General Principles

Shock is a clinical syndrome of inadequate tissue oxygenation. In addition to treatment of the primary underlying process, therapeutic efforts involve optimizing and balancing oxygen delivery and oxygen consumption. Efforts to reduce oxygen requirements at a time when oxygen delivery is compromised are important. Intubation, mechanical ventilation, sedation, paralysis, and control of fever are ways to reduce oxygen consumption. Even routine nursing procedures can increase oxygen consumption by up to 20% to 30% in healthy adults.¹²

Intubation and Mechanical Ventilation

Viires et al.¹³ studied spontaneously breathing dogs during cardiogenic shock. During a low cardiac output state, blood flow to the diaphragm was substantially increased, while blood flow to the liver, brain, and quadriceps was significantly decreased. Intubation, mechanical ventilation, and paralysis resulted in redistribution of blood flow from the diaphragm to the liver, brain, and quadriceps. A similar study of endotoxic shock in dogs demonstrated that respiratory muscle blood flow rose significantly in spontaneously breathing dogs.¹⁴ During shock states, there is often increased work of breathing and respiratory distress related to capillary leak and acidosis.

Intubation and mechanical ventilation can allow redistribution of cardiac output from the muscles of respiration to vital organs during shock (when cardiac output and oxygen delivery are compromised). Positive pressure ventilation also has the effect of reducing afterload to the left ventricle (potentially improving stroke volume) (see Chapter 26).

Fluid Resuscitation

Regardless of the underlying insult, all patients in shock have an absolute or relative hypovolemia. A primary goal of initial therapy must be restoration of effective circulating volume. Early fluid resuscitation is the cornerstone of immediate therapy.^15,16 In a study of pediatric septic shock patients, Carcillo et al.¹⁵ correlated the volume of fluid given in the first hour of presentation and reversal of hypovolemia to outcome. Patients who received the largest volume of fluid in the first hour of resuscitation had the lowest mortality. Persistent hypovolemia was associated with increased mortality. Fluid resuscitation must be guided by repeated evaluation of the patient’s hemodynamic status.

Vasoactive Infusions

Vasoactive infusions are commonly used when patients have been adequately fluid-resuscitated but hemodynamics remain deranged. Infusions of catecholamines (dopamine, dobutamine, epinephrine, norepinephrine), phosphodiesterase inhibitors (inamrinone, milrinone), and vasopressin are most commonly used. The choice of vasoactive infusion is dependent on the physiologic derangement requiring treatment (Table 29-1). Catecholamines work through stimulation of α₁, α₂, β₁, β₂, and dopaminergic receptors to increase intracellular cyclic guanosine monophosphate (cGMP) and cause the appropriate response (Table 29-2). Phosphodiesterase inhibitors increase cGMP by preventing its degradation within the cell (see Chapter 25). Vasopressin causes vasoconstriction by direct stimulation of vascular smooth muscle cell V1 receptors.^17–22 Vasopressin also potentiates systemic adrenergic effects.^12,24–26 Vasopressin^20–22 and terlipressin^27–31 (a synthetic analog of vasopressin with a similar pharmacodynamic profile, but with a significantly longer half-life) have also shown some utility in the treatment of catecholamine-resistant shock.

Table 29–1 Therapies for Hemodynamic Patterns in Shock States

Table 27–2 Vasoactive Medications

Other Therapies

The finding of hypocalcemia in infants who present in shock should raise the suspicion of left ventricular dysfunction. Hypocalcemia causes left ventricular dysfunction in neonates and is reversible with calcium therapy.³² Of note, 30% of neonates with DiGeorge syndrome are hypocalcemic.

Neonates, who have low glycogen stores and increased metabolic requirements during shock, may quickly develop hypoglycemia.³² Shock in neonates is frequently complicated by pulmonary hypertension.

Adrenal insufficiency should be suspected in patients with refractory shock resulting from trauma (head or abdominal), history of steroid use within past 6 months, sepsis, or treatment with etomidate. Direct damage to the hypothalamus, anterior pituitary, or adrenals may result in cortisol deficiency. In septic shock, adrenal hemorrhage has been the paradigm of adrenal insufficiency, but increasing evidence indicates transient relative or functional adrenal insufficiency in septic shock (see section on septic shock).

Extracorporeal membrane oxygenation (ECMO) has been used to support patients of all ages with shock. The Extracorporeal Life Support Organization (ELSO) maintains a database of patients treated with ECMO from member institutions around the world. The registry was searched for data on patients treated with ECMO (from 1985 through January 2010) with any mention of the diagnosis of shock (Lynn Hernan, personal communication, 2010). The registry revealed 1512 pediatric patients (age ≤21 years old) who were treated with ECMO for any diagnosis which included the descriptor shock. The overall mortality was 60%. Sixty-five percent of patients were 1 year of age or younger. Forty-four percent of pediatric patients treated with ECMO for shock were neonates. In patients aged 21 years or younger treated with ECMO, the etiology of shock was cardiogenic in 46%, septic in 22%, hypovolemic in 11%, traumatic or surgical in 1%, and other or unspecified in 20%. The mortality across the groups ranged from 56% to 64%.

Respiratory

Respiratory failure frequently accompanies shock states. It may result from failure of the ventilator pump (i.e., respiratory muscle fatigue) and/or deterioration of lung function (i.e., acute respiratory distress syndrome). For these reasons and for maximizing oxygen delivery, increased inspired oxygen is essential in all children with shock. Early tracheal intubation protects the airway, provides relief from respiratory muscle fatigue, facilitates provision of positive airway pressure, redistributes blood flow from the muscles of respiration to core organs, afterload-reduces the left ventricle, and reduces oxygen demands of respiratory muscles. Patients should be ventilated with a lung protective strategy (see Chapter 51).

Renal

Renal failure may develop in association with any of the shock syndromes. Shock-related renal failure is a continuum of acute prerenal azotemia through classic acute tubular necrosis to cortical necrosis. Renal support is essential to prevent prolonged renal shutdown in shock states. Volume augmentation to correct absolute or relative hypovolemia is essential. Although low-dose dopamine (3 to 5 μg/kg/min) improves renal blood flow,^36,37 it also impairs renal oxygen kinetics, inhibits protective feedback loops with the kidney, and may worsen tubular injury.^38,39 It has failed to show benefit in preventing or altering the course of acute renal failure in adults.^38,39 Dopamine may also inhibit secretion of prolactin, growth hormone, and thyrotropin in critically ill children.⁴⁰

Acute anuric renal failure may require treatment with peritoneal dialysis, ultrafiltration, continuous hemofiltration or hemodiafiltration, or hemodialysis (see Chapter 72). High-output renal failure may occur in shock states without previous oliguria. The polyuria associated with this condition may falsely suggest adequate renal perfusion and adequate vascular volume at a time when the patient’s intravascular volume is, in fact, depleted. Restoration of renal perfusion pressure remains the standard of care.

Populations for whom early renal replacement therapies result in decreased mortality have not been consistently identified.^41,42 There is evidence that fluid overload is related to mortality in critically ill children with renal dysfunction.⁴³ If renal dysfunction exists, all medications and therapies should be adjusted for creatinine clearance.

Coagulation

Coagulation abnormalities (e.g., disseminated intravascular coagulation) probably occur to some extent in all forms of shock. Monitoring of prothrombin time, partial thromboplastin time, and platelet count and observation for abnormal bleeding are essential. Replacement therapies specifically designed to replace absent clotting factors seem to be the most advantageous treatments. Use of vitamin K, fresh-frozen plasma, cryoprecipitate, and platelet transfusions should correct most coagulopathies. If general replacement therapy is ineffective, and the patient is at risk for complications, specific factor therapy may be indicated.

Coagulopathy is ubiquitous in all patients with severe sepsis.⁴⁴ Recombinant activated protein C has been shown to decrease mortality in adults with severe sepsis (see section on septic shock).

Use of plasmapheresis, plasma exchange, and plasma filtration as therapy for treating sepsis-induced multiple organ system failure and improving outcome remains experimental.^42,45–49

Hepatic

The degree of hepatic dysfunction may determine a patient’s ultimate outcome in severe shock states. Maintaining adequate circulation helps maintain liver function and prevents further hepatocellular damage. Liver function tests should be performed early and followed frequently. If dysfunction exists, drugs requiring hepatic metabolism must be carefully titrated.

Gastrointestinal

Gastrointestinal disturbances after hypoperfusion and stress include bleeding, ileus, and bacterial translocation. Ileus may result from electrolyte abnormalities, administration of narcotic medications, or from shock itself. Abdominal distension from ileus or ascites may cause respiratory compromise, especially in infants. Use of prophylactic medications (H₂ blockers, protein pump inhibitors, sucralfate) to prevent gastrointestinal hemorrhage is unproven.⁵⁰ Use of histamine antagonists has been associated with an increased incidence of nosocomial pneumonias.^50,51

Acute nonocclusive mesenteric ischemia is a devastating condition characterized by intense, prolonged splanchnic vasoconstriction, intestinal mucosal hypoxia, and acidosis. Mesenteric ischemia eventually leads to transmural necrosis of the bowel, bacterial translocation, sepsis, and multisystem organ dysfunction.^52–54 Morbidity and mortality for this condition are high because the signs/symptoms are nonspecific, delaying diagnosis. Prevention of gut ischemia through adequate oxygen delivery may prevent bacterial translocation. Some clinicians advocate the use of selective gut decontamination and early enteral nutrition.^55–56 Most children with shock will tolerate postpyloric enteral feeding, although GI feeding complications are more common than in critically ill patients without shock.^57,58

Endocrine

Multiple endocrine problems involving fluid, electrolytes, and mineral balance may arise and complicate the management of children in shock. Severe abnormalities of calcium homeostasis can occur during the course of acute hemodynamic deterioration.

Hypoadrenalism may exacerbate the shock state. Patients who have been administered corticosteroids within 6 months preceding the onset of shock should be considered for stress doses of glucocorticoids. Patients in shock because of head or abdominal trauma may have disruption of the hypothalamic-anterior pituitary-adrenal axis. Adrenal hemorrhage has been demonstrated as a manifestation of severe sepsis, but more commonly patients may develop a relative or functional adrenal insufficiency (see section on septic shock).

Etiology and Pathophysiology

Hypovolemia is the most common cause of shock in infants and children. Hypovolemic shock is best defined as a decrease in the intravascular blood volume to such an extent that effective tissue perfusion cannot be maintained. Etiologies include hemorrhage (see Chapter 112), fluid and electrolyte loss (see Chapter 67), endocrine disease (see Chapter 77), and plasma loss (Box 29-3).

Hypovolemia causes a decrease in preload leading to a decrement of stroke volume and reduction in cardiac output. Activation of peripheral and central baroreceptors produces an outpouring of catecholamines, and the resulting tachycardia and peripheral vasoconstriction are initially adequate to support the blood pressure with little or no evidence of hypotension. Acute losses of 10% to 15% of the circulatory blood volume may be well tolerated in healthy children who have intact compensatory mechanisms. An acute loss of 25% or more of the circulating blood volume, however, frequently results in a clinically apparent hypovolemic state that requires immediate, aggressive management.

The most reliable indicators of early, compensated hypovolemic shock in children are persistent tachycardia, cutaneous vasoconstriction, and diminution of the pulse pressure. The best clinical evidence of decreased tissue perfusion is skin mottling, prolonged capillary refill, cool extremities, and decreased urine output. Systemic arterial blood pressure is frequently normal, the result of increased systemic vascular resistance, making blood pressure measurement of limited value in managing the patient with compensated hypovolemic shock. Neurologic status is normal or only minimally impaired.

With continued loss of blood volume or with delayed or inadequate blood volume replacement, the intravascular fluid losses surpass the body’s compensatory abilities, causing circulatory and organ dysfunction. Stroke volume and cardiac output are decreased. The pronounced systemic vasoconstriction and hypovolemia produce ischemia and hypoxia in the visceral and cutaneous circulations. Altered cellular metabolism and function occur in these areas, resulting in damage to blood vessels, kidneys, liver, pancreas, and bowel. Patients become hypotensive, acidotic, lethargic or comatose, and oliguric or anuric. It is important to emphasize that arterial blood pressure falls only after compensations are exhausted, which may occur long after the precipitating event and only after a severe reduction in cardiac output. Terminal phases of hypovolemic shock are characterized by myocardial dysfunction and widespread cell death.

Therapy

Initial treatment of the child in hypovolemic shock is similar regardless of etiology. Therapy begins with the establishment or assurance of adequate oxygenation and ventilation. Oxygen should always be the first drug administered. Once the airway is assured or established (may require intubation) and ventilation is adequate, measures to restore an effective circulating blood volume should begin immediately. Placement of an adequate intravenous or intraosseous catheter and rapid volume replacement are the most important therapeutic maneuvers to reestablish the circulation (see Chapter 15). Central venous catheterization is infrequently necessary during initial resuscitation.

The choice of fluid depends on the nature of the loss. Early correction of hypovolemia is the major factor preventing the later complications of shock. Isotonic crystalloid solutions, which are readily available, safe, and the least expensive, should be used in initial volume resuscitation. The first fluid bolus (20 mL/kg) should be administered as rapidly as possible. Heart rate, pulse pressure, blood pressure, peripheral perfusion, quality of mentation, and volume of urine output should be monitored. Improvement in these measurements should be expected if the blood volume loss is approximately 20%. Under these conditions, a rapid response to resuscitation can be anticipated. Maintenance fluid administration then can be initiated and vital signs monitored. The appropriate maintenance fluid depends on the measurements of serum electrolytes, total protein, and hematocrit.

The end point of fluid resuscitation should be normalization of arterial blood pressure, pulse pressure, peripheral perfusion, and heart rate; establishment of adequate urine output; and a decrease in the metabolic acidosis. If shock persists, continued aggressive fluid resuscitation in aliquots of 20 mL/kg should be initiated with rapid assessment of response to therapy. If the patient does not show improvement after several isotonic fluid boluses, more aggressive monitoring and reevaluation of the diagnosis may be required. Causes of ongoing vascular depletion should be sought. Patients in profound hypovolemic shock will require frequent or continuous monitoring of heart rate, arterial blood pressure, arterial blood gases, central venous pressure (CVP), and urinary output.

Uncomplicated, promptly treated hypovolemic shock usually does not lead to a significant capillary injury and leak. However, severe, prolonged hypovolemic shock, traumatic shock with extensive soft-tissue injury, burn shock, or sepsis complicating hypovolemic shock may seriously impair capillary integrity. Therefore, once adequate circulation and urine output have been restored, fluid administration may be reduced unless there are demonstrable ongoing fluid losses. Continued assessment of hemodynamic status and vascular volume is essential to guide further therapy.

The amount of fluid necessary to restore effective circulating blood volume depends on the amount lost (deficit) and the rate of ongoing loss. The total amount of fluid given often exceeds the total volume lost because of expanded capacitance of the vascular space and dysfunction of cellular membranes. Ongoing fluid losses from chest tube drains, biliary drains, bowel, edema formation, or other losses of bodily fluids may dictate the use of solutions other than crystalloid. Enough fluid must be given to provide adequate cardiac filling pressure. Adequate filling pressure only ensures that one determinant of cardiac performance—preload—has improved. It does not ensure adequate contractility, ejection of blood, and perfusion of tissue beds. A child with nonhemorrhagic hypovolemic shock should respond to 40 mL/kg of crystalloid solution. If a child is unresponsive to this amount of fluid resuscitation, the child must be evaluated for complicating factors. Causes of refractory shock include unrecognized pneumothorax or pericardial effusion, intestinal ischemia (volvulus, intussusception, necrotizing enterocolitis), sepsis, myocardial dysfunction, adrenocortical insufficiency, and pulmonary hypertension.

The first approach to further diagnosis of patients in persistent hypovolemic shock is the establishment of a central venous catheter for measurement of CVP. In the hypotensive patient, a CVP of less than 10 mm Hg, in the absence of pulmonary edema, should be carefully augmented by fluid infusion until that level of preload is reached. If there is no improvement in blood pressure, peripheral perfusion, or urine output, cardiogenic causes of circulatory failure must be considered. Arterial blood gases, hematocrit, serum electrolytes, glucose, and calcium should be reevaluated. Correction of acidosis, hypoxemia, or metabolic derangements is essential. Blood and other appropriate sites must be cultured and broad-spectrum parenteral antibiotic coverage begun if sepsis is suspected. Shock persisting in the face of a CVP exceeding 10 mm Hg may be an indication for placement of a flow-directed thermodilution pulmonary artery catheter and/or an echocardiogram.

Because many factors affect preload measurements, the absolute value of the CVP and pulmonary capillary pressure measurement may be less important than the change in measurement in response to therapeutic interventions. Used this way, these measurements allow detection of limitation in cardiac competence and therefore provide an important guide for volume replacement. Fluid administration should be discontinued when ventricular filling pressure rises without evidence of improvement in cardiovascular performance. At such a time, an inotropic agent may be necessary.

In the case of hemorrhagic hypovolemia, blood must be obtained and transfused if hypotension persists despite early crystalloid infusions. The patient with severe anemia in shock may need emergency transfusion of uncrossmatched blood as part of the initial resuscitation. The hematocrit may be a poor indicator of the severity of hemorrhage because it may not immediately decline in the setting of acute hemorrhagic shock. The possibility of occult intrathoracic or intraabdominal bleeding must be considered. Concomitant with fluid resuscitation of hemorrhagic shock, early surgical intervention may be indicated to control the source of bleeding. In the setting of hemorrhagic shock caused by penetrating trauma in adults, surgical control of the bleeding site may be more important than initial fluid resuscitation in improving patient outcome.¹⁴

Etiology and Pathophysiology

Cardiac shock is the pathophysiologic state in which an abnormality of cardiac function is responsible for the failure of the cardiovascular system to meet the metabolic needs of tissues. The common denominator is depressed cardiac output, which in most instances is the result of decreased myocardial contractility. Cardiogenic shock or congestive heart failure (CHF) during infancy and childhood is a diagnostic and therapeutic challenge because of its myriad etiologies (Box 29-4).

Cardiac function can be depressed in patients with shock of noncardiac origin. Myocardial dysfunction is frequently a late manifestation of shock of any etiology. Although the cause of myocardial dysfunction in such patients is not completely understood, the following mechanisms have been proposed: (1) specific toxic substances released during the course of shock that have a direct cardiac depressant effect, (2) myocardial edema, (3) adrenergic receptor dysfunction, (4) impaired sarcolemmic calcium flux, and (5) reduced coronary blood flow resulting in impaired myocardial systolic and diastolic function.²⁰

Another form of cardiogenic shock is caused by diastolic dysfunction. Impaired myocardial relaxation changes the pressure-to-volume ratio during diastole and increases ventricular pressure at any volume. This lack of myocardial relaxation is hemodynamically unfavorable because increased left ventricular diastolic pressure is transmitted to the lung and results in pulmonary edema and dyspnea. Elevated left ventricular diastolic pressure also decreases myocardial perfusion pressure and can lead to subendocardial ischemia. Such patients present with “heart failure” but may have normal left ventricular systolic function. Diastolic properties of the ventricle appear to be the first to become abnormal in patients with ischemic heart disease or disorders associated with ventricular hypertrophy.^61,62 Therefore when approaching a patient with cardiogenic shock, it is important to characterize both systolic and diastolic function. Therapy designed to improve systolic function may impair myocardial diastolic function (see Chapter 19).⁶²