Shock

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Chapter 64 Shock

Shock is an acute syndrome characterized by the body’s inability to deliver adequate oxygen to meet the metabolic demands of vital organs and tissues. Patients in shock have insufficient oxygen at the tissue level to support normal aerobic cellular metabolism, resulting in a shift to less efficient anaerobic metabolism. Increases in tissue oxygen extraction are unable to compensate for this deficiency in oxygen delivery, leading to progressive lactic acidosis and possible clinical deterioration. If inadequate tissue perfusion persists, adverse vascular, inflammatory, metabolic, cellular, endocrine, and systemic responses worsen the physiologic instability.

Compensation for inadequate oxygen delivery involves a complex set of responses that attempt to preserve oxygenation of the vital organs (i.e., brain, heart, kidneys, liver) at the expense of other organs (i.e., skin, gastrointestinal tract, muscles). Of importance, the brain is especially sensitive to periods of poor oxygen supply, given its lack of capacity for anaerobic metabolism. Initially, shock may be well compensated, but it may rapidly progress to an uncompensated state requiring more aggressive therapies to achieve clinical recovery or improvement. The combination of a continued presence of an inciting trigger and a body’s exaggerated and potentially harmful neurohumoral, inflammatory, and cellular responses leads to the progression of shock. Untreated shock causes irreversible tissue and organ injury (i.e., irreversible shock) and, ultimately, death. Irrespective of the underlying cause of shock, the specific pattern of response, pathophysiology, clinical manifestations, and treatments may vary significantly, depending on the specific etiology (which may be unknown), the clinical circumstances, and an individual patient’s biologic response to the shock state.

Epidemiology

Shock occurs in approximately 2% of all hospitalized infants, children, and adults in the USA (≈400,000 cases/yr), and the mortality rate varies according to the clinical circumstances. Most patients who die do so not in the acute hypotensive phase of shock, but rather as a result of associated complications. Multiple organ dysfunction syndrome (MODS) is defined as any alteration of organ function that requires medical support for maintenance, and the presence of MODS in patients with shock substantially increases the probability of death. In pediatrics, the mortality rate for shock is decreasing as a consequence of educational efforts and the utilization of standardized management guidelines, which emphasize early recognition and intervention along with the rapid transfer of critically ill patients to a pediatric intensive care unit (Fig. 64-1).

Figure 64-1 Algorithm for time-sensitive, goal-directed, stepwise management of hemodynamic support in infants and children. CI, cardiac index; CRRT, continuous renal replacement therapy; CVP, central venous pressure; ECMO, extracorporeal membrane oxygenation; FATD, femoral arterial thermodilution; Hgb, hemoglobin; IM, intramuscular; IO, intraosseous; IV, intravenous; MAP, mean arterial pressure; PICCO, pulse contour cardiac output.

(From Brierly J, Carcillo JA, Choong K, et al: Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine, Crit Care Med 37:666–688, 2009.

Definition

Shock classification systems generally define 5 major types of shock: hypovolemic, cardiogenic, distributive, obstructive, and septic (Table 64-1). Hypovolemic shock, the most common cause of shock in children worldwide, is most frequently caused by diarrhea, vomiting, or hemorrhage. Cardiogenic shock is seen in patients with congenital heart disease (before or after surgery, including heart transplantation) or with congenital or acquired cardiomyopathies, including acute myocarditis. Obstructive shock stems from any lesion that creates a mechanical barrier that impedes adequate cardiac output; examples of this obstructive process are pericardial tamponade, tension pneumothorax, pulmonary embolism, and ductus-dependent congenital heart lesions when systemic blood flow decreases as the ductus arteriosus closes. Distributive shock is caused by inadequate vasomotor tone, which leads to capillary leak and maldistribution of fluid into the interstitium. Septic shock is often discussed synonymously with distributive shock, but the septic process usually involves a more complex interaction of distributive, hypovolemic, and cardiogenic shock.

Table 64-1 TYPES OF SHOCK

Pathophysiology

An initial insult triggers shock, leading to inadequate oxygen delivery to organs and tissues. Compensatory mechanisms attempt to maintain blood pressure by increasing cardiac output and systemic vascular resistance. The body also attempts to optimize oxygen delivery to the tissues by increasing oxygen extraction and redistributing blood flow to the brain, heart, and kidneys (at the expense of the skin and gastrointestinal tract). These responses lead to an initial state of compensated shock, in which blood pressure is maintained. If treatment is not initiated or is inadequate during this period, decompensated shock develops, with hypotension and tissue damage that may lead to multisystem organ dysfunction and ultimately to death (Fig. 64-2, Tables 64-2 and 64-3).

Figure 64-2 Algorithm for decompensated shock.

Table 64-2 CRITERIA FOR ORGAN DYSFUNCTION

ORGAN SYSTEM	CRITERIA FOR DYSFUNCTION
Cardiovascular	Despite administration of isotonic intravenous fluid bolus ≥60 mL/kg in 1 hour: Decrease in BP (hypotension) <5th percentile for age or systolic BP <2 SD below normal for age OR Need for vasoactive drug to maintain BP in normal range (dopamine >5 µg/kg/min or dobutamine, epinephrine, or norepinephrine at any dose) OR Two of the following: Unexplained metabolic acidosis: base deficit > 5.0 mEq/L Increased arterial lactate: >2× upper limit of normal Oliguria: urine output <0.5 mL/kg/hr Prolonged capillary refill: >5 sec Core to peripheral temperature gap >3°C

ORGAN SYSTEM

CRITERIA FOR DYSFUNCTION

Cardiovascular

Despite administration of isotonic intravenous fluid bolus ≥60 mL/kg in 1 hour: Decrease in BP (hypotension) <5th percentile for age or systolic BP <2 SD below normal for age

Need for vasoactive drug to maintain BP in normal range (dopamine >5 µg/kg/min or dobutamine, epinephrine, or norepinephrine at any dose)

Two of the following:

Unexplained metabolic acidosis: base deficit > 5.0 mEq/L

Increased arterial lactate: >2× upper limit of normal

Oliguria: urine output <0.5 mL/kg/hr

Prolonged capillary refill: >5 sec

Core to peripheral temperature gap >3°C

Respiratory

PaO₂/FIO₂ ratio <300 in absence of cyanotic heart disease or pre-existing lung disease

PaCO₂ >65 torr or 20 mm Hg over baseline PaCO₂

Proven need for >50% FIO₂ to maintain saturation ≥92%

Need for nonelective invasive or noninvasive mechanical ventilation

Neurologic

GCS score ≤11

Acute change in mental status with a decrease in GCS score ≥3 points from abnormal baseline

Hematologic

Platelet count <80,000/mm³ or a decline of 50% in the platelet count from the highest value recorded over the last 3 days (for patients with chronic hematologic or oncologic disorders)

INR >2

Renal Serum creatinine ≥2× upper limit of normal for age or 2-fold increase in baseline creatinine value Hepatic

Total bilirubin ≥4 mg/dL (not applicable for newborn)

Alanine transaminase level 2× upper limit of normal for age

BP, blood pressure; GCS, Glasgow Coma Scale; INR, International Normalized Ratio; SD, standard deviation.

Table 64-3 SIGNS OF DECREASED PERFUSION

In the early phases of shock, multiple compensatory physiologic mechanisms act to maintain blood pressure and preserve tissue perfusion and oxygen delivery. These responses include increases in heart rate, stroke volume, and vascular smooth muscle tone, which are regulated through sympathetic nervous system activation and neurohormonal responses. Increased respiratory rate with greater CO₂ elimination is a compensatory response to the metabolic acidosis and increased CO₂ production from poor tissue perfusion. Renal excretion of hydrogen ions and retention of bicarbonate also increase in an effort to maintain normal body pH (Chapter 52.7). Maintenance of intravascular volume is facilitated via sodium regulation through the renin-angiotensin-aldosterone and atrial natriuretic factor axes, cortisol and catecholamine synthesis and release, and antidiuretic hormone secretion. Despite these compensatory mechanisms, the underlying shock and host response lead to vascular endothelial cell injury and significant leakage of intravascular fluids into the interstitial extracellular space.

All forms of shock affect cardiac output via several mechanisms. Changes in heart rate, preload, afterload, and myocardial contractility may occur separately or in combination (Table 64-4). Hypovolemic shock is characterized primarily by fluid loss and decreased preload. Tachycardia and an increase in systemic vascular resistance are the initial compensatory responses to maintain cardiac output and systemic blood pressure. Without adequate volume replacement, hypotension develops, followed by tissue ischemia and further clinical deterioration. When there is pre-existing low plasma oncotic pressure (due to nephrotic syndrome, malnutrition, hepatic dysfunction, acute severe burns, etc.), even further volume loss and exacerbation of shock may occur because of endothelial breakdown and worsening capillary leak.

Table 64-4 PATHOPHYSIOLOGY OF SHOCK

EXTRACORPOREAL FLUID LOSS

Hypovolemic shock may be due to direct blood loss through hemorrhage or abnormal loss of body fluids (diarrhea, vomiting, burns, diabetes mellitus or insipidus, nephrosis)

LOWERING PLASMA ONCOTIC FORCES

Hypovolemic shock may also result from hypoproteinemia (liver injury, or as a progressive complication of increased capillary permeability)

ABNORMAL VASODILATION

Distributive shock (neurogenic, anaphylaxis, or septic shock) occurs when there is loss of vascular tone—venous, arterial, or both (sympathetic blockade, local substances affecting permeability, acidosis, drug effects, spinal cord transection)

INCREASED VASCULAR PERMEABILITY

Sepsis may change the capillary permeability in the absence of any change in capillary hydrostatic pressure (endotoxins from sepsis, excess histamine release in anaphylaxis)

CARDIAC DYSFUNCTION

Peripheral hypoperfusion may result from any condition that affects the heart’s ability to pump blood efficiently (ischemia, acidosis, drugs, constrictive pericarditis, pancreatitis, sepsis)

In contrast, the underlying pathophysiologic mechanism leading to distributive shock is a state of abnormal vasodilation. Sepsis, hypoxia, poisonings, anaphylaxis, spinal cord injury, or mitochondrial dysfunction can cause vasodilatory shock (Fig. 64-3). The lowering of systemic vascular resistance (SVR) is accompanied initially by a maldistribution of blood flow away from vital organs and a compensatory increase in cardiac output. This process leads to significant decreases in both preload and afterload. Therapies for distributive shock must address both of these problems simultaneously.

Figure 64-3 Mechanisms of vasodilatory shock. Septic shock and states of prolonged shock causing tissue hypoxia with lactic acidosis increase nitric oxide synthesis, activate the adenosine triphosphate (ATP)–sensitive and calcium-regulated potassium channels (K_ATP and K_Ca, respectively) in vascular smooth muscle, and lead to depletion of vasopressin. cGMP, cyclic guanosine monophosphate.

(From Landry DW, Oliver JA: The pathogenesis of vasodilatory shock, N Engl J Med 345:588–595, 2001.)

Cardiogenic shock may be seen in patients with myocarditis, cardiomyopathy, congenital heart disease, or arrhythmias, or following cardiac surgery (Chapter 433). In these instances, myocardial contractility is affected, leading to systolic and/or diastolic dysfunction. The later phases of all forms of shock frequently have a negative impact on the myocardium, leading to development of a cardiogenic component to the shock state.

Septic shock is often a unique combination of distributive, hypovolemic, and cardiogenic shock. Hypovolemia from intravascular fluid losses occurs through capillary leak. Cardiogenic shock results from the myocardium-depressant effects of sepsis, and distributive shock is the result of decreased systemic vascular resistance. The degree to which a patient exhibits each of these responses varies, but there are frequently alterations in preload, afterload, and myocardial contractility.

In septic shock, it is important to distinguish between the inciting infection and the host inflammatory response. Normally, host immunity prevents the development of sepsis via activation of the reticular endothelial system along with the cellular and humoral immune systems. This host immune response produces an inflammatory cascade of toxic mediators, including hormones, cytokines, and enzymes. If this inflammatory cascade is uncontrolled, derangement of the microcirculatory system leads to subsequent organ and cellular dysfunction.

The systemic inflammatory response syndrome (SIRS) is an inflammatory cascade that is initiated by the host response to an infectious or noninfectious trigger (Table 64-5). This inflammatory cascade is triggered when the host defense system does not adequately recognize and/or clear the triggering event. The inflammatory cascade initiated by shock can lead to hypovolemia, cardiac and vascular failure, acute respiratory distress syndrome (ARDS), insulin resistance, decreased cytochrome P450 (CYP450) activity (decreased steroid synthesis), coagulopathy, and unresolved or secondary infection. Tumor necrosis factor (TNF) and other inflammatory mediators increase vascular permeability, causing diffuse capillary leak, decreased vascular tone, and an imbalance between perfusion and metabolic demands of the tissues. TNF and interleukin-1 (IL-1) stimulate the release of pro-inflammatory and anti-inflammatory mediators, causing fever and vasodilatation. Arachidonic acid metabolites lead to the development of fever, tachypnea, ventilation-perfusion abnormalities, and lactic acidosis. Nitric oxide, released from the endothelium or inflammatory cells, is a major contributor to hypotension. Myocardial depression is caused by myocardium-depressant factors, TNF, and some interleukins through direct myocardial injury, depleted catecholamines, increased β-endorphin, and production of myocardial nitric oxide.

Table 64-5 DIFFERENTIAL DIAGNOSIS OF SYSTEMIC INFLAMMATORY RESPONSE SYNDROME

INFECTION

Bacteremia or meningitis (Streptococcus pneumoniae, Haemophilus influenzae type b, Neisseria meningitidis, group A streptococcus, S. aureus)

Viral illness (influenza, enteroviruses, hemorrhagic fever group, herpes simple virus, respiratory syncytial virus, cytomegalovirus, Epstein-Barr virus)

Encephalitis (arboviruses, enteroviruses, herpes simplex virus)

Rickettsiae (Rocky Mountain spotted fever, Ehrlichia, Q fever)

Syphilis

Vaccine reaction (pertussis, influenza, measles)

Toxin-mediated reaction (toxic shock, staphylococcal scalded skin syndrome)

CARDIOPULMONARY

Pneumonia (bacteria, virus, mycobacteria, fungi, allergic reaction)

METABOLIC-ENDOCRINE

Adrenal insufficiency (adrenogenital syndrome, corticosteroid withdrawal)

Electrolyte disturbances (hyponatremia or hypernatremia; hypocalcemia or hypercalcemia)

Diabetes insipidus

Diabetes mellitus

Inborn errors of metabolism (organic acidosis, urea cycle, carnitine deficiency, mitochondrial disorders)

Hypoglycemia

Reye syndrome

GASTROINTESTINAL

Gastroenteritis with dehydration

Volvulus

Intussusception

Appendicitis

Peritonitis (spontaneous, associated with perforation or peritoneal dialysis)

Necrotizing enterocolitis

Hepatitis

Hemorrhage

Pancreatitis

HEMATOLOGIC

Anemia (sickle cell disease, blood loss, nutritional)

Methemoglobinemia

Splenic sequestration crisis

Leukemia or lymphoma

Hemophagocytic syndromes

NEUROLOGIC

Intoxication (drugs, carbon monoxide, intentional or accidental overdose)

Intracranial hemorrhage

Infant botulism

Trauma (child abuse, accidental)

Guillain-Barré syndrome

Myasthenia gravis

OTHER

Anaphylaxis (food, drug, insect sting)

Hemolytic-uremic syndrome

Kawasaki disease

Erythema multiforme

Hemorrhagic shock–encephalopathy syndrome

Poisoning

Toxic envenomation

Macrophage activation syndrome

The inflammatory cascade (Fig. 64-4) is initiated by toxins or superantigens via macrophage binding or lymphocyte activation. The vascular endothelium is both a target of tissue injury and a source of mediators that may cause further injury. Biochemical responses include the production of arachidonic acid metabolites, release of myocardial depressant factors, release of endogenous opiates, activation of the complement system, as well as the production and release of many other mediators, which may be either pro-inflammatory or anti-inflammatory. The balance between these mediator groups for an individual patient contributes to the progression of disease and affects the chance for survival.

Figure 64-4 Hypothetical pathophysiology of the septic process.

Clinical Manifestations

A classification system for shock is shown in Table 64-1. Categorization is important, but there may be significant overlap among these groups, especially in septic shock. The clinical presentation of shock depends in part on the underlying etiology. If unrecognized and untreated, all forms of shock follow a common and untoward progression of clinical signs and pathophysiologic changes that may ultimately lead to irreversible shock and death (see Fig. 64-2).

Shock may initially manifest as only tachycardia or tachypnea. Progression leads to decreased urine output, poor peripheral perfusion, respiratory distress or failure, alteration of mental status, and low blood pressure (see Table 64-3). A significant misconception is that shock occurs only with low blood pressure. Because of compensatory mechanisms, hypotension is often a late finding and is not a criterion for the diagnosis of shock. Tachycardia, with or without tachypnea, may be the first or only sign of early compensated shock. Hypotension reflects an advanced state of decompensated shock and is associated with increased mortality.

Hypovolemic shock often manifests initially as orthostatic hypotension and is associated with dry mucous membranes, dry axillae, poor skin turgor, and decreased urine output. Depending on the degree of dehydration, the patient with hypovolemic shock may present with either normal or slightly cool distal extremities, and peripheral or even central (femoral) pulses may be normal, decreased, or absent. Because of decreased cardiac output and compensatory peripheral vasoconstriction, the presenting signs of cardiogenic shock are tachypnea, cool extremities, delayed capillary filling time, poor peripheral and/or central pulses, declining mental status, and decreased urine output (Chapter 436.1). Obstructive shock often also manifests as inadequate cardiac output due to a physical restriction of forward blood flow; the acute presentation may quickly progress to cardiac arrest. Distributive shock manifests initially as peripheral vasodilation and increased but inadequate cardiac output.

Regardless of etiology, uncompensated shock, with hypotension, high systemic vascular resistance, decreased cardiac output, respiratory failure, obtundation, and oliguria, occurs late in the progression of disease. Hemodynamic findings in various shock states are listed in Table 64-6. Additional clinical findings in shock include cutaneous lesions such as petechiae, diffuse erythema, ecchymoses, ecthyma gangrenosum, and peripheral gangrene. Jaundice can be present either as a sign of infection or as a result of MODS.

Table 64-6 HEMODYNAMIC VARIABLES IN DIFFERENT SHOCK STATES

Sepsis is defined as SIRS resulting from a suspected or proven infectious etiology. The clinical spectrum of sepsis begins when a systemic (e.g., bacteremia, rickettsial disease, fungemia, viremia) or localized (e.g., meningitis, pneumonia, pyelonephritis) infection progresses from sepsis to severe sepsis (the presence of sepsis combined with organ dysfunction). Further deterioration leads to septic shock (severe sepsis plus the persistence of hypoperfusion or hypotension despite adequate fluid resuscitation or a requirement for vasoactive agents), MODS, and possibly death (Table 64-7). This is a complex spectrum of clinical problems that is a leading cause of mortality in children worldwide. Outcomes improve with early recognition and treatment.

Table 64-7 INTERNATIONAL CONSENSUS DEFINITIONS FOR PEDIATRIC SEPSIS

Infection

Suspected or proven infection or a clinical syndrome associated with high probability of infection

Systemic inflammatory response syndrome (SIRS)

2 out of 4 criteria, 1 of which must be abnormal temperature or abnormal leukocyte count:

1 Core temperature >38.5°C or <36°C (rectal, bladder, oral, or central catheter)

2 Tachycardia:

Mean heart rate >2 SD above normal for age in absence of external stimuli, chronic drugs or painful stimuli

Unexplained persistent elevation over 0.5-4 hr

In children <1 year old, persistent bradycardia over 0.5 hour (mean heart rate <10th percentile for age in absence of vagal stimuli, β-blocker drugs, or congenital heart disease)

3 Respiratory rate >2 SD above normal for age or acute need for mechanical ventilation not related to neuromuscular disease or general anesthesia

4 Leukocyte count elevated or depressed for age (not secondary to chemotherapy) or >10% immature neutrophils

Sepsis SIRS plus a suspected or proven infection Severe sepsis Sepsis plus 1 of the following:

2 Acute respiratory distress syndrome (ARDS) as defined by the presence of a PaO₂/FIO₂ ratio ≤300 mm Hg, bilateral infiltrates on chest radiograph, and no evidence of left heart failure

Sepsis plus 2 or more organ dysfunctions (respiratory, renal, neurologic, hematologic, or hepatic)

Septic shock Sepsis plus cardiovascular organ dysfunction as defined above Multiple organ dysfunction syndrome (MODS) Presence of altered organ function such that homeostasis cannot be maintained without medical intervention

SD, standard deviation.

Although septic shock is primarily distributive in nature, other and multiple elements of pathophysiology are represented in this disease process. The initial signs and symptoms of sepsis include alterations in temperature regulation (hyperthermia or hypothermia), tachycardia, and tachypnea. In the early stages (hyperdynamic phase or “warm” shock), the cardiac output increases in an attempt to maintain adequate oxygen delivery and meet the greater metabolic demands of the organs and tissues. As septic shock progresses, cardiac output falls in response to the effects of numerous inflammatory mediators, leading to a compensatory elevation in systemic vascular resistance and the development of “cold” shock.

Diagnosis

Shock is diagnosed clinically on the basis of a thorough history and physical exam (see Tables 64-2 and 64-3). Of note, septic shock has a specific consensus conference definition (see Table 64-7). In cases of suspected septic shock, an infectious etiology should be sought through culture of clinically appropriate specimens and prompt initiation of empiric antimicrobial therapy based on patient age, underlying disease, and geographic location. Cultures take time for incubation and their results may not always be positive. Additional evidence for identifying an infectious etiology as the cause of SIRS includes physical examination findings, imaging findings, presence of white blood cells in normally sterile body fluids, and suggestive rashes such as petechiae and purpura. Affected children should be admitted to an intensive care unit or other highly monitored environment, as indicated by clinical status and the resources of the medical facility, where continuous, close invasive monitoring can be performed, including central venous pressure and arterial blood pressure monitoring as clinically indicated.

Laboratory Findings

Laboratory findings often include evidence of hematologic abnormalities and electrolyte disturbances. Hematologic abnormalities may include thrombocytopenia, prolonged prothrombin and partial thromboplastin times, reduced serum fibrinogen level, elevations of fibrin split products, and anemia. Elevated neutrophil counts and increased immature forms (i.e., bands, myelocytes, promyelocytes), vacuolation of neutrophils, toxic granulations, and Döhle bodies can be seen with infection. Neutropenia or leukopenia may be an ominous sign of overwhelming sepsis.

Glucose dysregulation, a common stress response, may manifest as hyperglycemia or hypoglycemia. Other electrolyte abnormalities are hypocalcemia, hypoalbuminemia, and metabolic acidosis. Renal and/or hepatic function may also be abnormal. Patients with ARDS or pneumonia have impairment of oxygenation (decreased PaO₂) as well as of ventilation (increased PaCO₂) in the later stages of lung injury (Chapter 65).

The hallmark of uncompensated shock is an imbalance between oxygen delivery (DO₂) and oxygen consumption (). This state is manifested clinically by increased lactic acid production (high anion gap, metabolic acidosis) due to anaerobic metabolism and a low mixed venous oxygen saturation () due to the compensatory increase in tissue oxygen extraction. The gold standard measurement of is from a pulmonary arterial catheter measurements from this location are often not clinically feasible. Sites such as the right ventricle, right atrium, superior vena cava (SvcO₂), or inferior vena cava are often used as for surrogate measures of mixed venous blood.

Oxygen delivery normally exceeds oxygen consumption by threefold. The oxygen extraction ratio is approximately 25%, thus producing a normal of 75-80%. A falling value, as measured by co-oximetry, reflects an increasing oxygen extraction ratio and documents a decrease in oxygen delivery relative to consumption. This increase in oxygen extraction by the end-organs is an attempt to maintain adequate oxygen delivery at the cellular level. Along with , serum lactate measurements may be used as a marker for the adequacy of oxygen delivery and the effectiveness of therapeutic interventions.

Treatment

Initial Management

Early recognition and prompt intervention are extremely important in the management of all forms of shock (Table 64-8). Baseline mortality is much lower in pediatric shock than in adult shock, and further improvements in mortality may occur with early interventions (see Fig. 64-1). The initial assessment and treatment of the pediatric shock patient should include stabilization of airway, breathing, and circulation (the ABCs) as established by the American Heart Association’s pediatric advanced life support (PALS) and neonatal advanced life support (NALS) guidelines (Chapter 62). Depending on the severity of shock, further airway intervention, including intubation and mechanical ventilation, may be necessary to lessen the workload of breathing and decrease the body’s overall metabolic demands. Neonates and infants in particular may have profound glucose dysregulation in association with shock. Glucose levels should be checked routinely and treated appropriately, especially early in the course of illness.

Table 64-8 GOAL-DIRECTED THERAPY OF ORGAN SYSTEM DYSFUNCTION IN SHOCK

Given the predominance of sepsis and hypovolemia as the most common causes of shock in the pediatric population, most therapeutic regimens are based on guidelines established in these settings. Immediately following establishment of intravenous (IV) or intraosseous (IO) access, aggressive, early goal-directed therapy (EGDT) should be initiated unless there are significant concerns for cardiogenic shock as an underlying pathophysiology. Rapid IV administration of 20 mL/kg isotonic saline or, less often, colloid should be initiated in an attempt to reverse the shock state. This bolus should be repeated quickly up to 60-80 mL/kg; it is not unusual for severely affected patients to require this volume within the first hour.

If shock remains refractory following 60-80 mL/kg of volume resuscitation, inotropic therapy (dopamine, norepinephrine, or epinephrine) should be instituted while additional fluids are administered. Current guidelines recommend administration of these inotropic agents via peripheral intravenous (PIV) lines, with very close monitoring of the PIV sites while central venous access is being obtained, because a delay in the initiation of inotropes in shock has been associated with increased mortality.

Rapid fluid resuscitation using 60-80 mL/kg or more is associated with improved survival without an increased incidence of pulmonary edema. Fluid resuscitation in increments of 20 mL/kg should be titrated to normalize heart rate (according to age-based heart rates), urine output (to 1 mL/kg/hr), capillary refill time (to <2 sec), and mental status. Fluid resuscitation may sometimes require as much as 200 mL/kg. It must be stressed that hypotension is often a late and ominous finding, and normalization of blood pressure alone is not a reliable endpoint for assessing the effectiveness of resuscitation. Although the type of fluid (crystalloid vs colloid) is an area of ongoing debate, fluid resuscitation in the first hour is unquestionably essential to survival in septic shock, regardless of the fluid type administered.

Additional Early Considerations

In septic shock specifically, early administration of broad-spectrum antimicrobial agents is associated with a reduction in mortality. The choice of antimicrobial agents depends on the predisposing risk factors and the clinical situation. Bacterial resistance patterns in the community and/or hospital should be considered in the selection of optimal antimicrobial therapy. Neonates should be treated with ampicillin plus cefotaxime and/or gentamicin. Acyclovir should be added if herpes simplex virus is suspected clinically. In infants and children, community-acquired infections with Neisseria meningitidis can be treated empirically with a 3rd-generation cephalosporin (ceftriaxone or cefotaxime) or high-dose penicillin. Haemophilus influenzae infections can be treated empirically with a 3rd-generation cephalosporin (ceftriaxone or cefotaxime). The prevalence of resistant Streptococcus pneumoniae often requires the addition of vancomycin, depending on the specific clinical scenario. Suspicion of community- or hospital-acquired, methicillin-resistant Staphylococcus aureus infection warrants coverage with vancomycin, depending on local resistance patterns. If an intra-abdominal process is suspected, anaerobic coverage should be included with an agent such as metronidazole, clindamycin, or piperacillin-tazobactam.

Nosocomial sepsis should generally be treated with at least a 3rd- or 4th-generation cephalosporin or a penicillin with an extended gram-negative spectrum (e.g., piperacillin-tazobactam). An aminoglycoside should be added as the clinical situation warrants. Vancomycin should be added to the regimen if the patient has an indwelling medical device (Chapter 172), gram-positive cocci are isolated from the blood, or methicillin-resistant S. aureus infection is suspected, or as empiric coverage for S. pneumoniae in a patient with meningitis. Empirical coverage for fungal infections should be considered for selected immunocompromised patients (Chapter 171). It should be noted that these are broad, generalized recommendations that must be tailored to the individual clinical scenario and to the local resistance patterns of the community and/or hospital.

Distributive shock that is not secondary to sepsis is caused by a primary abnormality in vascular tone. Cardiac output in affected patients is usually maintained and may initially be supranormal. These patients may benefit temporarily from volume resuscitation, but the early initiation of a vasoconstrictive agent to increase SVR is an important element of clinical care. Patients with spinal cord injury and spinal shock may benefit from either phenylephrine or vasopressin to increase SVR. Epinephrine is the treatment of choice for patients with anaphylaxis (Table 64-9). This agent has peripheral α-adrenergic as well as inotropic effects that may improve the myocardial depression seen with anaphylaxis and its associated inflammatory response (Chapter 143).

Table 64-9 CARDIOVASCULAR DRUG TREATMENT OF SHOCK

Patients with cardiogenic shock have poor cardiac output secondary to systolic and/or diastolic myocardial depression, often with a compensatory elevation in SVR. These patients may show poor response to aggressive fluid resuscitation and, in fact, may demonstrate decompensation quickly when fluids are administered. Smaller boluses of fluid (5-10 mL/kg) should be given in cardiogenic shock. In any patient with shock whose clinical status deteriorates with fluid resuscitation, a cardiogenic etiology should be considered, and further administration of intravenous fluids should be performed cautiously. Early initiation of myocardial support with dopamine or epinephrine to improve cardiac output is important in this context. Consideration should be given to administering an inodilator, such as milrinone, early in the process.

Despite adequate cardiac output with the support of inotropic agents, a high SVR with poor peripheral perfusion and acidosis may persist in cardiogenic shock. Therefore, if not already started, milrinone therapy may improve systolic function and decrease SVR without causing a significant increase in heart rate. Furthermore, this agent has the added benefit of enhancing diastolic relaxation. Dobutamine or other vasodilating agents, such as nitroprusside, may also be considered in this setting (Table 64-10). Dosage titration of these agents should target clinical endpoints, including increased urine output, improved peripheral perfusion, resolution of acidosis, and normalization of mental status. Agents that improve blood pressure by increasing SVR, such as norepinephrine and vasopressin, should generally be avoided in patients with cardiogenic shock (although they may be helpful for other causes of shock). These agents may cause further decompensation and potentially precipitate cardiac arrest as a result of the increased afterload and additional work imposed on the myocardium. The combination of inotropic and vasoactive agents administered must be tailored to the pathophysiology of the individual patient. Close and frequent reassessment of the patient’s cardiovascular status is essential.

Table 64-10 VASODILATORS/AFTERLOAD REDUCERS

For patients with obstructive shock, fluid resuscitation may be briefly temporizing in maintaining cardiac output, but the primary insult must be immediately addressed. Examples of lifesaving therapeutic interventions for such patients are pericardiocentesis for pericardial effusion, pleurocentesis or chest tube placement for pneumothorax, thrombectomy/thrombolysis for pulmonary embolism, and the initiation of a prostaglandin infusion for ductus-dependent cardiac lesions. There is often a “last drop” or “last straw” phenomenon associated with some obstructive lesions, in that further small amounts of intravascular volume depletion may lead to a rapid deterioration, including cardiac arrest, if the obstructive lesion is not corrected.

Regardless of the etiology of shock, metabolic status should be meticulously maintained (see Table 64-8). Electrolyte levels should be monitored closely and corrected as needed. Hypoglycemia is common and should be promptly treated. Hypocalcemia, which may contribute to myocardial dysfunction, should be treated with a goal of normalizing the ionized calcium concentration. There is no evidence that supranormal calcium levels benefit the myocardium, and hypercalcemia may actually be associated with increased myocardial toxicity.

Hydrocortisone replacement may be beneficial in pediatric shock. Up to 50% of critically ill patients may have absolute or relative adrenal insufficiency. Patients at risk for adrenal insufficiency include those with congenial adrenal hypoplasia, abnormalities of the hypothalamic-pituitary axis, and recent therapy with corticosteroids (including patients with asthma, rheumatic diseases, malignancies, and inflammatory bowel disease). These patients are at high risk for adrenal dysfunction and should receive stress doses of hydrocortisone. Steroids may also be considered in patients with shock that is unresponsive to fluid resuscitation and catecholamines. Determination of baseline cortisol levels prior to steroid administration may be beneficial in guiding therapy, although this idea remains controversial.

Considerations for Continued Therapy

After the first hour of therapy and attempts at early reversal of shock, focusing of therapies on goal-directed endpoints should continue in an intensive care setting (see Fig. 64-1 and Table 64-8). These clinical endpoints serve as global markers for organ perfusion and oxygenation. Laboratory parameters such as (or ScvO₂), serum lactate concentration, cardiac index, and hemoglobin level serve as adjunctive measures of tissue oxygen delivery. On the basis of guidelines published in 2009, hemoglobin should be maintained >10 g/dL, (or ScvO₂) >70%, and cardiac index at 3.3-6 L/min/m² to optimize oxygen delivery in the acute phase of shock (although it should be noted that cardiac index is rarely monitored in the clinical setting owing to the limited use of pulmonary artery catheters and the lack of accurate noninvasive cardiac output monitors for infants and children). Blood lactate levels and calculation of base deficit from arterial blood gas values are very useful markers for the adequacy of oxygen delivery. It is important to note that these parameters are all indicators of global oxygen delivery and utilization, but there are no currently available clear indicators for adequate measurement of local tissue oxygenation.

Respiratory support should be used as clinically appropriate. When shock leads to ARDS or acute lung injury (ALI) requiring mechanical ventilation, lung-protective strategies to keep plateau pressure below 30 cm H₂O and maintain tidal volume at 6 mL/kg have been shown to improve mortality in adult patients (Chapter 65). These data are extrapolated to pediatric patients because of the lack of definitive pediatric studies in this area. Additionally, after the initial shock state has been reversed, renal replacement therapy and fluid removal may also be useful in children with anuria or oliguria and resultant severe fluid overload (Chapter 529). Intravenous immunoglobulin infusion or plasmapheresis may also be considered in certain circumstances as therapeutic adjuncts for shock. Other interventions include correction of coagulopathy with fresh frozen plasma or cryoprecipitate and platelet transfusions as necessary, especially in the presence of active bleeding.

In addition to symptomatic care and treatment of any underlying infectious causes, therapies to augment host defense, block trigger events, prevent leukocyte-endothelium interaction, and inhibit vasoactive substances, cytokines, or lipid mediators are being investigated. To date, the results of clinical trials investigating drugs targeting the mediators of SIRS have been disappointing. Trials have been conducted with anti-endotoxin antibodies, antioxidant compounds, an IL-1 receptor antagonist, IL-1 antibodies, bradykinin receptor antibodies, cyclooxygenase inhibitors, thromboxane antagonists, platelet-activating factor (PAF) antagonists, inhibitors of leukocyte adhesion molecules, nitric oxide antagonists, anti-TNF antibody, bactericidal permeability–increasing protein, and recombinant human activated protein C (drotrecogin-α). Studies of drotrecogin-α have shown improvement in the 28-day survival rate in adults, but enrollment in the pediatric trial was closed early because of an increased risk of intracranial bleeding and an unfavorable risk : benefit ratio, particularly in neonates. The best treatment for shock consists of early recognition, early antimicrobial therapy (for suspected septic shock), aggressive fluid resuscitation (except in cardiogenic shock), and early goal-directed therapy.

If shock remains refractory despite maximal therapeutic interventions, mechanical support with extracorporeal membrane oxygenation (ECMO) or a ventricular assist device (VAD) may be indicated. ECMO may be lifesaving in cases of refractory shock regardless of underlying etiology. Similarly, a VAD may be indicated for refractory cardiogenic shock in the setting of cardiomyopathy or recent cardiac surgery. Systemic anticoagulation, which is required while patients are receiving mechanical support, may be difficult, given the significant coagulopathy often encountered in refractory shock, especially when the underlying etiology is sepsis. Mechanical support in refractory shock poses substantial risks but can improve survival in specific populations of patients.