Circulatory Shock in Children: An Overview

Christine A. McKiernan and Stephen A. Lieberman

Pediatr. Rev. 2005;26;451-460
DOI: 10.1542/pir.26-12-451

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pedsinreview.aappublications.org/cgi/content/full/26/12/451

Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
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 Article critical care

Circulatory Shock in Children:

An Overview
Christine A. McKiernan,
Objectives After completing this article, readers should be able to:
MD,* Stephen A.
Lieberman, MD* 1. Review the basic underlying pathophysiology of circulatory shock in children.
2. Characterize the physiologic derangements that occur with the different types of
circulatory shock.
Author Disclosure 3. Discuss the clinical and laboratory manifestations of the acute respiratory distress
Drs McKiernan and syndrome and disseminated intravascular coagulation.
Lieberman did not 4. Review the general supportive measures used for initial stabilization of patients who
disclose any financial have circulatory shock.
relationships relevant 5. Describe some of the new therapeutic modalities directed at reversing the immunologic
to this article. abnormalities that are part of the pathogenesis of circulatory failure.

Introduction
For the myriad practitioners who come into contact with critically ill children, the term
“shock” has acquired a unique lexicon. For example, a call to our pediatric intensive care
unit from a community emergency department physician was highlighted by the com-
ment: “I have a lethargic 3-month-old who looks ‘shocky’ to me.” A frantic page from one
of our residents led to this exchange: “We have a 2-year-old down here who is developing
diffuse petechiae—she really looks ‘septic’.” A 16-year-old admitted for worsening respi-
ratory distress and an increasing oxygen requirement underwent echocardiography, which
was read by the cardiologist as a “moderate-size pericardial effusion with no evidence of
either right atrial compression or cardiac tamponade.” Are these physicians talking about
different pathophysiologic entities in their respective patients? Not really. Each simply is
describing one of the protean manifestations of a diverse and complex syndrome: circula-
tory shock.
The primary function of the cardiovascular system is to provide oxygen and other
substrate to the cells. Inextricably linked to this function is the timely and effective removal
of the end products of a wide variety of metabolic processes. Circulatory shock or
cardiovascular failure ensues when systemic oxygen and nutrient supply become acutely
inadequate to meet the metabolic demands of the body’s organ systems. The resulting
anaerobic state inefficiently generates intracellular adenosine triphosphate, causing accu-
mulation of lactic acid, an objective indicator of the functional status of the circulatory
system. The effects of impaired perfusion are reversible for a period of time, but ultimately
reach a point of irreversible disruption of essential biochemical processes necessary to
maintain cellular integrity. This malfunction of the energy-dependent cell membrane
pumps leads to intracellular edema and acidosis and eventually cell death. On a macro-
scopic level, this state of global hypoxemia causes multisystem organ failure and ultimately
the patient’s demise.
The pathophysiologic pathway to cardiovascular failure results from impairment of
cardiac output (CO), systemic vascular resistance (SVR), or both. It can be caused by a
variety of direct-acting or systemic insults. CO is the product of heart rate and stroke
volume. Stroke volume is determined by left ventricular filling pressure and myocardial
contractility. SVR represents the impedance to left ventricular ejection (afterload) as well
as the “tone” of the peripheral vasculature. In the lexicon of “shock,” a predominance of
vasoconstriction is classified as “cold shock” and predominant vasodilation comes under

*Assistant Professor of Pediatrics, Tufts University School of Medicine, Boston, Mass.

Pediatrics in Review Vol.26 No.12 December 2005 451

critical care circulatory shock

the rubric of “warm shock.” The early recognition and conditions of decreased ventricular preload, impaired
management of the various types of circulatory failure are myocardial contractility, or congenital heart disease cat-
crucial to restoring adequate tissue perfusion before ir- egorized by an anatomic left-to-right shunt. Stroke vol-
reparable end-organ damage and a bradycardic/asystolic ume is determined by ventricular filling (preload), the
cardiac arrest occurs. impedance to ventricular ejection (afterload), and intrin-
This article reviews basic cardiovascular physiology in sic pump function (myocardial contractility).
children, attempts to characterize the pathophysiologic In addition to CO, the primary regulator of blood
derangements that occur with different types of circula- pressure is SVR. Children maximize SVR to maintain a
tory shock, and examines a therapeutic regimen that normal blood pressure, even with significant decreases in
comprises both general supportive measures as well as their CO. Increases in SVR are due to peripheral vaso-
some of the newer, more specific agents being developed constriction mediated by the sympathetic nervous system
to reverse the immunologic and coagulation abnormali- and angiotensin. As a result, blood flow is redistributed
ties that are being recognized increasingly as key players from nonessential vascular beds such as the skin, skeletal
in the pathogenesis of circulatory failure. muscles, kidneys, and splanchnic organs, to the brain,
heart, lungs, and adrenal glands. Such regulation of
Pathophysiology of Shock vascular tone, either endogenously or exogenously via
A common pediatric axiom is “children are not small vasoactive medications, can normalize blood pressure
adults.” This statement is particularly cogent when dis- independent of CO. Therefore, in pediatric patients,
cussing total body water distribution and the compensa- blood pressure is a poor indicator of cardiovascular ho-
tory cardiovascular responses of children during states of meostasis. The evaluation of heart rate and end-organ
perfusion, including capillary re-
fill, the quality of the peripheral

.pressure
. . inis apediatric
pulses, mentation, urine output,
and acid-base status, is more valu-
patients, blood able than blood pressure in deter-
mining a child’s circulatory status.
poor indicator of The relationship between heart
cardiovascular homeostasis. rate, stroke volume, and SVR are
of paramount importance, partic-
ularly when deciding whether to
use volume resuscitation, vaso-
progressive circulatory insufficiency. Signs and symp- pressors, or an inotropic agent as the initial therapeutic
toms of shock that are easily discerned in adults may approach to the patient in circulatory failure. Although
remain subtle in children, leading to delays in recognition there are an almost inexhaustible number of potential
and underestimation of the severity of shock states. Al- causes for circulatory shock in children, the choice nar-
though children’s greater percent of total body water might rows if the clinician uses a purely physiologic classifica-
be assumed to protect them from cardiovascular collapse, tion. The more common situation, exemplified by hypo-
increased resting metabolic rate, increased insensible water volemic or cardiogenic shock, is manifested by the
loss, and decreased renal concentrating ability actually make presence of a low CO and compensatory elevated SVR.
children more susceptible to organ hypoperfusion. The The second scenario, seen in distributive shock, is char-
early signs and symptoms of volume depletion can be subtle acterized by the presence of an elevated CO and dimin-
in children, but as the disease progresses, the physical find- ished SVR. The presentation of sepsis in newborns and
ings become more impressive compared with an adult who children is more variable than in adults and can include
has a similar degree of hypovolemia. any combination of hemodynamic abnormalities. Table
The compensatory cardiovascular responses of the 1 outlines the hemodynamic changes and treatments of
child to states of decreased ventricular preload, impaired various forms of shock, which are described in more
myocardial contractility, and alterations in vascular tone detail in the text.
differ from those of adults. In the pediatric patient, CO is The shock syndrome, when unresponsive to thera-
more dependent on heart rate than on stroke volume due peutic interventions, is characterized by a series of in-
to the lack of ventricular muscle mass. Tachycardia is the creasingly ominous clinical and physiologic changes, in-
child’s principal means of maintaining an adequate CO in cluding steadily deteriorating respiratory, hematologic,

452 Pediatrics in Review Vol.26 No.12 December 2005

 critical care circulatory shock

Pathophysiology, Signs and Symptoms, and Treatment of the

Table 1.

Various Forms of Shock

Type of Shock Pathophysiology Signs and Symptoms Treatment
Hypovolemic 2CO, 1SVR intravascular ⴞ 1HR, 2pulses, delayed CR, Repeat boluses of 20 mL/kg crystalloid as
interstitial volume loss hyperpnea, dry skin, sunken indicated
eyes, oliguria Blood products as indicated for acute
BP normal until late blood loss
Septic 1CO, 2SVR (classic adult, 1HR, 2BP, 1pulses, delayed CR, Repeat boluses of 20 mL/kg crystalloid;
20% pediatric) hyperpnea, MS changes, third- may need >60 mL/kg in first hour
spacing, edema Consider colloid if poor response to
crystalloid
Pharmacologic support of BP with
dopamine or norepinephrine
2CO, 1SVR (60% pediatric) 1HR, normal to 2BP, 2pulses, Repeat boluses of 20 mL/kg crystalloid;
delayed CR, hyperpnea, MS may need >60 mL/kg in first hour
changes, third-spacing, edema Consider colloid if poor response to
crystalloid
Pharmacologic support of CO with
dopamine or epinephrine
2CO, 2SVR (20% pediatric) 1HR, 2BP, 2pulses, delayed CR, Repeat boluses of 20 mL/kg crystalloid;
hyperpnea, MS changes, third- may need >60 mL/kg in first hour
spacing, edema Consider colloid if poor response to
crystalloid
Pharmacologic support of CO and BP with
dopamine or epinephrine
Distributive Anaphylaxis: 1CO, 2SVR Angioedema, rapid third-spacing Repeat boluses of 20 mL/kg crystalloid as
of fluids, 2BP, respiratory indicated
distress Pharmacologic support of SVR with
norepinephrine or phenylephrine
Spinal Cord Injury: normal CO, 2BP with normal HR, paralysis Pharmacologic support of SVR with
2SVR with loss of vascular tone norepinephrine or phenylephrine
Fluid resuscitation as indicated by clinical
status and associated injuries
Cardiogenic 2CO, normal to 1SVR Normal to 1HR, 2pulses, Pharmacologic support of CO with
delayed CR, oliguria, JVD, dobutamine, milrinone, dopamine
hepatomegaly Judicious fluid replacement as indicated
BP normal until late in course clinically
CO⫽cardiac output, SVR⫽systemic vascular resistance, HR⫽heart rate, BP⫽blood pressure, CR⫽capillary refill, MS⫽mental status, JVD⫽jugular venous
distension

and hemodynamic abnormalities. Most prominently, appearance of hypotension in an infant or young child is
these changes include the development of acute respira- worrisome and often the harbinger of full cardiopulmo-
tory distress syndrome (ARDS), manifested by the pa- nary arrest. Consequently, early recognition and aggres-
tient’s need for increasing amounts of oxygen and venti- sive treatment of shock states in the pediatric age group
latory support. Disseminated intravascular coagulation are crucial to a successful outcome. The neurologic se-
(DIC) results in an imbalance between the clotting and quelae in children following an asystolic event, even if
fibrinolytic pathways, with concomitant anemia and circulation is restored, invariably are devastating.
thrombocytopenia. Early on, homeostatic mechanisms
such as elevations in heart rate and changes in SVR can Classification of Shock
compensate effectively for circulatory insufficiency. Hypovolemic Shock
When regulatory mechanisms become overwhelmed, The most common form of circulatory failure in children
however, the patient may decompensate rapidly. The is hypovolemic shock. Today, in developing countries,

Pediatrics in Review Vol.26 No.12 December 2005 453

critical care circulatory shock

Septic Shock
Common Causes of
Table 2. Septic shock, with an annual incidence of 0.56 cases per
1,000 children, can present with a variety of hemody-
Hypovolemic Shock in Children namic abnormalities. The classic adult presentation of
Hemorrhagic high CO and low SVR (warm shock) is seen in only 20%
of septic pediatric patients. Up to 60% of patients have
● Gastrointestinal bleeding
● Surgery decreased CO and elevated vascular resistance (cold
● Trauma shock); others have a decrease in both CO and SVR. In
● Hepatic or splenic rupture 1992, sepsis was defined by a consensus conference of the
● Major vessel injury Society of Critical Care Medicine and the American
● Intracranial bleeding
College of Chest Physicians as the systemic response to
● Long bone fractures
infection. (1) Severe sepsis is associated with hypoten-
Nonhemorrhagic sion, hypoperfusion, or organ dysfunction. Septic shock
● Vomiting/diarrhea is defined as sepsis with hypotension despite adequate
● Heat stroke/water deprivation fluid resuscitation, combined with perfusion abnormali-
● Pharmacologic (eg, diuretics) ties (lactic acidosis, oliguria, altered mental status). Sepsis
● Burns may be caused by bacterial, viral, or fungal agents. The
● Nephrotic syndrome
● Pancreatitis
systemic inflammatory response syndrome (SIRS) is a
● Diabetes mellitus widespread inflammatory response that may be caused by
● Diabetes insipidus systemic infection or some other severe insult, such as
trauma, that presents similarly with hyper- or hypother-
mia, increased heart rate and respiratory rate, and in-
creased white blood cell count with a left shift.
Susceptibility to infection depends on the patient’s
hypovolemic shock remains a major cause of mortality in
age and pre-existing medical conditions, such as immu-
children. Fortunately, in the United States, deaths have
nologic disorders, neoplastic disease, neurodevelopmen-
been decreasing steadily. Hypovolemic shock may be due
tal disorders, cardiac disease, and the presence of indwell-
to a variety of insults, the two major categories being
ing catheters of any type. The incidence of sepsis is
hemorrhagic and nonhemorrhagic (Table 2).
highest in infants (5.16 cases per 1,000 population an-
Regardless of etiology, the final common pathway to
nually), particularly newborns. The implementation of
circulatory insufficiency is diminished intravascular vol-
antepartum treatment for group B streptococcal (GBS)
ume. This volume reduction results in decreased systemic
infection has reduced the incidence of early-onset GBS
venous return and ventricular filling pressure (preload), disease dramatically. Implementation of vaccines, such as
yielding decreased stroke volume. Children suffering against Haemophilus influenzae type b, has reduced sig-
hypovolemic shock due to fluid and electrolyte losses nificantly the number of patients who have invasive dis-
have both intravascular and interstitial depletion. Clinical ease caused by these organisms. Further immunization
findings include sunken eyes, a sunken anterior fonta- programs may continue to alter the microbiologic etiol-
nelle, dry mucous membranes, poor skin turgor, delayed ogy of sepsis.
capillary refill, and cool extremities. In contrast, patients
afflicted with hypovolemic shock due to increased capil- Distributive Shock
lary permeability, such as with burns, have intravascular Distributive (vasodilatory) shock occurs because of a loss
hypovolemia in the setting of interstitial euvolemia or of SVR, resulting in abnormal distribution of blood flow
hypervolemia. Their clinical presentation tends to be within the microcirculation, or functional hypovolemia.
dominated by signs of decreased end-organ perfusion, Cardiac contractility is increased initially, although CO
such as mental status changes, decreased urine output, eventually may be compromised by the lack of preload.
and cool, but often swollen, distal extremities. They do Causes include anaphylactic and neurogenic (injury to
not exhibit classic signs of dehydration. Once again, the central nervous system [CNS]) shock.
hypotension is a late finding and may not occur until
intravascular volume has decreased by 30% to 40%, re- ANAPHYLACTIC SHOCK. Anaphylactic shock is an im-
flecting failure of the child’s compensatory increase in mediate, life-threatening systemic reaction to an allergic
heart rate and SVR. stimulus. The stimulus may be a food, medication, or

454 Pediatrics in Review Vol.26 No.12 December 2005

 critical care circulatory shock

exposure such as a bee sting, which precipitates an intensive care unit, improve outcomes for patients. Pro-
immunoglobulin E-mediated hypersensitivity response vision of oxygen, stabilization of the airway, and estab-
with massive release of cytokines from mast cells and lishment of vascular access are immediate goals, followed
basophils. Patients in anaphylactic shock may have respi- rapidly by fluid resuscitation. Supplemental oxygen
ratory distress from angioedema in addition to hypoten- should be administered to all patients, with oxygenation
sion and hypoperfusion caused by rapid loss of vascular measured by pulse oximetry. Intubation may be required
tone and third-spacing of intravascular volume. for airway stabilization when mental status changes occur
to prevent imminent respiratory failure or to decrease the
NEUROGENIC SHOCK. Neurogenic shock is a rare and work of breathing and oxygen consumption.
usually transient disorder that follows an acute injury to Two large-bore peripheral intravenous catheters
the CNS. The clinical presentation is unique and results should be established. If peripheral access is not readily
from the generalized loss of sympathetic vascular and obtained, intraosseous (IO) access may be established
autonomic tone. Cardiac contractility usually is pre- quickly and reliably in patients of any age. In older
served, although CO eventually may be compromised patients, an IO needle may be placed in the distal tibia or
due to the lack of venous return and preload. Conse- the sternum. Subsequently, a central venous line may be
quently, the physical examination reveals hypotension in required for vasoactive infusions, for central venous pres-
the absence of tachycardia. sure monitoring, and to provide a more stable form of
vascular access. If a child has a central venous catheter
Cardiogenic Shock already in place (as in an oncology patient), it should be
Cardiogenic shock in children may result from either used for resuscitation.
impaired myocardial contractility, dysrhythmias, or redi- Vigorous fluid resuscitation restores perfusion and
rected blood flow caused by congenital anatomic heart prevents end-organ damage in hypovolemic and septic
lesions in which myocardial con-
tractility may be impaired. Con-
genital heart defects that present
with shock are those that have left
ventricular outflow tract obstruc-
tion and, rarely, those that have
Ifintraosseous
peripheral access is not readily obtained,
access may be established
large left-to-right shunts. Neo-
nates born with hypoplastic left
quickly and reliably in patients of any age.
heart syndrome may have dimin-
ished CO as the natural drop in
pulmonary vascular resistance “steals” ductal-dependent shock. Boluses of 20 mL/kg of isotonic crystalloid or
right ventricular-to-systemic blood flow. Coronary insuf- colloid should be administered rapidly and repeated until
ficiency leading to decreased contractility ensues. Vol- perfusion improves. Patients may require 60 mL/kg or
ume overload to the left side of the heart may result from more within the first 30 to 60 minutes; often, 100 to
left-to-right intracardiac shunts as in ventricular septal 200 mL/kg is needed in the first few hours of resuscita-
defect, patent ductus arteriosus, or endocardial cushion tion. In the absence of acute tubular necrosis or other
defect. However, these lesions are more likely to present intrinsic renal disease, urine output of 1 to 2 mL/kg per
with chronic heart failure. Arterial-venous malformations hour may be the best indicator of adequate organ perfu-
in neonates, when the shunt is large, may be profoundly sion. Serum calcium and blood glucose concentrations
symptomatic. Decreased myocardial contractility occurs should be measured and corrected if low. Fluids should
most commonly in critical coarctation or stenosis of the be limited only if primary cardiac dysfunction is highly
aorta or in diseases of the myocardium such as myocar- suspected as the cause of the patient’s shock. Blood
ditis, cardiomyopathy, ischemic myocardial injury, and products may be indicated for cases of hemorrhagic
following cardiopulmonary bypass. shock or for patients in septic shock who have evidence of
DIC.
Treatment Patients who have sepsis and remain hypotensive or
Recognition and aggressive treatment of the various poorly perfused despite aggressive fluid resuscitation and
types of shock, beginning in community offices or hos- those who develop signs of pulmonary edema from fluid
pitals and continued en route to a specialized pediatric resuscitation require vasoactive medications. Careful as-

Pediatrics in Review Vol.26 No.12 December 2005 455

critical care circulatory shock

Table 3. Vasoactive Medications

Agent (dose range) Site of Action Clinical Effect
Dopamine (3 to 20 mcg/kg per min) Beta, increasing alpha with Inotrope, vasoconstriction, chronotrope,
increasing dose increases PVR
Dobutamine (1 to 20 mcg/kg per min) Beta2>beta1 Inotrope, vasodilation (beta2), decreases
PVR
Epinephrine (0.01 to 1.0 mcg/kg per min) Beta>alpha Inotrope, chronotrope, vasoconstriction
Norepinephrine (0.01 to 1.0 mcg/kg per min) Alpha>beta Vasoconstriction, increases SVR, inotrope,
chronotrope
Phenylephrine (0.1 to 0.5 mcg/kg per min) Alpha Vasoconstriction, increases SVR
Amrinone (1 to 20 mcg/kg per min) Type III phosphodiesterase inhibitor Inotrope, chronotrope, vasodilator
Milrinone (0.25 to 1.0 mcg/kg per min)
Nitroprusside (0.5 to 10 mcg/kg per min) Vasodilator, arterial>venous Decreases afterload
Vasopressin (0.0003 to 0.008 U/kg per min) V1 vascular receptor Vasoconstriction, vasodilation of circle of
Willis, stimulation of cortisol secretion
PVR⫽pulmonary vascular resistance, SVR⫽systemic vascular resistance

sessment of the child’s hemodynamic status is required those aimed at modulating the inflammatory and coag-
because children in septic shock can present with various ulation cascades, are being explored.
combinations of increased or decreased CO and SVR. Patients in anaphylactic shock who have hypotension
Vasoactive medications should be chosen based on the and hypoperfusion due to rapid loss of vascular tone and
desired cardiac and peripheral vascular effects (Tables third-spacing of intravascular volume are treated with
1 and 3). Adrenal insufficiency should be suspected in fluid and vasopressor resuscitation, as described previ-
children who display catecholamine-resistant hypoten- ously. Additionally, antihistamines and steroids may slow
sion, who have a history of CNS abnormality or steroid the release of mediators and help reverse symptoms. The
use, or who present with purpura fulminans. Hydrocor- offending agent should be sought and further exposure
tisone 50 mg/m2 can be administered as an initial bolus, prevented. Treatment of neurogenic shock consists of
followed by a similar daily dose divided every 6 hours. pharmacologic support of vascular tone and volume re-
Neonatal shock often is complicated by persistent pul- suscitation, as indicated by perfusion status and the pres-
monary hypertension, which may result in right ventric- ence of any additional traumatic injuries.
ular failure. Because of these differences from adults, the Cardiogenic shock requires a careful assessment of
American College of Critical Care Medicine published volume status prior to initiation of fluids because patients
guidelines for the hemodynamic support of children and may present with hypo-, hyper-, or euvolemia. Because
newborns with septic shock. (2) These recommendations of the availability of a wide and ever-expanding array of
are summarized in Figs. 1 and 2. inotropic and vasoactive agents that have differing mech-
As other measures are applied, the source of sepsis anisms of action (Table 3), treatment of cardiogenic
should be identified and treated as quickly as possible. shock requires a thorough understanding of the under-
lying pathophysiology. In children, this information is
The history and physical examination may reveal poten-
obtained best and most easily by echocardiography and
tial sources and should guide microbiologic evaluation
serial clinical examinations.
and antimicrobial coverage. Whenever possible, cultures
of appropriate body fluids or sites should be obtained,
and aerobic and anaerobic blood cultures always should Crystalloid Versus Colloid
be obtained. Empiric broad-spectrum antimicrobial cov- Crystalloid solutions used in the resuscitation of shock in
erage should be chosen based on suspected sources and pediatric patients include 0.9% normal saline and lactated
organisms and can be narrowed as results of cultures and Ringer solution. The advantages of crystalloid include
sensitivities become available. availability, low cost, and lack of exposure to blood
Because septic shock remains a significant cause of products. Colloid solutions include 5% albumin, dextran,
morbidity and mortality for patients of all ages, numer- hydroxyethyl starch, and blood products. These solu-
ous alternative and experimental strategies, specifically tions contain large molecules that are relatively imperme-

456 Pediatrics in Review Vol.26 No.12 December 2005

 critical care circulatory shock

Figure 2. Recommendation for stepwise management of he-

Figure 1. Recommendations for stepwise management of
hemodynamic support with goals of normal perfusion and modynamic support with goals of normal perfusion and
perfusion pressure (MAP-CVP) and pre- and postductal oxy- perfusion pressure (MAP-CVP) in infants and children who
gen saturation difference less than 5% in near-term newborns have septic shock. Proceed to next step if shock persists.
who have septic shock. RDSⴝrespiratory distress syndrome, PALSⴝPediatric Advanced Life Support, PICUⴝpediatric in-
NRPⴝNeonatal Resuscitation Program, NICUⴝneonatal inten- tensive care unit, MAPⴝmean arterial pressure, CVPⴝcentral
sive care unit, PPHNⴝpersistent pulmonary hypertension of venous pressure, SVCⴝsuperior vena cava, CIⴝcardiac index,
the newborn, CVPⴝcentral venous pressure, LVⴝleft ventric- ECMOⴝextracorporeal membrane oxygenation, Type III PDE
ular, RVⴝright ventricular, ECMOⴝextracorporeal membrane inhibitorⴝamrinone or milrinone. From Carcillo JA, Fields AI,
oxygenation, Type III PDE inhibitorⴝamrinone or milrinone. From Task Force Committee Members. Clinical practice parameters
Carcillo JA, Fields AI, Task Force Committee Members. Clinical for hemodynamic support of pediatric and neonatal patients
practice parameters for hemodynamic support of pediatric and in septic shock. Crit Care Med. 2002;30:1365–1378
neonatal patients in septic shock. Crit Care Med. 2002;30:1365–
1378
Blood Product Replacement
Patients in shock may require transfusion of blood prod-
able to the capillary membrane. This property leads to ucts to replace blood lost from trauma or active bleeding
decreased extravasation and an increased percentage of or abnormal blood component consumption, as in DIC.
the infused volume remaining intravascular. Studies in Ideally, blood product replacement is guided by labora-
adults show that the same physiologic parameters can be tory values, and specific component therapy is provided.
achieved with either fluid, but up to three to seven times However, in the case of hyperacute volume loss, labora-
the volume may be required if crystalloid alone is used. tory values may not reflect equilibration, and transfusion
This effect is not deleterious and actually may serve to must be based on the patient’s hemodynamic status and
replace extravascular losses, particularly in hypovolemic response to crystalloids. Crossmatched blood is prefera-
shock. In practice, unless the child has an underlying ble, but type-specific or O-negative packed red blood
process that contributes to loss of oncotic pressure, the cells (RBCs) may be given if necessary.
initial 40 to 60 mL/kg should be administered as crys- Packed RBC transfusions replace volume and oxygen-
talloid, followed by reassessment of interstitial volume carrying capacity, and 15 to 20 mL/kg should increase
status and consideration of colloid for additional fluid hemoglobin by approximately 5 g/dL (50 g/L). If
replacement. bleeding continues after the patient has received several

Pediatrics in Review Vol.26 No.12 December 2005 457

critical care circulatory shock

packed RBC transfusions, replacement of platelets and enhancing the sensitivity of the vasculature to cat-
clotting factors should be initiated. Platelets given in a echolamines. Vasopressin also stimulates cortisol secre-
volume of 1 U/10 kg of body weight increase the tion by increasing adrenocorticotropic hormone produc-
platelet count by approximately 105. Fresh frozen plasma tion and release. Studies in adults suggest that the
(FFP) is given at a dose of 10 to 20 mL/kg to maintain addition of vasopressin may be useful when standard
normal prothrombin and partial thromboplastin times. vasoactive medications are ineffective or when catechol-
Cryoprecipitate is indicated only in cases of documented amine toxicity is present. No randomized, placebo-
hypofibrinogenemia (fibrinogen ⬍100 mg/dL [1.0 g/ controlled trials are available to support the use of vaso-
L]) because of its increased infectious risk as a multiple pressin in children specifically, but anecdotal reports
donor product. suggest it may be safe and effective in the dose range of
Transfusion of blood products may be associated with 0.0003 to 0.008 U/kg per minute. (3)
complications, the most common of which are transfu-
sion reactions, hypothermia, hypocalcemia, and hyperka- Recombinant Human Activated Protein C
lemia. Transfusion reactions may consist of fever, rash, or Infection and other systemic insults result in the release
hypotension and are treated supportively and with dis- of tumor necrosis factor-alpha (TNF-alpha) as well as
continuation of that unit of blood product. Because interleukins from activated monocytes and other cells.
hypothermia may result from transfusing large volumes These cytokines recruit and further activate other cells,
of cold blood, blood should be warmed before being resulting in the release of inflammatory mediators, which
transfused. Hypocalcemia, which may decrease myocar- cause endothelial injury and activate the coagulation
dial contractility, can result from chelation of calcium by cascade. This series of events can result in SIRS, ARDS,
the citrate contained in banked blood, particularly FFP. and DIC. In DIC, the balance between the procoagulant
Ionized calcium levels should be measured and calcium and anticoagulant systems is altered in favor of coagula-
repleted as indicated. Hyperkalemia may result from tion, which results in fibrin deposition and further in-
hemolyzed RBCs in banked blood, particularly in older flammation in an effort to limit microbial dissemination.
units. Potassium levels should be monitored, particularly Activated Protein C (aPC) is a critical endogenous reg-
in patients receiving multiple units of packed cells or in ulator of coagulation and inflammation that has the
those who have pre-existing renal disease or other risk following properties: (3)
factors. ● Antithrombotic: inhibits thrombin formation by inhib-
iting factors V and VIII
Vasoactive Medications ● Profibrinolytic: inhibits plasminogen activator inhibi-
Children who continue to show signs of shock and
tor activity
hypoperfusion despite adequate volume resuscitation ● Anti-inflammatory: decreases TNF-alpha production
should be treated with vasoactive medications (Table
and neutrophil endothelial action
3) to correct the specific cardiovascular abnormalities
present. The pathophysiology of various shock states Patients in severe shock display acquired deficiencies of
guides the choice of the appropriate pharmacologic aPC. Treatment of adults suffering severe sepsis with
agent(s) to improve cardiovascular function. Vasoactive recombinant human-aPC (drotrecogin alfa [activated])
medications should not be withheld when clinically indi- at a dose of 24 mcg/kg per hour for 96 hours resulted in
cated while waiting for central venous access. a 19.4% reduced risk of death, with some increased risk of
bleeding (3.5%). (4) An international, multicenter phase
Vasopressin III trial of 83 pediatric patients who had severe sepsis
Catecholamines, as described previously, are first-line documented similar deficiency of endogenous protein C.
therapy for septic patients who require support of myo- (5) The risk of bleeding in children treated with aPC was
cardial contractility or vascular resistance. The utility of similar to that of adults (4.8% for all bleeding or 2.4% for
these agents, however, may be limited by resultant tachy- serious bleeding). Because no placebo group was in-
cardia or decreased splanchnic flow. In such patients, cluded, outcomes, particularly death, could only be com-
vasopressin may play a role. The physiologic effects of pared with predicted mortality. A subsequent random-
vasopressin (antidiuretic hormone) include systemic vaso- ized, double-blind, placebo-controlled study in children
constriction, but with vasodilation of the circle of Willis was stopped for futility after a planned interim analysis
and the pulmonary vasculature at higher doses. In addi- showed lack of improvement with aPC versus placebo in
tion, vasopressin may be synergistic with other pressors, time to resolution of organ failure (personal communi-

458 Pediatrics in Review Vol.26 No.12 December 2005

 critical care circulatory shock

cation, Eli Lilly and Company, April 21, 2005). In failure and guidelines for the use of innovative therapies in sepsis.
addition, the rate of CNS bleeding was increased in the Crit Care Med. 1992;20:864
2. Carcillo JA, Fields AI, Task Force Committee Members. Clinical
aPC group versus the placebo group, with three of the
practice parameters for hemodynamic support of pediatric and
four intracranial hemorrhages occurring in patients age neonatal patients in septic shock. Crit Care Med. 2002;30:
60 days or less. At present, aPC is not indicated for use in 1365–1378
children who have sepsis. 3. Brilli RJ. The role of steroids, vasopressin and activated protein
C in the treatment of patients with sepsis. Presented at Current
Conclusions Concepts in Pediatric Critical Care Course. San Antonio, Tex; Jan
28 –29, 2003
Shock is a pathophysiologic state of inadequate delivery
4. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of
of oxygen and substrate to the body tissues. Various recombinant human activated protein C for severe sepsis. N Engl
insults causing a disturbance either in CO or SVC can J Med. 2001;344:699 –709
lead to this impaired perfusion. Causes include the broad 5. Barton P, Kalil AC, Nadel S, et al. Safety, pharmacokinetics and
categories of hypovolemic, septic, distributive, and car- pharmacodynamics of drotrecogin alfa (activated) in children with
diogenic shock. The presentation of shock should be severe sepsis. Pediatrics. 2004;113:7–17
viewed as a continuum, and the earlier the recognition
and intervention, the better the outcome for the patient.
Early signs include tachycardia, tachypnea, poor skin Suggested Reading
perfusion with mottling or delayed capillary refill, and American Heart Association. Pediatric Advanced Life Support
oliguria. Hypotension is a late and ominous finding in (PALS) Course. Dallas, Tex: American Heart Association; 2001
children who are in shock. Treatment involves stabiliza- Carcillo JA. New developments in the management of septic shock
tion of the airway, provision of oxygen and adequate and multiple organ failure in infants and children. Presented at
Current Concepts in Pediatric Critical Care Course. San Anto-
ventilation, establishment of vascular access, and aggres-
nio, Tex; Jan 28 –29, 2003
sive fluid resuscitation. Further treatments, including Goldstein B, Zimmerman JJ. New horizons, the science and prac-
transfusion of blood products or support with vasoactive tice of acute medicine: critical care of pediatric shock. Crit Care
medications, should be guided by the evolving clinical Med. 1998;6(suppl):120 –154
situation. New experimental therapies aimed at modulat- Pomerantz WJ, Roback MG. Definition, classification and initial
assessment of shock in children. UptoDate. Available at www.
ing the immune response to systemic insult show prom-
uptodate.com. Accessed Jan 20, 2004
ise, particularly in septic shock. Tabbutt S. Heart failure in pediatric septic shock: utilizing inotropic
support. Crit Care Med. 2001;29:S231–S236
Tobias JD. Cardiovascular physiology, shock, inotropic agents,
References and invasive hemodynamic monitoring. In: Pediatric Critical
1. American College of Chest Physicians/Society of Critical Care Care, The Essentials. Armonk, NY: Futura Publishing; 1999:
Medicine. Consensus conference: definitions for sepsis and organ 17–35

Pediatrics in Review Vol.26 No.12 December 2005 459

critical care circulatory shock

PIR Quiz
Quiz also available online at www.pedsinreview.org.

10. A 1-week-old boy presents with a history of poor feeding, lethargy, and rapid breathing for 1 day.
Examination reveals a sick-appearing infant whose extremities are pale and mottled. His weight is 3 kg.
His vital signs are: rectal temperature, 33°C (91.4°F); heart rate, 145 beats/min; respirations, 48 breaths/
min; and blood pressure, 64/40 mm Hg. His pulses are equal in all extremities. His capillary refill time is
4 seconds. Multiple petechiae are noted on his trunk and extremities. His chest is clear to auscultation,
his heart sounds are normal, and no abnormality is noted on his abdominal examination. Pulse oximetry
on supplemental oxygen shows 100% saturation. Intravenous access is obtained. Of the following, the
most appropriate next step in management is:
A. Endotracheal intubation.
B. Infusion of 60 mL 0.9% saline over the next 20 minutes.
C. Infusion of 60 mL fresh frozen plasma over the next hour.
D. Infusion of dopamine at 5 mcg/kg per minute.
E. Lumbar puncture.

11. A 2-week-old girl presents with poor feeding and rapid respirations for 1 day. Examination reveals pale,
cool, and mottled extremities. Her vital signs are: rectal temperature, 38°C (100.4°F); respirations, 60
breaths/min; heart rate, 130 beats/min; and blood pressure, 80/50 mm Hg. Her pulses are equal in all
extremities. Her lungs are clear to auscultation. A gallop rhythm is heard. Her liver is 4 cm below the
right costal margin. Chest radiography shows mild cardiomegaly. You diagnose circulatory shock.
Compared with adults, which of the following is more important in infants to increase cardiac output?
A. Decreasing afterload.
B. Increasing blood pressure.
C. Increasing heart rate.
D. Increasing myocardial contractility.
E. Increasing preload.

12. A 10-year-old boy is brought to the emergency department after being struck by an automobile while
riding his bicycle. His Glasgow coma scale score is 13. He is intubated and manually ventilated at 20
breaths/min for ineffective respirations. His neck and spine are immobilized by a cervical collar and a rigid
body board. His vital signs are: rectal temperature, 36.8°C (98.2°F); heart rate, 60 beats/min; and blood
pressure, 70/40 mm Hg. His air entry is equal bilaterally, and heart sounds are normal. His abdomen is
soft and nontender. No bruising is noted anywhere on his body. The capillary refill time is 1 second.
Following appropriate intravascular expansion with normal saline over the next hour, his heart rate is 62
beats/min and blood pressure is 72/40 mm Hg. Which of the following is the most likely explanation for
his persistent hypotension?
A. Fat embolism.
B. Myocardial contusion.
C. Rupture of solid abdominal organ.
D. Septic shock.
E. Spinal cord injury.

13. A 10-year-old girl has been undergoing chemotherapy for acute myelogenous leukemia. She has an
indwelling catheter for long-term vascular access. Over the last 12 hours, she has developed fever and
shaking chills. In the emergency department, her vital signs are: oral temperature, 39.8°C (103.6°F); heart
rate, 148 beats/min; respirations, 22 beaths/min; and blood pressure, 68/34 mm Hg. Her extremities are
warm and well-perfused, with a capillary refill time of 1 second. Findings on the rest of the physical
examination are unremarkable. After receiving 60 mL/kg 0.9% saline, her heart rate is 130 beats/min and
blood pressure is 70/36 mm Hg. Appropriate antibiotic therapy has been instituted. Intravenous infusion
of which of the following is the most appropriate next step in her management?
A. Dopamine.
B. Milrinone.
C. Norepinephrine.
D. Phenylephrine.
E. Recombinant human activated protein C.

460 Pediatrics in Review Vol.26 No.12 December 2005

 Circulatory Shock in Children: An Overview
Christine A. McKiernan and Stephen A. Lieberman
Pediatr. Rev. 2005;26;451-460
DOI: 10.1542/pir.26-12-451

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