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Recognition and Management of Sepsis in Children

Practice Patterns in the Emergency Department

Graham C. Thompson, MD, FRCPC; Charles G. Macias, MD, MPH

J Emerg Med. 2015;49(4):391-399.

Abstract and Introduction

Abstract

Background: Pediatric sepsis remains a leading cause of morbidity and mortality. Understanding current practice patterns and
challenges is essential to inform future research and education strategies.

Objective: Our aim was to describe the practice patterns of pediatric emergency physicians (PEPs) in the recognition and
management of sepsis in children and to identify perceived priorities for future research and education.

Methods: We conducted a cross-sectional, internet-based survey of members of the American Academy of Pediatrics, Section on
Emergency Medicine and Pediatric Emergency Research Canada. The survey was internally derived, externally validated, and
distributed using a modified Dillman methodology. Rank scores (RS) were calculated for responses using Likert-assigned
frequency values.

Results: Tachycardia, mental-status changes, and abnormal temperature (RS = 83.7, 80.6, and 79.6) were the highest ranked
clinical measures for diagnosing sepsis; white blood cell count, lactate, and band count (RS = 73.5, 70.9, and 69.1) were the
highest ranked laboratory investigations. The resuscitation fluid of choice (85.5%) was normal saline. Dopamine was the first-line
vasoactive medication (VAM) for cold (57.1%) and warm (42.2%) shock with epinephrine (18.5%) and norepinephrine (25.1%) as
second-line VAMs (cold and warm, respectively). Steroid administration increased with complexity of presentation (all-comers
3.8%, VAM-resistant shock 54.5%, chronic steroid users 72.0%). Local ED-specific clinical pathways, national emergency
department (ED)-specific guidelines, and identification of clinical biomarkers were described as future priorities.

Conclusions: While practice variability exists among clinicians, PEPs continue to rely heavily on clinical metrics for recognizing
sepsis. Improved recognition through clinical biomarkers and standardization of care were perceived as priorities. Our results
provide a strong framework to guide future research and education strategies in pediatric sepsis.

Introduction

Sepsis is a leading cause of morbidity and mortality worldwide.[1] The burden of sepsis on survivors, their families, and health care
systems is immense; the estimated all-comer mortality rates approach 30%, and annual health care costs are well over $15 billion
United States (US) dollars.[2] Despite advances in prevention and management of pediatric sepsis, high-quality outcomes remain
suboptimal. Children continue to be at risk of death from sepsis, although mortality rates are lower than those in adults.[3,4] During
the last decade, there has been renewed worldwide efforts to improve both the awareness of sepsis in the public sector and the
recognition and management of sepsis in the health care sector.

Because the vast majority of previously healthy children have an innate ability to adapt and compensate to physiological stressors,
recognition of sepsis in the early stages can often be difficult. The standard research definitions of the sepsis continuum are difficult
to implement in the clinical setting; for example, many stable infants with bronchiolitis meet sepsis criteria (i.e., suspected infection,
tachycardia, tachypnea, fever).[5] The sensitivity and specificity for the "classic" clinical triad of thermodysregulation, perfusion
changes, and altered mental status has not been established formally.[6] In addition, the test characteristics of laboratory
investigations (i.e., markers of infection, inflammation, and perfusion) have yet to be confidently established in children, although
recent evidence regarding lactate and procalcitonin appears promising.[7–10] Current internationally recognized practice parameters
recommend utilization of clinical examination for early identification of pediatric sepsis.[6]

Emergency departments (EDs) are often the first point of contact for children with sepsis. In the United States, 100,000 children
present to EDs with severe sepsis annually.[11] In the adult population, the use of standardized, goal-directed protocols or pathways
has led to improved patient outcomes and a reduction in mortality.[12,13] Certainly, there does exist a scientific curiosity as to
whether the pediatric population would benefit from increased pathway/protocol presence. However, there is some reluctance to
adopt certain aggressive processes in the pediatric population (i.e., central vascular lines, invasive monitoring techniques), which
may stem from the paucity of pediatric literature demonstrating benefit, the low frequency of invasive procedures performed on the
young child, and the large resource utilization.[14] Still, the cornerstones of managing pediatric sepsis remain early recognition,
early aggressive fluid administration, early antibiotic administration, and transfer to tertiary level intensive care facilities.[6]
Implementation of screening tools and clinical protocols in the pediatric ED have shown improvement in these clinical processes,
although further well-designed outcomes-based studies are required.[15–17]

In order to address these deficiencies, the American Academy of Pediatrics Section on Emergency Medicine (AAP-SOEM) has
recently established a Sepsis/Shock Collaborative through its Committee on Quality Transformation. Expert opinion confirmed that
a lack of resources for the early recognition and management of pediatric sepsis exists, and highlighted the need for an
assessment of current practice patterns across the continent. As such, the primary objective of this study was to describe the
current variation in practice of emergency physicians (EPs) for the recognition, monitoring, and management of sepsis in children
aged 3 months to 17 years. Secondary objectives were to describe the self-reported level of comfort in managing a child with
sepsis or severe sepsis, and to solicit perceived priorities on future research and education strategies for addressing pediatric
sepsis.

Methods
Study Design and Population

We performed a cross-sectional, anonymous, internet-based survey of pediatric emergency physicians across North America.
Invitations to participate in the study were distributed to members of two national Pediatric Emergency Medicine organizations: the
AAP-SOEM and Pediatric Emergency Research Canada (PERC). Those members who belonged to both organizations were
limited to completing the survey once.

The survey was developed by the investigators based on expert opinion elicited through the AAP-SOEM Septic Shock
Collaborative. It was subsequently pre- and pilot-tested by a panel of specialists/subspecialists from across North America. Face
validity, content validity, and clinical sensibility were evaluated. The survey was made available in both English and French.

The structure of the survey included a variety of multiple choice, Likert-type, ranking, and open-ended questions. Topics included
strategies for the diagnosis and management of pediatric sepsis as well as perceived clinical, education, and research priorities
(Appendix: Recognition and Management of Sepsis in Children: Survey).

Surveys were distributed using SurveyMonkey (SurveyMonkey Inc, Luxembourg) according to a modified Dillman methodology,
including an initial e-mail invitation with subsequent reminders at 1, 3, and 5 weeks after the initial invitation.[18] Two weeks after the
final invitation, the survey was closed to completion. Distribution followed standard AAP-SOEM and PERC survey policies
(http://www2.aap.org/sections/PEM/default.cfm, http://perc.srv.ualberta.ca).

Participation in the study was voluntary and completion of any portion of the survey implied consent to participate. This study was
reviewed and approved by the Conjoint Health Research Ethics Board of the University of Calgary as well as the survey oversight
committees of AAP-SOEM and PERC.

Data Analysis

Respondent demographics were evaluated using descriptive statistics. Chi-square was used to determine the significance of
differences between categorical variables. Fisher's exact test was used where sample sizes were small. Continuous variables were
compared with independent t-tests. Analyses were performed using STATA software, version 12 (Stata Corp, College Station, TX).

In order to rank the perceived importance of responses to Likert-type questions, rank scores were calculated. Responses were
assigned a value (1 through 5) related to the frequency of use category (1 = never, 2 = rarely, 3 = sometimes, 4 = more often than
not, 5 = always). For each survey item, the number of responses in each reported frequency category was multiplied by its
assigned category value, and the sum of all frequency categories was calculated. This was divided by the maximum possible score
(the value of the highest frequency category multiplied by the total number of respondents = 5 × n) to give the final rank score.

Results

A total of 1341 individuals of the AAP-SOEM and PERC membership received an invitation to complete the survey. Results from a
total of 422 surveys were available for analysis, giving an overall response rate of 31.5%. The majority of respondents had
completed a pediatric emergency medicine fellowship (73.5%) and had been practicing for >10 years (49.8%). The health care
sites at which respondents primarily practiced were most commonly university-associated hospitals (75.4%), had an annual ED
census of >50,000 (50.2%) and had pediatric intensive care facilities (90.9%). Complete participant demographics are reported in

Table 1. Respondent Demographics

PERC, n (%) AAP-SOEM, n (%) Total, n (%)

Survey distribution
Invited 273 1045 1341
Completed 149 (50.3) 273 (26.1) 422 (31.5)
Training*
Emergency medicine 28 (18.8) 15 (5.5) 43 (10.2)
General practice 16 (10.7) 1 (0.4) 17 (4.0)
Internal medicine 1 (0.7) 2 (0.7) 3 (0.7)
Pediatric EM 82 (55.0) 228 (83.5) 310 (73.5)
Pediatrics 73 (49.0) 177 (64.8) 250 (59.2)
Other 5 (3.4) 7 (2.6) 12 (2.8)
Years in practice
In training 1 (0.7) 22 (8.1) 23 (5.5)
0 to 5 y 37 (24.8) 62 (22.7) 99 (23.5)
6 to 10 y 41 (27.5) 43 (15.8) 84 (19.9)
11 to 20 y 51 (34.2) 92 (33.7) 143 (33.9)
>20 y 17 (11.4) 50 (18.3) 67 (15.9)
Not practicing EM 2 (1.3) 4 (1.5) 6 (1.4)
Age category
 20 to 30 y 4 (2.7) 8 (1.9) 9 (2.1)
31 to 40 y 59 (39.6) 101 (37.3) 160 (37.9)
41 to 50 y 60 (40.3) 93 (34.3) 153 (36.3)
>50 y 26 (17.5) 72 (26.6) 98 (23.2)
Hospital type*
Rural 2 (1.3) 1 (0.4) 3 (0.7)
Community 2 (1.3) 34 (12.5) 36 (8.5)
Urban 45 (30.2) 135 (49.5) 180 (42.7)
University 131 (87.9) 187 (68.5) 318 (75.4)
ED census
<10,000 4 (2.8) 6 (2.3) 10 (2.5)
10,000 to 25,000 9 (6.3) 61 (22.9) 70 (17.2)
25,001 to 50,000 50 (35.2) 68 (25.6) 118 (28.9)
50,001 to 100,000 71 (50.0) 118 (44.4) 189 (46.3)
>100 000 4 (2.8) 12 (4.5) 16 (3.9)
ICU facilities
PICU 125 (88) 246 (92.5) 371 (90.9)
No ICU 2 (1.4) 4 (1.5) 6 (1.5)

AAP-SOEM = American Academy of Pediatrics Section on Emergency Medicine; ED = emergency department; EM = emergency
medicine; ICU = intensive care unit; PERC = Pediatric Emergency Research Canada; PICU = pediatric intensive care unit.
*Respondents can choose more than one option.

The vast majority of respondents reported being comfortable or very comfortable with managing a child with sepsis (n = 366
[86.7%]). The proportion of respondents with similar levels of comfort was slightly lower for managing a child with severe sepsis
(340 [80.7%]). Age of the child (3 to 36 months, 3 to 6 years, 7 to 12 years, and 13 to 17 years) did not influence the reported level
of comfort in either sepsis or severe sepsis. More clinicians reported managing a child with sepsis within the preceding month (161
[45.3%]) compared with severe sepsis (86 [20.3%]). Thirty respondents (7.1%), reported that a year had passed without managing
a child with sepsis, and that number increased to 94 (22.3%) for managing a patient with severe sepsis.

Clinicians ranked tachycardia as the most used clinical measure in the diagnosis of sepsis in children (rank score [RS] = 83.7).
Mental status changes, fever, peripheral capillary refill, and respiratory rate were also reported as important clinical measurements.
White blood cell count, neutrophil count, and band count were reported as the most utilized laboratory measure, followed by lactate
and renal function. Measures for monitoring success of resuscitation included heart rate, mental status, systolic blood pressure,
diastolic blood pressure, and peripheral capillary refill (, Figures 1–3).

Table 2. Top 5 Clinical and Laboratory Elements used in the Diagnosis and Monitoring of a Child with Sepsis

Overall PERC AAP-SOEM

Clinical signs and symptoms used to assist in recognizing a child with sepsis*
Tachycardia 83.7 80.3 (1) 85.6 (1)
Altered mental status 80.6 76.5 (3) 82.9 (2)
Abnormal temperature 79.6 77.3 (2) 80.8 (4)
Peripheral capillary refill 78.4 73.4 (5) 81.1 (3)
Tachypnea 76.7 75.8 (4) 77.2 (5)
Laboratory investigations used to assist in recognizing a child with sepsis†
Leukocyte count 73.5 73.6 (1) 73.4 (1)
Neutrophil count 70.9 71.1 (3) 70.8 (2)
Band count 69.1 68.7 (4) 69.2 (3)
Lactate 68.1 72.1 (2) 65.9 (5)
Renal function tests 67.2 67.2 (5) 67.1 (4)
Elements used to monitor resuscitation efforts in a child with severe sepsis‡
Heart rate 86.1 83.0 (1) 87.8 (1)
Mental status 84.6 79.7 (3) 87.3 (2)
Systolic blood pressure 84.4 81.5 (2) 86.0 (3)
 Diastolic blood pressure 80.8 76.5 (4) 82.9 (5)
Peripheral capillary refill 79.6 73.3 (5) 83.0 (4)

Values are reported as score (rank). Italic type indicates rank difference ≥ 2 between PERC and AAP-SOEM.
*Clinical elements evaluated included temperature change, tachycardia, tachypnea, hypotension, wide pulse pressure, peripheral
capillary refill, central capillary refill, reported urine output, measure urine output, mental status, and core:peripheral temperature
difference.
†Laboratory elements evaluated included venous gas, arterial gas, capillary gas, anion gap, leukocyte count, neutrophil count,
band count, lactate, procalcitonin, erythrocyte sedimentation rate, C-reactive protein, interleukin-6, renal function tests, hepatic
enzyme/function tests, and coagulation tests.
‡Monitoring elements included heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, mental status,
peripheral capillary refill, central capillary refill, measured urine output, venous gas, arterial gas, capillary gas, hemoglobin, anion
gap, serial lactate, serial procalcitonin, central venous pressure, central venous oxygenation, cardiac ultrasound/echo, and cardiac
index.

Figure 1.

Utilization of clinical signs and symptoms for the recognition of a child with sepsis. U/O = urine output; C:P Temp = central to
peripheral temperature difference.

Figure 2.
Utilization of laboratory investigations for the recognition of a child with sepsis. CRP = C-reactive protein; ESR = erythrocyte
sedimentation rate; IL-6 = interleukin 6; LFTS = liver function tests; RFTs = renal function tests; WBC = white blood cell count.

Figure 3.

Variables used to monitor resuscitation efforts in a child with severe sepsis. CCF = central capillary refill time; CVP = central
venous pressure; DBP = diastolic blood pressure; MAP = mean arterial pressure; PCF = peripheral capillary refill time; SBP =
systolic blood pressure; ScVO2 = central venous oxygenation; US = ultrasound.

describes strategies reported in the management of a child presenting with fluid-resistant sepsis. The most frequently reported
procedures included urinary catheterization (RS = 69), endotracheal intubation (RS = 41.5), and intraosseous insertion (RS =
35.5). Respondents most commonly reported using normal saline over Ringer's lactate for fluid resuscitation. Dopamine,
epinephrine, and norepinephrine were the most commonly reported vasoactive medications (VAM) used in septic shock. Reported
steroid administration strategies were variable; >50% of physicians reported using steroids in children with previous chronic steroid
use and in fluid and VAM-resistant shock.

Table 3. Strategies Used in the Management of the Child with Septic Shock

n (%)
Procedures
Intraosseous insertion 150 (35.5)
Central venous line insertion 71 (16.8)
Arterial line insertion 19 (4.5)
Urinary catheter insertion 291 (69.0)
Vascular cutdown 4 (0.9)
Endotracheal intubation 175 (41.5)
Fluids
0.9% sodium chloride bolus 361 (85.5)
Ringer's lactate bolus 6 (1.4)
Vasoactive medications*
Cold shock, first line
Dopamine 241 (57.1)
Epinephrine 78 (18.5)
Cold shock, second line
Epinephrine 174 (41.2)
Norepinephrine 54 (12.8)
Warm shock, first line
Dopamine 178 (42.2)
Norepinephrine 106 (25.1)
 Warm shock, second line
Norepinephrine 122 (28.9)
Epinephrine 102 (24.2)
Steroids
All patients with septic shock 16 (3.8)
Fluid resistant septic shock 62 (14.7)
Fluid and VAM-resistant septic shock 230 (54.5)
Chronic steroid use 304 (72.0)
Immunosuppressed 147 (34.8)

VAM = vasoactive medication.

*Choice from dopamine, dobutamine, epinephrine, norepinephrine, vasopressin, milrinone, and other.

Priorities for clinical resources development, education, and research are reported in . Respondents ranked the development of
clinical pathways (RS = 65.1), guidelines (RS = 61.0), and tools for early recognition (RS = 60.5) as top priorities within each of
these categories.

Table 4. Top Five Perceived Priorities for Clinical Resource Development, Education, and Research in Pediatric Sepsis

Score
Clinical resource development
ED specific pathways/protocols 65.1
ED screening tools 61.3
Standardized order sets 46.1
Standardized ED documentation 37.9
Standardized transfer documents 22.5
Education development
National emergency medicine guidelines 61.0
Review articles 49.1
Human patient simulation scenarios 43.5
Sepsis websites 31.3
Continuing medical education courses 30.6
Research priorities
Clinical markers for early recognition 60.5
Biomarkers for early recognition 48.2
Resuscitation monitoring goals 41.8
Outcome measures 35.0
Role of echocardiography/ultrasound 14.5

ED = emergency department.

Discussion

The ED is often the point of first contact for children with sepsis and septic shock. Although there have been improvements in
patient outcomes over the last several decades, pediatric sepsis continues to result in significant morbidity, mortality, and health
care–related expenditures. As such, clinicians practicing in the ED must be prepared to quickly identify and manage a child
presenting with sepsis. In this study, we describe current practice patterns and identify priorities for future knowledge translation
and research strategies based on survey responses from members of two national pediatric EM organizations. Our results
demonstrate that, while many clinicians reported feeling comfortable managing a child with sepsis, there is variation in the
strategies used for identifying, managing, and monitoring these children in the ED. This wide variability in practice demonstrates
the need for identifying strategies to drive more timely recognition of children with suspected septic shock, as well as replicable
practices for improving patient outcomes. Similar variations in practice have been described after surveys of adult clinicians.[19,20]

One of the most significant challenges in pediatric sepsis remains identification in the clinical setting. We have found that clinicians
continue to rely heavily on clinical signs and symptoms to identify children with sepsis and severe sepsis. Our results have shown
that vital sign changes, mental status changes, and perfusion changes were most often used for the identification of the septic
child. These results are in keeping with the current American College of Critical Care Medicine (ACCM) recommendations for the
diagnosis of sepsis, which includes a suspicion of infection (temperature abnormality) and signs of inadequate tissue perfusion.[6]
Thompson et al. recently demonstrated that children with one or more changes in vital signs (temperature > 39°C, tachycardia,
SpO2 ≤ 94%) or prolonged capillary refill were significantly more likely to have intermediate or serious infection than those with
minor or no infection.[21] While many clinicians rely on tachycardia as a sign of potential sepsis, heart rates in the ED can easily be
elevated due to fear, pain, and fever. As a result, recent studies have focused on adjusting heart rate for temperature.[22,23] While
some institutions have implemented screening tools based on temperature-adjusted tachycardia, there is some suggestion that
temperature adjustment does not improve upon the accuracy of tachycardia alone.[16,22]

RS for the top five laboratory investigations most commonly used in recognizing sepsis (range 67.2 to 73.5) were lower than those
for clinical signs and symptoms (range 76.7 to 83.7). This is in keeping with the current ACCM practice parameter that
recommends using clinical examination for early recognition of sepsis/septic shock over biochemical tests.[6] Overall, the most
commonly used laboratory investigations reported by our population centered around the measuring levels of circulating infection-
fighting cells, white blood cells, neutrophils, and band counts. Lactate, a measure of tissue perfusion, was also commonly used. RS
for lactate measurement differed between the two national organizations in our population; PERC members reported using lactate
significantly more often than AAP-SOEM members, ranking it second, only slightly behind white blood cell count. Studies in adults
presenting with sepsis have demonstrated that elevated initial lactates and delayed lactate clearance is related to poor outcomes.
[24–27]
Until recently, there has been a paucity of pediatric literature to support its use. Studies by Scott et al. and Reed et al. have
now demonstrated that children with elevated lactate have increased risk of hospitalization, organ dysfunction, critical illness, and
resource consumption.[7,8] Of note, two members of the ACCCM practice parameter team suggested that lactate should be
included in the early diagnosis of septic shock. Further studies looking at the use of lactate for the identification of the septic child
as well as outcome prediction are warranted.

The current ACCCM recommendations for managing sepsis/septic shock include early fluid resuscitation with crystalloid (level II
evidence), followed by initiation of vasoactive medications (first line: dopamine or epinephrine, second line: epinephrine for cold
shock and norepinephrine for warm shock; level II evidence) and hydrocortisone for those with risk of adrenal insufficiency/adrenal-
pituitary axis failure (level III evidence).[6] The vast majority of our study population reported initiating fluid resuscitation with normal
saline; very few reported the use of Ringer's lactate or albumin. VAM and steroid use was certainly more variable within our
population. This again may be related to the limited number of studies that directly compare VAM and steroid-management
strategies in the septic pediatric population.[6,28–30]

In our study, clinicians caring for septic children identified that standardizing care through the use of department-specific pathways,
screening tools, and national EM guidelines was of high priority. Several of these strategies are already taking hold. Cruz et al.,
Larsen et al., and Paul et al. have reported success in improving hospital metrics that relate to patient outcomes after local
implementation of sepsis guidelines.[16,17,31] The AAP-SOEM has established a sepsis collaborative, implementing pathways at
multiple sites across the United States. The state of New York has created legislation related to screening children for sepsis, and
the Canadian Association of Pediatric Health Centres is developing a screening tool to implement nationwide. Additional local and
national initiatives should be explored by clinicians, educators, and administrators in order to optimize patient outcomes. Future
research priorities, as identified by our study population, should focus on improving the early identification of sepsis and septic
shock (through clinical markers and biomarkers), therapeutic endpoints, and outcome measures.

Limitations

As in the majority of survey studies, the primary limitation of our results is generalizability due to selection bias, mostly related to
response rate. Web-based survey studies are prone to self-selection bias, with respondents more likely to be interested/invested in
the topic or in research itself. We sought the responses of two different national organizations (i.e., PERC and AAP-SOEM) in
order to improve generalizability. We recognize that the populations surveyed are more likely to have pediatric-specific training, be
employed at academic-affiliated hospitals, and participate in research and education initiatives, and the majority of children across
North America who present to the ED do so at their local community-based hospital. As such, we invited responses from clinicians
employed at a variety of hospital sizes and types, although the number of respondents was small. Future studies targeting general
ED providers are certainly warranted. Finally, we did not included infants aged 0 to 3 months, as these children are often
diagnosed and managed according to separate guidelines.

Conclusions

We have demonstrated that, despite the recognition that variability exists among clinicians, emergency physicians caring for
children continue to rely heavily on clinical metrics for recognizing and monitoring sepsis, with particular attention to altered vital
signs and mental status changes. Priorities of pediatric EM providers in the care of the child with suspected sepsis relate to
improved early recognition through clinical biomarkers of disease and standardization of care. The results of this study provide a
strong framework upon which administrators, researchers, and educators can base future strategic planning regarding pediatric
sepsis. As the majority of children across North America are managed outside of tertiary care pediatric EDs, an understanding of
perceived needs and resource availability at nontertiary environments may shed light on practice patterns, care capacities, and
outcomes in these settings.

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Acknowledgments
The authors thank the Pediatric Emergency Research Canada (PERC), the American Academy of Pediatrics, Section on
Emergency Medicine (AAP-SOEM), and the Center for Clinical Effectiveness (Baylor College of Medicine).

J Emerg Med. 2015;49(4):391-399. © 2015 Elsevier Science, Inc.

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