Shock in Pediatrics 

Shock is a leading cause of morbidity and mortality in the pediatric population. Shock is a clinically diagnosed condition that results from many varied etiologies. It 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 from shock 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.

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.

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 adenosine triphosphate (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.

Oxygen delivery

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 O₂/100 mL blood) × CO (L/min) × 10

The CaO₂ depends on how much oxygen-carrying capacity is available, which is a function of the hemoglobin (Hb) level and the Hb oxygen content, defined as the arterial oxygen saturation (SaO₂). A small, but clinically irrelevant, amount of oxygen is directly dissolved in the blood rather than bound to Hb. Therefore, CaO₂ may be defined by the following formula:

CaO₂ (mL/100 mL) = Hb (g/100 mL) × SaO₂ × 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) × SV (mL/beat)

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 (see the image below).

Several etiologic classifications of shock are recognized. In each of these classifications, one or more of the physiologic principles that govern oxygen delivery are disturbed. The major categories are as follows:

• Hypovolemic
• Distributive
• Cardiogenic
• Septic
• Obstructive
• Miscellaneous

The etiologic frequency of the different causes of shock varies around the world.^[1] Hypovolemia resulting from gastroenteritis is the major cause of shock in developing regions. In developed regions, a study by Fisher et al of pediatric patients who presented to a pediatric emergency department over an 8-year period identified sepsis as the leading cause of shock, occurring in 57% of patients, followed by hypovolemic shock (24%), distributive shock (14%), and cardiogenic shock (5%).^[1]

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. Causes of hypovolemic shock include the following:

• Intravascular volume loss (eg, from gastroenteritis, burns, diabetes insipidus, heat stroke)
• Hemorrhage (eg, from trauma, surgery, GI bleeding)
• Interstitial loss (eg, from burns, sepsis, nephrotic syndrome, intestinal obstruction, ascites)

Gastroenteritis

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.^[2] Rehydration is often impeded by concurrent vomiting, and deterioration may be rapid.

Common infectious causes of gastroenteritis include bacteria such as Salmonella, Shigella,Campylobacter species, Escherichia coli, and Vibrio cholerae and viruses such as rotaviruses, adenoviruses, norovirus, and enteroviruses. Worldwide, 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 (ie, dysentery) may reduce Hb content, resulting in decreased CaO₂.

Trauma

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.^[3] A major component of traumatic death is hemorrhage. Hemorrhagic shock reduces both CaO₂ and preload, resulting in decreased DO₂ to the tissues.

Third spacing

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 overloaded with total-body fluid; however, they may be significantly intravascularly depleted, with inadequate preload, and in significant shock. By understanding the physiologic disturbance affecting intravascular volume and preload, such patients need additional fluid administration despite their overall edematous appearance, in order to improve DO₂ and prevent or correct a state of shock.

Distributive shock

In certain clinical states, normal peripheral vascular tone becomes inappropriately relaxed. Vasodilation results in increased venous capacitance, causing 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.

Common causes of distributive shock include anaphylaxis, neurologic injury (eg, head injury, spinal shock), sepsis, and drug-related causes. Causes of anaphylaxis include the following:

• Medications (eg, antibiotics, vaccines, other drugs)
• Blood products
• Envenomation
• Foods
• Latex

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 T1, 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 lose sympathetic vascular tone (resulting in vasodilation) while being 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 distributive shock. (Sepsis is discussed in more detail below.)

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 of cardiogenic shock include the following:

• Congestive heart failure
• Ischemic heart disease (common in adults, rare in children)
• Cardiomyopathy
• Cardiac tamponade
• Sepsis
• 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. Ultimate treatment in such cases clearly depends on surgical correction or palliation of the physical obstruction. As a temporizing measure, these neonates may require maintaining the patency of the ductus arteriosus in order to bypass the obstruction until more definitive surgery can be performed.

Sepsis

Sepsis may be defined as a systemic inflammatory response triggered by the presence of infectious agents or their toxins.^[4] Disturbances of virtually every variable in the DO₂ equation may result from 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–alpha; interleukins such as IL-1, IL-2, and IL-6; products of the coagulation cascade; complement activation; and bradykinins.

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. Overactivation of the clotting cascade can result in disseminated intravascular coagulation (DIC), which can directly plug and block critical tissue capillary beds, resulting in microvascular obstructive shock, as well as hemorrhage, which further depletes 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 therefore disturbs many, if not all, of the physiologic variables that determine systemic DO₂.

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.

Worldwide, shock accounts for more morbidity and mortality in children than any other diagnosis. Dehydration and hypovolemic shock alone result in 6-20 million deaths annually in infants and children worldwide.

Morbidity from shock may be multisystemic and can include the following:

• Renal failure
• Brain damage
• Gut ischemia
• Hepatic failure
• Metabolic derangements
• DIC
• Acute respiratory distress syndrome (ARDS)
• Cardiac failure