This 2 month old male infant with a 4 day history of vomiting and diarrhea is brought to the emergency department by his mother. Initial findings in the emergency department include:
Airway: Breath sounds are normal. Airway is patent.
Breathing: Breathing is regular at 45 breaths per minute, unlabored.
Circulation: Proximal pulses are poor, distal pulses are absent, and extremities are cool. Feeling from the 5th toe upwards, the legs are cool up to the knee. Capillary refill is 8 seconds. Heart rate is 209 beats per minute, and blood pressure is 70mmHg systolic.
ECG: There are narrow QRS complexes with sinus tachycardia on the monitor.
The infant does not recognize his parents, is extremely lethargic, and responds to pain only, with a minimal grimace.
You are unable to start an IV line, 100% oxygen is started. The mucous membranes of the mouth are pink. An intraosseous (IO) is placed in the left tibia and 20cc/kg of normal saline is infused as rapidly as possible. The infant is reassessed. Airway and breathing remain stable. The heart rate is now 195. A repeat bolus of 20cc/kg is given and the patient is reassessed. After the 3rd fluid bolus is given, the patient becomes more alert, distal pulses return, and the patient improves throughout resuscitation. The heart rate has come down to 160. However, a rapid bedside glucose analysis reveals a blood sugar of only 32, which is quickly treated. This case represents a patient in compensated hypovolemic shock (and hypoglycemia) secondary to vomiting and diarrhea.
Shock is a clinical syndrome of circulatory dysfunction resulting in inadequate oxygen and nutrient delivery, with inability to meet the metabolic demands of the tissues (cells). This results in a cascade of events resulting in altered cellular metabolism, function, structure, and ultimately death. Shock is NOT necessarily hypotension. It begins with a normal blood pressure and progresses over time.
Normal circulatory function depends on 3 components: 1) adequate cardiac function (the pump), 2) appropriate vascular tone (the pipes) and 3) adequate blood volume (the fuel). When one of more of these circulatory components fail, shock results. Adequate delivery of oxygen and nutrients is dependent on adequate cardiac output (CO). Cardiac output in turn is dependent on two cardiac factors, 1) heart rate (HR) and 2) stroke volume (SV). As children are "heart rate dependent", the heart rate is the single most important vital sign when determining shock. The heart rate itself is regulated by two factors: 1) vagal tone and 2) catecholamines. Catecholamines are released in response to stress and have two major circulatory effects in children: 1) increase in heart rate (i.e., tachycardia), and 2) increase in peripheral vascular tone (resistance) (i.e., vasoconstriction, resulting in cool, clamped down extremities).
Stroke volume is the second determinant of cardiac output, and is dependent on three factors: 1) preload (intravascular volume/blood often called "venous return"), (the fuel), 2) myocardial contractility (heart muscle function), (the pump), and 3) afterload (systemic vascular resistance) (the pipes). Children are particularly dependent upon adequate intravascular volume, and when volume depleted, they peripherally vasoconstrict to maintain stroke volume. The myocardium in infants is "stiff" and plays little role in increasing cardiac output. Therefore, the heart rate must increase in order to maintain adequate circulatory function. Remember C.O.=H.R. x S.V.
Shock is a dynamic process that if untreated, progresses through three phases: 1) compensated, then 2) uncompensated, and finally 3) irreversible. Compensated shock, by definition, occurs in a body, which has successfully compensated to a circulatory disruption and is maintaining adequate vital organ perfusion and oxygenation. This may be difficult to differentiate from the patient's normal status. Blood pressure is normal. Tachycardia is usually present, and as catecholamine release increases, the heart rate increases and peripheral vasoconstriction with prolonged (delayed) capillary refill occurs. Utilizing my exam technique, "The pediatrician's handshake", I first feel the 5th toe. If the 5th toe is cold with a prolonged capillary refill, I progress to the other toes, up the foot, then the leg. The further up the leg the capillary refill is prolonged and the leg(s) is cool, the more vasoconstricted the body is, and when counted, the faster the heart rate will be. Normal capillary refill is 2 seconds or less, about the time I take to say "pepperoni pizza". If I need to add "more toppings" to my pizza, then I know the capillary refill is prolonged and the body is "in shock". There are pitfalls when interpreting capillary refill; if the body is developing a fever, or in a cold environment, vasoconstriction results and capillary refill is not a reliable sign of shock. Like any other single sign, this must be taken in context with all other findings.
As shock progresses (hopefully by now you will have intervened and are reversing and treating the cause and it will not progress), the compensatory mechanisms (i.e., increasing heart rate and vasoconstriction) reach their maximum ability and cannot increase further, then suddenly the body decompensates. Metabolic demands are not met, and cellular ischemia results in the release of vasoactive mediators which affect the microcirculation resulting in end-organ compromise and acidosis, with signs including hypotension, altered mentation, oliguria, acidosis, mottled pale skin with cool extremities, tachypnea and dyspnea, tachycardia and the obvious appearance of an "sick body". At this point irreversible damage of key organs (heart, brain, kidneys) may have occurred, but aggressive therapy is still indicated in chance that cardiovascular measurements can still be normalized. Unfortunately, despite aggressive therapy, death may occur regardless of therapy.
The main point to reemphasize is: the early recognition and treatment of compensated shock (better prognosis) is essential to prevent decompensated and irreversible shock (poor prognosis, high risk of death). Remember, hypotension is a late sign of shock and should not be allowed to occur.
Important historical information and physical exam findings must be included when considering the clinical manifestations and differential diagnosis of shock. Historical information asked must include: 1) age, 2) preexisting conditions/illness, 3) fever, 4) vomiting/diarrhea, 5) poor feeding, 6) urine output, 7) lethargy, 8) trauma, 9) toxic ingestion. The physical exam must include: 1) general appearance/alertness/eye contact/activity, 2) heart rate, 3) skin perfusion, a) capillary refill, b) color, c) skin temperature, 4) oliguria (if an observation period is permitted), 5) altered mental status, 6) tachypnea, 7) fever, 8) blood pressure, to name a few.
Utilizing history and physical exam information, it is important to classify the shock syndrome into one of 3 major etiologies: 1) hypovolemic shock, a) absolute, b) relative, 2) septic shock, or 3) cardiogenic shock. Hypovolemic shock is the most common cause of shock in children. A loss of circulating blood volume results in decreased preload (the fuel) with resultant decreased cardiac output. Absolute hypovolemia has three major causes; 1) dehydration secondary to a) diarrhea and vomiting or b) poor intake; 2) hemorrhage or 3) renal losses of fluid from a) diabetes mellitus or b) diabetes insipidus.
"Relative" hypovolemic shock is also called "distributive shock" where the problem is not related to absolute volume but to loss of vessel tone resulting in vasodilation and therefore a larger intravascular space (secondary to vasodilation) with a "normal blood volume", which results in a "relative" hypovolemia. There are four major causes of this: 1) sepsis, 2) anaphylaxis, 3) spinal cord injury or 4) drug reactions secondary to drugs such as barbiturates, phenothiazines, and antihypertensives.
Septic shock is a microcirculatory dysfunction that results from activation of a systemic inflammatory response from age-group specific bacterial pathogens. Those at risk for septic shock include: oncology patients, those with central venous (oncology) catheters, on chronic high dose steroids, or with a congenital or acquired immunodeficiency. Gram negative bacterial endotoxin-mediated septic shock results in activation of numerous mediators of circulatory failure. The end result is impaired myocardial contractility, alteration in vascular tone, and capillary leak.
Lastly, cardiogenic shock (the pump) may be the primary cause of shock or a late manifestation of other forms of shock. Here, there is an abnormality in cardiac function due to depressed myocardial contractility. Etiologies include 1) congenital heart disease, 2) myocardial infarction (e.g., Kawasaki's), 3) myocarditis or pericarditis, 4) congestive heart failure, 5) cardiac trauma, 6) dysrhythmia, or 7) drugs affecting myocardial contractility.
The table below compares the cardiac output (CO), systemic vascular resistance (SVR) and central venous pressure (CVP) in the three shock syndromes. An increase in CVP will clinically be seen as distended neck veins and an enlarged liver. An increase in SVR will be seen as cold, clamped down extremities with weak pulses and prolonged capillary refill.
Common Etiologies of Shock Syndromes
1) Hypovolemic Shock
. . . . . a) Absolute Hypovolemia: water and electrolyte losses (diarrhea, vomiting, diabetes insipidus, renal losses, heat stroke, intestinal obstruction, burns), hemorrhage (trauma, surgery, GI bleeding), plasma losses (burns, nephrotic syndrome, sepsis, intestinal obstruction, peritonitis).
. . . . . b) Relative Hypovolemia (distributive shock): anaphylaxis (antibiotics, blood products, insects, vaccines, local anesthetics, foods, etc.), neurologic injury (head injury, spinal shock), drug intoxication (barbiturates, phenothiazines, tranquilizers, antihypertensives), sepsis., toxic shock
2) Septic Shock
. . . . . a) Bacterial: Group A streptococcus, Haemophilus influenzae type b, Neisseria meningitidis, Streptococcus pneumoniae, Group B Streptococcus, Gram negative bacilli (predominantly E. coli), Staphylococcus aureus.
. . . . . b) Other: viral, fungal, rickettsial
3) Cardiogenic Shock:
. . . . . Congenital heart disease (ductal-dependent systemic blood flow, post-operative complications), dysrhythmias, drug intoxication, myocarditis (viral, other inflammatory), hypoxic-ischemic injury (Kawasaki syndrome, perinatal asphyxia, near-drowning, near-SIDS), primary cardiomyopathy, metabolic derangement (hypoglycemia, acidosis), hypothermia, late sepsis, toxic shock.
4) Miscellaneous Shock Syndromes
. . . . . a) Obstructive Shock: pericardial tamponade, tension pneumothorax, pulmonary embolus
. . . . . b) Dissociative Shock: carbon monoxide poisoning, methemoglobinemia
Regardless of etiology, initial therapy is universal. All patients should receive 100% supplemental oxygen by face mask, followed by the correction of the mismatch between metabolic supply and demand. Early recognition and aggressive treatment is the key. Anticipation of the effects of shock as a dynamic, clinical syndrome with multi-system consequences, which can be reversed, with optimization of cardiac output is essential to prevent decompensation and irreversible shock.
Treatment can be classified broadly into: 1) oxygenation, 2) vascular access, 3) fluid administration, and 4) drug therapy. Oxygenation includes providing 100% oxygen and also assuring adequate hemoglobin, stopping hemorrhage, and replacing blood if the hematocrit is less than 30%. Consider endotracheal intubation, but be aware of the cardiovascular effects that intubation and positive ventilation can cause, such as bradycardia, hypotension or reduced venous return. Vascular access includes insertion of a (preferably two) large intravenous catheters, and obtaining necessary lab tests (CBC, blood culture, electrolytes, BUN, creatinine, glucose, calcium, coagulation profile and blood gas). If vascular access is difficult to obtain, use an intraosseous (IO) device and insert this into the tibia. New guidelines allow IO use in children of all ages. There are 2 major types of fluid that can be administered, crystalloid or colloid. Crystalloid is either volume expanding isotonic (normal saline or Ringer's lactate) or hypertonic (3% saline). Crystalloid is an effective volume expander in resuscitation but requires 2-4 times the volume of blood loss to restore hemodynamic parameters. Of the isotonic volume infused into the extracellular compartment (i.e., intravenous or I.O.), only 25% remains intravascular, while 75% eventually goes interstitial. This has led to the use of hypertonic saline (3% sodium chloride solution) in certain situations (such as hemorrhagic shock), as it is an effective vascular volume expander using less volume, working by expanding the ECF by a greater amount than the volume infused because it pulls water from the ICF compartment. Although there is less potential for edema as a result of its use, there are complications including increased serum osmolarity, increased serum Na and C1 levels, metabolic acidosis, and cerebral dehydration and hemorrhage.
Colloid refers to 5% albumin, fresh frozen plasma (FFP) or blood. Albumin's major advantage is that it remains primarily within the intravascular space (less enters the interstitial space). In addition, it can draw extravascular water into the intravascular space because of its oncotic pressure effect. FFP is an effective volume expander with the added benefit of procoagulant factors, while blood (whole or packed RBCs) is an effective volume expander with the added benefit of oxygen carrying capacity.
Most often fluid administration in the form of volume resuscitation is accomplished by the infusion of 0.9% sodium chloride (normal saline) or Ringer's lactate 20 ml/kg IV bolus as quickly as possible. Then reevaluate and repeat the bolus depending on the clinical status/changes. Search for other causes such as sepsis or occult hemorrhage. Central venous pressure monitoring will help fluid management in critical patients. General guidelines are to be liberal and aggressive with fluid resuscitation, giving 20 ml/kg initially and repeating as needed. For septic shock, more than 40ml/kg in the first hour has been shown to improve outcome. When approaching 80 ml/kg, consider the use of an inotropic agent such as dopamine or epinephrine.
Pharmacologic support includes medications that: 1) augment cardiac contractility (inotropic/cardiotonic), vasoconstrictors to reverse inappropriate vasodilation, and sometimes vasodilator drugs to reduce preload and afterload in cardiogenic etiologies, 2) antibiotics (for septic shock), 3) sodium bicarbonate, 4) calcium, 5) immunotherapies, and 6) controversial therapy. However, before specific drugs are described, a review of adrenergic receptor physiology is indicated. Each receptor has a different physiologic response, as noted here:
Increased myocardial contractility (inotropy)
Increased heart rate (chronotropy)
Bronchial smooth muscle relaxation
Smooth muscle relaxation
Increase renal blood flow
Examples of classic agonists include phenylephrine (pure alpha), isoproterenol (pure beta, both beta-1 and beta-2), dobutamine (selective beta-1), albuterol (selective beta-2), epinephrine (both alpha and beta).
Three commonly used inotropic drugs include dopamine, dobutamine and epinephrine. Dopamine effects are dependent on the dose infused. Low dose (1-2 mcg/kg/min) results in vasodilation of the splanchnic (renal) and cerebral vascular beds. Mid-dose (3-10 mcg/kg/min) has primarily a beta effect (chronotropic and inotropic), while a higher dose (> 10 mcg/kg/min) has a pure alpha effect (pressor). Dobutamine has a pure beta-1 (chronotropic and inotropic) effect, the effective dose used ranging from 2-20 mcg/kg/min or greater. Epinephrine at an infusion dose of 0.05-2 mcg/kg/min has both beta and alpha effects, and may cause severe peripheral vasoconstriction or arrhythmias.
Examples of vasodilator drugs used for "afterload reduction" in a failing heart to ease the work of "pumping" are nitrates such as nitroprusside and nitroglycerine. Nitroprusside, infused continuously at a rate between 1-10 mcg/kg/min, is a vasodilator working on both resistance and capacitance sides of the circulation; however with time, a toxic cyanide metabolite is formed.
Consider the use of sodium bicarbonate after assuring adequate volume resuscitation and ventilation, at a dose of 1-2 mEq/kg.
Calcium: Hypocalcemia can occur after tissue hypoperfusion of any etiology and can result in myocardial depression and hypotension. If hypocalcemia is documented in a symptomatic patient not responding to inotropes and pressors, then consider treating the hypocalcemia. The dose used is 10-20 mg/kg CaCl (0.1-0.2 ml/kg of 10% solution). Monitor ionized calcium levels to determine its need.
Antibiotics are used for septic shock (or presumed septic shock). For ages less than 6 weeks, a combination of ampicillin plus cefotaxime can be used. For ages greater than 6 weeks cefotaxime or ceftriaxone can be used.
Immunotherapies include the use of anti-endotoxin (HA-1A or E5), anti-tumor necrosis factor (TNFa) and interleukin-1 (IL-1) receptor antagonist. These are beyond the scope of this chapter, but will be important adjuncts to antibiotics and intensive care treatment in the future. Controversial therapy includes primarily the use of steroids. Although theoretically it may be of benefit modulating the immune response to sepsis, there has been no benefit (actually increased mortality) in humans, therefore it is NOT currently recommended. A more detailed description of additional medications utilized for resuscitation can be found in the chapter on pediatric pulmocardiac resuscitation.
Ongoing assessment of the patient in shock includes repeated reassessments of the physical exam, and monitoring equipment including pulse oximetry, cardiorespiratory monitoring, repeated blood pressures, central venous pressure (if indicated), and urine output through a catheter. Physical exam findings will be reflected in signs of improved perfusion which will include improvement in appearance, including alertness (mental status), eye contact, skin capillary refill, color and temperature, heart rate and pulse strength, urine output, respiratory pattern and rate, and blood pressure. Resolving metabolic acidosis and declining serum lactate levels are lab findings indicating improvement of perfusion.
In summary, shock is a clinical syndrome NOT defined by blood pressure alone. Worldwide, hypovolemic shock from diarrhea represents the leading cause of death. Normal circulatory function depends on three factors: cardiac function (the pump), vascular tone (the pipes), and blood volume (the fuel). A disturbance in one or more, resulting in inadequate delivery of oxygen and nutrients to the tissues, leads to shock. Shock is a progressive, dynamic process where early recognition and immediate management (initially in the form of IV fluids) is essential to prevent deterioration into decompensated and finally irreversible shock.
1. Prioritize the initial management of the child with shock:
. . . . . a. Administer oxygen
. . . . . b. Administer volume resuscitation
. . . . . c. Support a patent airway
. . . . . d. Support blood pressure and perfusion with cardioactive drugs
. . . . . e. Administer antibiotics
. . . . . f. Address oxygen carrying capacity with administration of blood if anemia is present
2. The most sensitive indicator of intravascular volume in the pediatric patient is:
. . . . . a. Cardiac output
. . . . . b. Preload
. . . . . c. Heart rate
. . . . . d. Stroke volume
3. In the trauma patient with compensated shock, who is otherwise stable blood should be considered as part of volume resuscitation:
. . . . . a. Immediately after the airway is secured and intravenous access
. . . . . b. After 20 cc/kg of isotonic fluid has been administered without clinical response
. . . . . c. After 40 cc/kg of isotonic fluid has been administered without clinical response
. . . . . d. After 60 cc/kg of isotonic fluid has been administered without clinical response
. . . . . e. After isotonic fluid administration has resulted in inadequate clinical response and the patient requires operative repair
4. Which circulatory finding is the hallmark of the diagnosis of late (decompensated) shock?
. . . . . a. Capillary refill of 4 seconds
. . . . . b. Altered mental status
. . . . . c. Depressed anterior fontanelle
. . . . . d. Hypotension
. . . . . e. Absent distal pulses
5. An alert, 6 month old male has a history of vomiting and diarrhea. He appears pale and has an RR of 45 breaths per minute, HR of 180 beats per minute, and a systolic blood pressure of 85 mm Hg. His extremities are cool and mottled with a capillary refill time of 4 seconds. What would best describe his circulatory status?
. . . . . a. Normal circulatory status
. . . . . b. Early (compensated) shock caused by hypovolemia
. . . . . c. Early (compensated)shock caused by supraventricular tachycardia
. . . . . d. Late (decompensated) shock caused by hypovolemia
. . . . . e. Late (decompensated) shock caused by supraventricular tachycardia
6. Appropriate initial management for the child described in question 6 would include which of the following?
. . . . . a. Initiation of oral rehydration therapy
. . . . . b. Placement of an intraosseous line, fluid bolus of 20 ml/kg of normal saline
. . . . . c. Placement of an intravenous (IV) line, fluid bolus of 20 ml/kg of normal saline
. . . . . d. Placement of an IV line, adenosine 0.1 mg/kg IV
7. A 2 month old infant is brought to the ED with a pulse of 180 and BP 50/35 mm Hg. A liver edge is palpable to the umbilicus. Skin is mottled, capillary refill is 6 seconds with weak distal pulses. Chest x-ray reveals cardiomegaly. During the administration of 20 ml/kg of Ringer's lactate, respirations become labored and rales are heard. The next step would be:
. . . . . a. Sodium bicarbonate 1 mEq/kg IV
. . . . . b. Repeat fluid bolus 20 ml/kg
. . . . . c. Dopamine 5 to 10 mcg/kg/min IV infusion
. . . . . d. Synchronous cardioversion 0.5 joule/kg
. . . . . e. Epinephrine 0.01 mg/kg of the 1:10,000 solution IV
1. AAP, ACEP. APLS: The Pediatric Emergency Medicine Course, Third Edition, 1998.
2. Atici A, Satar M, Alparslan N. Serum interleukin-1 beta in neonatal sepsis. Acta Pediatr 1996;85:371-374.
3. Bell LM. Shock. In: Fleisher GR, Ludwig S (eds). Textbook of Pediatric Emergency Medicine, 4th edition. 2000, Baltimore: Lippincott, Williams and Wilkins, pp. 47-57.
4. Bone RC. A critical evaluation of new agents for the treatment of sepsis. JAMA 1991;266(12):1686-1691.
5. Cardillo JA, Davis AL, Zaritsky A. Role of early fluid resuscitation in pediatric septic shock. JAMA 1991;266:1242-1245.
6. Bhende MS, Thompson AE, Orr RA. Utility of an end-tidal carbon dioxide detector during stabilization and transport of critically ill children. Pediatrics 1992;89-1042-1044.
7. Griffel MI, Kaufman BS. Pharmacology of colloids and crystalloids. Crit Care Clin 1992;8(2):235-253.
8. Velasco AL, et al. Intraosseous infusion of fluids in the initial management of hypovolemic shock in young subjects. J Pediatr Surg 1991;26(1):4-8.
9. Tobin JR, Wetzel RC. Shock and Multi-Organ System Dysfunction. In: Rogers MC, Nichols DG (eds). Textbook of Pediatric Intensive Care, Williams and Wilkins, Philadelphia 1996, pp. 555-605.
10. Witte MK, Hill JH, Blumer JL. Shock in the Pediatric Patient. Adv Pediatr 1987;34:139173.
Answers to questions
7. c. This represents a case of cardiomyopathy with four classic findings of congestive heart failure. Note that the patient's condition worsened with fluid administration. Dopamine would be the first agent to try. Epinephrine may be used later in desperation since its alpha effect may have detrimental consequences on overall circulation.