AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Physiology
• Etiology
• Diagnosis
• Treatment of Shock
• Pharmacologic Therapy
• Multimedia
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Physiology
• Etiology
• Diagnosis
• Treatment of Shock
• Pharmacologic Therapy
• Multimedia
• References

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

Section 3 of 9  

• Authors and Editors
• Introduction
• Physiology
• Etiology
• Diagnosis
• Treatment of Shock
• Pharmacologic Therapy
• Multimedia
• References

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 (DO₂) 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 DO₂, 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 DO₂ is critical in either hypoxic or ischemic shock, considering DO₂ 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, DO₂ 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 PaO₂)

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

Section 4 of 9  

• Authors and Editors
• Introduction
• Physiology
• Etiology
• Diagnosis
• Treatment of Shock
• Pharmacologic Therapy
• Multimedia
• References

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 DO₂. 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 CaO₂ 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 DO₂ 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
• • Gastroenteritis
  • Burns
  • Diabetes insipidus
  • Heat stroke
• Hemorrhage
• • Trauma
  • Surgery
  • GI bleeding
• Interstitial loss
• • Burns
  • Sepsis
  • Nephrotic syndrome
  • Intestinal obstruction
  • 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
• • Medications (eg, antibiotics, vaccines, other drugs)
  • Blood products
  • Envenomation
  • Foods
  • Latex
• Neurologic causes
• • Head injury
  • 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 DO₂. 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 gram-positive 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 IL-1, IL-2, and IL-6; products of the coagulation cascade; complement activation; and bradykinins may lead to disturbances of virtually every variable in the DO₂ 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 DO₂. 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

Section 5 of 9  

• Authors and Editors
• Introduction
• Physiology
• Etiology
• Diagnosis
• Treatment of Shock
• Pharmacologic Therapy
• Multimedia
• References

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 ductal-dependent 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 fifth–percentile 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 DO₂ 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 SaO₂ (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 near-infrared 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 DO₂ 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 H₂O. Pressures much higher than 10 cm H₂O 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 H₂O 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/m²K.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

Section 6 of 9  

• Authors and Editors
• Introduction
• Physiology
• Etiology
• Diagnosis
• Treatment of Shock
• Pharmacologic Therapy
• Multimedia
• References

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 (PaO₂) 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

Section 7 of 9  

• Authors and Editors
• Introduction
• Physiology
• Etiology
• Diagnosis
• Treatment of Shock
• Pharmacologic Therapy
• Multimedia
• References

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 end-organ 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.¹³ Dopamine 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 patient’s 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 0.05-0.1 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 acid-base 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 large-scale 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/m²/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.²² Patients 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.

MULTIMEDIA

Section 8 of 9  

• Authors and Editors
• Introduction
• Physiology
• Etiology
• Diagnosis
• Treatment of Shock
• Pharmacologic Therapy
• Multimedia
• References

Media file 1:  Chest radiograph of patient with cardiomegaly, which may accompany cardiogenic shock.
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Media type:  Radiograph

Media file 2:  Determinants of cardiac function and oxygen delivery to tissues.26
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Media file 3:  Hemodynamic response to hemorrhage model for cardiovascular response to hypovolemia from hemorrhage (based on normal data).27
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Media type:  Graph

Media file 4:  Definitions of shock include the following:13 Cold or warm shock: Decreased perfusion including decreased mental status, capillary refill more than 2 seconds (cold shock) or flash capillary refill (warm shock) and diminished (cold shock) or bounding (warm shock) peripheral pulses; mottled cool extremities (cold shock) or decreased urine output less than 1 mL/kg/h Fluid-refractory, dopamine-resistant shock: Shock persists despite more than 60 mL/kg fluid resuscitation in the first hour and dopamine infusion to 10 mg/kg/min Catecholamine-resistant shock: Shock persists despite use of catecholamines epinephrine or norepinephrine Refractory shock: Shock persists despite goal-directed use of inotropic agents, vasopressors, vasodilators, and maintenance of metabolic (glucose and calcium) and hormonal (thyroid and hydrocortisone) homeostasis
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Media type:  Illustration

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Physiology
• Etiology
• Diagnosis
• Treatment of Shock
• Pharmacologic Therapy
• Multimedia
• References

1. Tobin JR, Wetzel RC. Shock and multi-organ system failure. In: Rogers MC, ed. Textbook of Pediatric Intensive Care. Baltimore, Md: Lippincott, William & Wilkins; 1996:555-605.
2. Guyer B, Hoyert DL, Martin JA, et al. Annual summary of vital statistics--1998. Pediatrics. Dec 1999;104(6):1229-46. [Medline]. [Full Text].
3. Versmold HT, Kitterman JA, Phibbs RH, et al. Aortic blood pressure during the first 12 hours of life in infants with birth weight 610 to 4,220 grams. Pediatrics. May 1981;67(5):607-13. [Medline].
4. Horan MJ. Report of the Second Task Force on Blood Pressure Control in Children--1987. Task Force on Blood Pressure Control in Children. National Heart, Lung, and Blood Institute, Bethesda, Maryland. Pediatrics. Jan 1987;79(1):1-25. [Medline].
5. Hazinski MF. Children are different. In: Hazinski MF, ed. Nursing Care Critically Ill Child. 2nd ed. 2^nd ed. St. Louis, Mo: Mosby Year Book; 1992.
6. American Heart Association. Recognition of respiratory failure and shock. In: Chameides L, Hazinski MF, eds. Pediatric Advanced Life Support. Dallas, Tx: American Heart Association; 1997.
7. Saavedra JM, Harris GD, Li S, Finberg L. Capillary refilling (skin turgor) in the assessment of dehydration. Am J Dis Child. Mar 1991;145(3):296-8. [Medline].
8. Katz RW, Pollack MM, Weibley RE. Pulmonary artery catheterization in pediatric intensive care. Adv Pediatr. 1983;30:169-90. [Medline].
9. Ferrari M, Mottola L, Quaresima V. Principles, techniques, and limitations of near infrared spectroscopy. Can J Appl Physiol. Aug 2004;29(4):463-87. [Medline].
10. Adcock LM, Wafelman LS, Hegemier S, et al. Neonatal intensive care applications of near-infrared spectroscopy. Clin Perinatol. Dec 1999;26(4):893-903, ix. [Medline].
11. Sibbald WJ, Calvin J, Driedger AA. Right and left ventricular preload and diastolic ventricular compliance: implications for therapy in critically ill patients. In: Shoemaker WC, Thompson WL, eds. Critical Care-State of the Art. Fullerton, Calif: Society of Critical Care Medicine; 1982.
12. Carcillo JA, Davis AL, Zaritsky A. Role of early fluid resuscitation in pediatric septic shock. JAMA. Sep 4 1991;266(9):1242-5. [Medline].
13. Carcillo JA, Fields AI, American College of Critical Care Medicine Task Force Committee Members. Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock. Crit Care Med. Jun 2002;30(6):1365-78. [Medline].
14. Ramamoorthy C, Anderson GD, Williams GD, Lynn AM. Pharmacokinetics and side effects of milrinone in infants and children after open heart surgery. Anesth Analg. Feb 1998;86(2):283-9. [Medline]. [Full Text].
15. Broner CW, Stidham GL, Westenkirchner DF, Watson DC. A prospective, randomized, double-blind comparison of calcium chloride and calcium gluconate therapies for hypocalcemia in critically ill children. J Pediatr. Dec 1990;117(6):986-9. [Medline].
16. Cingolani HE, Mattiazzi AR, Blesa ES, Gonzalez NC. Contractility in isolated mammalian heart muscle after acid-base changes. Circ Res. Mar 1970;26(3):269-78. [Medline].
17. Pannier JL, Leusen I. Contraction characteristics of papillary muscle during changes in acid-base composition of the bathing-fluid. Arch Int Physiol Biochim. Sep 1968;76(4):624-34. [Medline].
18. Arieff AI. Indications for use of bicarbonate in patients with metabolic acidosis. Br J Anaesth. Aug 1991;67(2):165-77. [Medline].
19. Walley KR, Cooper J, Baile EM. Bicarbonate does not improve left ventricular contractility during resuscitation from hypovolemic shock in pigs. J Crit Care. 1992;7:14-21.
20. Makisalo HJ, Soini HO, Nordin AJ, Hockerstedt KA. Effects of bicarbonate therapy on tissue oxygenation during resuscitation of hemorrhagic shock. Crit Care Med. Nov 1989;17(11):1170-4. [Medline].
21. Cronin L, Cook DJ, Carlet J, et al. Corticosteroid treatment for sepsis: a critical appraisal and meta- analysis of the literature. Crit Care Med. Aug 1995;23(8):1430-9. [Medline].
22. Bollaert PE, Charpentier C, Levy B, et al. Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med. Apr 1998;26(4):645-50. [Medline].
23. Pizarro CF, Troster EJ, Damiani D, Carcillo JA. Absolute and relative adrenal insufficiency in children with septic shock. Crit Care Med. Apr 2005;33(4):855-9. [Medline].
24. McCune S, Short BL, Miller MK, et al. Extracorporeal membrane oxygenation therapy in neonates with septic shock. J Pediatr Surg. May 1990;25(5):479-82. [Medline].
25. DiCarlo JV, Dudley TE, Sherbotie JR, et al. Continuous arteriovenous hemofiltration/dialysis improves pulmonary gas exchange in children with multiple organ system failure. Crit Care Med. Aug 1990;18(8):822-6. [Medline].
26. Strange GR. APLS: The Pediatric Emergency Medicine Course. 3^rd ed. Elk Grove Village, Ill: American Academy of Pediatrics; 1998:34.
27. Schwaitzberg SD, Bergman KS, Harris BH. A pediatric trauma model of continuous hemorrhage. J Pediatr Surg. Jul 1988;23(7):605-9. [Medline].

Article Last Updated: Feb 13, 2008