Chapter 19: Shock

• Tachycardia and pallor should be treated as shock until proven otherwise.

• Effortless tachypnea signifies respiratory compensation for metabolic acidosis.

• Hypotension in pediatrics heralds impending cardiac arrest.

• Hypovolemic shock is the most common cause of shock worldwide.

• Early and aggressive therapy for shock is necessary to restore oxygenation and tissue perfusion.

• Overaggressive fluid resuscitation in cardiogenic shock can be harmful—listen for rales or gallops. Feel for enlarged liver or spleen.

Shock is a reflection of inadequate oxygen and substrate delivery to cells relative to metabolic demand. Oxygen delivery depends on multiple variables and includes heart rate, preload, contractility, afterload, hemoglobin content, oxygen saturation, and dissolved oxygen in the blood (Fig. 19-1). Disease processes create alterations in the above variables and the body has developed compensatory mechanisms to adjust. When the ability to adjust is exceeded, there is progression to impairment of organ function, irreversible organ failure, and death.

Children differ from adults with respect to their anatomy and physiology. In infants, cardiac output is dependent on heart rate since stroke volume is relatively fixed. In contrast, insufficient cardiac output is often due to low stroke volume. Maintaining oxygen delivery to tissues activates compensatory mechanisms. The first line of defense in maintaining cardiac output is tachycardia and this is the first subtle sign of shock.¹ Other common reasons for tachycardia in the emergency department other than shock include fever, pain, anxiety, hypoxia, and medications (e.g., albuterol).

The next compensatory mechanism is the redirection of blood from nonvital to vital organs through increasing systemic vascular resistance. Blood is shunted away from the skin, gut, kidneys, and muscle and is clinically reflected by cool extremities, delayed capillary refill, and decreased urine output. Mechanisms such as increase in contractility and increasing smooth muscle tone to move blood from the venous system to the heart are other ways to augment increases in cardiac output.

The physiologic “fight or flight” response to stress involves central and sympathetic nervous system activation. Catecholamines increase cardiac output by increasing heart rate and stroke volume and the result is an increase in blood pressure. Glucagon is also released to provide glucose via glycogenolysis and gluconeogenesis.

In contrast, the shock response results from decreased oxygen and energy substrate delivery. The levels of cortisol and catecholamines are 5 to 10 times higher in the shock state compared with the stress response.² Intravascular volume is preserved and oliguria results. Supraphysiologic levels of cortisol and catecholamines with glucagon cause hyperglycemia. Ironically, hyperglycemia in sepsis is considered potentially harmful since research suggests that it impairs neutrophil function,^3,4 acts as a procoagulant, induces cellular apoptosis, increases risk of infection, and impairs wound healing.³

Shock can be subcategorized into compensated and hypotensive (uncompensated) shock. Presence of inadequate perfusion with normal systolic blood pressure maintained by compensatory mechanisms delineates compensated shock. Signs of inadequate perfusion include tachycardia, delayed capillary refill, cool pale skin, and weak pulses. Once the body is unable to physiologically maintain normal systolic blood pressure, hypotension results and heralds impending cardiac arrest. The transition from compensated to hypotensive shock progresses along a physiologic continuum. Deterioration in mental status is a clinical observation that is indicative of compromised perfusion to the brain.

Shock can be subdivided into four general categories: hypovolemic, distributive, cardiogenic, and obstructive (Table 19-1). These categories of shock have pathophysiologic etiologies related to components of stroke volume (preload), contractility, and afterload. Preload is the volume of blood present in the ventricle before contraction and is estimated by the central venous pressure (CVP). Total blood volume in a newborn is estimated at 85 mL/kg, whereas in infants it is estimated to be 65 mL/kg.² Distribution of blood in the arterial, veins, and capillaries is estimated to be 8%, 70%, and 12%, respectively.² Contractility is defined as the strength of contraction. Afterload is the resistance through which the ventricle is contracting. Together, these components affect the volume of blood ejected by the heart with each beat.

Hypovolemia is the most common cause of shock in children worldwide.¹ Fluid losses due to diarrhea and electrolyte abnormalities are a major cause of infant mortality in the Third World countries. Other causes of hypovolemic shock include acute hemorrhage following trauma, burns, and osmotic diuresis from diabetic ketoacidosis.

Volume depletion results in reduced preload and stroke volume with compensatory tachycardia. In acute hemorrhage from trauma, the reduction volume is compounded with the concomitant reduction in hemoglobin. Decreased cardiac output and oxygen content synergistically reduce oxygen delivery. Compensatory mechanisms such as catecholamines increase heart rate, contractility, and systemic vascular resistance, whereas the neuroendocrine system facilitates retention of sodium and water. Failure to correct volume depletion and oxygen-carrying capacity will progress to organ dysfunction, circulatory failure, and death.

Distributive shock is characterized by inappropriate distribution of blood volume causing inadequate organ and tissue perfusion. The three types of distributive shock include septic shock, anaphylactic shock, and neurogenic shock. All three have common features that include problems with vascular tone and integrity in the venous, capillary, or arterial vessels. The high cardiac output in distributive shock is unique since the other forms of shock all have low cardiac outputs.¹

An international consensus definition of sepsis is infection plus systemic manifestations of infection (i.e., fever, tachycardia, tachypnea, or leukocytosis). Severe sepsis is sepsis with sepsis-induced organ dysfunction or tissue hypoperfusion (i.e., hypotension, hypoxemia, oliguria, metabolic acidosis, thrombocytopenia, or obtundation). Septic shock is defined as sepsis-induced hypotension despite adequate fluid resuscitation.^3,5

Sepsis is the culmination of complex interactions between infecting organisms and host immune, inflammatory, and coagulation responses. Existing research suggests that although early sepsis may be characterized by increases in pro-inflammatory mediators, as sepsis persists, there is a shift toward an anti-inflammatory immunosuppressive state.^3,4

Neurogenic shock is often due to acute spinal cord injury with resultant disruption of sympathetic control of blood vessels and the heart. Commonly caused by cervical trauma, injuries to the thoracic spine above T6 can result in failure of sympathetic tone and subsequent neurogenic shock leading to decreased peripheral resistance, hypotension, bradycardia, and decreased cardiac output.⁷

Anaphylaxis is a type I hypersensitivity reaction⁸ leading to the release of mediators that cause increase in vascular permeability, bronchospasm, and vasodilation.¹ Most common causes of anaphylaxis in children are foods (peanut, tree nuts, shellfish, fish, milk, and eggs),⁹ medications, Hymenoptera (wasps, bees, and ants) envenomations, blood products, latex, vaccines, and radiographic contrast media.⁸ Diagnosis depends on involvement of two organ systems, but may present as an acute cardiac or respiratory event or with hypotension as the only manifestation. Target organs involved include skin (80%–90% of episodes), respiratory tract (70% of episodes), gastrointestinal tract (30%–45% of episodes), heart and vascular (10%–45% of episodes), and CNS (10%–15% of episodes).⁹

Cardiogenic shock is defined as persistent hypotension and tissue hypoperfusion due to cardiac dysfunction.¹⁰ Cardiac dysfunction can be associated with poor contractility (i.e., myocarditis, cardiomyopathy, sepsis, infarction, trauma, poisoning, or toxicity), structural abnormalities (i.e., congenital heart disease), and rhythm disturbances (i.e., arrhythmia). The hallmark of cardiogenic shock is low cardiac output and high systemic vascular resistance.¹

Cardiac muscle fibers are unique as they have the ability to increase contractility when stretched as long as the fibers are not overstretched. Increased venous return and, therefore, preload causes a greater force of contraction and results in increased stroke volume and cardiac output. When the fibers are overstretched however, contractility decreases and heart failure occurs. Dysfunctional cardiac contractility results in poor cardiac output and blood pressure. The compensatory neurohormonal response leads to tachycardia, systemic vasoconstriction, and fluid retention. This response is harmful in cardiogenic shock since tachycardia increases myocardial oxygen demand shifting aerobic to anaerobic metabolism with resultant lactic acid production. In addition, increased vasoconstriction increases afterload and leads to decreased stroke volume and compromises cardiac output further.

Obstructive shock occurs when cardiac output is compromised due to physical obstruction of blood flow. Types of obstructive shock include cardiac tamponade, tension pneumothorax, ductal-dependent congenital heart lesions, and massive pulmonary embolism.¹ Obstruction leads to diminished cardiac output and compensatory systems cause tachycardia and increased systemic vascular resistance.

Cardiac tamponade occurs when fluid or air accumulates within the pericardial space. Increased intrapericardial pressure and compression of the heart prevents venous and pulmonary venous return and reduces ventricular filling resulting in reduced cardiac output.¹ Risk factors include trauma, cardiac surgery, infections, or inflammatory disorders.

Tension pneumothorax occurs when air progressively accumulates in the pleural space to create positive intrathoracic pressure. The result is compression of lung tissue and mediastinal structures to the contralateral side that leads to respiratory failure and impaired return of blood to the heart. Risk factors include penetrating chest trauma and positive-pressure ventilation.

Fetal circulation bypasses the pulmonary system in utero because oxygenated blood comes from the mother via the placenta. This diversion from the pulmonary circuit is a right-to-left shunt through the patent ductus arteriosus and allows systemic perfusion. Closure of the ductus arteriosus occurs during the first few weeks after delivery. During this transition, certain structural malformations of the cardiac system are dependent on this conduit for systemic perfusion—these are also known as left-ventricular outflow tract obstructive lesions and include coarctation of the aorta, interrupted aortic arch, critical aortic stenosis, and hypoplastic left heart syndrome.¹ With closure of the ductus, flow bypassing the left-sided obstruction is no longer possible; systemic vascular resistance increases with closure of the ductus and stroke volume decreases along with cardiac output. Maintaining patency of the ductus arteriosus is critical for survival in these patients.

Pulmonary embolism is the partial or total obstruction of flow to the pulmonary artery from thrombus, fat, air, amniotic fluid, or catheter fragments. Although rare in pediatrics, predisposing factors include indwelling central venous catheters, sickle cell disease, malignancy, connective tissue disorders, and hypercoagulable states (i.e., antithrombin III, protein C, and protein S deficiencies).

Pediatric physiology is unique as a progressive decline in cardiac output is masked by tachycardia. Early recognition of compensated shock is imperative so that interventions can be directed to preventing progression to decompensated shock. Hypotension is an ominous sign and heralds impending cardiac arrest (Fig. 19-2).

History: Events preceding the presentation to the emergency department can provide important clues as to the etiology of the disease process. Progressive vomiting and diarrhea in an infant or significant femur deformity in a child after a vehicular accident represents likely mechanisms for the development of hypovolemia. Fever and purpura in a teen or tachycardia in a child with leukemia and a central venous line after induction chemotherapy have a high likelihood for sepsis. Similarly, urticaria, vomiting, facial swelling, and difficulty breathing within minutes of IV contrast or after eating peanuts are consistent with anaphylaxis. Trauma with bradycardia, flaccid paralysis, and priapism are indicative of a spinal cord injury. Ingestions of calcium or β-blockers are toxic to the myocardium and will progress to cardiogenic shock. Diaphoresis with feeding, difficulty breathing with feeds, poor weight gain, or cyanosis suggests a structural cardiac lesion. At other times, the etiology is not obvious—the 2-week-old infant with lethargy, poor feeding, and poor perfusion can be hypovolemia, hypoglycemia, sepsis, an inborn error of metabolism, or an undiagnosed cardiac lesion in failure.

Physical exam: A crying or frightened or febrile child is tachycardic and tachypneic. Distinguishing minor problems from a case of impending shock is challenging. Tachycardia is the most sensitive sign of circulatory compromise in children. Persistent tachycardia in a calm, afebrile child reflects a metabolic abnormality. Tachypnea can be observed in two forms: effortless or distress. Effortless tachypnea also described as “quiet” tachypnea is the respiratory compensation for metabolic acidosis. There is minimal accessory muscle use and is classically described for children in early severe sepsis. Respiratory distress with tachypnea implies lung pathology from ventilation/perfusion (V/Q) mismatch, hypoxemia, pulmonary edema, heart failure, or obstructive shock. Blood pressure is used to distinguish between compensated and hypotensive shock. Normal blood pressures signify increased vascular resistance in early shock states. Widened pulse pressure is consistent with low systemic vascular resistance suggestive of distributive shock. As compensatory mechanisms fail, hypotension occurs and heralds impending cardiac arrest. Perfusion can be used as a surrogate marker for cardiac output and when capillary refill time is greater than 2 seconds and this suggests that cardiac output is compromised.^11,12 Warm skin and bounding pulses in a febrile child with borderline hypotension is consistent with warm shock; conversely, cold skin and weak pulses in a febrile child with borderline hypotension match cold shock. Other clinical markers suggestive of compromised perfusion include altered mental status, diminished peripheral pulses, and mottled extremities. The diagnosis of shock can be difficult and all information available needs to be carefully and repeatedly considered to reach the diagnosis correctly.

Laboratory studies: Although shock is a clinical diagnosis, laboratory evaluation can aid in determining severity of disease. Rapid tests that are helpful in delineating treatment include glucose, ionized calcium, and blood gas to evaluate for hypoglycemia, hypocalcemia, and whether acidosis is respiratory or metabolic. In trauma, serial hemoglobins can be helpful and misleading as well. Lactate is often used as a biochemical marker for anaerobic metabolism and is felt to be predictive of mortality in cardiogenic shock,² trauma,¹⁴ and septic shock.¹⁵ Other considerations include uremia, diabetic ketoacidosis, alcohol ketoacidosis, and acute ingestions of aspirin, ethylene glycol, methanol, and paraldehyde. Leukocytosis is common in sepsis, whereas neutropenia and lymphopenia indicate overwhelming infection and immunosuppression^3,4 in septic shock preceding death. Renal dysfunction and failure results from the release of renal tubular cells into the tubules after low-flow shock states persist. Low-flow shock states provide conditions conducive for coagulation to occur within vessels resulting in prolongation of the prothrombin time (PT) and partial thromboplastin time (PTT).

Early and aggressive intervention is crucial in the management of shock; the longer the shock persists before the start of resuscitation, the worse the outcome. Intervention strategies for shock are twofold. Restore oxygen delivery to the tissues by optimizing oxygen content of the blood.¹³ Improve tissue perfusion by improving volume and distribution of cardiac output.¹³

Oxygen content is influenced by oxygen-carrying capacity (hemoglobin) and percent of hemoglobin that is saturated with oxygen (O₂ saturation). Administration of 100% oxygen increases bound and dissolved oxygen in the blood. Provide a secure airway via intubation if necessary. With intubation and pharmacologic paralysis, the work of breathing is reduced while simultaneously decreasing oxygen demand. Etomidate is not recommended for children with septic shock as it was associated with increased severity of illness and mortality in adults and children.¹⁴ Improving ventilation/perfusion (V/Q) abnormalities using continuous positive airway pressure (CPAP) and positive end expiratory pressure (PEEP) helps to correct V/Q abnormalities.¹² Correction of anemia can dramatically increase oxygen-carrying capacity. Less often considered but causes of reduced oxygen delivery are abnormal hemoglobin states from carbon monoxide and nitrites exposure creating carboxyhemoglobin and methemoglobin, respectively.¹³ Also consider toxins that induce cellular hypoxia despite adequate oxygenation supply—cyanide and hydrogen sulfide exposure.¹³

In most cases, fluid resuscitation is critical to improving cardiac output. The only contraindication to aggressive fluid management is congestive heart failure. Dehydration and the maldistribution of blood volume can create challenges for vascular access. If intravenous access is difficult, early establishment of intraosseous access is encouraged.¹⁵ Current research does not favor colloid over crystalloid fluids for shock resuscitation⁵ unless septic shock is caused by malaria where colloid is superior to crystalloid in reducing mortality.^16,17 Furthermore, provided there is no hepatomegaly or rales to suggest heart failure, rapid and successive 20 cm³/kg boluses of fluid up to 60 cm³/kg or more are warranted until perfusion is restored. In severe sepsis, persistent capillary leak from the systemic inflammatory response syndrome (SIRS) can result in persistent maldistribution of blood volume and significant pulmonary edema. If blood loss is the etiology of shock, it is sensible to replenish the vascular space with blood, as two goals will be accomplished: restoration of intravascular volume and increased oxygen-carrying capacity of the circulating blood volume.

In septic shock, the speed and effectiveness of therapy influences the outcome.⁵ The preferred emergency strategy of adult septic shock is early goal-directed therapy; this included monitoring central mixed venous oxygen saturation (>70%), mean arterial pressure (>65 mm Hg), CVP (between 8 and 12 mm Hg), and hematocrit (>30%).¹⁸ Studies in pediatrics are limited but two studies^11,12 support early goal-directed therapy for septic shock in children; perfusion represented by capillary-refill was used as a surrogate marker for cardiac output.

An international consortium developed guidelines for the management of severe sepsis and septic shock in adult and pediatric patients which was updated in 2008.^19,20 A proposed approach to pediatric septic shock is referenced in Figure 19-2.⁵ Therapeutic end-points of resuscitation for septic shock include normalization of heart rate, capillary refill <2 seconds, normal pulses, warm extremities, urine output >1 cm³/kg/h, and normal mental status. Other goal-directed management of pediatric shock is referenced in Figure 19-3.² Implementation of these guidelines have achieved best practice outcomes with reduction of fluid-refractory shock of 28-day mortality to 3% and hospital mortality of 6%.²¹

Early institution of peripheral inotrope delivery is recommended because mortality increased with delay in time to inotrope drug use.¹⁴ In both adults¹⁸ and children,²² goal-directed therapy of central venous saturations >70% significantly reduced mortality. Sedation and mechanical ventilation provides support for circulation as 40% of cardiac output may be required to support work of breathing. Sedation facilitates hemodynamic monitoring temperature control and reduces oxygen consumption.¹⁴ Hydrocortisone therapy should be reserved for use in children with recent steroid therapies, pituitary or adrenal abnormalities, septic shock and purpura, or proven adrenal insufficiency.¹⁴ Recombinant human activated protein C (rh-APC) is not recommended in children since this was associated with an increased risk of bleeding and amputations with no reduction in mortality.²³

Anaphylactic shock has the potential for airway obstruction due to swelling of the upper airway, so early airway intervention may be warranted. Epinephrine and oxygen are the most important therapeutic agents administered in anaphylaxis. Fluid resuscitation is needed to compensate for the vasodilation related to histamine release. Epinephrine (1:1000) administration intramuscularly to the anterolateral thigh is critical to decreasing morbidity and mortality and is superior to subcutaneous or intramuscular deltoid administration.²⁴ Epinephrine promotes vasoconstriction and decreases mucosal edema through α₁ effects. In addition, epinephrine increases heart rate and strength of contractility through β effects along with bronchodilation and stabilization of histamine-releasing mast cells and basophils.⁸ Repeated doses may be needed and when hypotension is persistent an epinephrine drip (1:10,000) should be started. Other adjunctive therapies include corticosteroids, H₁ and H₂ blockers, and nebulized albuterol. Patients on β-blockers show decreased effectiveness of epinephrine during anaphylactic episodes.²⁵ In these patients, glucagon may reverse refractory bronchospasm and hypotension. Recommended dose in children is 20 to 30 μg/kg.

Neurogenic shock results primarily through loss of sympathetic innervation from the central nervous system. The hypotension from the loss of vasomotor tone is not always responsive to fluid administration, but does respond to α₁ stimulation from norepinephrine and epinephrine.¹³ Warming measures may be needed since the vasodilation increases insensible heat loss. Bradycardia from loss of sympathetic input to the heart can be improved with epinephrine.

Cardiogenic shock requires therapies that increase the contractility of the heart while reducing the resistance that the heart is working against. Overzealous fluid administration can worsen cardiac function and pulmonary edema. Sedation, pain control, paralysis, and intubation can reduce oxygen demand. Reduction of systemic vascular resistance allows for increases in stroke volume and thus cardiac output. Buffering metabolic acidosis with bicarbonate is thought to improve the myocardial depression that occurs when the pH is less than 7.2.²⁶ Furosemide can be used to treat volume overload. Consultation with pediatric critical care and cardiology should be initiated at the earliest opportunity.

Physical obstructions that impede cardiac output such as tension pneumothorax and cardiac tamponade can be improved with needle thoracentesis and pericardiocentesis, respectively. For those congenital left-ventricular outflow tract lesions that are dependent on the ductus arteriosus for systemic perfusion, continuous prostaglandin E₁ infusion restores patency of the ductus by vasodilation.¹³ Other interventions include ventilatory support, inotropic agents to improve contractility, echocardiography to direct therapy, and correction of metabolic abnormalities (acidosis, hypocalcemia, and hypoglycemia) that impair cardiac function. Pulmonary embolism is rare in the pediatric population unless risk factors are present. Therapy primarily revolves around anticoagulation with heparin and early consultation with pediatric critical care and hematology.

Vasoactive agents are pharmacologic drugs that are indicated for shock after adequate volume resuscitation has optimized preload.¹³ These are adjunctive agents that stimulate adrenergic receptors in cardiac, pulmonary, and vascular beds. Table 19-3 is a review of tissue effects after stimulation of the adrenergic receptors.

Inotropes increase heart rate and cardiac contractility via the β₁ receptor. Examples include dopamine, dobutamine, epinephrine, and norepinephrine. Other drugs increase peripheral vascular resistance via the α₁ receptor and examples are epinephrine, norepinephrine, phenylephrine, and vasopressin. Phosphodiesterase inhibitors milrinone, amrinone, enoximone, and pentoxifylline have both inotrope and vasodilatory properties.² Table 19-4 contains a list of common vasoactive agents used in pediatric shock and their clinical effects.

Dopamine is also referred to as an indirect vasoactive agent since the α₁ and β₁ adrenergic effects are mediated through endogenous release of norepinephrine from sympathetics. Infants less than 6 months appear to have a reduced response to dopamine.² This phenomenon is also seen in older children and adults who have exhausted their catecholamine supply. Dobutamine has similar age-specific insensitivity in children less than 2 years of age.²⁷ Unlike catecholamines, which are metabolized in minutes, phosphodiesterase inhibitor metabolism occurs over hours. When organ dysfunction is present, the drug metabolism can be prolonged and can add to the duration of toxicities should they develop.

In summary, there are many causes of pediatric shock. Early recognition and treatment are very important. Fluid resuscitation with crystalloid or blood is crucial for increasing preload and cardiac output. Once this is optimized, cardiac output can be augmented with inotropes and vasopressors. Each shock state is unique and requires unique combinations of therapies. Shock represents a dynamic process requiring monitoring and adjustments in treatments (Table 19-5).