Etiology, clinical manifestations, evaluation, and management of neonatal shock

Author:
Beau Batton, MD
Section Editor:
Richard Martin, MD
Deputy Editors:
Melanie S Kim, MD
Carrie Armsby, MD, MPH

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2018. | This topic last updated: Mar 29, 2018.

INTRODUCTION — Shock is a dynamic and unstable pathophysiologic state characterized by inadequate

tissue perfusion. Although the effects of inadequate perfusion are reversible initially, prolonged hypoxemia
leads to the disruption of critical biochemical processes, which if not addressed results in cell death, end-
organ failure, and, possibly, death.

While the classification and underlying pathogenetic mechanisms of neonatal shock are the same as those
seen in pediatric and adult shock, the etiology and clinical manifestations vary and are often unique to
neonates. (See "Initial evaluation of shock in children" and "Definition, classification, etiology, and
pathophysiology of shock in adults".)

The pathogenesis, etiology, stages, clinical presentation, evaluation, and management of neonatal shock
will be reviewed here.

DEFINITION

●Shock, or circulatory failure, is defined as a physiologic state characterized by tissue hypoxia

due to reduced oxygen delivery and/or increased oxygen consumption or inadequate oxygen
utilization. It is manifested by physical findings of tissue hypoperfusion (eg, cold extremities,
acrocyanosis, and poor capillary refill), hypotension, and metabolic acidosis. It is important to
recognize that hypotension, which is commonly used to define shock states in adults, is generally a
late finding of shock in neonates. Shock is often initially reversible, but must be recognized and
treated immediately to prevent progression to irreversible organ dysfunction.
Of note, blood pressure (BP) values vary significantly based on gestational age (GA) and postnatal
age (figure 1 and figure 2), particularly for extremely preterm infants born <28 weeks GA. As such,
defining hypotension in this population is challenging. (See "Etiology, clinical manifestations,
evaluation, and management of low blood pressure in extremely preterm infants".)
●Undifferentiated shock refers to the clinical situation in which shock is recognized but the cause is
unclear.

The following parameters are used to assess circulation and cardiovascular status:
 ●Cardiac output (CO) is the volume of blood ejected by the heart each minute. It is the product of
heart rate (HR) and stroke volume (SV). SV is the volume of blood pumped out during each cardiac
contraction and is dependent on preload, afterload, and ventricular contractility:
CO = HR x SV
●Oxygen content in the arterial blood (CaO 2) depends on the hemoglobin concentration (Hgb),
oxygen saturation (SaO2), and, to a much lesser degree, the arterial oxygen partial pressure (PaO 2):
CaO2 = 1.36 x Hgb x SaO2 + (0.0031 x PaO2)
●Oxygen delivery (DO2) is the product of CO and the CaO2:
DO2 = CO x CaO2
●Systemic vascular resistance (SVR) is the resistance that the left ventricle must overcome to
pump blood through the systemic circulation. It is affected by the vessel diameter (constriction or
dilation), vessel length, and blood viscosity. Changes in SVR will alter the afterload and thereby
have an impact on SV.
●Blood pressure (BP) is the pressure exerted against the inner walls of the blood vessels and
depends on CO and SVR:
BP = CO x SVR

PATHOGENESIS — Shock, a state of cellular and tissue hypoxia, is due to reduced oxygen delivery,
increased oxygen consumption, and/or inadequate oxygen utilization [1-3]. Cellular hypoxia results in a
switch to anaerobic metabolism and accumulation of lactic acid. Increasing levels of lactic acid causes
metabolic acidosis, which interferes with cell and organ function and, if not addressed, cell death. Tissue
hypoperfusion also leads to endothelial dysfunction, stimulation of inflammatory and anti-inflammatory
cascades, and activation of local humoral processes that disrupt the microcirculation resulting in further
tissue injury. If untreated, these processes result in circulatory collapse, major organ failure, and death.

Shock is classified based on the following underlying pathophysiologic mechanisms. Neonatal shock may
be the result of more than one of these processes (multifactorial shock):

●Hypovolemic − Due to insufficient circulating blood volume, resulting in a reduction in cardiac

output (CO) (reduced preload) or reduced oxygen delivery.
●Distributive − Severely decreased systemic vascular resistance (SVR) due to impairment of
vascular tone, which results in maldistribution of blood within the microcirculation and regional and
global hypoperfusion.
●Cardiogenic − Cardiac dysfunction (pump failure) or arrhythmia, causing a decrease in CO
primarily due to deceased stroke volume (SV) (eg, impaired contractility). In cases of complete heart
block, the significant reduction in heart rate (HR) leads to inadequate CO.
●Obstructive – Extracardiac disorders that result in decreased CO (eg, tension pneumothorax,
cardiac tamponade, massive pulmonary embolism).

ETIOLOGIC CLASSIFICATION — The etiology of neonatal shock can be organized based on the
underlying pathogenesis: hypovolemic, distributive, cardiogenic, and obstructive shock (table 1). However,
these processes are not mutually exclusive, and neonates with circulatory failure may have a combination
of more than one form of shock (multifactorial shock). Undifferentiated shock refers to the situation where
shock is recognized but the cause is unclear.

Hypovolemic shock — Hypovolemic shock occurs due to insufficient circulating blood volume, resulting in
a reduction in cardiac output (CO) and reduced oxygen delivery. Neonatal shock due to hypovolemia is
most commonly due to hemorrhage [4].

Causes of hemorrhagic shock in the neonate include:

●Fetomaternal hemorrhage. (See "Massive fetomaternal hemorrhage".)

●Acute hemorrhage from umbilical cord prolapse or rupture associated with abnormal presentation
(vasa previa) or insertion (velamentous cord). (See "Umbilical cord prolapse" and "Velamentous
umbilical cord insertion and vasa previa".)
●Acute bleeding into the subgaleal space (subgaleal hemorrhage) following a vacuum-assisted
delivery. (See "Neonatal birth injuries", section on 'Subgaleal hemorrhage'.)
●Massive internal bleeding in the gastrointestinal (GI) tract, brain, lungs, or other major organ.
(See "Germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) in the newborn:
Pathogenesis, clinical presentation, and diagnosis" and "Clinical features and diagnosis of
necrotizing enterocolitis in newborns".)
●Tumor associated acute hemorrhage (eg, sacral coccygeal teratoma). (See "Sacrococcygeal germ
cell tumors".)

In addition, acute blood transfusion between monochorionic twins may result in hypovolemic shock.
(See "Twin-twin transfusion syndrome and twin anemia polycythemia sequence: Pathogenesis and
diagnosis".)

Other causes of hypovolemic shock include third spacing (ie, movement of intracellular fluid into the
extravascular space) as can occur with perinatal distress and acute intestinal injury (eg, volvulus,
necrotizing enterocolitis, intestinal perforation). Less common causes include excess GI fluid loss from
congenital chloridorrhea and polyuria due to congenital diabetes insipidus.

Distributive shock — Distributive shock results from severely reduced systemic vascular resistance
(SVR) due to impairment of vascular tone, which results in maldistribution of blood within the
microcirculation and regional and global hypoperfusion. The following are causes of neonatal distributive
shock:

●Sepsis − In neonates, sepsis is the most common cause of distributive shock. Sepsis releases
vasoactive mediators that depress autonomic nervous system regulation of the systemic circulations
resulting in diffuse vasodilation and impaired perfusion. However, the mechanisms by which this
occurs and the impact of altered autonomic nervous system function are different in septic newborn
infants compared with older patients. Sepsis may also cause myocardial dysfunction (cardiogenic
shock). (See "Pathophysiology of sepsis", section on 'Circulation' and "Clinical features, evaluation,
and diagnosis of sepsis in term and late preterm infants".)
 ●Adrenal insufficiency – Shock due to adrenal insufficiency is due to impaired synthesis or release of
adrenocortical hormones. This is most commonly associated with congenital adrenal hyperplasia.
(See "Causes and clinical manifestations of primary adrenal insufficiency in children", section on
'Adrenal crisis'.)
●Other rare conditions resulting in distributive shock include hydrops fetalis and toxic shock
syndrome [5]. (See "Postnatal care of hydrops fetalis" and "Staphylococcal toxic shock syndrome".)

Cardiogenic shock — Cardiogenic shock is due to cardiac dysfunction or failure which causes a
decrease in CO. Cyanosis and hypoxemia are common manifestations when there is also inadequate
pulmonary blood flow. Cardiac dysfunction in the neonate is caused by a variety of conditions including the
following [4]:

●Myocardial ischemia/hypoxemia can lead to myocardial damage resulting in poor contractility.

Myocardial injury and dysfunction may be complications associated with intrapartum asphyxia,
systemic bacterial infection, and chronic fetal hypoxemia.
●Congenital heart disease (CHD) – Some infants with critical CHD may present in the early
neonatal period in cardiogenic shock as the ductus arterious closes and systemic perfusion
decreases. Most commonly, this is seen in infants with unsuspected critically obstructive left heart
lesions (table 2), including:
•Hypoplastic left heart syndrome (HLHS) (figure 3) (see "Hypoplastic left heart syndrome:
Anatomy, clinical features, and diagnosis").
•Critical aortic valve stenosis (see "Valvar aortic stenosis in children", section on 'Critical AS').
•Critical coarctation of the aorta (COA) (figure 4) (see "Clinical manifestations and diagnosis of
coarctation of the aorta").
•Interrupted aortic arch (figure 5).
Infants with total anomalous pulmonary venous connection (TAPVC) (figure 6) most commonly
present with cyanosis and tachypnea. However, if there is significant obstruction at the atrial
communication, systemic perfusion will be impaired. (See "Identifying newborns with critical
congenital heart disease", section on 'Shock'.)
●Cardiac arrhythmias
•Complete congenital heart block due to maternal antibodies
to SSA/Ro and/or SSB/La (Sjögren's syndrome type A and B antigens) in mothers with
systemic lupus erythematosus and Sjögren's syndrome. (See "Neonatal lupus: Epidemiology,
pathogenesis, clinical manifestations, and diagnosis", section on 'Heart block'.)
•Supraventricular tachycardia. (See "Clinical features and diagnosis of supraventricular
tachycardia in children".)
•Ventricular tachycardia. (See "Causes of wide QRS complex tachycardia in children".)
●Myocarditis may occur as an isolated illness or as a component of a systemic illness. In the
newborn, myocarditis is usually due to viral infection, most commonly coxsackievirus.
●Congenital cardiomyopathy is a rare cause of cardiac dysfunction that typically presents with
hydrops fetalis.
Obstructive shock — Obstructive shock occurs when extracardiac diseases lead to impaired CO.
Obstructive shock is categorized as either pulmonary vascular (eg, pulmonary embolus, severe pulmonary
hypertension) or mechanical (eg, tension pneumothorax, pericardial tamponade, constrictive pericarditis).
These are rare causes of neonatal shock.

Multifactorial shock — Neonatal multifactorial shock may be observed in the following clinical settings. It
is important to identify the multiple etiologies in order to guide treatment decision.

●Sepsis – As noted above, sepsis is typically classified as distributive shock. However, patients may
exhibit cardiogenic shock due to myocardial depression and hypovolemic shock due to capillary leak
and third spacing (movement of intracellular fluid into the extravascular space). (See "Clinical
features and diagnosis of bacterial sepsis in the preterm infant (<34 weeks gestation)", section on
'Severe sepsis and septic shock'.)
●Severe intestinal injury – Patients with severe intestinal injury (eg, Stage III necrotizing enterocolitis
[NEC]) may develop circulatory collapse due to hypovolemic shock due to third spacing and
distributive shock due to sepsis. (See "Clinical features and diagnosis of necrotizing enterocolitis in
newborns".)
●Pulmonary hypertension – Pulmonary hypertension is typically classified as obstructive shock.
However, patients with severe disease commonly have biventricular dysfunction leading to
cardiogenic shock. (See "Persistent pulmonary hypertension of the newborn".)

CLINICAL MANIFESTATIONS

Overview — Shock is initially reversible, but must be recognized and treated immediately to prevent
progression to irreversible organ dysfunction. Although the clinical presentation of neonatal shock may
vary depending upon the type and cause of shock, almost all neonates present with the following:

●Signs of poor peripheral perfusion:

•Cool extremities
•Acrocyanosis
•Pallor
●Tachycardia is a common finding; however, bradycardia can be seen as a sign of failing cardiac
function and is often a terminal finding.
●Metabolic acidosis with elevated levels of lactic acid/lactate.

Physical findings — The following physical findings are usually present in neonatal shock regardless of
the underlying etiology.

Vital signs

●Abnormal heart rate – In general, tachycardia (heart rate [HR] >180 beats per minute) is a
common but nonspecific finding in neonatal shock, which occurs when the infant tries to maintain
cardiac output (CO) by a compensatory increase in HR when there is a limited capacity to increase
 stroke volume (SV) [6]. In addition, variability of HR may be an early sign of septic shock [7]. In term
infants, bradycardia (HR <90 beats per minute) is a late sign of failing cardiac function and is often a
terminal finding; whereas in preterm infants, bradycardia may be an earlier manifestation of shock.
●Hypotension – Low blood pressure (BP) (hypotension) is generally a late finding of shock, and
ideally shock is diagnosed prior to the onset of hypotension [6]. In neonates, BP increases with both
increasing gestational age (GA) at birth and postnatal age (in hours) over the first postnatal week
(figure 1 and figure 2). However, there is wide variability in observed BP values for all infants,
particularly extremely preterm infants (see "Etiology, clinical manifestations, evaluation, and
management of low blood pressure in extremely preterm infants"). As such, there is not a standard
definition of hypotension in term or preterm infants (see "Short-term complications of the preterm
infant", section on 'Low blood pressure').
Furthermore, BP correlates poorly with systemic blood flow in infants [8-10] such that BP
measurements alone are imperfect tests to detect low blood flow in the early stages of shock.
Hypotension does not occur as a manifestation of hypovolemic shock until the neonate has lost 30 to
40 percent of its blood volume. As such, the presence of this symptom with hypovolemic shock is
indicative of the need for massive volume resuscitation.
Antihypotensive therapy is indicated for neonates with BP that is below the expected range in
conjunction with evidence of poor perfusion (see 'Decreased peripheral perfusion' below). Therapy is
also considered for neonates with a persistent decrease in the mean arterial BP of at least 5 mmHg.
●Abnormal body temperature – Fever is often present with neonatal sepsis. However, infants with
shock due to any etiology (including sepsis) may have impaired autonomic nervous system function
which can result in hypothermia.

Decreased peripheral perfusion — Signs of decreased peripheral perfusion include:

●Cool extremities, acrocyanosis, and pallor are initial signs of decreasing CO, as
vasoconstrictive mechanisms compensate for decreased tissue perfusion by redirecting blood from
the periphery to the vital organs (eg, coronary, cerebral, and adrenal perfusion). These signs may be
difficult to differentiate from findings in the normal neonate whose hands and feet are often cool to
the touch with varying degrees of acrocyanosis. Pallor may also be an indication of anemia.
●Delayed capillary refill >4 seconds is suggestive of neonatal shock [8,9]. However, the predictive
value of capillary refill is poor, and it is not a reliable physical finding to either confirm the diagnosis
of shock or to assess response to therapy in newborns [8,11]. In addition, no definitive correlation
between tissue perfusion, BP, and outcome has been established [12].

Other clinical manifestations — Other end-organ changes may develop in the brain, kidney, respiratory,
and gastrointestinal track.

●Neurologic – In the initial stages of shock, neurologic changes vary from lethargy (including poor
feeding) to irritability. In the later stages, there is progression to stupor or coma. Other neurologic
findings include hypotonia at rest, decreased spontaneous movements of the extremities, diminished
deep tendon reflexes, and absence of developmental reflexes (also referred to as primitive reflexes),
 such as the palmar grasp reflex, Moro reflex, and rooting reflex. (See "Neurologic examination of the
newborn".)
●Renal – There is a strong correlation between low urinary output (oliguria) and low systemic blood
flow. However, there is often a time delay between the development of circulatory compromise and
the recognition of oliguria, because urine output is often low or not closely monitored immediately
after birth [13]. Shock will result in renal injury and impairment, which is manifested by increasing
serum creatinine and blood urea nitrogen (BUN) levels.
●Respiratory – The following nonspecific respiratory findings may be seen in neonatal shock:
•Tachypnea is generally seen in infants with septic or cardiogenic shock as a compensatory
response to metabolic acidosis due to lactate production from poorly perfused tissue.
•Other signs of respiratory distress, such as grunting, retractions, nasal flaring, and gasping,
often accompany tachypnea. These are observed especially in patients with primary
pulmonary disease (eg, pneumonia) or cardiopulmonary compromise with pulmonary edema.
•Periodic breathing and apnea are usually centrally mediated and are more likely to be
associated with decreased cerebral perfusion or significant metabolic acidosis that impairs
cerebral function. As a result, these findings can present in all forms of neonatal shock.
•Hypoxemia may be present in infants with shock due to cardiac dysfunction or obstructed
blood flow, but isolated hypoxemia is rare. Hypoxemia associated with neonatal shock may be
due to persistent pulmonary hypertension that may accompany bacterial infections, especially
those caused by group B streptococcus (GBS), cyanotic congenital heart disease (CHD), and
severe anemia. (See "Persistent pulmonary hypertension of the newborn", section on
'Maladaptation' and "Cardiac causes of cyanosis in the newborn".)
●Gastrointestinal (GI) – The following nonspecific GI findings may be seen in patients with neonatal
shock:
•Poor feeding due to lethargy and/or respiratory distress.
•Vomiting as a manifestation of decreased motility that results from non-mechanical disruption
of the normal coordinated propulsive motor activity of the GI tract, which may progress to
paralytic ileus. Bilious emesis is uncommon and when present it should prompt an
investigation into intra-abdominal causes of shock (eg, malrotation with midgut volvulus or
necrotizing enterocolitis). (See "Intestinal malrotation in children" and "Clinical features and
diagnosis of necrotizing enterocolitis in newborns".)
•Abdominal distension as a manifestation of ileus.
•Liver dysfunction due to decreased perfusion is manifested by increased serum bilirubin
levels, elevation in liver enzyme levels; and prolongation of the prothrombin time (PT), partial
thromboplastin time (PTT), and international normalized ratio (INR), which increases the
possibility of bleeding. (See "Acute liver failure in children: Etiology and evaluation".)

Laboratory findings — The most common laboratory feature characteristic of neonatal shock is metabolic
acidosis with decrease in serum/plasma bicarbonate and an increase in lactate due to increased anaerobic
metabolism (increased lactate production) and decreased clearance of lactate.

Other less common laboratory features include:

 ●Anemia due to blood loss observed in hemorrhagic hypovolemic shock [14,15], or hemolysis in
septic shock.
●Prolonged PT/INR and PTT tests can occur with consumptive coagulopathy, which may be present
in infants with septic shock or complications from pregnancy including fetal anoxia/birth asphyxia
(distributive shock) and placental abruption (hypovolemic shock). (See "Disseminated intravascular
coagulation in infants and children", section on 'Neonates'.)
●Glucose levels may be elevated or decreased during neonatal shock. The glucose level varies
depending upon catecholamine release during the body's stress response (which affects insulin
release and peripheral utilization of glucose) and the body stores of glucose and glycogen.
(See "Neonatal hyperglycemia" and "Pathogenesis, screening, and diagnosis of neonatal
hypoglycemia".)
●Hyperkalemia is a result of release of intracellular potassium stores due to tissue injury and cell
death, and decreased excretion with renal function impairment. (See "Neonatal acute kidney injury:
Pathogenesis, etiology, clinical presentation, and diagnosis", section on 'Presentation due to other
laboratory abnormalities'.)
●Serum bilirubin levels and liver enzymes may be elevated due to hepatic injury and dysfunction.
●Serum creatinine and BUN may be elevated due to renal injury and dysfunction.

DIAGNOSIS — The diagnosis of shock is clinically based on a constellation of clinical, biochemical, and
hemodynamic features. These include physical findings of tissue hypoperfusion (eg, cold extremities,
acrocyanosis, and poor capillary refill), and metabolic acidosis. Patients in the early stages of shock may
present with normal blood pressure (BP) but with tachycardia and compensatory peripheral
vasoconstriction (eg, cold extremities and acrocyanosis). Hypotension is typically found only in the late
stages of shock and bradycardia is usually observed in the terminal stage in term infants, but may be an
early finding in preterm infants. (See 'Clinical manifestations' above.)

INITIAL STABILIZATION — Stabilization of the patient's hemodynamic status takes precedence over any
diagnostic evaluation. Resuscitation should not be delayed to obtain history, perform a physical
examination, or obtain laboratory tests. The goals of the initial evaluation of neonatal shock include rapid
recognition and correction of circulatory compromise and other life-threatening conditions.

The following approach is directed to initial stabilization of the hemodynamic status of neonates in shock:

●Airway/breathing – Assess and stabilize the infant's airway and respiratory status, including
administration of supplemental oxygen and/or mechanical ventilation. Neonates in shock generally
are in respiratory distress or are apneic and almost always require positive pressure ventilation,
endotracheal intubation, and mechanical ventilation. (See "Mechanical ventilation in neonates".)
●Vascular access – Vascular access should be established and blood samples obtained for initial
testing. If feasible, central lines for frequent blood drawing and consistent vascular access should be
considered. Arterial access for invasive BP monitoring should also be considered, but peripheral
arterial lines can be difficult to establish in neonates with poor perfusion. (See 'Basic laboratory
studies' below.)
●Fluid resuscitation – Initial fluid resuscitation with isotonic crystalloid infusion of 20 mL/kg over 10
to 15 minutes should be performed for neonates with undifferentiated shock. Further aggressive fluid
resuscitation is generally needed for patients with hypovolemic or distributive shock. For patients
with obstructive shock, initial volume expansion may also be beneficial as it improves cardiac
preload. In contrast, fluid expansion may be harmful for infants with cardiogenic shock. Excessive
isotonic fluid administration (>30 mL/kg) in preterm infants is associated with an increased risk of
death and intraventricular hemorrhage (IVH). As a result, assessing the response to the initial fluid
bolus (monitoring heart rate [HR], blood pressure [BP], peripheral perfusion) is important to
determine if further fluid resuscitation is warranted. (See 'Monitoring response' below and 'Fluid
resuscitation' below.)
●Diagnostic evaluation – Ongoing diagnostic evaluation is performed concomitantly with
resuscitative steps including a brief review of the history, physical examination, and obtaining basic
laboratory tests (electrolytes, blood gas, complete blood count, lactate, blood culture, renal and liver
function tests, and type and cross). In addition, other tests (eg, chest radiograph, electrocardiogram
(ECG), or echocardiography) may be indicated based on the history or physical examination.
(See 'Diagnostic evaluation' below.)
●Empiric antibiotics – Because neonates are at-risk for sepsis, intravenous (IV) empiric antibiotics
are administered pending results from blood cultures. The empiric antibiotic regimen should include
agents active against group B streptococcal and other organisms that cause neonatal sepsis
(eg, Escherichia coli). The combination of ampicillin and gentamicin or ampicillin and a third
generation cephalosporin (eg, cefotaxime, if available) are potential regimens that provide empiric
coverage for these organisms until culture results are available. (See "Clinical features, evaluation,
and diagnosis of sepsis in term and late preterm infants", section on 'Empiric antibiotic therapy'.)
●Other measures – Other physiologic disturbances are common in neonates with shock, and if
present, should be promptly corrected. These may include:
•Abnormal glucose levels – Glucose levels should be monitored and both hyper- or
hypoglycemia should be corrected. (See "Management and outcome of neonatal
hypoglycemia" and "Neonatal hyperglycemia", section on 'Management'.)
•Hypothermia. (See "Neonatal resuscitation in the delivery room", section on 'Temperature
control'.)
•Electrolyte disturbances. (See "Fluid and electrolyte therapy in newborns".)
•Thrombocytopenia. (See "Clinical manifestations, evaluation, and management of neonatal
thrombocytopenia", section on 'Management'.)
•Coagulopathy. (See "Disseminated intravascular coagulation in infants and children", section
on 'Treatment'.)
●Other immediate interventions – The need for more specific immediate or early interventions
should be assessed so that lifesaving therapies can be administered promptly. These include:
•Suspected congenital heart disease – For patients with suspected ductal-dependent
congenital heart defects (table 2), prompt administration of prostaglandin E1 (0.01 mcg/kg per
minute) is necessary. Deterioration of the clinical status after starting prostaglandin E1 usually
indicates the presence of rare congenital cardiac defects associated with pulmonary venous or
 left atrial obstruction. (See "Diagnosis and initial management of cyanotic heart disease in the
newborn", section on 'Prostaglandin E1'.)
•Arrhythmia – For patients with arrhythmias:
-Patients with supraventricular tachycardia should be treated with adenosine
(0.2 mg/kg/dose via rapid IV injection) or synchronized cardioversion (0.5 to
2 Joules/kg). (See "Management of supraventricular tachycardia in children", section on
'Hemodynamically unstable'.)
-Neonates with bradycardia should receive epinephrine or atropine (if atrioventricular
[AV] block is present) and may require cardiac compressions and subsequent cardiac
pacing. A pediatric cardiologist should be consulted promptly for treatment of persistent
bradycardia in the setting of neonatal shock or if the etiology of shock is thought to be a
primary cardiac rhythm disturbance (eg, congenital heart block). (See "Bradycardia in
children", section on 'Poor perfusion'.)
-Patients with ventricular tachycardia should undergo synchronized cardioversion.
(See "Management and evaluation of wide QRS complex tachycardia in children",
section on 'Unstable patient'.)
•Pneumothorax/tamponade – Patients with obstructive shock (eg, tension pneumothorax,
cardiac tamponade) require emergent specific interventions to relieve the obstruction to blood
flow (eg, thoracentesis, pericardiocentesis). (See "Pulmonary air leak in the newborn", section
on 'Thoracentesis' and "Emergency pericardiocentesis".)
•Acute blood loss – For patients with significant blood loss, red blood cell (RBC) transfusion
is indicated. In life-threatening circumstances, any available RBC product that is compatible
with the infant's blood type can be administered. If O-negative RBCs are available in the
delivery room as an emergency transfusion for the mother, this blood also can be used in the
neonate. (See "Red blood cell transfusions in the newborn", section on 'Acute blood
loss' and "Red blood cell transfusions in the newborn", section on 'Products for acute life-
threatening blood loss'.)

DIAGNOSTIC EVALUATION — When a patient is suspected of having shock, diagnostic evaluation to

determine the underlying cause should occur in concert with resuscitation. The type and cause of shock
can generally be determined from the history, physical examination, and diagnostic studies, which may
impact on overall management and treatment of the underlying condition [6]. (See 'Goal-directed
therapy' below.)

History — The newborn history, including review of maternal health issues, antenatal screening, and
pregnancy and delivery complications, often can identify the underlying cause of shock. The following
historical findings identify the underlying mechanism of shock (table 1) (see 'Etiologic classification' above):

●Hypovolemic shock:
•Significant blood loss from placental anomalies, maternal bleeding, or umbilical cord
abnormalities. (See "Placenta previa: Epidemiology, clinical features, diagnosis, morbidity and
mortality".)
 •Internal bleeding due to traumatic vacuum assisted delivery (eg, subgaleal bleed).
(See "Neonatal birth injuries".)
●Septic shock (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm
infants", section on 'Maternal risk factors'):
•Prolonged rupture of membranes
•Fetal tachycardia
•Maternal chorioamnionitis
●Cardiogenic shock:
•Maternal history of systemic lupus erythematosus or Sjögren's syndrome resulting in neonatal
heart block. (See "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and
diagnosis".)
•Antenatal asphyxia with abnormal heart rate (HR) pattern. (See "Systemic effects of perinatal
asphyxia", section on 'Myocardial dysfunction'.)
•Congenital heart disease (CHD) detected by prenatal ultrasound or newborn screening.
(See "Fetal cardiac abnormalities: Screening, evaluation, and pregnancy
management" and "Identifying newborns with critical congenital heart disease", section on
'Prenatal diagnosis'.)
●Hydrops fetalis may be associated with distributive, cardiogenic, or multifactorial shock.
(See "Postnatal care of hydrops fetalis".)

In some cases, neonates who are more likely to require resuscitation can be identified prior to delivery. As
a result, the neonatal team can be alerted and set up preparations for resuscitation in the delivery room.
(See "Neonatal resuscitation in the delivery room", section on 'High-risk delivery'.)

Physical examination — The physical examination is important to assess the severity of shock and to
monitor the response to therapeutic interventions. (See 'Physical findings' above and 'Monitoring
response' below.)

In most cases, physical findings are nonspecific and not helpful for identifying the underlying cause of
shock. However, if present, the following findings may be helpful in determining the etiology:

●Pathologic murmurs and/or gallop rhythm may raise suspicion for a cardiac cause, however, some
forms of critical CHD may not have an appreciable murmur (eg, hypoplastic left heart syndrome
[HLHS]). Murmurs commonly occur in some non-cardiac causes of neonatal shock (eg, tricuspid
regurgitation murmur in birth asphyxia).
●Weak or absent lower extremity pulses (particularly in comparison to upper extremity pulses) might
suggest cardiogenic shock due to critical coarctation of the aorta. (See "Clinical manifestations and
diagnosis of coarctation of the aorta", section on 'Neonates'.)
●Abdominal distension might suggest necrotizing enterocolitis and sepsis. (See "Clinical features
and diagnosis of necrotizing enterocolitis in newborns", section on 'Clinical presentation'.)
●Skin findings might suggest an infectious etiology (cellulitis, vesicles [herpes simplex virus]).
(See "Neonatal herpes simplex virus infection: Clinical features and diagnosis", section on 'Neonatal
HSV'.)
 ●Chest asymmetry and absent breath sounds on one side might suggest tension pneumothorax.
●Ambiguous genitalia should raise suspicion for the possibility of distributive shock due to adrenal
insufficiency (table 3). (See "Causes and clinical manifestations of primary adrenal insufficiency in
children", section on 'Adrenal crisis' and "Causes and clinical manifestations of primary adrenal
insufficiency in children", section on 'Congenital adrenal hyperplasia'.)
●Rash comprising erythematous annular lesions or arcuate macules located primarily on the scalp
and periorbital area is one of the physical diagnostic findings neonatal lupus, which is also
associated with congenital heart block and the possibility of cardiogenic shock. (See "Neonatal
lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Rash'.)

Basic laboratory studies — The following tests may be helpful in identifying the cause, severity, and the
initial treatment of shock.

●Arterial blood gas – The arterial blood gas measures the degree of acidosis and hypoxemia,
which are important factors in the assessment and management of patients with shock. The blood
gas does not help to distinguish between different types of shock but rather confirms shock and
assesses its severity. Blood gases are also an important to assess the effectiveness of interventions.
(See 'Monitoring response' below.)
•Metabolic acidosis is observed in most cases primarily due to accumulation
of lactate/lactic acid.
•Respiratory acidosis may be seen, particularly in patients with apnea or primary pulmonary
disease (eg, pneumonia).
•Hypoxemia is often, but not always, observed depending on the degree of respiratory
compromise and underlying etiology (eg, cyanotic CHD and primary pulmonary disorders are
likely to present with hypoxemia).
Some point-of-care blood gas analyzers permit simultaneous measurement of electrolytes and
lactate, which provides additional useful information.
●Lactate – Serum lactate is a marker of tissue perfusion and is used to measure the severity of
shock (lactate levels increase as the severity increases). Lactate is obtained at baseline and can be
serially measured to follow the response to therapy. (See 'Monitoring response' below.)
●Complete blood count (CBC) with differential − Abnormalities of any of the three cell lines may
occur in neonatal shock; however, these are nonspecific findings and may not be useful in
diagnosing the underlying cause:
3 3
•Both elevated (>20,000/mm ) and depressed (<5000/mm ) total white blood cell (WBC)
counts are associated with systemic bacterial infection, which may result in septic shock.
(See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants",
section on 'Complete blood count'.)
•Thrombocytopenia may be suggestive of disseminated intravascular coagulation due to
complications from pregnancy including fetal anoxia/birth asphyxia (distributive shock) or
placental abruption (hypovolemic shock), or neonatal septic shock [16]. (See "Disseminated
intravascular coagulation in infants and children", section on 'Neonates'.)
 •Anemia is seen in neonatal shock due to massive blood loss or hemolysis from overwhelming
sepsis.
●Blood chemistries – Basic chemistry tests include electrolytes, glucose, renal (blood urea nitrogen
[BUN] and creatinine) and liver function studies:
•As noted above, hyperkalemia and both hypo- and hyperglycemia may occur in neonatal
shock.
•Serum bicarbonate is depressed as an indication of metabolic acidosis.
•Baseline renal and liver function studies should be obtained and levels should be monitored
to detect any abnormalities indicating end-organ damage and recovery.
•Hyponatremia and hyper- and hypoglycemia are typical manifestations of distributive shock
due to adrenal insufficiency.
●Blood cultures – Blood cultures should be obtained in any infant who may have septic shock or
shock without an identifiable cause.
●Type and cross – Blood type, antibody screen, and crossmatching should be performed for infants
with hypovolemic shock due to blood loss who will require red blood cell transfusion. (See "Red
blood cell transfusions in the newborn", section on 'Acute blood loss' and "Red blood cell transfusion
in infants and children: Selection of blood products", section on 'Newborns and young infants'.)

Additional studies — Depending on the results of the initial evaluation (history and basic laboratory
studies) and response to initial therapy, the following studies may be useful in the assessment of neonatal
shock.

●Echocardiography is recommended to evaluate patients in whom cardiogenic shock is suspected to

measure cardiac output (CO), assess global and regional systolic and diastolic function, and
evaluate for structural cardiac disease including ductal-dependent congenital heart defects [17].
●Electrocardiogram (ECG) is recommended to detect arrhythmias that may result in cardiogenic
shock (eg, complete heart block, supraventricular and ventricular tachycardia).
●Chest radiography can be useful for neonates with respiratory distress, an abnormal
cardiopulmonary examination, or poor response to initial management. An abnormal chest
radiograph may be indicative of primary cardiac (eg, cardiomegaly, abnormal pulmonary vascular
markings, pulmonary venous congestion) or pulmonary disease (eg, tension pneumothorax,
pneumonia).
●Abdominal radiography may be useful in the evaluation of infants with a suspected abdominal
source for sepsis or shock (eg, necrotizing enterocolitis [NEC] or volvulus).
●Ultrasonography can be used to detect bleeding into the brain, abdomen, or kidney.
●Computed tomography or magnetic resonance imaging of the head can differentiate subgaleal
hemorrhage, which has a high mortality rate, from other cranial pathologic conditions. However,
subgaleal bleeding should be diagnosed clinically, as it is important to initiate treatment as quickly as
possible. (See "Neonatal birth injuries", section on 'Subgaleal hemorrhage'.)
●A positive test for fetal cells in a sample of maternal blood can be indicative of fetomaternal
hemorrhage as a cause for hypovolemic shock [18]. (See "Massive fetomaternal hemorrhage",
section on 'Kleihauer-Betke'.)
 ●Near-infrared spectroscopy (NIRS) has been used in research settings to assess blood flow to the
brain, gastrointestinal (GI) tract, and kidneys because blood pressure (BP) is not a reliable
measurement of perfusion of critical organs [19-21]. Preliminary data suggest decreased cerebral
blood flow (CBF) predicts poor neurologic outcome [22,23], but that BP values correlate poorly with
measurements of CBF [24]. However, reliable NIRS data to guide therapeutic decision making for
neonatal shock are not yet available.

GOAL-DIRECTED THERAPY

Goals — Successful management of neonatal shock requires the rapid initiation of treatment to restore
hemodynamic stability regardless of the underlying etiology. During this initial stabilization, evaluation to
determine the etiology should occur concomitantly in order to best direct subsequent therapy and quickly
identify patients who may be harmed by or not respond to specific therapeutic interventions.

Physiologic goal-oriented parameters — The goal of initial stabilization is to restore tissue perfusion
based on improving physiologic parameters; however, identifying accurate physiologic indicators to
monitor the effectiveness of resuscitation for neonatal shock is challenging due to the relative immaturity of
the cardiovascular and nervous systems, technical challenges with invasive monitoring, and potential
difficulty with both obtaining blood samples and establishing intravenous (IV) access in a compromised
neonate.

Nevertheless, we utilize the following physiological indicators to establish the goals of therapy and to
monitor response to therapeutic interventions:

●Improved quality of central and peripheral pulses (eg, strong brachial and femoral pulses, easily
palpable radial and posterior tibial pulses)
●Improved skin perfusion (warm extremities, less mottling, capillary refill <3 seconds)
●Improved acid-base balance (resolving metabolic acidosis, decreasing lactate level)
●Improved neurologic status (grimace, spontaneous movement, response to stimulation, presence
of normal newborn reflexes)
●Rise in blood pressure (BP) if hypotensive (figure 1 and figure 2). When antihypotensive therapy is
initiated, the goal should be to increase the BP to values observed before the onset of shock at a
rate of 5 to 10 mmHg over several hours. A greater accelerated rate of rise in BP in preterm infants
is associated with an increased risk of intraventricular hemorrhage (IVH).

These physiologic parameters are assessed before and after each intervention to guide further
management. Response or lack of response may also be helpful in identifying the underlying etiology. As a
result, the management of neonatal shock requires close monitoring and observation of the following:

●Continuous heart rate (HR) and pulse oximetry monitoring.

●Frequent BP monitoring (either continuously via an arterial line or non-invasive cuff measurements
every 15 to 30 minutes).
●Clinical observation and assessment every one to two hours to evaluate changes in perfusion.
 ●Blood gas monitoring every three to four hours.
●Urine output should be monitored at least every four hours.
●Electrolyte levels, complete blood counts, and coagulation studies are often needed several times
per day as well.

Although, we use these specific parameters, it is important to recognize that they are evaluated together to
provide an assessment of the infant's global condition. So for example, if we reach the BP goal but there
are persistent signs of poor perfusion and elevated lactate levels, it is reasonable to assume that the
chosen BP goal is not adequate and further intervention is warranted. Similarly, escalation of intervention
is not necessary, even when the BP goal has not been attained but the infant seems to be improving
based on the other parameters (normalization of lactate levels and improved perfusion and neurologic
examination).

Monitoring response — The following changes in the directed goal-therapy physiologic indicators
indicate a positive response to ongoing management (see 'Physiologic goal-oriented parameters' above):

●HR:
•Decrease in HR for patients who are tachycardic (HR >180 beats per minute)
•Increase in HR for patients who are bradycardic (HR <90 beats per minute)
●Peripheral perfusion:
•Improving color and warmth of distal extremities
•Decreasing time for capillary refill
●Metabolic acidosis – Evidence of resolving metabolic acidosis based on point-of-care testing as
follows:
•Increase in blood pH
•Increase in serum/plasma bicarbonate level
•Decrease in serum/plasma lactate
●Neurologic status – Increased neurologic activity based on increased movement including facial
expression (grimace), which is either spontaneous or in response to stimulation.
●BP:
•Increase in BP for neonates with hypotension

SUBSEQUENT THERAPY — Subsequent therapy is based on the response to initial stabilization and the
ongoing diagnostic evaluation that identifies the underlying type of shock.

●Ongoing fluid resuscitation – For all patients with shock, response to initial fluid administration
and ongoing assessment of the patient's volume status determine whether additional fluid
resuscitation should be continued. Positive response to the initial fluid administration should be
observed in patients with hypovolemic and distributive shock, and ongoing fluid therapy should be
given until the goals of therapy are reached. In contrast, ongoing fluid resuscitation may be harmful
in patients with cardiogenic shock, who should not have responded (or had limited response) to
initial fluid therapy. In patients with likely septic shock, 20 to 30 mL/kg of isotonic fluid is typically
 adequate for restoring intravascular blood volume. In patients with hypovolemic shock, isotonic
fluid and/or blood products should be infused until there is a clear improvement in hemodynamic
status. (See 'Goals' above.)
●Vasopressors – For patients who remain hypotensive despite adequate fluid resuscitation,
vasoactive agents may be useful in restoring adequate tissue perfusion. Vasopressor therapy has
little role in the management of patients with purely hemorrhagic or hypovolemic shock and may be
harmful in this setting. (See 'Vasoactive agents' below.)
●Hydrocortisone – Hydrocortisone is commonly administered to infants with distributive or
cardiogenic shock that is refractory to fluid resuscitation and dopamine.
(See 'Hydrocortisone' below.)
●Specific interventions – Specific interventions for the underlying cause, once the etiology has
been determined.

THERAPEUTIC INTERVENTIONS

Fluid resuscitation — Fluid resuscitation aims to improve preload, thereby increasing stroke volume (SV)
and cardiac output (CO). Data are limited concerning the type of solution and optimal amount and rate of
fluid administration for neonates with shock.

Type of solution — Several studies suggest that isotonic crystalloid solutions (eg, normal saline or
Ringer's lactate) are preferable to colloid solutions (eg, albumin). Normal saline is the most commonly
administered isotonic fluid in neonates and is the solution of choice [25].

Volume and rate — Infants with hypovolemic shock, as well as many infants with distributive shock,
require aggressive fluid resuscitation. In these patients, we administer 20 mL/kg per bolus of normal saline
infused over 10 to 15 minutes. Therapy is repeated, as needed, up to four times if there is no clinical
evidence of improvement and there are no signs of fluid overload (rales or hepatomegaly).
(See 'Monitoring response' above.)

Additional therapies, such as transfusion of blood products in neonates with shock due to hemorrhage or
vasoactive drug therapy and corticosteroid administration in patients with septic shock may be required
depending on the response to fluid administration.

However, aggressive fluid resuscitation may be harmful for neonates with cardiogenic shock or those who
have compensated shock with certain comorbidities (eg, prematurity, acute renal failure, intrinsic
respiratory diseases). Patients with obstructive shock may also require volume expanders to improve
cardiac preload, but therapy should focus on emergent correction of the underlying cause (eg, needle or
chest tube thoracostomy for tension pneumothorax or pericardiocentesis for cardiac tamponade).

Vasoactive agents — Vasopressor and inotropic agents are used to support neonates with distributive
shock who have not improved with initial fluid resuscitation and those with cardiogenic shock who have
ongoing myocardial depression despite addressing reversible causes (eg, hypoxia, arrhythmia,
hypothermia). Vasoactive therapy has little role in the management of patients with purely hemorrhagic or
hypovolemic shock, and may be harmful in this setting.
Commonly used vasoactive agents include dopamine, epinephrine, dobutamine, and milrinone. Dopamine
is the most commonly used agent in neonates, based on longer clinical experience and familiarity with its
use. Epinephrine is often beneficial for the management of shock in older patients, but its pharmacologic
properties are less well understood in neonates. Dobutamine is typically the first inotrope administered for
cardiogenic neonatal shock. The pharmacologic properties of these agents and their use in older children
and adults are discussed in greater detail separately. (See "Initial management of shock in children",
section on 'Pharmacologic therapy' and "Use of vasopressors and inotropes".)

The pharmacokinetics of the various vasopressor agents are considerably more variable in neonates
compared with older patients and it is challenging to accurately predict the effects of these medications on
myocardial contractility, heart rate (HR), and systemic vascular resistance (SVR). In addition, there are no
definitive data demonstrating that one agent is more efficacious over another.

Dopamine — For infants with distributive shock who do not respond adequately to fluid resuscitation,
dopamine is infused beginning at a rate of 5 mcg/kg per min with titration up to a maximum of
15 mcg/kg per min based on the infant's clinical response. Dopamine can also be used for the
management of cardiogenic shock.

Limited data suggest gestational and postnatal ages have little effect on dopamine pharmacokinetics [26].
In addition, plasma dopamine concentration cannot be predicted accurately from the dopamine infusion
rate. Dopamine clearance is much lower in patients with renal or hepatic failure, and careful titration is
necessary.

Epinephrine — There are limited safety and efficacy data on epinephrine in neonates. Epinephrine
increases myocardial contractility and is a potent vasoconstrictor. It is sometimes used for distributive
shock that is refractory to dopamine or as a first-line vasoactive therapy for cardiogenic shock. Epinephrine
is typically started at a rate of 0.1 mcg/kg per min and titrated up to a maximum of 1 mcg/kg per min based
on the infant's clinical response.

Dobutamine — Dobutamine increases CO via improved myocardial contractility and increased HR. Since
it can also decrease SVR and cause hypotension, it is useful for patients with decreased myocardial
function due to cardiogenic shock who are normotensive. It is typically reserved for neonates with
cardiogenic shock refractory to dopamine or epinephrine. Dobutamine infusion begins at a rate of
5 mcg/kg per min with titration up to a maximum of 20 mcg/kg per min based on the infant's clinical
response.

Milrinone — Milrinone is a phosphodiesterase enzyme inhibitor which improves myocardial contractility

and reduces afterload through systemic vasodilation. It may be useful for some causes of cardiogenic
shock, but should only be instituted after an echocardiograph has been obtained to fully evaluate cardiac
anatomy and function, preferably in consultation with a pediatric cardiologist due to the risk of decreased
BP. (See "Heart failure in children: Management", section on 'Milrinone'.)

Hydrocortisone — For neonates with distributive (particularly septic) or cardiogenic shock that is
refractory to fluid resuscitation and vasoactive therapy (eg,
dopamine, dobutamine, epinephrine), hydrocortisone is commonly used to improve hemodynamics and
facilitate weaning of vasopressors. Limited data suggest it is effective in this setting [27]. For infants with
known or suspected adrenal insufficiency based on clinical findings (eg, ambiguous genitalia),
hydrocortisone should be administered at an earlier stage in the management if possible. (See "Treatment
of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children", section
on 'Management in neonates'.)

Hydrocortisone is initially administered at a dose of 1 mg/kg. If a rise in BP and clinical improvement is

noted within six to eight hours, continuation of hydrocortisone at a dose of 0.5 to 1 mg/kg every eight hours
should be considered. As the infant's condition improves, the dose of hydrocortisone should be gradually
tapered over a period of at least 7 to 10 days.

Transfusion — For neonates with shock due to acute blood loss, red blood cell (RBC) transfusion can be
lifesaving. (See "Red blood cell transfusions in the newborn", section on 'Acute blood loss'.)

Neonates with shock undergo frequent phlebotomy and even if they are not initially anemic, they are likely
to become anemic at some point. The need for transfusion should be revisited throughout their course and
once the patient's condition stabilizes, the threshold for transfusion should be raised to avoid unnecessary
exposure to blood products. Indications for RBC transfusion in neonates are reviewed in greater detail
separately. (See "Red blood cell transfusions in the newborn".)

SUMMARY AND RECOMMENDATIONS — Shock is a dynamic and unstable pathophysiologic state

characterized by inadequate tissue perfusion due to reduced oxygen delivery and/or increased oxygen
consumption or inadequate oxygen utilization. If untreated it leads to tissue/cellular damage that results in
end-organ failure and, in some cases, death.

●The causes of neonatal shock are classified into four pathophysiologic mechanisms (table 1).
However, neonatal shock may be the result of more than one of these processes (multifactorial
shock). (See 'Etiologic classification' above.):
•Hypovolemic shock is due to significant fluid losses (eg fetomaternal bleeding) that impairs
cardiac output (CO). (See 'Hypovolemic shock' above.)
•Distributive shock is due to maldistribution of blood within the microcirculation and regional
and global hypoperfusion caused by a severely decreased systemic vascular resistance
(SVR). Sepsis is the most common cause of distributive shock. (See 'Distributive
shock' above.)
•Cardiogenic shock is due to cardiac dysfunction or arrhythmia resulting in decreased CO.
(See 'Cardiogenic shock' above.)
•Obstructive shock is caused by extracardiac disorders (eg, tension pneumothorax) that result
in decreased CO. (See 'Obstructive shock' above.)
●Regardless of the etiology, neonates with shock typically present with signs of poor perfusion (cool
extremities, acrocyanosis, pallor), tachycardia, and metabolic acidosis. Late signs of shock include
bradycardia and hypotension. (See 'Clinical manifestations' above and 'Laboratory findings' above
 and "Etiology, clinical manifestations, evaluation, and management of low blood pressure in
extremely preterm infants".)
●Stabilization of the patient's hemodynamic status take precedence over any diagnostic evaluation,
and resuscitation should not be delayed. However, diagnostic evaluation can be conducted in
concert with resuscitative efforts.
●The history, physical examination, and laboratory testing may help determine the underlying cause
of shock and guide further management decisions. (See 'Initial stabilization' above.)
●The goal of initial stabilization is to improve physiological indicators of poor perfusion.
(See 'Physiologic goal-oriented parameters' above.)
●Key elements of the initial resuscitation include (see 'Initial stabilization' above):
•Stabilization of the airway and respiratory status
•Vascular access
•Initial fluid resuscitation
•Administration of empiric antibiotics
•Use of specific interventions based on the underlying etiology as determined by the
concurrent diagnostic evaluation
●Subsequent therapy including the use of vasoactive agents is dependent on the response to initial
stabilization and the ongoing diagnostic evaluation. (See 'Monitoring response' above
and 'Subsequent therapy' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Lisa Adcock, MD,
who contributed to an earlier version of this topic review.

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