NOVEMBER 2022 | VOLUME 19 | ISSUE 11

PEDIATRIC

Emergency Medicine Practice Evidence-Based Education • Practical Application

CLINICAL CHALLENGES
• Which vasoactive agents are
preferred first-line choices for
pediatric patients with septic shock?

• Which patients require additional

blood products?
• What are potential consequences of
placing an invasive airway?

Authors
Ara Festekjian, MD, MS
Associate Professor of Clinical Pediatrics, Children’s
Hospital Los Angeles, Division of Emergency
Medicine and Transport, Los Angeles, CA

Julia Glavinic, MD
Emergency Department, Riverside, CA

Peer Reviewers
Julia K. Lloyd, MD
Assistant Professor of Pediatrics, Nationwide
Children’s Hospital, Columbus, OH
Louis A. Spina, MD
Assistant Professor, Department of Emergency
Medicine, Icahn School of Medicine at Mount Sinai,
New York, NY
Prior to beginning this activity, see the
“CME Information” on page 2.
Pediatric Septic Shock:
Recognition and Management
in the Emergency Department
n Abstract
Sepsis is a leading cause of mor­bidity and mortality in chil-
dren. Early recognition and timely initiation of empiric broad-
spectrum antibiotics and crystalloid fluid administration have
been as­sociated with better outcomes. Although evidence for
diagnosis and treatment of septic shock was first generated in
adult studies, it is clear that pediatric studies are needed for
management of septic shock in children. This issue provides
guidance for managing septic shock in children, with a focus on
early recognition and appropriate resuscitation.

For online For mobile

access: app access:

This issue is eligible for 4 CME credits. See page 2. EBMEDICINE.NET

 CME Information
Date of Original Release: November 1, 2022. Date of most recent review: October 1, 2022. Termination date: November 1, 2025.
Accreditation: EB Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing
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ACEP Accreditation: Pediatric Emergency Medicine Practice is approved by the American College of Emergency Physicians for 48 hours of ACEP Category
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Target Audience: This enduring material is designed for emergency medicine physicians, physician assistants, nurse practitioners, and residents.
Goals: Upon completion of this activity, you should be able to: (1) identify areas in practice that require modification to be consistent with current evidence
in order to improve competence and performance; (2) develop strategies to accurately diagnose and treat both common and critical ED presentations; and
(3) demonstrate informed medical decision-making based on the strongest clinical evidence.
CME Objectives: Upon completion of this activity, you should be able to: (1) recognize features of pediatric septic shock; (2) adhere to sepsis bundles in
the treatment of septic shock; (3) recognize the importance of bundle compliance in light of the clinical response seen in a patient; and (4) maximize use of
inotropes to improve treatment outcomes.
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 Case Presentations
An 8-year-old boy is brought in by his parents for fever, redness to his left shin, vomiting, and diarrhea...
• The boy’s parents tell you he scraped his shin 5 days earlier while playing at a park. His shin became
progressively red and hot. He has had fever with vomiting and diarrhea for 3 days. He started to seem
CASE 1

unusually tired, prompting their visit to the ED.

• On examination, the boy is lethargic, with shallow respirations. His vital signs are: temperature, 38.9°C;
heart rate, 176 beats/min; respiratory rate, 35 breaths/min; and blood pressure, 80/57 mm Hg. After an
initial response to bag-valve mask ventilation, the patient's mental status again deteriorated.
• If the patent needs an advanced airway, what medications should you choose to secure his airway?
What are the possible consequences of initiating rapid sequence induction?

A 2-year-old boy with a history of short-bowel syndrome presents with fever and fatigue for 1 day…
• The boy’s short-bowel syndrome is secondary to necrotizing enterocolitis, and he has total parenteral
nutrition dependence. He was well 1 day prior and started to have loose stools on the day of presenta-
tion. His temperature at home was 38.7°C axillary, and he received a 15 mg/kg dose of acetaminophen
CASE 2

en route to the ED.

• The boy’s presenting vital signs are: temperature, 37.8°C; heart rate, 176 beats/min; respiratory rate, 28
breaths/min; blood pressure, 97/42 mm Hg; and oxygen saturation, 95% on his home 0.5 L/min oxy-
gen. He seems tired and is noted to have bounding radial pulses.
• You immediately suspect septic shock based on his fever, fatigue, central line, tachycardia, tachypnea,
and bounding pulses. Which antibiotics would be best for this patient? If vasoactive support is needed,
which agents should be used first?

A 16-year-old girl with a diagnosis of leukemia presents after a syncopal episode...

• The girl recently completed induction chemotherapy. She was at her routine hospital discharge follow-
up visit and had a syncopal episode while walking to the restroom. She has normal mental status,
denies fever or vomiting, and reports still feeling dizzy when walking, despite drinking several bottles of
CASE 3

water prior to the ED visit.

• The laboratory values obtained from her portacath during her clinical visit do not reveal neutropenia,
and her hemoglobin is 10.2 g/dL, with normal electrolytes and a negative pregnancy test. Her vital
signs are as follows: temperature, 37.6° C; heart rate, 110 beats/min; respiratory rate, 22 breaths/min;
blood pressure, 110/72 mm Hg; and oxygen saturation, 99% on room air.
• What is the cause of her syncope? Why does she remain dizzy?

sepsis and septic shock include rapid identification,

n Introduction
Sepsis continues to be a leading cause of morbidity
and mortality in children, especially those with pre-
existing conditions.1-10 Mortality in children depends
on patient variables such as underlying comorbidities
and environmental factors, including differences be-
tween high- and low- to middle-income countries.1-11
Mortality in high-income countries is estimated to be
up to 4%, whereas in low-income countries (eg, sub-
Saharan Africa), it can be up to 50%1-11 Established
protocols and early goal-directed therapy (starting
from emergency department [ED] triage) have been
shown to improve outcomes in pediatric septic shock,
hence reinforcing the need to have a system in place
regardless of the clinical setting.6,11-16 In 2020, the
Society of Critical Care Medicine (SCCM) published
new guidelines for managing pediatric septic shock
and sepsis-associated organ dysfunction.11 Funda-
mental components of optimizing care for pediatric
appropriate and timely antibiotic administration,
fluid resuscitation, frequent reassessment of volume
status, and early vasoactive hemodynamic support if
indicated.8-16 Identification and early goal-directed
therapy utilizing sepsis bundles have been shown to
reduce in-hospital mortality among pediatric patients
with sepsis and septic shock.4,8-20 This issue of Pedi-
atric Emergency Medicine Practice reviews pediatric
septic shock management, reinforcing the importance
of early recognition and rapid resuscitation. It also
underscores the need for frequent reassessments and
appropriate modifications to the treatment approach,
depending on individual patient response.
n Critical Appraisal of the Literature
PubMed was searched in both a vertical manner
(seminal articles) and a horizontal manner with the
following search terms: pediatric sepsis, septic shock,

NOVEMBER 2022 • www.ebmedicine.net 3 © 2022 EB MEDICINE

hypotension, fluid resuscitation, shock in immuno-
compromised patients, and sepsis algorithms and
guidelines. There is growing literature on pediatric
septic shock, including work represented by the
Surviving Sepsis Campaign (SSC), which was formed
in 2001 by the SCCM, European Society of Intensive
Care Medicine, and the International Sepsis Forum.
The goal of the SSC was to develop evidenced-based
guidelines and recommendations for the treatment of
septic shock. The work was published initially in 2004
and updated every 4 years thereafter. In 2016, sepa-
rate task forces were created for children and adults.
In accordance with the SSC, septic shock bundles
and algorithms were developed that have resulted
in improvements in care for pediatric septic shock.
There has been a focus on improving recognition and
adherence to sepsis bundles.20-24
Evidence for pediatric septic shock manage-
ment was first generated in adult studies, with recent
awareness that pediatric-dedicated studies are
needed, due to important differences in pediatric and
adult physiology.11,16 There have been specific stud-
ies focusing on differences in adult and pediatric sep-
tic shock treatment approaches such as: intravenous
immunoglobulin (IVIG), corticosteroids, recombinant
protein C, and the type of fluids used in resuscitation
(buffered solution vs 0.9% saline).25-28
A review of the ClinicalTrials.gov website revealed
several noteworthy studies to mention: GRACE,
PRoMPT BOLUS, SHIPSS, OPTISEPSIS, SQUEEZE,
and SEPTICUS. In the Australian and New Zealand
Clinical Trials Registry, the following study is notewor-
thy: RESPOND ED. Thus, new evidence may emerge
paving the way for potential management changes in
treating pediatric septic shock.
n Definitions
For this issue, pediatric septic shock will be defined
according to the definition in the Surviving Sepsis
Campaign International Guidelines for the Manage-
ment of Septic Shock in Children 2016: pediatric
septic shock is a “severe infection leading to cardio-
vascular dysfunction including hypotension, need
for vasoactive medication, or impaired perfusion.”16
Sepsis-associated organ dysfunction is defined as
“severe infection leading to cardiovascular and/or
non-cardiovascular organ dysfunction.”11,16 Sepsis-3
definitions and criteria that have been implemented
in adults have not yet been implemented in children.3
With Sepsis-3, adult sepsis is defined as “life-threat-
ening organ dysfunction caused by a dysregulated
host response to infection.”3,11 This definition also
utilizes the Sequential [Sepsis-related] Organ Failure
Assessment (SOFA) score as part of the algorithm
in identifying patients with sepsis.29 Septic shock is
defined as “a subset of sepsis in which particularly
profound circulatory, cellular, and metabolic abnor-
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malities are associated with a greater risk of mortality
than with sepsis alone.”11,16 These updated defini-
tions, once applied to pediatric septic shock, will
provide greater consistency for epidemiologic studies
and clinical trials.30
Other common terms in use are compensated
shock and uncompensated shock, referring to a
child's ability to maintain mean arterial pressure by
a robust increase in systemic vascular resistance.
Compensated shock refers to sepsis without hypoten-
sion, whereas uncompensated shock is sepsis with
hypotension (septic shock) that requires vasopressors
to maintain blood pressure. In the absence of hypo-
tension, the danger is 2-fold. First, late recognition:
persistent tachycardia is often the first sign of shock
in children. Second, if not addressed early, there may
be a precipitous decompensation, resulting in hypo-
tension, which requires vasopressor therapy and is
associated with greater mortality.
The sepsis bundle consists of intravenous (IV) crys-
talloid fluid resuscitation and parenteral antibiotic ad-
ministration after blood cultures are obtained.11,14,15
The timeliness of antibiotic administration and
crystalloid fluid resuscitation seems to be particularly
crucial for patients in uncompensated shock. Sepsis
bundle creation and implementation have resulted in
improvements in mortality and have demonstrated
decreased hospital length of stay and decreased rates
of kidney injury resulting from sepsis.17-20
n Etiology and Pathophysiology
A large proportion of patients admitted with pediat-
ric septic shock are children with a chronic illness.4-8
Compared to children who are previously healthy,
outcomes are also worse for children with a chronic
disease, with in-hospital mortality suggested to be as
much as 5 times greater.7-9
Many pathogens have been identified as causes
of septic shock, hence the importance of administer-
ing empiric broad-spectrum antibiotics. However, in
certain circumstances, it is prudent to consider certain
pathogens first. Group B Streptococcus (GBS) causes
severe sepsis in neonates.11 Staphylococcus aureus
is a common cause of sepsis in children with central
lines and in those with cerebrospinal fluid ventriculo-
peritoneal shunts.31 Streptococcus pneumoniae is the
most common organism in children with asplenia.31
Highly resistant pathogens must also be considered,
particularly in the immunocompromised child. Resis-
tant gram-negative examples include Pseudomonas
aeruginosa and extended-spectrum beta-lactamase–
producing Escherichia coli. Resistant gram-positive
examples include methicillin-resistant Staphylococcus
aureus (MRSA) and Enterococcus species resistant to
ampicillin and vancomycin.31
© 2022 EB MEDICINE
n Differential Diagnosis
General categories of shock include cardiogenic, ob-
structive, hypovolemic, and distributive. See Table 1
for a list of shock types and subtypes. Pediatric septic
shock may be the result of a multifactorial presentation
including hypovolemia and cardiac dysfunction.32 Early
recognition and rapid initiation of resuscitation remain
crucial steps, regardless of shock etiology.11,19
Given sepsis physiology surrounding compen-
sated shock, it is crucial to consider sepsis even when
there is no hypotension.11 For any child presenting
with a febrile illness, even those without hypotension,
consider the possibility of sepsis. Hypotension is a
late and dire finding, and fluid resuscitation should
not be withheld until hypotension develops, as delay
of appropriate resuscitation has been shown to be
associated with poorer outcomes.33 With septic
shock, there can be cardiac dysfunction, making it
challenging to recognize concurrent cardiogenic
shock. Judicious use of IV crystalloid fluids and titra-
tion of vasoactive agents with frequent reassessments
are required when the underlying primary etiology
is not certain.11,34,35 In this pandemic environment,
another important entity a clinician needs to be
familiar with is multisystem inflammatory syndrome in
children (MIS-C).36,37 MIS-C can mimic septic shock in
clinical presentation and initial resuscitation manage-
ment but diverges in terms of therapy to address
underlying MIS-C–specific cardiac abnormalities.
Allergen exposure may be a clue for anaphylaxis,
which presents as a distributive shock, with peripheral
vasodilation. This same peripheral vasodilation may
be seen in sepsis. For immunocompromised patients,
or patients with technological dependence or central
line dependence, always consider pediatric septic
shock.8,11 A cardiac history or exposure to cardio-
toxic medications as part of a chemotherapy regimen
should serve as clues to the possibility of cardiogenic
shock. Frequent reassessments are needed to monitor
Table 1. Shock Types and Subtypes
Type of Shock Subtypes of Shock
Distributive • Septic shock
shock • Anaphylactic shock
• Neurogenic shock
Cardiogenic • Heart failure
shock • Dilated cardiomyopathy
• Kawasaki disease
• Multisystem inflammatory syndrome in children
Obstructive • Cardiac tamponade
shock • Constrictive pericarditis
• Pulmonary embolism
• Tension pneumothorax
Hypovolemic • Blood loss: hemorrhagic shock
shock • Fluid loss: vomiting/diarrhea
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NOVEMBER 2022 • www.ebmedicine.net 5
for the development of a gallop, crackles, or increas-
ing oxygen requirement. In this context, strict adher-
ence to sepsis bundles recommending large amounts
of volume may have to be modified with an earlier
start to inotropes, since volume overload would wors-
en the outcomes.11 Patients with cancer who have re-
ceived chimeric antigen receptor (CAR)-T cell therapy
may present with cytokine release syndrome, which
may clinically mimic septic shock with tachycardia,
hypotension, capillary leak syndrome, and multiorgan
failure.38-40 Prolonged use of a tampon or wound or
nasal packing may be clues for toxic shock syndrome,
for which broad-spectrum antibiotics, volume resusci-
tation, and vasopressor administration are key aspects
of treatment, similar to septic shock.41,42
n Prehospital Care
The goals for emergency medical services (EMS)
in treating pediatric septic shock are to recognize
symptoms of sepsis in children; provide basic support
of airway, breathing, and circulation; and transport
the patient expeditiously to an appropriate ED. Given
the complexities in managing pediatric septic shock,
there is very little evidence regarding the impact of
prehospital care in pediatric sepsis outcomes. How-
ever, there is evidence that patients with septic shock
arriving via EMS are more likely to be admitted to a
critical care setting than those who arrive via other
modes.43 It is surmised that the more severe clinical
presentations of septic shock arrive via EMS.43
n Emergency Department Evaluation
History
Given the time-sensitive nature and the potentially
fatal consequences of pediatric septic shock, informa-
tion should be gathered concurrently with initiation of
workup and resuscitation, particularly in the acutely
ill-appearing child. For the well-appearing febrile
child, there may be historical clues that could indicate
sepsis; specific examples include confusion; rapid,
shallow breathing; sweating; fatigue; unexplained
agitation; syncope; chills/shaking; lethargy; tempera-
ture instability; and poor urine output. These types
of symptoms should make the emergency clinician
consider sepsis even in the absence of fever prior to
presentation. Any type of extremity injury preced-
ing the illness, especially if redness or warmth has
developed at the injury site, may provide additional
clues. Parents may also report limping in a child with
hematogenous osteomyelitis or septic arthritis. The
variability and nonspecific nature of these historical
findings underscore the difficulty in recognizing sepsis
and the need to consider it as a possibility.
For chronically ill children with special healthcare
needs, a history of immunocompromised status,
indwelling central lines or other catheters (eg, dialy-
© 2022 EB MEDICINE
sis), technological dependence (eg, feeding tubes),
and stage in therapy of their underlying illness (eg,
chemotherapy cycle if being treated for leukemia) are
important when considering sepsis.8 For example,
perineal pain may be reported by a neutropenic can-
cer patient with perineal abscess. A history of persis-
tent abdominal pain in the setting of neutropenia may
indicate typhlitis, with a report of acutely worsening
pain being ominous for potential perforation. A histo-
ry of pus or redness at a central line site may provide
additional clues to the presence of line sepsis.
A patient’s medication and allergy history may
also provide insight. For example, patients on pro-
phylactic antibiotic therapy for recurrent urinary tract
infections may have sepsis caused by extended-spec-
trum beta-lactamase–producing E coli. Knowledge
of previous chemotherapy agents for the treatment
of leukemia or other malignancies (eg, immunosup-
pressants), immune-modulating agents for organ
transplantation, or chronic systemic corticosteroid use
may play a role in guiding septic shock management
beyond antibiotic choice. Allergy history may become
relevant in the antibiotics chosen for treating sepsis,
with cephalosporin-allergic patients receiving cipro-
floxacin and clindamycin instead.
Because of the variability of presentations of pe-
diatric sepsis, further research into the development
of automatic and electronic sepsis recognition tools
will improve management of children with special
healthcare needs.19-24,44
Physical Examination
Physical examination findings in sepsis and septic
shock are variable and nonspecific. Vital signs may
be abnormal, with tachycardia and hypotension, but
hypotension is not always present initially. A patient
may be hypothermic, normothermic, or hyperther-
mic. A neonate may have apneic episodes, while an
older child may have tachypnea and shallow respira-
tions. The combination of temperature extremes and
tachycardia in an ill-appearing child would be highly
concerning. Unexplained tachycardia, particularly
when persistent, may serve as a clue to the presence
of sepsis. Persistent tachycardia may serve as a clue
to the presence of shock physiology prior to the de-
velopment of hypotension.
Some clinically obvious findings potentially sug-
gestive of severe septic shock include altered mental
status, inability to walk, confusion, pallor, easy bruising
and petechiae (reflecting associated thrombocytope-
nia), oozing from IV sites (reflecting associated dissemi-
nated intravascular coagulation [DIC]), and markedly
delayed capillary refill time. An erythematous site on
an extremity combined with fever and tachycardia (or
tachycardia alone) may serve as a clue to the presence
of sepsis. Pain out of proportion to the extent of red-
ness or crepitus may suggest septic shock or evolving
necrotizing fasciitis. Skin findings may be subtle and
NOVEMBER 2022 • www.ebmedicine.net 6
possibly located in an overlooked area such as the
perineum. Perineal infections may serve as the nidus
for septic shock, particularly in febrile neutropenic can-
cer patients. For a severely neutropenic patient with
typhlitis, perineal tenderness coupled with persistent
abdominal tenderness may be an ominous finding
suggestive of perforation. For the highly irritable infant,
sepsis should be considered as a potential diagnosis.
A crucial aspect to consider is that all of these findings
may be present to varying degrees and can occur in
compensated shock without hypotension, highlighting
the importance of early recognition and treatment.11
Septic Shock with Concurrent Cardiogenic Shock
When treating septic shock, one must anticipate the
development of concurrent cardiogenic shock. A pa-
tient may present with a gallop and possibly jugular
venous distention or they may develop these findings
during resuscitation, emphasizing the importance of
frequent reassessments and allowing for modifica-
tions to the treatment approach. In another example,
a widened pulse pressure may be present at the
beginning when treating septic shock.45 As pediatric
septic shock evolves, a patient may begin to exhibit a
narrowed pulse pressure, a gallop, and cool extremi-
ties. This continuum is reflected in the multimodal
features of septic shock with potentially both distribu-
tive and cardiogenic shock physiology.45
Warm and Cold Shock
The designations of “warm” and “cold” shock have
historically guided therapy. Warm shock is differenti-
ated from cold shock based on extremity tempera-
ture, capillary refill, pulse strength, and widened
versus narrowed pulse pressure.11,45
Patients with warm shock typically present with
fever, tachycardia, bounding pulses, and hypoten-
sion. Warm shock is treated with fluid resuscitation
and norepinephrine, reflecting the presence of low
systemic vascular resistance and high cardiac index.
Crystalloid IV fluid resuscitation and norepinephrine
aid in increasing the vascular tone and improving
organ perfusion. Early and aggressive resuscitation,
with early initiation of norepinephrine is recommend-
ed and is associated with improved outcomes.11,45,46
Patients with central lines are more likely to present
with warm shock.
In contrast to patients with warm shock, patients
with cold shock have cooler extremities and high
systemic vascular resistance. In cold shock, a low
cardiac index predominates, in contrast to the high
cardiac index and decreased vascular tone of warm
shock.11,45 The goal of treatment of cold shock with
fluid-refractory hypotension is to increase cardiac
output by administering epinephrine.11,45,46
Most children with sepsis present with cold shock,
unlike adult patients with sepsis, of which the major-
ity present with warm distributive shock. An example
© 2022 EB MEDICINE
is the child with community-acquired pneumonia
who presents in cold shock, with cool extremities and
diminished pulses.11,45 It is important to note that
patients may present with a continuum of findings,
and frequent reassessments are needed to modify the
treatment regimen based on patient response.
There is scant evidence for these warm and cold
shock recommendations, and these differentiations
based on subjective examination findings do not
accurately identify cardiac dysfunction.46 However,
in the absence of invasive hemodynamic monitoring,
clinical signs of increased systemic vascular resistance
(cold shock) or bounding pulses (warm shock) have to
suffice at the bedside during the initial resuscitation.
This serves as another reminder of the importance of
early recognition and aggressive IV crystalloid fluid
resuscitation, with frequent clinical assessments, for
success in restoring organ perfusion.46
Evolving Physical Examination Findings
While treating septic shock, physical examination find-
ings may change over time. Petechiae may coalesce
and form purpura. Erythema, fluctuance, and tender-
ness over a shin may develop into hemorrhagic bullae
and necrosis in necrotizing fasciitis. A patient may
initially have crackles on lung examination and later
develop a gallop with cardiac dysfunction resulting
from cardiogenic shock or worsening septic shock. If
mechanical ventilation is needed, be prepared for the
subsequent development of poorer lung compliance,
decreased vascular return due to increased intratho-
Table 2 lists basic laboratory variables obtained
in the evaluation of patients with sepsis or those at
risk for developing sepsis. Table 2 also demonstrates
the multitude of systems affected by sepsis and helps
highlight the importance of sepsis bundles and treat-
ment algorithms that address the potential conse-
quences resulting from sepsis.11 The value in obtain-
ing hematologic parameters lies beyond the predic-
tive value of severe neutropenia. For example, if he-
moglobin levels are below 7 g/dL, sepsis algorithms
suggest packed red blood cell transfusion for septic
shock.11,16 Fresh frozen plasma (FFP) transfusion may
be needed to address DIC. Electrolyte abnormalities
need to be corrected aggressively to prevent worsen-
ing outcomes.11,16 Concurrent pancreatitis revealed
with an elevated lipase portends a poor outcome.49
Kidney injury in the setting of sepsis is also associ-
ated with poorer outcomes.18 A normal serum lactate
level does not exclude sepsis, but persistently high
levels require aggressive IV fluid resuscitation and are
associated with greater mortality.47,48 Similarly, mixed
venous saturation from a centrally placed line may
Table 2. Laboratory Studies for Sepsis
Category Laboratory Study
Hematologic • Complete blood cell count with differentiala
• Disseminated intravascular coagulation
panel11
• Type and cross-match

racic pressures, hemodynamic instability, and cardio- Comprehensive • Serum transaminase levels
metabolic panel • Serum albumin level
vascular collapse, regardless of preceding resuscita-
• Serum lipase
tion efforts.11 Ultimately, the spectrum of physical • Serum bilirubin
examination findings from patient to patient and the
Infectious disease • Fluid cultures
evolution of findings over time in the same patient lAerobic/anaerobic blood culture (some
emphasize the importance of earlier recognition, ap- centers do both)
propriate management, and frequent reassessment. It lUrine culture/urinalysis (urosepsis)
is crucial to maintain an openness to adjusting man- lSputum (tracheostomy patients)
agement as the patient's condition changes. lCerebrospinal fluid (meningitis)
• Inflammatory markers (nonspecific elevation)
lErythrocyte sedimentation rate

n Diagnostic Studies C-reactive protein

l

lProcalcitonin
Laboratory Studies Blood gas b
• Serum lactate47,48
Laboratory studies are a critical part of the manage- • Serum pH
ment approach to sepsis and septic shock. Both aca- • Mixed venous saturation (if sample from a
demic and community settings have developed sep- central line)
sis recognition tools to facilitate earlier recognition of Chemistry • Electrolytes
sepsis and prompt initiation of the sepsis bundle.14,15 lGlucose level
Calcium level
Septic shock treatment, by design, is initiated based
l

lPotassium level
on the history and physical examination, without hav- lSodium level
ing immediate laboratory values available for evalu- • Renal function (blood urea nitrogen/
ation. Aside from obtaining blood cultures, there are creatinine)c
other laboratory studies that are utilized after initiat-
a
ing therapies for suspected sepsis. In compensated b
Severe neutropenia if absolute neutrophil count <500 cells/mcL.
Bedside blood gas helpful in quickly assessing for electrolyte
shock, when sepsis has not yet been identified as the
abnormalities.
potential diagnosis, there are values that may provide c
Acute kidney injury associated with sepsis.
clues to the presence of sepsis. www.ebmedicine.net

NOVEMBER 2022 • www.ebmedicine.net 7 © 2022 EB MEDICINE

aid in optimizing therapy with regard to IV crystalloid
fluid resuscitation and vasoactive medication use.50
Imaging Studies
In contrast to laboratory studies for sepsis, imaging
studies are not algorithm- or bundle-based, and are
tailored to the individual patient presentation. A chest
radiograph may assess for pulmonary edema, pneu-
monia, and cardiomegaly, or it may be necessary to
confirm advanced airway and central line placement.
A computed tomography (CT) scan of the brain may
be needed to assess for hemorrhagic complications,
given the presence of concurrent DIC and altered
mental status or prior to a lumbar puncture, if indicat-
ed. Abdominal CT scan with contrast may be needed
to identify typhlitis in the severely neutropenic patient
receiving chemotherapy for a malignancy.
Echocardiography may be needed to assess for
cardiac dysfunction, particularly for patients who do
not respond to the treatment regimen. This may also
aid in treating sepsis in patients with underlying con-
genital heart disease. Point-of-care ultrasonography
(POCUS) use has increased in recent years in some
centers; however, there is no current recommendation
or standard for its use in managing pediatric septic
shock, though there may be a theoretical benefit in
managing volume resuscitation.11,16,51 Other imaging
modalities will depend on individual patient char-
acteristics, such as osteomyelitis requiring magnetic
resonance imaging.
n Treatment
The key aspects of therapy for sepsis are recognition
and prompt initiation of broad-spectrum antibiotics
(after obtaining blood cultures), fluid resuscitation,
vasoactive support (if needed), and frequent reas-
sessments in a highly monitored setting.11,16,18,19 The
2017 American College of Critical Care Medicine
(ACCM) clinical practice parameters for hemodynamic
support of pediatric and neonatal septic shock pro-
vide algorithms outlining best practices in pediatric
septic shock management.16 (See the algorithms on
pages 19 and 20.)
An important aspect to consider is the establish-
ment of intraosseous (IO) or IV access very early in
the resuscitation.11,16 One of the main best-practice
statements from the SSC was the utilization of IV or
IO access for adherence to bundle elements.11,17,52
The algorithm recommends individual 20-mL/kg
crystalloid IV fluid boluses up to 60 mL/kg, with
frequent monitoring for the development of crack-
les, hepatomegaly, and cardiac dysfunction. (See
the algorithm on page 19.) Additional peripheral
IV lines may be needed in the presence of a central
line when more products need to be administered or
there is difficulty in accessing a pediatric central line
(eg, a portacath).11,16
NOVEMBER 2022 • www.ebmedicine.net 8
Medications
Table 3 lists suggested empiric broad-spectrum
antibiotic choices for treating sepsis.53 Each hospital
setting needs to pay close attention to locally specific
bacterial trends and susceptibility profiles for targeted
antimicrobial delivery.11
Epinephrine and norepinephrine are the preferred
starting medications, instead of dopamine, according
to a best-practice statement with low quality of evi-
dence.11,54 In settings in which epinephrine and nor-
epinephrine may not be readily available, dopamine
may be the starting agent.11,16 If using dopamine,
one must be aware of its greater association with
potentially fatal dysrhythmias. In a meta-analysis of 13
separate randomized trials compiling data from 3146
patients, dopamine use led to a higher incidence of
arrhythmias than norepinephrine (odds ratio [OR],
2.69; 95% confidence interval [CI], 2.08 to 3.47).54
Table 4, page 9 lists the most common vasoactive
medications and their respective starting doses.11,55,56
Peripheral IV and IO access is also utilized for admin-
istering vasoactive medications.57
Airway Management
Another important aspect to consider while manag-
ing pediatric septic shock is the potential need for an
advanced airway. Medications used concurrently for
induction and positive-pressure ventilation may result
in drop in preload with decreased venous return
and decreased cardiac output, potentially triggering
Table 3. Empiric (Initial) Antibiotic Choices
for Treating Pediatric Sepsis53
Type of Sepsis/ Medication Recommendations
Infection
Community-acquired • Third-generation cephalosporin:
sepsis ceftriaxone 50 mg/kg IV, IO, or IM
(max, 2 g)
• If methicillin-resistant Staphylococcus
aureus is prevalent, add vancomycin 15
mg/kg IV (max, 500 mg)
Neonatal sepsis • Include coverage for Listeria: ampicillin
50 mg/kg IV (max, 2 g)
• Consider coverage for herpes simplex
virus: acyclovir 10 mg/kg IV (max, 800
mg)
Sepsis in • Antipseudomonal cephalosporin:
immunocompromised cefepime 50 mg/kg IV (max, 2 g)
patients
Toxic shock syndrome • Include medications limiting toxin
production: clindamycin 10 mg/kg IV
(max, 1200 mg) or lincomycin 10 mg/kg
IV (max, 1 g)
Intra-abdominal • Include coverage for anaerobic bacteria:
infections third-generation cephalosporin with
metronidazole 10 mg/kg IV (max, 500
mg) or piperacillin/tazobactam 80 mg of
piperacillin/kg IV (max, 3.375 g)
© 2022 EB MEDICINE
hemodynamic collapse.11 In the presence of sep-
tic shock, a component of cardiac dysfunction may
already exist, and this added stress may contribute
to worsening pulmonary edema, resulting in rapid
deterioration and desaturation during intubation.11,16
Thus, there is the best-practice recommendation to
administer IV crystalloid fluids and vasoactive medica-
tion prior to induction for intubation.11,16
There are certainly circumstances in which suf-
ficient fluid administration cannot occur prior to
medications for intubation induction. For example,
a patient in septic shock may present in extremis
(cardiorespiratory failure) and immediately require an
airway. Alternatively, a newborn may require intuba-
tion for apnea related to sepsis. Adjunctive airway
measures such as oxygen via nasal cannula, facial
mask (simple vs nonrebreather), and heated high-flow
nasal cannula (HHFNC) may be utilized as a means to
bridge the gap to intubation, providing time for fluid
administration prior to intubation induction medica-
tions. Preliminary trials are underway in adults for
evaluation of HHFNC in severe sepsis (OPTISEPSIS).
Equivalent studies in children are lacking. There is a
role for instituting the use of mechanical ventilation
as part of management of pediatric septic shock, as it
can result in improved oxygenation and organ perfu-
sion by minimizing the work of breathing and cardiac
stress in sepsis-induced cardiac dysfunction.11,16
With regard to induction agents, ketamine is the
medication of choice. Etomidate has been commonly
used for rapid sequence intubation for its rapid onset,
short duration, and minimal hemodynamic effects,
and emergency medicine-based literature suggests
that a 1-time induction dose of etomidate given in
the ED is not associated with worse outcomes in
Table 4. Vasoactive Agents for Septic
Shock11,55,56
Type of Medication Dosage
Medication
Vasopressors Epinephrinea Starting rate: 0.05 mcg/kg/min
Range: 0.02-1 mcg/kg/min
Norepinephrinea Starting rate: 0.05 mcg/kg/min
Range: 0.01-2 mcg/kg/min
Starting rate: 5 mcg/kg/min
Dopamineb
Range: 2.5-20 mcg/kg/min
Inotropes Dobutamine Starting rate: 0.5 mcg/kg/min
Range: 0.5-20 mcg/kg/min
Milrinone Loading dose (optional): 50 mcg/kg
IVP
Range: 0.25-0.75 mcg/kg/min
a
Preferred starting agents: best-practice recommendation.
b to patients assigned to a higher hemoglobin thresh-
Caution regarding greater incidence of arrhythmias.
Abbreviation: IVP, intravenous push.
www.ebmedicine.net
NOVEMBER 2022 • www.ebmedicine.net 9
septic shock.58-61 However, the SSC suggests not us-
ing etomidate “when intubating children with septic
shock or other sepsis-associated organ dysfunction”
(weak recommendation, low quality of evidence).11
Although etomidate offers hemodynamic neutrality as
a sedative agent, ketamine remains the drug of choice
in pediatric septic shock. Unlike etomidate, ketamine
has no effect on the adrenal axis and supports cardiac
output with its adrenergic properties.11,16,62,63
n Special Populations
Patients With Febrile Neutropenia and
Septic Shock
For febrile cancer patients at risk for neutropenia,
there are nationally accepted best-practice algorithms
calling for rapid initiation of empiric broad-spectrum
antibiotics covering gram-negative bacteria (door-to-
antibiotic time [after obtaining blood cultures], <60
minutes).11,64 Table 3, page 8 describes the antibiot-
ics utilized in treating septic shock in immunocom-
promised patients. Beyond treating for septic shock,
one must be aware of the greater mortality associated
with pancreatitis complicating septic shock in the on-
cology patient.49 Furthermore, persistent abdominal
pain or physical examination findings suggestive of
an acute abdomen should prompt appropriate imag-
ing and surgical consultation for typhlitis occurring in
the severely neutropenic patient.65,66 The presence of
perforation in septic shock is an ominous finding and
a predictor of greater mortality.66
Blood products are an important treatment as-
pect to consider in pediatric septic shock, particularly
in cancer patients receiving chemotherapy and in
organ transplant recipients receiving immunocom-
promising medications. The current best-practice
recommendation is transfusion of red blood cells to
maintain blood hemoglobin >7 g/dL in hemodynami-
cally responsive patients.11 In the TRIPICU study,
children with septic shock who did not need esca-
lating vasoactive medications were randomized to
maintain hemoglobin >7 g/dL (restrictive group) or
>9.5 g/dL (liberal group).67 The groups demonstrated
no differences in mortality and subsequent progres-
sion to worsening organ failure. This provided the
basis for the best-practice recommendation, though
with low quality of evidence. The SSC did not make a
recommendation about transfusions in the setting of
unstable pediatric septic shock, as there is no pedi-
atric study in this patient population.11 However, in
an adult study on hemoglobin thresholds for blood
transfusion in septic shock with hypotension (TRISS
clinical trial), patients assigned to a lower hemoglo-
bin threshold (7 g/dL) had similar 90-day mortality,
life support use, and ischemic event rates compared
old (9.5 g/dL), potentially suggesting the use of the
same recommendation for unstable pediatric septic
© 2022 EB MEDICINE
shock.68 In the context of active bleeding or place-
ment on extracorporeal life support, prophylactic
transfusion is recommended (red blood cells to a
higher threshold, FFP to correct coagulation abnor-
malities, or platelets to correct thrombocytopenia),
though with low quality of evidence.11
Leukemia patients who have suffered a relapse
may have received CAR-T cell therapy, and they
may present with cytokine release syndrome.38-40
Though cytokine release syndrome mimics septic
shock, excessive IV fluid administration will worsen
the outcome.38-40 Febrile CAR-T cell patients should
receive a total of 10 mL/kg of IV crystalloid fluid, and
inotropes should be started early in the resuscita-
tion, with admission to a critical care setting. Patients
who are 3 to 4 weeks post allogeneic or autogeneic
bone marrow transplant are at risk for veno-occlusive
disease, which can mimic sepsis.69 Fluid overload is a
risk factor in this population as well, requiring minimi-
zation of fluid administration and earlier initiation of
vasoactive medications.69
Newborns With Septic Shock
The cardiopulmonary circulation of newborns
continues the transformation triggered by the birthing
process. In utero, the right ventricle is pumping
blood primarily to the placenta via the patent ductus
arteriosus (PDA) and largely avoiding sending blood
to the lungs. Following birth, vascular resistance
decreases in the pulmonary artery, blood volume
to the lungs is increased, and the PDA begins to
close. Newborns with septic shock develop acidosis
resulting in increased shunting through the PDA
and elevation of pulmonary pressures (persistent
pulmonary hypertension of the newborn), placing
a greater burden on the right ventricle.11,16 Thus,
newborns with septic shock benefit from early
transfer to a neonatal intensive care unit (NICU)
where dedicated echocardiography will guide
management for left-sided ventricular dysfunction
and right-sided ventricular dysfunction. As seen
in the Algorithm on page 20, this distinction
between right-sided versus left-sided heart failure
will dictate the choice of vasoactive medications. In
the presence of persistent pulmonary hypertension
of the newborn, inhaled nitric oxide becomes part of
the approach, a treatment not seen in the algorithm
for older children.16,70,71 (See the algorithm on page
20.) Milrinone also plays a greater role in treating
newborns with septic shock, further emphasizing
the importance of earlier transfer to an appropriate
clinical setting.72,73
Newborns with septic shock may also have physi-
cal examination findings that may be different from
older children with septic shock. Table 5 lists findings
seen more commonly in newborns with septic shock.
GBS infection is also crucial to consider in new-
borns. GBS infection continues to be the most com-
NOVEMBER 2022 • www.ebmedicine.net 10
mon cause of neonatal early-onset sepsis (occurring
on days 1-6 of life) and an important cause of late-
onset sepsis (occurring on day 7 of life to 3 months
of age [rarely older]).74,75 Mortality from early-onset
GBS disease in preterm and term infants is 19.2% and
2.1%, respectively.74,75 Mortality from late-onset GBS
disease in preterm and term infants is 3.4% and 7.8%,
respectively.74,75 Antibiotic administration at the time
of delivery for women who have screened positive
for GBS remains an effective therapy for early-onset
GBS disease.70 Such a preventive treatment strategy
does not exist for late-onset sepsis. A characteristic
of GBS infection in both early- and late-onset disease
is the presence of cerebrospinal fluid culture-positive
meningitis in the absence of bacteremia.75 Delayed
recognition and treatment of GBS bacteremia and
meningitis has devastating consequences.75 Hence,
a highly conservative approach is warranted when
evaluating newborns for early- or late-onset GBS
disease.
n Controversies and Cutting Edge
Volume of Fluid Resuscitation
Despite overwhelming evidence demonstrating
improved outcomes with bundle implementation and
adherence, there are specific aspects in the treat-
ment of septic shock that remain without conclusive
evidence.11,14,16-19,52 Historically, children with septic
shock have required relatively greater fluid resuscita-
tion compared to adults.76,77 For children with septic
Table 5. Newborn Sepsis Physical
Examination Findings
Examination Findings
Vital signs • Temperature instability
• Bradycardia
• Apnea
• Differences in preductal and postductal
saturations
Cardiopulmonary • Right- and left-sided dysfunction
• Holosystolic murmur of patent ductus
arteriosus
Abdominal • Blood in stool
• Development of necrotizing enterocolitis
Neurologic • Irritability
• Difficult arousal
• Decreased tone
• Bulging fontanelle
• Seizure
Extremity • Weaker pulses
• Markedly delayed capillary refill time
Skin • More mottling
• Vesicles/bullae (in context of herpes simplex
virus)
• Jaundice
www.ebmedicine.net
© 2022 EB MEDICINE
shock and abnormal perfusion, the SSC recommenda-
tion is to administer 40 to 60 mL/kg of IV crystalloid
fluid in the first hour of resuscitation while assessing
markers of cardiac output and discontinuing fluid
administration when there is fluid overload.11,17-19,76,77
The SSC provides a weak recommendation for this
approach, given that there are no high-quality ran-
domized controlled trials addressing the exact total
volume needed in a short amount of time.11 However,
several observational studies have demonstrated
improved outcomes with up to 60 mL/kg of IV crystal-
loid fluid administered within the first hour of resus-
citation.11,17-19,76-78 The key aspect to consider is the
combined features of septic shock and the greater
dependence on cardiac output for pediatric patients.
Most children will tolerate 60 mL/kg of IV crystalloid
fluid resuscitation without development of cardiac
dysfunction. However, vasoactive support must
not be delayed when there has not been sufficient
improvement in perfusion or for the development of
fluid-refractory shock.11,44,47,76-78 Maintenance fluids
are an important aspect to consider, particularly in
low-resource settings. Following the initial resuscita-
tion period, patients will require sugar-containing
maintenance fluids for continued baseline fluid losses
and for maintaining perfusion to the kidneys in the
context of likely nephrotoxic medications. In contrast
to the recommendation for aggressive fluid resuscita-
tion in high-resource settings, the FEAST randomized
control trial in Africa (considered a low-resource set-
ting) demonstrated lower mortality in children receiv-
ing maintenance fluids only (no bolus fluids) versus
those receiving bolus fluids.79
Type of Resuscitation Fluid
Normal saline and balanced fluids such as lactated
Ringer's solution have been shown to be effective in
reversing shock in pediatric sepsis. The current SSC
recommendation is to administer balanced fluids
rather than 0.9% (normal) saline, but this is consid-
ered a weak recommendation with a very low quality
of evidence.11 This recommendation stems from 2
large observational studies in children with sepsis.80,81
Though observational in nature, they included a
total of 30,532 children with sepsis, and it was shown
that patients receiving balanced fluids compared to
normal saline had lower mortality (OR, 0.79; 95% CI,
0.65–0.95).80,81 Compared to normal saline, bal-
anced fluids such as lactated Ringer's solution have
a chloride concentration that is lower and closer to
the physiologic amount found in serum. The higher
chloride concentration in normal saline has been
postulated to result in greater kidney dysfunction in
septic shock, potentially resulting in greater long-
term kidney dysfunction and morbidity. Thus, the use
of balanced fluids is considered a weak recommenda-
tion until definitive evidence may be obtained from a
large well-controlled trial. The PRoMPT BOLUS trial is
NOVEMBER 2022 • www.ebmedicine.net 11
currently underway to address this question. Similar
randomized controlled trials in adults have dem-
onstrated the benefit of balanced fluids in treating
septic shock.82
Time to Antibiotic Administration
Another topic of discussion in septic shock is the time
to antibiotic administration. In children with septic
shock, the SSC recommendations are to start antimi-
crobial therapy as soon as possible, within 1 hour of
sepsis recognition (strong recommendation, very low
quality of evidence).11 However, in children with sep-
sis but not shock, SSC recommendations are to start
antimicrobial therapy as soon as possible after appro-
priate evaluation, within 3 hours of recognition (weak
recommendation, very low quality of evidence).11 This
aspect is crucial when issues related to overcrowd-
ing and lack of sufficient bed space are considered.
Most quality improvement programs will err on the
side of administering antimicrobials within 1 hour,
similar to the recommendations for cancer patients
with febrile neutropenia.64,83,84 In severe sepsis and
septic shock, convincing evidence exists that delay-
ing antimicrobial therapy is associated with worsened
outcomes.52,76-78,83,84 Nonetheless, the benefit of anti-
microbials given within 1 hour of recognition for the
patient without severe sepsis or septic shock has not
yet been proven conclusively.
5 Recommendations
To Apply in Practice
5 Things That Will
5 Recommendations
Change To
Your Practice
Apply in Practice
1. Automatic electronic tools for early recogni-
tion and bundle adherence are associated
5
with improved Recommendations
outcomes.
To Apply in Practice
2. Epinephrine and norepinephrine are pre-
ferred first-line vasoactive agents in pediatric
septic shock. Dopamine is associated with a
greater incidence of fatal arrhythmias.
3. When approaching fluid volume that is close
to 40 to 60 mL/kg, consider beginning a va-
soactive medication to avoid fluid overload.
4. Corticosteroid use can be avoided in children
who have responded to fluid resuscitation
and vasopressor therapy.
5. For patients stabilized with fluid administra-
tion who no longer require vasoactive medica-
tion escalation, additional blood products are
not needed unless hemoglobin is <7 g/dL.
© 2022 EB MEDICINE
 Case Conclusions
For the 8-year-old boy who was brought in by his parents for fever, redness to his left shin, vomiting,
and diarrhea...
The boy presented in uncompensated septic shock. After receiving bag-valve mask ventilation and fluid
administration, his lethargy and blood pressure improved. He received broad-spectrum antibiotics within 24
CASE 1

minutes of arrival. Though his blood pressure and mental status initially improved, he developed hypoten-
sion again following IV ceftriaxone administration. He was started on an epinephrine infusion of 0.2 mcg/
kg/min and a decision was made to secure his airway. He was given IV ketamine and an IV paralytic agent.
He developed poor lung compliance, and fluid was seen returning into the endotracheal tube. With per-
sistent hypotension, a norepinephrine infusion was started at 0.15 mcg/kg/min along with blood products,
including packed red blood cells and FFP for DIC. He was transferred to a critical care setting where he
later succumbed to his illness. Blood cultures grew Staphylococcal aureus.

For the 2-year-old boy with short-bowel syndrome and parenteral nutrition dependence who pre-
sented with fever and fatigue…
The boy was started on the sepsis bundle, with IV antibiotics (ceftriaxone and vancomycin) and 60 mL/kg
CASE 2

of IV crystalloid fluid resuscitation. A norepinephrine infusion was started that quickly escalated up to 0.2
mcg/kg/min, and he was also started on an epinephrine infusion at 0.1 mcg/kg/min. The boy developed
DIC, diffuse pulmonary edema, and signs of renal failure. He required multiple blood products, an invasive
airway, and later succumbed to his illness while in the critical care unit. Five hours after arrival, his blood
cultures were positive for MRSA.

For the 16-year-old girl with leukemia who presented after a syncopal episode…
You observed and monitored the girl in the ED. At her 1-hour reassessment, she complained of continued
dizziness and fatigue, and her vital signs were as follows: temperature, 40°C axillary; heart rate, 137 beats/
CASE 3

min; and blood pressure, 87/45 mm Hg. After blood cultures were obtained, she was immediately started
on IV antibiotics (meropenem and vancomycin), and she was given 60 mL/kg of IV crystalloid fluid. Within
the first hour of resuscitation, she was started on an epinephrine drip to 0.1 mcg/kg/min. With improve-
ment in her perfusion and reversal of her shock state, she was able to ambulate without syncope, and her
dizziness and fatigue resolved. On her third hospital day, she was walking without syncope. She was later
discharged from the medical-surgical unit, neurologically intact.

Corticosteroid Use
Inconclusive recommendations remain for corticoste-
roid use in patients without previous chronic cortico-
steroid exposure, congenital adrenal hyperplasia, or
known hypothalamic-pituitary-adrenal axis disorders.
Outside of this population, the SSC recommends,
with low quality of evidence, against using corticoste-
roids (specifically IV hydrocortisone) in children with
septic shock who have responded to fluid resuscita-
tion and vasoactive medications.11
n Disposition
Patients with septic shock require hospital admission,
most likely to a critical care setting, with some centers
needing to arrange for early transfer to the appropri-
ate setting. Critical care admission criteria include
need for vasoactive medications and central venous
access, advanced airway management, and frequent
bedside assessments (such as need for blood pres-
sure monitoring with an arterial line) not typically
possible in a routine medical-surgical unit.11 Patients
with stable hemodynamics, documented improve-
ment in their perfusion, mental status, and reversal of
shock findings may be admitted to a non–critical care
monitored setting.
n Summary
Pediatric septic shock remains a significant burden in
both low-resource and high-resource settings, and it
continues to be a leading cause of morbidity and mor-
tality. Patient factors associated with greater mortality
from septic shock include age <1 year, immunocom-
promised status, underlying congenital heart disease,
persistently elevated lactate when receiving resuscita-
tion, need for mechanical ventilation, and acute kidney
injury. The cornerstone of therapy for septic shock
is early recognition, rapid initiation of sepsis bundle
elements, and meticulous attention to volume status
and clinical response. Bundle elements include empiric

NOVEMBER 2022 • www.ebmedicine.net 12 © 2022 EB MEDICINE


broad-spectrum antibiotic administration after obtain-
ing blood cultures, judicious use of IV crystalloid fluid
administration, and vasoactive medications to support
hemodynamics. Best-practice recommendations have
evolved with the availability of more evidence from
both adult and pediatric studies. While most of the
evidence has come from observational studies, well-
designed randomized controlled trials are underway
that may pave the way for evidence-based modifica-
tions to septic shock management.
n Time- and Cost-Effective Strategies
• It is reasonable to downgrade to regular hospital
floor care after confirming the patient's stability
without vasoactive medications. Reversal of
shock and correction of abnormal perfusion may
serve as markers in de-escalating therapy for
septic shock. Be careful not to make this decision
in haste when there is continued unexplained
tachycardia or possibly inadequate urine output,
even if able to wean some aspect of the septic
shock treatment.
• With shock reversal and correction of coagulation
abnormalities, there is no need for continuous
packed red blood cell infusion once the patient is
stabilized without escalating vasoactive medica-
tions and the hemoglobin level is above 7g/dL.
However, if there is a need for escalating vasoac-
tive infusions, invasive procedures, or if there are
bleeding complications, continued resuscitation
with blood products may be necessary.
• HHFNC may help avoid invasive mechanical
ventilation in a certain subset of patients, thus
decreasing length of stay in an intensive care unit.
• Always assess for potential cardiac dysfunction
in treating septic shock, as this is associated with
greater mortality and poorer outcomes.
n References
Evidence-based medicine requires a critical appraisal
of the literature based upon study methodology and
number of subjects. Not all references are equally
robust. The findings of a large, prospective, random-
ized, and blinded trial should carry more weight than
a case report.
To help the reader judge the strength of each refer-
ence, pertinent information about the study, such as the
type of study and the number of patients in the study is
included in bold type following the references, where
available. The most informative references cited in this
paper, as determined by the authors, are noted by an
asterisk (*) next to the number of the reference.
1. Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, et al. The
global burden of paediatric and neonatal sepsis: a systematic
review. Lancet Respir Med. 2018;6(3):223-230. (Systematic
NOVEMBER 2022 • www.ebmedicine.net 13
review; 15 studies)
2. Kohn-Loncarica G, Fustiñana A, Santos C, et al. Clinical out-
come of children with fluid-refractory septic shock treated with
dopamine or epinephrine. A retrospective study at a pediatric
emergency department in Argentina. Rev Bras Ter Intensiva.
2020;32(4):551-556. (Retrospective study; 118 patients)
3. Singer M, Deutschman CS, Seymour CW, et al. The Third
International Consensus definitions for sepsis and septic shock
(Sepsis-3). JAMA. 2016;315(8):801-810. (Consensus guideline)
4. Watson RS, Carcillo JA, Linde-Zwirble WT, et al. The epide-
miology of severe sepsis in children in the United States. Am
J Respir Crit Care Med. 2003;167(5):695-701. (Retrospective
observational cohort; 42,364 patients)
5. Hartman ME, Linde-Zwirble WT, Angus DC, et al. Trends in
the epidemiology of pediatric severe sepsis*. Pediatr Crit
Care Med. 2013;14(7):686-693. (Retrospective observational
cohort; 72,355 patients)
6.* Paul R, Melendez E, Stack A, et al. Improving adherence to
PALS septic shock guidelines. Pediatrics. 2014;133(5):e1358-
e1366. (Prospective cohort study; 242 patients)
DOI: 10.1542/peds.2013-3871
7.* Weiss SL, Balamuth F, Hensley J, et al. The epidemiology of
hospital death following pediatric severe sepsis: when, why,
and how children with sepsis die. Pediatr Crit Care Med.
2017;18(9):823-830. (Retrospective observational study; 79
patients) DOI: 10.1097/pcc.0000000000001222
8. Prout AJ, Talisa VB, Carcillo JA, et al. Children with chronic
disease bear the highest burden of pediatric sepsis. J Pediatr.
2018;199:194-199. (Retrospective cohort study; 14,243
patients)
9.* Balamuth F, Weiss SL, Neuman MI, et al. Pediatric severe
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© 2022 EB MEDICINE
17.* Lane RD, Funai T, Reeder R, et al. High reliability pediatric
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Risk Management Pitfalls in Pediatric
Patients With Septic Shock
1. “The patient had a pulse oximetry reading of
94%, so I weaned his oxygen to room air.”
During septic shock, perfusion is limited by poor
cardiac output and decreased carrying capacity
in blood, particularly for patients who are anemic
while receiving chemotherapy for leukemia. Oxy-
gen supplementation serves to increase carrying
capacity and improve perfusion of vital organs,
and it should not be stopped in this setting.
2. “My patient's blood pressure was normal. I did
not consider septic shock.” Most patients with
septic shock present with compensated shock
without hypotension, but they still have shock
physiology. Hypotension is a later finding in pedi-
atric septic shock, and tools are in place that can
trigger recognition of shock without concurrent
hypotension. Unexplained tachycardia, changes
in mental status, and poor capillary refill may be
present prior to the development of hypotension.
A key aspect in quality improvement programs is
addressing this gap in recognition that exists in
pediatric septic shock across multiple settings.
3. “I wanted to wait for the results from labora-
tory analysis prior to starting broad-spectrum
antibiotics.” When treating septic shock, broad-
spectrum antibiotics need to be given in a timely
manner. Delay in antibiotic administration is
associated with increased in-hospital risk-adjusted
mortality. If no IV access is available, antibiotics
may also be administered via an IO line.
NOVEMBER 2022 • www.ebmedicine.net 14
clinician identification. Ann Emerg Med. 2017;70(6):759-768.
(Prospective cohort study; 1112 patients)
23. Bradshaw C, Goodman I, Rosenberg R, et al. Implementation of
an inpatient pediatric sepsis identification pathway. Pediat-
rics. 2016;137(3):e20144082. (Prospective cohort study; 963
encounters)
24. Balamuth F, Alpern ER, Grundmeier RW, et al. Comparison of
two sepsis recognition methods in a pediatric emergency de-
partment. Acad Emerg Med. 2015;22(11):1298-1306. (Obser-
vational cohort study; 3301 patients)
25. Antequera Martín AM, Barea Mendoza JA, Muriel A, et al.
Buffered solutions versus 0.9% saline for resuscitation in
critically ill adults and children. Cochrane Database Syst Rev.
2019;7(7):CD012247. (Systematic review; 21 randomized
controlled trials, 20,213 participants)
26. Alejandria MM, Lansang MA, Dans LF, et al. Intravenous im-
munoglobulin for treating sepsis, severe sepsis and septic shock.
Cochrane Database Syst Rev. 2013;2013(9):CD001090. (System-
atic review; 43 randomized controlled trials, 19,252 patients)
27. Annane D, Bellissant E, Bollaert PE, et al. Corticosteroids for
treating sepsis in children and adults. Cochrane Database Syst
Rev. 2019;12(12):CD002243. (Systematic review; 61 trials,
12,192 participants)
4. “My patient deteriorated right when I was
about to secure an advanced airway.” For
patients with septic shock, cardiovascular collapse
must be anticipated when using induction or
paralytic agents. If possible, the SSC recommends
fluid administration and vasoactive medications
prior to intubation, if the clinical situation allows.
Ketamine is the induction agent of choice, given
its adrenergic properties.
5. “The patient did not have hypoxemia, so I
stopped checking for crackles.” When treating
septic shock, concurrent cardiac dysfunction may
be present and will manifest only when under the
stress of volume resuscitation. Frequent cardio-
vascular examinations are needed to monitor for
development of a gallop or pulmonary edema,
which would result in modifying the bundle ap-
proach to treating septic shock and initiation of
vasoactive medications without necessarily reach-
ing the 60 mL/kg fluid resuscitation threshold.
6. “I thought it was better to treat a patient with
septic shock who is in DIC with fresh frozen
plasma rather than packed red blood cells.”
Packed red blood cell transfusion should be given
for hemoglobin levels <7 g/dL in a patient with
septic shock (best-practice recommendation in
the setting of septic shock stabilized on catechol-
amines). Of note, there is no current recommen-
dation in the setting of septic shock that has not
been stabilized.
© 2022 EB MEDICINE
28. Martí-Carvajal AJ, Solà I, Gluud C, et al. Human recombi-
nant protein C for severe sepsis and septic shock in adult
and paediatric patients. Cochrane Database Syst Rev.
2012;12(12):CD004388. (Systematic review; 6 randomized
clinical trials, 6781 participants)
29. Matics TJ, Sanchez-Pinto LN. Adaptation and validation of a
pediatric sequential organ failure assessment score and evalu-
ation of the Sepsis-3 definitions in critically ill children. JAMA
Pediatr. 2017;171(10):e172352. (Retrospective observational
cohort study; 6303 patients)
30. Li S, Liu J, Chen F, et al. A risk score based on pediatric
sequential organ failure assessment predicts 90-day mortality
in children with Klebsiella pneumoniae bloodstream infection.
BMC Infect Dis. 2020;20(1):916. (Retrospective cohort study;
146 patients)
31. American Academy of Pediatrics Committee on Infectious Dis-
eases. Red Book (2018): Report of the Committee on Infectious
Diseases. American Academy of Pediatrics; 2018. (Textbook)
32. Chan KH, Sanatani S, Potts JE, et al. The relative incidence of
cardiogenic and septic shock in neonates. Paediatr Child Health.
2020;25(6):372-377. (Retrospective review; 1641 patients)
33. Ninis N, Phillips C, Bailey L, et al. The role of healthcare
7. “We did not need to obtain chest radiographs
for the patient being treated for septic shock
since she had normal pulse oximetry read-
ings.” Cardiac dysfunction may be present early
on in septic shock, and continued volume resus-
citation may aggravate this dysfunction. Thus, in
the right setting, chest imaging or echocardiogra-
phy may aid in decision-making for some pa-
tients, such as those who have received cardio-
toxic medications.
8. “I did not think corticosteroids were part of
the treatment algorithm for septic shock.”
There are some instances in which corticosteroids
will be part of the treatment of septic shock. For
example, in an organ transplant recipient, predni-
sone (sometimes high doses) is utilized to prevent
rejection and graft versus host disease. Resuscita-
tion in this setting may also require corticoste-
roids, possibly preventing the need for vasoactive
medications. In other circumstances, corticoste-
roids are utilized in fluid- and catecholamine-
refractory hypotension.
NOVEMBER 2022 • www.ebmedicine.net 15
delivery in the outcome of meningococcal disease in chil-
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34. McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis,
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Heart Association. Circulation. 2017;135(17):e927-e999. (Sys-
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35. Zheng Z, Huang Y, Wang Z, et al. Clinical features in children
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36. Whittaker E, Bamford A, Kenny J, et al. Clinical characteris-
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38. Hill JA, Li D, Hay KA, et al. Infectious complications of CD19-
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9. “Even though a gallop developed, I continued
to give IV crystalloid fluid boluses up to 60
mL/kg to adhere to elements of the sepsis
bundle.” For certain patient subsets, excessive
volume resuscitation will lead to further cardiac
dysfunction and worsen outcomes related to
septic shock. Patients with a history of leukemia
who have received cardiotoxic medications as
part of their chemotherapy regimen may need
earlier initiation of vasoactive medications to treat
septic shock. Thus, IV fluid administration should
be provided judiciously, with the patient’s clinical
response dictating subsequent steps in therapy.
Septic shock will still need to be treated aggres-
sively, but with vasoactive medications rather
than additional IV fluid administration.
10. “I thought I could ignore premature ventricular
contractions while treating septic shock with
dopamine.” Higher dosages of dopamine (ie,
>10 mcg/kg/min) are associated with the devel-
opment of arrhythmias in septic shock, and hence
part of the reason behind recent changes to best-
practice recommendations. Dopamine may still
be used in escalating doses, but with caution, as
it may trigger a potentially fatal arrhythmia.
© 2022 EB MEDICINE
 apy. Blood. 2018;131(1):121-130. (Prospective case cohort;
133 patients)
39. Hay KA. Cytokine release syndrome and neurotoxicity after
CD19 chimeric antigen receptor-modified (CAR-) T cell therapy.
Br J Haematol. 2018;183(3):364-374. (Disease review)
40. Hay KA, Hanafi LA, Li D, et al. Kinetics and biomarkers of
severe cytokine release syndrome after CD19 chimeric antigen
receptor-modified T-cell therapy. Blood. 2017;130(21):2295-
2306. (Phase 1/2 clinical trial)
41. Schmitz M, Roux X, Huttner B, et al. Streptococcal toxic shock
syndrome in the intensive care unit. Ann Intensive Care.
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42. Berger S, Kunerl A, Wasmuth S, et al. Menstrual toxic shock
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pital care on outcomes in sepsis: a systematic review. West J
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44. Larsen GY, Mecham N, Greenberg R. An emergency depart-
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45. Brierley J, Peters MJ. Distinct hemodynamic patterns of septic
shock at presentation to pediatric intensive care. Pediatrics.
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J Am Coll Emerg Physicians Open. 2020;1(5):981-993. (Review)
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in children. JAMA Pediatr. 2017;171(3):249-255. (Observational
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48. Scott HF, Brou L, Deakyne SJ, et al. Lactate clearance and normal-
ization and prolonged organ dysfunction in pediatric sepsis. J Pe-
diatr. 2016;170:149-155. (Prospective cohort study; 77 patients)
49. Wig JD, Kochhar R, Ray JD, et al. Endotoxemia pre-
dicts outcome in acute pancreatitis. J Clin Gastroenterol.
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50. Ospina-Tascón GA, Bautista-Rincón DF, Umaña M, et al. Persis-
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51. Arya B, Kerstein D, Leu CS, et al. Echocardiographic assess-
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52. Weiss SL, Fitzgerald JC, Balamuth F, et al. Delayed antimicro-
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53. Bruns N, Dohna-Schwake C. Antibiotics in critically ill children-
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1. Which of the following would suggest septic
shock?
a. Blood pressure of 79/36 mm Hg after IV crys-
talloid fluid administration
b. Hyperglycemia at 275 mg/dL
c. Serum sodium at 132 mEq/L
d. Leukocytosis of 19 × 109 cells/L
2. Which of the following has been shown to
decrease mortality in patients with sepsis?
a. Early administration of corticosteroids
b. Positive pressure ventilation
c. Blood cultures drawn from 2 separate sites
prior to antibiotic administration
d. Timely antibiotic administration after arrival to
the emergency department (ED)
3. A 2-year-old boy with a history of relapsed
acute lymphocytic leukemia is brought to the
ED for fever and lethargy. His vital signs are:
temperature, 39.8ºC; heart rate, 178 beats/
min; respiratory rate, 52 breaths/min; blood
pressure, 90/40 mm Hg; and oxygen satura-
tion, 96% on room air. He has shallow respira-
tions without crackles. Which of the following
management options should take priority?
a. Securing an advanced airway
b. Administration of oxygen at 2 L/min via nasal
cannula
c. Administration of corticosteroids
d. Administration of IV antibiotics and crystalloid
fluids
4. A 13-year-old boy is brought in for right knee
pain that started approximately 1 week ago
and has gotten worse. The boy is now unable
to ambulate due to severe pain. Vital signs are:
temperature, 39.5°C; heart rate, 125 beats/min;
respiratory rate, 28 breaths/min; blood pres-
sure, 121/83 mm Hg; and oxygen saturation,
98% on room air. Arthrocentesis is performed
and found to be cloudy, with WBC of 100,000
cells/mcL, with mostly neutrophils. What would
be the appropriate initial dose of IV crystalloid
fluid to use in resuscitation?
a. 20 mL/kg IV 0.9% saline or lactated Ringer’s
b. 30 mL/kg IV 0.9% saline or lactated Ringer’s
c. 40 mL/kg IV 0.9% saline or lactated Ringer’s
d. 60 mL/kg IV 0.9% saline or lactated Ringer’s
© 2022 EB MEDICINE
5. A 4-year-old girl with aplastic anemia comes
to the ED with fever and lethargy. She seems
fatigued but answers questions and follows
commands. Her capillary refill time is 4 sec-
onds and her extremities are cool. Her vital
signs are: temperature, 39.5ºC; heart rate,
175 beats/min; respiratory rate, 36 beats/min;
blood pressure, 72/36 mm Hg; and oxygen
saturation, 93% on room air. Which of the fol-
lowing should be done next?
a. Administer 20 mL/kg of IV crystalloid fluids.
b. Infuse 2 units of packed red blood cells.
c. Perform endotracheal intubation.
d. Request formal echocardiography.
6. An 8-year-old boy with a history of leukemia
on chemotherapy is suspected of having septic
shock. He received broad-spectrum antibiotics
and 40 mL/kg IV crystalloid fluid resuscitation
when crackles were auscultated. His vital signs
are: temperature, 38.3°C; heart rate, 145 beats/
min with bounding radial pulses; respiratory
rate, 32 breaths/min; blood pressure, 92/53 mm
Hg; and pulse oximetry, 94% on 2 L/min oxygen.
His perfusion remains poor. Which of the follow-
ing is the correct next step in the management
of his suspected septic shock?
a. Administer another 20-mL/kg IV fluid bolus to
a goal of 60 mL/kg total volume.
b. Increase oxygen delivery via nasal cannula to
3 L/min.
c. Start a dopamine infusion at 15 mcg/kg/min.
d. Start a norepinephrine infusion at 0.1 mcg/
kg/min.
7. A 5-year-old boy is brought in for a 1-week
history of cough, nasal congestion, and rhinor-
rhea that initially improved 3 days ago. Today
he developed difficulty breathing and leth-
argy. His vital signs are: temperature, 39.3°C;
heart rate, 155 beats/min; blood pressure,
80/44 mm Hg; respiratory rate, 38 breaths/
min; oxygen saturation, 94% on room air.
Broad-spectrum antibiotics and rapid fluid
resuscitation are initiated. After receiving 60
mL/kg of IV crystalloid fluid, his vital signs are:
temperature, 39°C; heart rate, 145 beats/min;
respiratory rate, 32 beats/min; blood pressure,
83/38 mm Hg; and oxygen saturation, 93% on
room air. What is the appropriate next step in
management?
a. Administer an additional 20 mL/kg of IV crys-
talloid fluids.
b. Initiate epinephrine infusion at 0.1 mcg/kg/
min.
c. Administer inhaled beta agonists.
d. Initiate positive pressure ventilation.
NOVEMBER 2022 • www.ebmedicine.net 18
8. Which of the following medications should be
utilized for sedation and analgesia for intuba-
tion in pediatric patients with septic shock?
a. Etomidate and rocuronium
b. Etomidate and succinylcholine
c. Ketamine and rocuronium
d. Ketamine and midazolam
9. An 8-year-old boy with a history of severe
persistent asthma on chronic systemic cortico-
steroid therapy presents with cough and fever
for 5 days. His vital signs are: temperature,
39.5°C oral; heart rate, 138 beats/min; respi-
ratory rate, 32 breaths/min; blood pressure,
77/40 mm Hg; and oxygen saturation, 90%
on room air. He has received broad-spectrum
antibiotics, 60 mL/kg of IV crystalloid fluid, an
epinephrine infusion that has been titrated up
to 0.15 mcg/kg/min, and a norepinephrine drip
titrated up to 0.1 mcg/kg/min. His repeat vital
signs are: temperature, 38.5°C oral; heart rate,
148 beats/min; respiratory rate, 30 breaths/
min; blood pressure 80/43 mm Hg; oxygen
saturation, 98% on 2 L/min oxygen via nasal
cannula. What is the next management step?
a. Increase oxygen to 5 L/min via face mask.
b. Administer dopamine at 10 mcg/kg/min.
c. Give additional IV crystalloid fluid boluses.
d. Administer IV corticosteroids.
10. A 6-year-old boy who has a history of hypo-
plastic left heart syndrome and is status post
his corrective surgeries of Norwood, Glenn,
and Fontan, is brought to the ED for fever,
headaches, and confusion that started last
night. His vital signs are: temperature, 39.6°C;
heart rate, 122 beats/min; respiratory rate, 26
breaths/min; blood pressure, 77/40 mm Hg;
and oxygen saturation, 90% on room air. The
physical examination reveals neck stiffness,
severe drowsiness, and an audible murmur for
his shunt. Broad-spectrum antibiotics are given
and resuscitation with a 20-mL/kg IV bolus of
crystalloid fluid is initiated. Repeat examina-
tion shows diffuse rales in bilateral lung fields
and a repeat blood pressure of 80/36 mm Hg.
What is the appropriate next step in manage-
ment?
a. Administer an additional 20-mL/kg IV crystal-
loid fluid bolus.
b. Stop fluids and initiate norepinephrine infu-
sion.
c. Secure an advanced airway.
d. Provide oxygen at 5 L/min with a simple face
mask.
© 2022 EB MEDICINE
 American College of Critical Care Medicine Algorithm for
Time-Sensitive, Goal-Directed Stepwise Management of
Hemodynamic Support in Infants and Children

Proceed to next step if shock persists. 1) First hour goals—restore and maintain heart rate thresholds, capillary refill ≤2 s, and normal blood pressure
in the first hour/emergency department. 2) Subsequent ICU goals—if shock not reversed proceed to restore and maintain normal perfusion pressure
(MAP – CVP) for age, ScvO2 > 70% (*except congenital heart patients with mixing lesions), and cardiac index >3.3 <6.0 L/min/m2 in PICU.
Reprinted from: Alan L. Davis, Joseph A. Carcillo, Rajesh K. Aneja, et al. American College of Critical Care Medicine clinical practice parameters for
hemodynamic support of pediatric and neonatal septic shock. Critical Care Medicine. Volume 45, Issue 6, Pages 1061-1093. https://journals.lww.com/
ccmjournal/pages/default.aspx with permission from the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.
Abbreviations: CI, cardiac index; ECMO, extracorporeal membrane oxygenation; FATD, femoral arterial thermodilution method; ICU, intensive care unit;
IM, intramuscular; IO, intraosseous; IV, intravenous; MAP-CVP, mean arterial pressure (MAP)-central venous pressure (CVP); PAC, pulmonary artery
catheter; PALS, Pediatric Advanced Life Support; PICCO, pulse index contour CO; PICU, pediatric intensive care unit; ScvO2, central venous oxygen
saturation; SVRI, systemic vascular resistance index.

NOVEMBER 2022 • www.ebmedicine.net 19 © 2022 EB MEDICINE

 American College of Critical Care Medicine Algorithm for
Time-Sensitive, Goal-Directed Stepwise Management of
Hemodynamic Support in Newborns

Proceed to next step if shock persists. 1) First-hour goals— restore and maintain heart rate thresholds, capillary refill ≤2 s, and normal blood pressure
in the (first hour). 2) Subsequent ICU goals—restore normal perfusion pressure (mean arterial pressure – central venous pressure), preductal and
postductal oxygen saturation difference <5%, and either ScvO2 >70% (*except congenital heart patients with mixing lesions), superior vena cava flow
>40 mL/kg/min, or cardiac index >3.3 L/min/m2 in NICU.
Reprinted from: Alan L. Davis, Joseph A. Carcillo, Rajesh K. Aneja, et al. American College of Critical Care Medicine clinical practice parameters for
hemodynamic support of pediatric and neonatal septic shock. Critical Care Medicine. Volume 45, Issue 6, Pages 1061-1093. https://journals.lww.com/
ccmjournal/pages/default.aspx with permission from the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.
Abbreviations: CI, cardiac index; ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit; IV, intravenous; LV, left ventricle; MAP-CVP,
mean arterial pressure (MAP)-central venous pressure (CVP); NICU, neonatal intensive care unit; NRP, Neonatal Resuscitation Program; PPHN,
persistent pulmonary hypertension of the newborn; PRA, patent ductus arteriosus; RDS, respiratory distress syndrome; RV, right ventricle; ScvO2,
central venous oxygen saturation; SVC, superior vena cava; VLBW, very low birth weight.

NOVEMBER 2022 • www.ebmedicine.net 20 © 2022 EB MEDICINE

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The Pediatric Emergency Medicine Practice Editorial Board
EDITORS-IN-CHIEF
Ilene Claudius, MD
Associate Professor; Director,
Process & Quality Improvement
Program, Harbor-UCLA Medical
Center, Torrance, CA
Tim Horeczko, MD, MSCR,
FACEP, FAAP
Associate Professor of Clinical
Emergency Medicine, David Geffen
School of Medicine, UCLA; Core
Faculty and Senior Physician, Los
Angeles County-Harbor-UCLA
Medical Center, Torrance, CA
EDITORIAL BOARD
Jeffrey R. Avner, MD, FAAP
Chairman, Department of
Pediatrics, Professor of Clinical
Pediatrics, Maimonides Children's
Hospital of
Brooklyn, Brooklyn, NY
Steven Bin, MD
Associate Clinical Professor, UCSF
School of Medicine; Medical
Director, Pediatric Emergency
Medicine, UCSF Benioff Children's
Hospital, San Francisco, CA
Richard M. Cantor, MD, FAAP,
FACEP
Professor of Emergency Medicine
and Pediatrics; Section Chief,
Pediatric Emergency Medicine;
Medical Director, Upstate Poison
Control Center, Golisano Children's
Hospital, Syracuse, NY
Steven Choi, MD, FAAP
Chief Quality Officer and Associate
Dean for Clinical Quality, Yale
Medicine/Yale School of Medicine;
Vice President, Chief Quality
Officer, Yale New Haven Health
System, New Haven, CT
Ari Cohen, MD, FAAP
Chief of Pediatric Emergency
Medicine, Massachusetts General
Hospital; Instructor in Pediatrics,
Harvard Medical School, Boston,
MA
Jay D. Fisher, MD, FAAP, FACEP
Associate Professor of Emergency Medicine;
Program Director, Pediatric Emergency
Medicine Fellowship, Kirk Kerkorian School
of Medicine at UNLV; Medical Director,
Pediatric Emergency Services, UMC
Children's Hospital, Las Vegas, NV
NOVEMBER 2022 • www.ebmedicine.net 23
Marianne Gausche-Hill, MD,
FACEP, FAAP, FAEMS
Medical Director, Los Angeles
County EMS Agency; Professor of
Clinical Emergency Medicine and
Pediatrics, David Geffen School
of Medicine at UCLA; Clinical
Faculty, Harbor-UCLA Medical
Center, Department of Emergency
Medicine, Los Angeles, CA
Michael J. Gerardi, MD, FAAP,
FACEP, President
Associate Professor of Emergency
Medicine, Icahn School of Medicine
at Mount Sinai; Director, Pediatric
Emergency Medicine, Goryeb
Children's Hospital, Morristown
Medical Center, Morristown, NJ
Sandip Godambe, MD, PhD, MBA
Chief Medical Officer, SVP Medical
Affairs, Attending Physician,
Pediatric Emergency Medicine,
Children’s Health of California
(CHOC) Children’s Hospital,
Orange, CA
Ran D. Goldman, MD
Professor, University of British Columbia,
Pediatric Emergency Physician, BC
Children’s Hospital, Vancouver, BC, Canada
Alson S. Inaba, MD, FAAP
Pediatric Emergency Medicine
Specialist, Kapiolani Medical
Center for Women & Children;
Associate Professor of Pediatrics,
University of Hawaii John A. Burns
School of Medicine, Honolulu, HI
Madeline Matar Joseph, MD,
FACEP, FAAP
Professor of Emergency Medicine
and Pediatrics, Associate Dean for
Inclusion and Equity, Emergency
Medicine Department, University
of Florida College of Medicine-
Jacksonville, Jacksonville, FL
Anupam Kharbanda, MD, MSc
Chief, Critical Care Services,
Children's Hospital Minnesota,
Minneapolis, MN
Tommy Y. Kim, MD
Health Sciences Clinical Professor
of Pediatric Emergency Medicine,
University of California Riverside
School of Medicine, Riverside
Community Hospital, Department
of Emergency Medicine, Riverside,
CA
Melissa Langhan, MD, MHS
Associate Professor of Pediatrics
and Emergency Medicine;
Fellowship Director, Director of
Education, Pediatric Emergency
Medicine, Yale University School of
Medicine, New Haven, CT
Robert Luten, MD
Professor, Pediatrics and
Emergency Medicine, University of
Florida, Jacksonville, FL
Garth Meckler, MD, MSHS
Associate Professor of Pediatrics,
University of British Columbia;
Division Head, Pediatric Emergency
Medicine, BC Children's Hospital,
Vancouver, BC, Canada
Joshua Nagler, MD, MHPEd
Associate Division Chief and
Fellowship Director, Division of
Emergency Medicine, Boston
Children's Hospital; Associate
Professor of Pediatrics and
Emergency Medicine, Harvard
Medical School, Boston MA
James Naprawa, MD
Attending Physician, Emergency
Department USCF Benioff
Children's Hospital, Oakland, CA
Joshua Rocker, MD, FAAP, FACEP
Chief, Division of Pediatric
Emergency Medicine, Associate
Professor of Pediatrics and
Emergency Medicine, Cohen
Children's Medical Center of New
York, New Hyde Park, NY
Steven Rogers, MD
Associate Professor, University of
Connecticut School of Medicine,
Attending Emergency Medicine
Physician, Connecticut Children's
Medical Center, Hartford, CT
Jennifer E. Sanders, MD, FAAP,
FACEP
Assistant Professor, Departments
of Pediatrics, Emergency Medicine,
and Education, Icahn School of
Medicine at Mount Sinai, New
York, NY
Christopher Strother, MD
Associate Professor, Emergency
Medicine, Pediatrics, and Medical
Education; Director, Pediatric
Emergency Medicine; Director,
Simulation; Icahn School of
Medicine at Mount Sinai, New
York, NY
Adam E. Vella, MD, FAAP
Associate Professor of Emergency
Medicine and Pediatrics, Associate
Chief Quality Officer, New
York-Presbyterian/Weill Cornell
Medicine, New York, NY
David M. Walker, MD, FACEP,
FAAP
Chief, Pediatric Emergency Medicine,
Joseph M. Sanzari Children's Hospital,
Hackensack University Medical Center;
Associate Professor of Pediatrics,
Hackensack Meridian School of Medicine,
Hackensack, NJ
Vincent J. Wang, MD, MHA
Professor of Pediatrics and
Emergency Medicine; Division
Chief, Pediatric Emergency
Medicine, UT Southwestern
Medical Center; Director of
Emergency Services, Children's
Health, Dallas, TX
INTERNATIONAL EDITOR
Lara Zibners, MD, FAAP, FACEP,
MMEd
Honorary Consultant, Paediatric
Emergency Medicine, St. Mary's
Hospital Imperial College Trust,
London, UK; Nonclinical Instructor
of Emergency Medicine, Icahn
School of Medicine at Mount Sinai,
New York, NY
PHARMACOLOGY EDITOR
Aimee Mishler, PharmD, BCPS
Emergency Medicine Pharmacist,
Program Director – PGY2
Emergency Medicine Pharmacy
Residency, Valleywise Health
Medical Center, Phoenix, AZ
© 2022 EB MEDICINE
 Points & Pearls
QUICK READ
NOVEMBER 2022 | VOLUME 19 | ISSUE 11
Points
• Consider sepsis in a patient with persistent, unex-
plained tachycardia.
• Pediatric septic shock physiology can occur with-
out hypotension.
• Perform frequent reassessments, and if there is
fluid overload, stop bolus fluid administration and
initiate vasoactive medications.11
• Recognition tools have been shown to improve
outcomes by facilitating earlier adherence to
evidence-based treatment regimens.19-24,44
• Be prepared to assess for and treat concurrent car-
diogenic shock.
• Consider disease processes outside of sepsis that
mimic septic shock, such as Kawasaki disease and
multisystem inflammatory syndrome in children
(MIS-C).
• Pediatric patients with comorbid conditions, par-
ticularly immunocompromised status and central
line dependence, are more likely to develop sep-
tic shock and suffer greater mortality risks.
• Consider toxic shock syndrome from tampon use
when an adolescent female presents with septic
shock.41,42
• Sepsis can occur in neonates without fever, and
they can present with apnea requiring intubation.
• When there is concern for chronic corticosteroid
use or in patients with underlying endocrinopa-
thies, administer hydrocortisone IV.
• With persistent hypotension, echocardiography is
necessary in guiding fluid and vasoactive medica-
tion management.
• Delaying fluid resuscitation and broad-spectrum
antibiotics is associated with poor outcomes.
• Epinephrine or norepinephrine are the first-line
recommended vasoactive medications for pediat-
ric septic shock.41,42
• Vasoactive medications can be administered pe-
ripherally or with intraosseous needles until central
access can be achieved.57
• When intubation is needed, be prepared for
hemodynamic collapse following administration of
medications for rapid sequence induction.11,16
NOVEMBER 2022 • www.ebmedicine.net 24
Pediatric Septic Shock:
Recognition and Management
in the Emergency Department
Pearls
l Prophylactic blood products above a
hemoglobin threshold are not required unless
treating active hemorrhage or the patient needs
extracorporeal support.11
l For patients in septic shock, dopamine
administration has greater association with fatal
arrhythmias.
l Cytokine release syndrome mimics septic
shock, and fluid administration >10 mL/kg is
associated with poor outcomes.
l Delayed treatment of neonatal GBS bacteremia
is associated with devastating consequences.
l Physical examination findings for septic shock
may evolve over time, requiring frequent
reassessments as a means to guide fluid and
vasoactive medication management.
• Noninvasive positive pressure ventilation may be
used to try to avoid mechanical ventilation if the
patient’s clinical condition allows.
• Mechanical ventilation aids in the management of
pediatric septic shock with improved oxygenation
and organ perfusion via minimization of the work
of breathing and cardiac stress in sepsis-induced
cardiac dysfunction.11,16
• In newborns with septic shock, consider early trans-
fer to a NICU.
• In newborns with septic shock, there is a greater
role for milrinone in management.72,73
• Group B Streptococcus (GBS) infection is the most
common cause of neonatal early- and late-onset
sepsis.74,75
• For patients who are responsive to fluid resuscita-
tion and vasoactive medications, a hemoglobin
threshold of 7 g/dL may be maintained.11
• For febrile neutropenic cancer patients, consider
typhlitis for persistent abdominal pain or when there
are even subtle changes found in the perineum.
© 2022 EB MEDICINE