardiac muscle.
Shock may cause alterations in available serum ionized calcium levels, despite normal total
serum calcium. Furthermore, administered blood products (which contain citrate) may bind free
available calcium, additionally decreasing available ionized calcium levels. The availability of
functioning ionized calcium also depends on serum acid-base status; an acid environment favors
the dissociation of calcium from proteins, making it available as a cofactor in cell function. Care
must be taken not to cause a drop in ionized calcium when treating acidosis. Therefore, calcium
therapy can be useful when treating shock in a patient with documented hypocalcemia. It is also
indicated for treating shock caused by arrhythmias precipitated by hyperkalemia,
hypermagnesemia, or calcium channel blocker toxicity.
Calcium may be provided either as calcium gluconate or calcium chloride. Calcium chloride has
been shown to produce higher and more consistent levels of available calcium and, therefore, is
recommended in the acute resuscitation of a child in shock. 15 The recommended dose is 10-20
mg/kg (0.1-0.2 mL/kg of calcium chloride 10%) IV administered at an infusion rate that does not
exceed 100 mg/min IV. Further therapy may be guided by repeat plasma ionized calcium
measurements.
Prostaglandin E1
Neonates who present with shock associated with a large liver, enlarged cardiac silhouette, or
heart murmur may have obstructive shock that presents because of closing of the ductus
arteriosus. Prior to closure, the ductus arteriosus allowed sufficient systemic blood flow to bypass

the obstructive lesion. In such patients, initiation of prostaglandin E1 (PGE1) to maintain or

reestablish patency of the ductus arteriosus may be life saving. The recommended dose is 0.050.1 mcg/kg/min IV as a continuous infusion. Adverse effects may include fever, apnea, or
hypotension due to vasodilation. Evaluation of cardiac anatomy with echocardiography
performed by a pediatric cardiologist should be obtained as soon as possible.
Sodium bicarbonate
The use of sodium bicarbonate in the treatment of shock is controversial. During shock, acidosis
develops, which impairs myocardial contractility and optimal function of catecholamines.
However, treatment with bicarbonate may worsen intracellular acidosis while it corrects serum
acidosis. This occurs because bicarbonate is an ion that does not readily traverse semipermeable
cell membranes. Hence, bicarbonate combines with acid in serum, resulting in the production of
carbon dioxide and water as defined by the Henderson-Hasselbalch equation.
If the increased carbon dioxide is not removed via ventilation, it readily enters the cell and drives
the Henderson-Hasselbalch reaction in the opposite direction, increasing intracellular acidosis.
Worsened myocardial intracellular acidosis may result in a decrease in myocardial contractility.16,
17
In addition, bicarbonate administration may result in hypernatremia and hyperosmolality,
decreasing the availability of ionized calcium.
Finally, laboratory and clinical data have not demonstrated that bicarbonate administration
improves the ability to defibrillate, improves DO2, or improves survival rates in shock and cardiac
arrest.18, 19, 20 Thus, acidosis that results from shock should ideally be corrected with increased
perfusion from volume supplementation and judicious use of cardiotropic medications together
with optimal ventilation.
In patients with persistent shock or ongoing bicarbonate loss (eg, severe diarrhea), careful
replacement of bicarbonate may be indicated. The appropriate dose of bicarbonate may be
calculated from the known base deficit obtained from an ABG sample according to the following
formula:
HCO3 - (mEq) = Base deficit X patient's weight (in kg) X 0.30
Generally, half of the calculated bicarbonate deficit may be administered initially, and repeat acidbase status may be determined. Alternatively, 0.5-1 mEq/kg/dose IV infused over 1-2 minutes
may be administered if indicated. Studies in patients with cardiovascular arrest have not
demonstrated improved survival rates associated with the use of bicarbonate.
Corticosteroids
The use of corticosteroids, particularly in patients with septic shock, is controversial. Many largescale controlled trials in animals and human beings have not demonstrated improved outcome
with corticosteroid use, with some potential associated morbidity.21 Nevertheless, a question
remains as to whether patients in severe septic shock or purpura fulminans have adequate levels
of circulating glucocorticoids to support their physiology when severely stressed.
Adrenocortical failure or infarction, known as Waterhouse-Friderichsen syndrome, may result in
cardiovascular failure and hyporesponsiveness to catecholamines. In such patients, initiation of

stress-dose hydrocortisone, in the range of 50-100 mg/m 2/d IV, may be beneficial and lifesaving. A
serum cortisol level may be drawn prior to initiating the first dose of corticosteroids, and if the
random serum cortisol level is low, then replacement doses may be beneficial.
Moreover, some data suggest a potential role for corticosteroid replacement therapy in select
patients with septic shock. A study of adult patients with septic shock who had survived 48 hours
and were dependent on inotropic agents showed some benefit when treated with
supraphysiologic doses of hydrocortisone compared with controls. 22Patients in the treatment
group received 100 mg hydrocortisone IV 3 times a day for 5 days compared with controls, who
received a placebo. At the end of 7 days, 68% of the hydrocortisone group had reversal of shock
compared with 21% of controls, a difference of 47% (P <0.007). In addition, the mortality rate was
32% in the hydrocortisone group compared with 65% in controls (P value not significant).
Furthermore, select patients may have adrenal insufficiency, rendering them hyporesponsive to
administration of catecholamines during resuscitation from shock. Many practitioners evaluate a
baseline serum cortisol level in children with fluid-refractory, catecholamine-resistant shock and/or
perform a corticotropin stimulation test with 250 mcg corticotropin, treating the patient with
hydrocortisone. Dosage recommendations range from 1-2 mg/kg hydrocortisone IV every 6 hours
to as much as a 50 mg/kg bolus followed by the same amount infused over 24 hours. 13 Therapy is
continued for patients who prove to have an absolute baseline cortisol level less than 20 mcg/dL
and/or a depressed response to the corticotropin stimulation test with a rise at 30 and 60 minutes
after administration of corticotropin less than 9 mcg/dL. 23
Other therapies
Obviously, for all causes of shock, the underlying etiology should be identified and treated. If the
cause is sepsis, isolate and treat the infectious organism with appropriate antibiotics. If the cause
is trauma, then ongoing bleeding may need to be surgically addressed. Convert malignant
arrhythmias to normal sinus rhythm as soon as possible.
Other modalities of supportive care must be ensured, such as optimizing and providing adequate
nutritional support in patients recovering from shock. Multiple system organ support may be
required, including such modalities as mechanical ventilation, renal dialysis, or even
extracorporeal circulatory support (ECMO).24, 25 All of the therapies discussed in this review are
aimed at restoring adequate perfusion to the tissues and organs of the body as soon as possible.
Ongoing support offers the body the opportunity to repair the hypoxic and ischemic damage
sustained, with the ultimate goal of functioning intact patient survival.