April 2021 - Pediatric Emergency Care

ORIGINAL ARTICLE
Evaluation of a Focused Cardiac Ultrasound Protocol

in a Pediatric Emergency Department
Antonio Riera, MD,*‡ Bevin Weeks, MD,†‡ Beth L. Emerson, MD,*‡ and Lei Chen, MD, MPH*‡
FoCUS can facilitate a targeted, more precise approach to

Objectives: The objective of this study was to evaluate the implementa- critically ill patients.7 Literature on the use of FoCUS in children
tion of a focused cardiac ultrasound (FoCUS) protocol in a pediatric emer- is limited. Case reports have described the value of FoCUS in
gency department (PED). the diagnosis of dilated cardiomyopathy and cardiac tamponade
Methods: We conducted a cross-sectional, observational, quality im- in the pediatric emergency department (PED).8,9 Pediatric emergency
provement project in a PED of an urban tertiary care children's hospital. medicine physicians undergoing goal-directed training can accurately
A FoCUS protocol was collaboratively developed by pediatric cardiology diagnose systolic dysfunction and pericardial effusion.10,11 Pediatric
and pediatric emergency medicine. This included a reference document emergency medicine programs should seek ways to effectively in-
with definitions, indications, image acquisition guidelines, and interpreta- tegrate this vital POCUS application throughout their department.
tion expectations. We measured physician-sonographer performance against In a collaboration between the sections of pediatric cardiol-
pediatric cardiologist interpretation of stored cine clips as our reference ogy and PEM, we designed and implemented a FoCUS protocol
standard. Focused cardiac ultrasound interpretation was dichotomized for at our institution with a quality assurance review process. Our
the presence or absence of pericardial effusion, depressed left ventricular FoCUS protocol established appropriate indications for use
function, and chamber size abnormalities. Run charts were used to com- and provided trainees with a standardized approach for image
pare the number FoCUS performed each month and the quality of captured acquisition and interpretation. The year before this intervention
cine clips with those from the previous year. 14 total FoCUS examinations were performed by 8 different
Results: Ninety-two FoCUSs were performed by 34 different physician- physician-sonographers in the PED. Of these, 44% of the cine
sonographers from January to December 2016. The prevalence of FoCUS clips reviewed were adequate in quality. To our knowledge, we
abnormalities was 18.5%. For pericardial effusion, sensitivity was 100% present the first investigation that has assessed a department wide
(95% confidence interval [CI], 48%–100%) and specificity was 99% (95% implementation and performance of a FoCUS protocol in a PED.
CI, 94%–100%). For depressed function, sensitivity was 100% (95% CI, We hypothesized that the adoption and implementation of
54%–100%) and specificity was 99% (95% CI, 94%–100%). For chamber a FoCUS protocol would increase the number of these studies
size abnormalities, sensitivity was 100% (95% CI, 54%–100%) and performed in our department. We aimed to measure physician-
specificity was 95% (95% CI, 89%–99%). The median number of monthly sonographer performance for the diagnosis of pericardial effusion,
FoCUS increased from 1 (preprotocol) to 5 (postprotocol), and the median qualitatively depressed left ventricular function, and chamber size
rate of adequate studies increased from 0% to 55%. abnormalities. We sought to increase the adequacy of recorded
Conclusions: We report the collaborative development and successful cine clips and measure adherence to the protocol instructions.
implementation of a PED FoCUS protocol. Physician-sonographer inter- Our project intended to promote timely care and reduce time to
pretation of FoCUS yielded acceptable results. Improvements in FoCUS imaging in cases of possible life-threatening illness by fostering
utilization and cine clip adequacy were observed. the use of a screening examination by physician-sonographers.
Key Words: ultrasound, focused cardiac ultrasound, quality improvement
(Pediatr Emer Care 2021;37: 191–198)
METHODS
F ocused cardiac ultrasound (FoCUS) aims to gather essential
time-sensitive information to diagnose pericardial effusion,
global cardiac function, and relative chamber size in symptomatic
Study Design
patients.1 Core FoCUS applications are considered a minimum This was a cross-sectional, observational study performed to
standard for emergency medicine,2 competency training, and pro- evaluate a quality improvement initiative in our PED. The ini-
gram accreditation.2,3 In 2013, consensus educational guidelines tiative met established criteria for a clinical quality improve-
were developed for focused cardiovascular applications pertinent ment project and was exempt from review by our institutional
to pediatric emergency medicine (PEM).4 The 2015 American review board.
Academy of Pediatrics policy statement and technical report
affirmed the importance of adequate training for PEM programs
in point-of-care ultrasonography (POCUS).5,6 Setting and Study Population
We performed this project in an urban PED with roughly
35,000 annual patient visits at an academic tertiary care children's
From the *Pediatric Emergency Medicine, †Pediatric Cardiology, Yale School
of Medicine, Yale University; and ‡Yale New Haven Children's Hospital,
hospital between January 2016 and December 2016. Comparison
New Haven, CT. data before FoCUS protocol adoption were obtained from January
Disclosure: The authors declare no conflict of interest. 2015 to December 2015. We evaluated data from a convenience
Reprints: Antonio Riera, MD, Pediatric Emergency Medicine, Yale School of sample of PED patients up to 21 years old who underwent FoCUS
Medicine, Yale University, 100 York St, Suite 1F, New Haven, CT 06511
(e‐mail: antonio.riera@yale.edu).
at the discretion of treating physicians. Eligibility and inclusion
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. criteria were delineated in our FoCUS protocol document. No
ISSN: 0749-5161 exclusion criteria were defined.
Pediatric Emergency Care • Volume 37, Number 4, April 2021 www.pec-online.com 191
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Riera et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
FoCUS Protocol requested that consultation with the primary service occurs before
a FoCUS was performed. Information cards were provided to
Our protocol specified definitions, indications, image acqui- families. The cards explained the limited scope of the FoCUS
sition guidelines, interpretation expectations, and information re- examination goals, that the study was not billable to insurers, and
lated to quality assurance measures. It was prepared by the lead that a follow-up echocardiogram could be necessary.
investigator (PEM physician and director of the POCUS program)
and reviewed by the chief of pediatric cardiology. Consensus on Physician-Sonographer Training
indications was achieved by these 2 individuals. The protocol
was disseminated via email to both PEM and emergency medicine Participating PEM fellows received an introductory FoCUS
(EM) residency programs and made accessible online, and a copy didactic lecture and hands-on training early in their first fellow-
was kept in our PED. ship year. This was supplemented with dedicated FoCUS instruc-
Focused cardiac ultrasound indications included the follow- tion at a regional PEM and critical care POCUS conference in
ing: (1) patients with undifferentiated shock, (2) patients with September. Participation in a 4-week ultrasound rotation with
cardiopulmonary arrest and return of spontaneous circulation, our EM program is structured to occur during the early stages of
(3) patients with concern for a pericardial effusion (examples their second fellowship year. Participating EM residents have
provided), (4) patients with concern for a pulmonary embolus, integrated FoCUS education throughout training and frequently
(5) patients with unexplained dyspnea, and (6) patients with perform these scans on adult patients. Participating PEM attend-
exertional syncope. ings, when performing a FoCUS alone, had prior formal training
A complete FoCUS included the following views: (1) a experiences with FoCUS. When a FoCUS was performed by a
parasternal long axis (PSLA), (2) a parasternal short axis (PSSA) trainee, a PEM attending was present on shift to provide supervision.
at the papillary muscle level, (3) an apical 4-chamber (A4C), and The amount of POCUS experience and proficiency by supervis-
(4) a subxyphoid inferior vena cava (IVC) seen entering the right ing PEM attendings, however, was heterogeneous.
atrium in long axis. A reference document available to the sonog-
raphers had pictures with examples of each view, the correct probe Sonography and Cine Clip Reviews
positioning, and a corresponding image as it should appear on Focused cardiac ultrasounds were performed using the
the monitor. phased-array S4-2 transducer (4–2 MHz) of a Philips Sparq ultra-
The protocol described how quality control and oversight sound system (Philips, Bothell, Wash). Grayscale 2-dimensional
would be maintained. Any concern for an abnormal finding on images were obtained. Cine clip recordings were preset at 3 seconds.
FoCUS triggered consultation with pediatric cardiology. A com- Acquired clips were uploaded to a secure POCUS workflow server
prehensive echocardiogram was performed at the discretion of where physicians could document their FoCUS interpretations
the consultant. For stable established cardiology patients, it was using a templated worksheet. All studies were reviewed by a
FIGURE 1. Key driver diagram for implementation of a FoCUS protocol.
192 www.pec-online.com © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Evaluation of a FoCUS Protocol in a PED
pediatric cardiologist who was blinded to physician-sonographer interval [CI], 12–611), and the negative LR was 0 (95% CI,
findings. A brief clinical history that included the patient's age, 0.01–1.20). For depressed function, FoCUS had a positive LR of
sex, pertinent physical examination findings, and the FoCUS indi- 86 (95% CI, 12–604), and the negative LR was 0 (95% CI,
cation was provided. 0.01–1.05). For chamber size abnormalities, FoCUS had a posi-
tive LR of 22 (95% CI, 8–60), and the negative LR was 0 (95%
Data Analysis CI, 0.01–1.09). Overall test characteristics and subgroup analysis
Physician-sonographer FoCUS assessments at the time of the of cases with follow-up echocardiograms are shown in Table 2.
patient care encounter were compared with pediatric cardiologist Adequate cine clips (80%) were most commonly recorded on
interpretation of the recorded cine clips. The cardiologist's assess- the PSLA view (91%), whereas limited clips (20%) were most
ment for effusion, global function, and chamber size abnormali- commonly recorded on the A4C view (40%). Cine clip categoriza-
ties was defined as our reference standard. Interpretation of the tion by view is provided in Table 3. The interrater reliability of clip
3 main components of FoCUS were dichotomized as follows: categorization as either adequate or limited between POCUS di-
(1) a pericardial effusion was present or absent, (2) the qualitative rector, and pediatric cardiologist was very good (κ = 0.90; 95%
left ventricular function was normal or depressed, and (3) the rel- CI, 0.71–1.0) with 95% agreement.
ative chamber sizes were normal or abnormal. Test characteristics A shift in the median number of FoCUS performed by month
and likelihood ratios (LRs) were calculated. These calculations from 1 to 5 was observed. This is calculated based on 8 sequential
were performed using an online MedCalc statistical software.12,13 data points (January 2016 to August 2016), all above the baseline
Each recorded PSLA, PSSA, and A4C video clip was inde- median from the preceding year in 2015 (Fig. 2). When compared
pendently inspected by the lead investigator and classified as with the previous year, an improvement in the median rate of
adequate or limited. Cine clips were classified as adequate when adequate cine clips obtained by month was observed from
all 3 of the following criteria were met: (1) the anatomy was re- 0% to 55%. Improvements were observed across each cardiac
corded in the orientation outlined by the reference document; view. The median adequate PSLA improved from 0% to 100%
(2) the depth setting maximized and centered key structures on (Fig. 3). The median adequate PSSA improved from 0% to
the monitor; and (3) the gain level used did not create cine clips 80% (Fig. 4). The median adequate A4C improved from 0%
that were too bright or too dark. A subset of cine clips was
rated in this same fashion by our study's pediatric cardiologist.
The interrater reliability of this assessment was tested with TABLE 1. Demographic Data
Cohen's κ coefficient.
Study Population N = 92
Quality Improvement Measures
FoCUS indications
To improve FoCUS utilization in our PED, we aimed to
Concern for pericardial effusion 46 (50%)
double the number of scans performed over the course of
12 months compared with the previous year. An additional goal Unexplained dyspnea 21 (23%)
was to increase the overall quality of cine clips obtained by Concern for pulmonary embolus 11 (12%)
physician-sonographers. A structured improvement roadmap Undifferentiated shock 8 (9%)
was developed (Fig. 1). Interventions leveraged towards these Cardiopulmonary arrest* 2 (2%)
aims included “buy-in” from pediatric cardiology, process stan- Exertional syncope 1 (1%)
dardization for trainees, timely review of cases with ongoing feed- Other (eg, vasovagal syncope) 3 (3%)
back, and accessibility to the FoCUS protocol document. Baseline Sex of patient
parameters were established by review of cine clips stored in our Male 49 (53%)
POCUS server from January to December 2015. Documentation Female 43 (47%)
of physician-sonographer FoCUS assessments during 2015 was
Age of patient
not consistently available to allow for comparison of cine clip
interpretation test characteristics before and after the protocol 0–2 mo 3 (3%)
roll-out. Metrics tracked throughout the implementation period 2–12 mo 3 (3%)
included FoCUS compliance with protocol indications and adher- 1–3 y 6 (7%)
ence to image acquisition guidelines. Medical record review was 4–12 y 20 (22%)
performed to track cardiology consultations, echocardiogram re- 13–21 y 60 (65%)
sults, and patient disposition and ensure that appropriate follow- Physician-sonographer level of training
up care was obtained. Performance on key quality measures was EM-1 4 (4%)
tracked using run charts, and standard run chart rules were applied EM-2 24 (26%)
to demonstrate improvement.14 EM-3 11 (12%)
EM-4 4 (4%)
RESULTS PEM-1 12 (13%)
Ninety-two FoCUS examinations performed by 34 different PEM-2 18 (20%)
physicians were evaluated during our 1-year study period. Demo- PEM-3 13 (14%)
graphic information is listed in Table 1. The prevalence of abnor-
PEM attending 6 (7%)
mal findings on FoCUS was 18.5%. There were 13 patients with
abnormal findings on FoCUS. These consisted of 5 cases of peri- Preexisting heart condition
cardial effusion (5.4%), 6 cases of depressed function (6.5%), and Yes 12 (13%)
6 cases of chamber size abnormalities (6.5%). In 2 patients, the No 80 (87%)
FoCUS concurrently revealed a pericardial effusion, depressed *Patients evaluated for cardiac standstill with a single view during
function, and a chamber size abnormality. For detection of pericar- cardiopulmonary resuscitation were not analyzed.
dial effusion, FoCUS had a positive LR of 87 (95% confidence
© 2018 Wolters Kluwer Health, Inc. All rights reserved. www.pec-online.com 193

TABLE 2. Overall Performance of FoCUS and Comparison With 24-Hour Follow-up Echocardiogram
N = 92 Cardiologist + Cardiologist − Test Characteristics % (CI)

Pericardial effusion
FoCUS + 5 1 Sensitivity | specificity 100 (48–100) | 99 (94–100)
FoCUS − 0 86 NPV | PPV 100 | 83 (42–97)
Depressed function
FoCUS − 0 85 NPV | PPV 100 | 86 (46–98)
Abnormal chamber size
FoCUS − 0 82 NPV | PPV 100 | 60 (37–80)
N = 23 Echo Report + Echo Report − Test Characteristics % (CI)
Pericardial effusion
FoCUS − 0 18 NPV | PPV 100 | 100
Depressed function
FoCUS − 0 17 NPV | PPV 100 | 100
Abnormal chamber size
FoCUS − 0 18 NPV | PPV 100 | 80 (37–96)
NPV indicates negative predictive value; PPV, positive predictive value.
to 50% (Fig. 5). These improvements over time were evident using A complete FoCUS with 3 cardiac views plus IVC assessment
standard run chart rules. occurred 61% of the time. Findings were documented by the
Overall adherence to protocol indications was high at 97%. physician-sonographer before the end of shift in 92% of cases.
Protocol deviations included a 16-year-old female with vasova- In all 7 cases with documentation omissions, the physician-
gal syncope, a 15-year-old female with costochondritis, and a sonographer was contacted by the lead investigator and cine clip
10-year-old girl with a murmur and a fixed split S2 on heart ex- interpretations were recorded before review by our pediatric cardi-
amination. This latter patient had been referred to our PED to ologist. Patients with preexisting heart conditions included cases
get intravenous fluid therapy for gastroenteritis symptoms. The of patent ductus arteriosus, mitral valve insufficiency, pulmonary
FoCUS revealed a markedly enlarged right ventricle and sug- valve insufficiency, hypertrophic cardiomyopathy, heart transplant,
gested that an atrial septal defect was present. The findings sub- hypoplastic left heart syndrome after surgical palliation, and 2 cases
sequently led to cardiology consultation, and the diagnosis was each of Duchenne muscular dystrophy, dilated cardiomyopathy,
confirmed with an echocardiogram performed as an outpatient. and tetralogy of Fallot after surgical repair. Cardiology consulta-
tion was performed in 52% of cases when a FoCUS was per-
formed. Follow-up echocardiograms performed within 24 hours
TABLE 3. Assessment of FoCUS Completeness and Cine Clip occurred 25% of the time and the admission rate for patients that
Adequacy received a FoCUS was 39%.
PSLA Window N = 92
Adequate 84 (91%) DISCUSSION
Limited 8 (23%) After the implementation of a FoCUS protocol that was
Omitted 0 collaboratively derived, physicians in our PED were observed
PSSA Window N = 89 to satisfactorily perform FoCUS studies and provide useful
Adequate 77 (87%) real-time interpretations. This adds to the existing body of litera-
Limited 12 (13%)
ture that has shown that focused pediatric echocardiography can
be accurately performed and interpreted by emergency physicians
Omitted 3
after receiving dedicated training.10,11,15 Our findings are unique
A4C Window N = 82 in that we did not evaluate the performance10,11,15 of individually
Adequate 49 (60%) trained physician-sonographers but rather the global training
Limited 33 (40%) received as part of the PEM fellow and EM residency
Omitted 10 POCUS curriculums.
IVC Window N = 65 In our study, FoCUS exhibited high specificity for the diag-
Adequate 54 (83%) nosis of pericardial effusion and depressed global function, with
Limited 11 (17%) narrow confidence intervals, making it an excellent test to rule in
Omitted 27 these conditions. Physician-sonographer assessment of chamber
size abnormalities exhibited similar performance, except for a

FIGURE 2. Number of FoCUS performed by month before and after protocol implementation.
notably lower positive predictive value. This finding coincides chambers can be compared in relation to one another.16 Obtaining
with the lowest adequate quality designation (60%) associated adequate A4C views may be a more operator-dependent as-
with the A4C view. The A4C is typically considered the most use- sessment that depends on patient positioning and the physician-
ful window to make chamber size determinations, as all 4 cardiac sonographer's level of skill and experience.
FIGURE 3. Parasternal long axis quality by month before and after protocol implementation.

FIGURE 4. Parasternal short axis quality by month before and after protocol implementation.
FIGURE 5. Apical 4-chamber quality by month before and after protocol implementation.

Findings related to protocol adherence will help inform Our study has several limitations. Individual goal-directed
future directions for our program. At the outset, we hoped that training before protocol roll-out was not done. The protocol was
setting indications for appropriate use would reach a concilia- integrated with regular clinical activities, and awareness of the
tory balance between clinical care needs and trainee education. practice change was raised at the outset. Our patient population
We planned to create appropriate indications so that patients was mainly adolescents with normal anatomy. There were few
with concerning cardiac complaints were candidates for FoCUS. cases of children younger than 12 months or with preexisting car-
Performing FoCUS when symptoms and physical examination were diac disease included for analysis, making our study findings less
consistent with more benign causes like gastroesophageal reflux, generalizable to infants or children with known congenital heart
costochondritis, and vasovagal syncope could lead to overutilization disease. In addition, we did not track cases where patients that
of resources and unnecessary testing. When our protocol was met FoCUS eligibility criteria did not have scans performed. We
applied to a 1-year convenience sample, the prevalence of abnor- also did not assess whether technical difficulties led to incomplete
mal findings was 18.5%. At this rate of pathology, the developed or aborted FoCUS scans. We acknowledge that our FoCUS
protocol indications seemed to generate an appropriate level of pathway may have impacted resource utilization, and we did not
FoCUS utilization. measure balancing metrics for its potential impact on interven-
A few poignant cases where our FoCUS pathway led to im- tions or costs. Review of annual trends with our pediatric cardiol-
proved patient care and staff education warrant further discussion. ogy division, however, did not reveal any measurable increase in
The first case was that of a 4-year old Nigerian girl who presented echocardiograms, PED consultation requests, or admissions.
with dyspnea. The parents reported cough, grunting noises, and Our test characteristic findings should be interpreted with
difficulty sleeping. At triage, the patient was categorized as a caution. The reference standard used was pediatric cardiologist
“work of breather,” and a nebulizer treatment was requested. On interpretation of a PEM or EM physician-sonographer FoCUS.
physical examination, she was found to have mild tachypnea, a Test characteristics may have been different if we had compared
heart murmur, lung crackles, and wheezing. Focused cardiac ultra- physician-sonographer FoCUS with a study obtained by a certified
sound performed 8 minutes after her triage found a pericardial echocardiogram technician or pediatric cardiologist. The wide
effusion, qualitatively depressed left ventricular function, a dilated sensitivity confidence intervals reflect the relatively low number
right atrium, and a plethoric IVC, as interpreted by the treating of positive findings. Of the 5 patients diagnosed with a pericardial
team. Pediatric cardiology was consulted immediately and subse- effusion, 1 had this finding on a prior echocardiogram. Of the
quently diagnosed mitral valve insufficiency secondary to rheumatic 6 patients diagnosed with depressed function, 3 had this finding
heart disease. The second case was a 13-year-old female with on a prior echocardiogram. Of the 6 patients diagnosed with
longstanding chest pain. She was transferred to our PED with a di- chamber size abnormalities, 3 had this finding on a prior echocar-
agnosis of pericarditis and a low voltage electrocardiogram. Her diogram. Physician-sonographer knowledge of these prior results
vital signs consisted of a fever to 38.1°C, a heart rate of 95 beats through our electronic medical record system could have biased
per minute, and a blood pressure of 107/47. On physical examination, their FoCUS interpretation. For FoCUS negative patients discharged
heart sounds were described as “muffled.” A FoCUS performed from our PED, medical record review did not reveal any missed
immediately after arrival revealed a large pericardial effusion as cases of pathology based on a subsequent ED visit or hospitaliza-
interpreted by the treating team. Pediatric cardiology and the tion at our same institution.
intensive care unit were notified immediately. She subsequently We did not assess the accuracy of physician-sonographer
underwent sedated pericardiocentesis, which aspirated close to evaluation of the IVC. Several methods have been described to es-
1 L of blood. This was felt to have been caused by an indolent timate volume status based on IVC measurements. Pediatric studies
accumulation of fluid after blunt trauma during a cheerleading have included different patient populations, transducer orientations,
injury several months before presentation. Finally, we report the modes of measurement, and locations where the IVC diameter was
case of a 2-week old who had a FoCUS performed after a cyanotic measured.17–20 Given this heterogeneity in the literature, we felt that
spell attributed as a possible brief resolved unexplained event. The a reliable reference standard measurement was more difficult to
FoCUS was interpreted by the treating team as having no signifi- define and would add to the complexity of the FoCUS protocol.
cant or abnormal findings. During the review session, our pediat- Because of these issues related to measurement certainty and
ric cardiologist pointed out the appearance of air bubbles seen in additional training requirements, we did not compare physician-
the left atrium on the PSLA view. The infant was getting a normal sonographer assessment with pediatric cardiologist interpretation
saline bolus at the time the FoCUS was performed. The patient of IVC volume status. We encouraged IVC assessment, however,
was found to have a small secundum atrial septal defect on echo- as this is an important POCUS skill to learn and considered
cardiogram. This layer of expertise allowed us to review our depart of the focused cardiovascular assessment in consensus
partmental protocols and perform reeducation related to filtering educational guidelines.4
intravenous lines in patients with congenital heart disease.
Goals for future improvement were identified. The first was
to attain a higher rate of complete FoCUS evaluations. Analysis CONCLUSIONS
of monthly trends over time did not reveal any improvement with We report the collaborative development and successful imple-
this metric. The omission of IVC windows may suggest either a mentation of a FoCUS protocol in a PED. Physician-sonographer
lack of familiarity or comfort level with this POCUS application. interpretation of FoCUS yielded acceptable results. Improvement
A second area was to increase the rate of adequate cine clip archiv- in FoCUS utilization and cine clip adequacy was observed.
ing, especially for the A4C view. One key driver for this process Pediatric emergency department programs should consider
may be hands-on instruction during clinical shifts. Dedicated collaborative implementation of FoCUS protocols tailored to
POCUS scanning shifts with real-time mentorship may increase trainee, patient care, and institutional needs.
the number of adequate scans. When real-time guidance is not
possible, timely cine clip review and feedback for physician-
sonographers are advisable. This quality assurance step ACKNOWLEDGMENTS
should identify individual areas for improving subsequent The authors thank Alan H. Friedman, MD, Professor of
FoCUS assessments. Pediatrics (Cardiology) and Chief of Pediatric Cardiology at

Yale-New Haven Children's Hospital, for his guidance and 10. Pershad J, Myers S, Plouman C, et al. Bedside limited echocardiography by
support with this project. the emergency physician is accurate during evaluation of the critically ill
patient. Pediatrics. 2004;114:e667–e671.
11. Longjohn M, Wan J, Joshi V, et al. Point-of-care echocardiography by
pediatric emergency physicians. Pediatr Emerg Care. 2011;27:693–696.
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ORIGINAL ARTICLE
Missed Diagnosis of Anaphylaxis in Patients With Pediatric

Urticaria in the Emergency Department
Woo Sung Jung, MD, Sun Hyu Kim, MD, PhD, and Hyeji Lee, MD
disseminated,7 they are subjective and symptom dependent. A

Objectives: This study was to determine the characteristics of missed single-objective diagnostic modality for anaphylaxis is still
diagnosis of pediatric anaphylaxis that were registered as urticaria only at lacking.8 Even if symptoms meet the diagnostic criteria, there is
the emergency department (ED) by comparing those who had only urticaria a possibility that a patient is registered simply according to their
symptoms with those who had both anaphylaxis and urticaria symptoms. symptoms, not as anaphylaxis, especially when there is cutaneous
Methods: Subjects were classified into missed anaphylaxis and urticaria symptom. This can eventually lead to diagnosis of simple urticaria
group according to whether satisfied anaphylaxis diagnostic criteria or not. or angiodedma.9 Because patients involved in previous studies
Anaphylaxis group, those who were initially registered as anaphylaxis with concerning prevalence of anaphylaxis are those who are only
urticaria and anaphylaxis symptoms simultaneously, were further investigated. registered as anaphylaxis, accurate diagnosis and registration are
Results: The missed anaphylaxis group included 37 patients of 1051 essential to obtain accurate prevalence data.
pediatric urticaria patients. The anaphylaxis group included 11 patients. Although most patients who come to ED with symptoms
The time from symptom onset to ED arrival in the missed anaphylaxis of urticarial have simple urticaria, some urticaria patients with
group was shorter than the urticaria group. More patients in the missed ana- partial symptoms of anaphylaxis should have been diagnosed as
phylaxis group had a history of past food allergy. Seafood, egg, and milk anaphylaxis. However, studies on characteristics of those falsely
were more common causes of allergy in the missed anaphylaxis group; diagnosed and registered patients are limited. Therefore, the
however, idiopathic causes were more common in the urticaria group. objective of this study is to determine the characteristics of missed
Symptom was more severe in the missed anaphylaxis group than the urti- diagnosis of anaphylaxis in pediatric patients who were registered
caria group. More treatments except antihistamine were performed at ED as urticaria only at ED by comparing those who had only urticaria
in the missed anaphylaxis group. Cardiovascular symptoms were more symptoms with those who had both anaphylaxis and urticarial
common in the anaphylaxis group than the missed anaphylaxis group. symptoms. Furthermore, missed diagnosis and correct diagnosis
Conclusions: Of all pediatric urticaria patients, 3.5% of patients were of anaphylaxis in pediatric urticaria patients were compared.
not registered as anaphylaxis although they had anaphylaxis symptoms.
Missed diagnosis of anaphylaxis in pediatric urticaria patients at ED was
associated with a history of past food allergy, milk, egg, and seafood as METHODS
causes of allergy, treated with fluid administration, steroid, and epinephrine. This retrospective study enrolled urticaria patients among
Key Words: anaphylaxis, urticaria, diagnosis a total of 28,792 pediatric patients who visited ED of a single
university hospital located in the southeast coast of South Korea
from January 2014 to December 2015. This study was reviewed
by our institutional review board.
U rticaria is one of the most frequent symptoms in the pediatric
emergency department (ED). It is also a common allergic
symptom along with rhinorrhea and asthma. The number of
According to International Statistical Classification of Dis-
ease and Related Health Problems-10, the following disease
classification codes were used to search urticaria patients:
patients who visit ED for symptoms of acute allergic reaction is
L28.2 (other prurigo, urticarial papulosa), L50.0 (allergic urti-
gradually increasing every year.1 The prevalence of anaphylaxis,
caria), L50.1 (idiopathic urticaria), L50.2 (urticaria due to cold
the most severe form of acute allergic reaction, is also increasing.
and heat), L50.3 (dermatographic urticaria), L50.4 (vibratory
Anaphylaxis also has various forms of symptoms, with a cutane-
urticaria), L50.5 (cholinergic uticaria), L50.6 (contact urticaria),
ous symptom being the most frequent one.2 Many studies have
L50.8 (other urticaria), and L50.9 (urticaria, unspecified). Medi-
been performed on the increasing prevalence of anaphylaxis.
cal records review was conducted for those who were registered
However, precise diagnosis of anaphylaxis is essential to obtain
with these disease classification codes. Those who failed to satisfy
an accurate result of its prevalence.3
the anaphylaxis diagnostic criteria were assigned to the urticaria
Clarifying the cause of anaphylaxis since the first attack is
group. Those who satisfied the anaphylaxis diagnostic criteria
very important because of its high prevalence in young children.4
were assigned to the missed anaphylaxis group. We also reviewed
In addition, most patients have a history of anaphylaxis.5 Because
patients registered as anaphylaxis. Those who had urticaria symp-
the frequency of ED visit due to pediatric anaphylaxis is in-
toms at the same time were classified into the anaphylaxis group.
creasing,6 prompt and precise diagnosis and treatment in ED are
As a result, all patients who were initially registered as anaphy-
crucial. Although definite diagnostic criteria of anaphylaxis are
laxis with urticaria symptom were included in the anaphylaxis
group (Fig. 1). Anaphylaxis diagnosis criteria written in world
allergy organization guidelines for assessment and management
From the Department of Emergency Medicine, University of Ulsan College of
Medicine, Ulsan University Hospital, Ulsan, Republic of Korea.
of anaphylaxis published in 2011 were used in this study.10
Disclosure: The authors declare no conflict of interest. General characteristics (age, sex, transport to ED, fever, recent
Reprints: Sun Hyu Kim, MD, PhD, Department of Emergency Medicine, Ulsan infection, history of allergy, and comorbidity), cause of urticaria,
University Hospital, University of Ulsan College of Medicine, 877 clinical characteristic, and treatment were collected. Fever was
Bangeojinsunhwando-ro, Dong-gu Ulsan 44033, Republic of Korea
(e‐mail: stachy1@paran.com).
defined as body temperature of 38°C or greater. Recent infection
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. was defined as sustaining fever longer than 1 day in recent
ISSN: 0749-5161 10 days. If the cause of urticaria was drug, it was subdivided into

Jung et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
FIGURE 1. Study subjects belonging to different groups.
nonsteroidal anti-inflammatory drug, penicillin, cephalosporin, Shock was defined as systolic blood pressure (SBP) of less than
and vaccination. In case of insect, it was subdivided into bee, 60 if the patient was between ages of 0 and 28 days, SBP of less
ant, etc. Food was subdivided into seafood, flour, buckwheat, pupa, than 70 if the patient was between the ages of 1 month and
nut, egg, beef, and milk/dairy product. For additional causes, 12 months, SBP of less than 70+ (age 2) if the patient was be-
exercise-induced, food-dependent exercise-induced, and idio- tween the ages of 1 year and 10 years, and SBP of less than 90 if
pathic were considered. Clinical characteristics included symp- the patient was older than 10 years.7 Treatment in ED included ox-
tom type, systemic symptom, symptom severity, blood pressure ygen (O2) supply, fluid administration, antihistamine use, steroid
at the time of ED visit, shock, and mental status. Symptom type use, epinephrine use, bronchodilator use, and diagnostic tests.
was defined as uniphasic (if the symptom happened briefly once), For comparison between the urticaria group and the missed
biphasic (if the symptom went away and came back shortly), and anaphylaxis group, univariate analysis was conducted using
protracted (if the symptom persisted for more than 1 day). Sys- χ2 test, Fisher exact test, Mann Whitney U test, and Student
temic symptom was subdivided into cutaneous, respiratory, car- t test. To identify factors affecting missed anaphylaxis, univariate
diovascular, gastrointestinal, and neurologic. Severity of allergic logistic regression analysis was performed. Using factors with
reaction was subdivided into the following 3 categories: mild (1 a P value of less than 0.05 from univariate analysis, multivariate
systemic symptom), moderate (2 or more systemic symptoms), logistic regression analysis was then performed using forward
and severe (shock, mental change, cardiac arrest, or apnea).11 method. For characteristic comparison between the missed
TABLE 1. General Characteristics of Patients With Urticaria or Missed Anaphylaxis
Urticaria (n = 1014) Missed Anaphylaxis (n = 37) P

Average age, y 3.9 ± 3.7* 4.1 ± 5.3* 0.772
Sex, male, % 562 (55.4) 18 (48.6) 0.501
Transportation to ED, % 0.000
Public ambulance 2 (0.2) 2 (5.4)
Individual transportation 1009 (99.5) 33 (89.2)
Other medical facility 3 (0.3) 2 (5.4)
Elapsed time from, min
Exposure to symptom onset 5 (0–90)† 10 (0–30)† 0.597
Symptom onset to ED arrival 240 (62.25–741)† 113 (38.5–360)† 0.014
History of allergy, % 205 (20.2) 16 (43.2) 0.001
Anaphylaxis 1 (0.1) 0 (0.0) 1.000
Asthma 12 (1.2) 1 (2.7) 0.374
Allergic rhinitis 32 (3.2) 1 (2.7) 1.000
Atopic dermatitis 71 (7.0) 2 (5.4) 1.000
Drug allergy 7 (0.7) 1 (2.7) 0.250
Food allergy 87 (8.6) 10 (27.0) 0.001
Comorbidity, % 25 (2.5) 2 (5.4) 0.245
Fever, % 78 (7.7) 5 (13.5) 0.206
Infection, % 159 (15.7) 6 (16.2) 0.930
*Mean ± standard deviation.
†
Median (interquartile range).

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Missed Anaphylaxis in Pediatric Urticaria
anaphylaxis group and the anaphylaxis group, univariate analysis

was performed using χ2 test, Fisher exact test, and Mann Whitney TABLE 3. Clinical Characteristics of Patients With Urticaria or
Missed Anaphylaxis
U test with factors of general character, clinical character, and
ED treatment. All data analyses were conducted using SPSS 21
Missed
(IBM Inc, Armonk, NY). Statistical significance was considered
Urticaria Anaphylaxis
at a P value of less than 0.05.
(n = 1014) (n = 37) P
Symptoms, %
RESULTS Cutaneous 1014 (100) 37 (100) NA
Of 1051 pediatric urticaria patients, 1014 (96.5%) belonged Respiratory 13 (1.3) 16 (43.2) 0.000
to the urticaria group whereas 37 (3.5%) were assigned to the Cardiovascular 1 (0.1) 0 (0.0) 1.000
missed anaphylaxis group. However, only 11 patients were origi- Gastrointestinal 24 (2.4) 24 (64.9) 0.000
nally registered to have anaphylaxis (Fig. 1). There was no differ- Neurologic 0 (0.0) 0 (0.0) NA
ence in age or sex between the urticaria group and the missed
Symptoms pattern 0.176
anaphylaxis group. Although most patients came to the ED using
their own transportation, more patients in the missed anaphylaxis Uniphasic 911 (89.8) 31 (83.8)
group used public ambulances or were transferred from other Biphasic 72 (7.1) 3 (8.1)
medical facilities. There was no significant difference in the time Protracted 31 (3.1) 3 (8.1)
from exposure to allergen to symptom onset between the 2 groups. Blood pressure, mm Hg
However, the time from symptom onset to ED arrival in the SBP 101 ± 9* 98 ± 19* 0.342
missed anaphylaxis group was shorter than that in the urticaria Diastolic blood pressure 64 ± 9* 61 ± 14* 0.145
group. Regarding allergic history, more patients in the missed Heart rate, beat/min 121 ± 27* 131 ± 33* 0.028
anaphylaxis group had a history of past food allergy (Table 1). Non-alert consciousness, % 1 (0.1) 0 (0.0) 1.000
Seafood, egg, and milk were more common causes of allergy Shock 0 (0.0) 0 (0.0) NA
in the missed anaphylaxis group. However, idiopathic causes were
Severity grade 0.000
more common in the urticaria group (48.2% vs 8.1%) (Table 2).
Respiratory and gastrointestinal symptoms were common in Mild 1001 (98.7) 0 (0.0)
the missed anaphylaxis group. Dominant symptom pattern was Moderate 13 (1.3) 37 (100)
uniphasic in both groups. There was no significant difference in Severe 0 (0.0) 0 (0.0)
blood pressures between the 2 groups. However, symptom sever- ED treatment, %
ity in the missed anaphylaxis group was all moderate, whereas O2 supply 0 (0.0) 1 (2.7) 0.035
mild severity was dominant in the urticaria group. Oxygen, fluid, Fluid administration 37 (3.6) 6 (16.2) 0.003
steroid, epinephrine, and bronchodilator were used more at Antihistamine use 997 (98.3) 34 (91.9) 0.030
ED in the missed anaphylaxis group. On the other hand, anti- Steroid use 140 (13.8) 13 (35.1) 0.000
histamine was used more in the urticarial group. Diagnostic Epinephrine use 12 (1.2) 4 (10.8) 0.002
tests such as complete blood count, eosinophil count, and total
Bronchodilator use 6 (0.6) 5 (13.5) 0.000
IgE were performed more often in the missed anaphylaxis
group (Table 3). Diagnostic tests, % 54 (5.3) 7 (18.9) 0.004
*Mean ± standard deviation.
NA indicates not available.
TABLE 2. Causes of Urticaria and Missed Anaphylaxis
Urticaria Missed Anaphylaxis Univariate logistic regression analysis was performed to iden-
(n = 1014) (n = 37) P tify factors affecting missed diagnosis of anaphylaxis in pediatric
Drug, % 46 (4.5) 3 (8.1) 0.246 urticaria patients at ED. Significant factors included past food
NSAIDs 7 (0.7) 1 (2.7) 0.250 allergy history, seafood, egg and milk as cause of allergy, heart
Penicillin 8 (0.8) 0 (0.0) 1.000
rate per minute, respiratory symptom, gastrointestinal symptom,
O2 supply, fluid administration, antihistamine use, steroid use,
Cephalosporin 6 (0.6) 0 (0.0) 1.000
epinephrine use, bronchodilator use, and diagnostic tests. After
Vaccine 6 (0.6) 1 (2.7) 0.222 excluding factors that might distort results because of too wide
Insect sting, % 6 (0.6) 0 (0.0) 1.000 confidence interval such as respiratory symptom, gastrointestinal
Food, % 237 (23.4) 31 (83.8) 0.000 symptom, and bronchodilator use, multivariate logistic regression
Seafood 44 (4.3) 5 (13.5) 0.025 analysis was performed using the rest of significant factors from
Wheat 24 (2.4) 1 (2.7) 0.596 univariate logistic regression analysis. Factors associated with
Buckwheat 1 (0.1) 1 (2.7) 0.069 missed diagnosis of anaphylaxis in pediatric urticaria patients
Pupa 1 (0.1) 0 (0.0) 1.000 were the following: past allergy history, seafood, egg and milk
Nut 11 (1.1) 1 (2.7) 0.351 as the cause of allergy, treatment with fluid administration, steroid,
Egg 36 (3.6) 4 (10.8) 0.048
and epinephrine. The odds ratio in case of antihistamine use was
0.198 (Table 4).
Pork 21 (2.1) 0 (0.0) 1.000
There was no difference in age or sex between the anaphy-
Cow milk 58 (5.7) 14 (37.8) 0.000 laxis group and the missed anaphylaxis group. However, an atopic
Idiopathic, % 489 (48.2) 3 (8.1) history was higher in the anaphylaxis group. Cardiovascular
NSAID indicates nonsteroidal anti-inflammatory drug. symptom was more common in the anaphylaxis group, where-
as gastrointestinal symptom was more common in the missed

Jung et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
organs of these patients. When they are exposed to milk, milk

TABLE 4. Risk Factors Associated With Missed Anaphylaxis allergy or anaphylaxis might have been triggered.16,19 Cutaneous,
respiratory, and gastrointestinal symptoms are frequently found to
Odds 95% Confidence
be associated with milk anaphylaxis.20 The severity of anaphy-
Ratio Interval P
laxis is more severe when it is accompanied by cardiovascular
Univariate logistic regression or neurologic symptoms.21 Because milk is easily and frequently
History of food allergy 3.946 1.849–8.422 0.000 exposed to children, clinicians need to pay more attention to pa-
Seafood, as allergen 3.445 1.280–9.268 0.014 tients with symptoms associated with milk.
Egg, as allergen 3.293 1.107–9.791 0.032 World allergy organization guidelines for the assessment and
management of anaphylaxis recommend that epinephrine should
Cow milk, as allergen 10.033 4.907–20.516 0.000
be injected intramuscularly immediately after anaphylaxis is diag-
Heart rate, beat/min 1.013 1.001–1.025 0.029 nosed.2,10 Although epinephrine is paramount in the treatment
Respiratory symptoms 58.667 25.077–137.247 0.000 of anaphylaxis, epinephrine is not always necessary for the treat-
Gastrointestinal symptoms 76.154 34.663–167.308 0.000 ment of anaphylaxis. A previous study has reported that although
Fluid administration 5.111 2.009–13.002 0.001 only 39% of adult patients have received epinephrine for anaphy-
Antihistamine use 0.193 0.054–0.691 0.011 laxis, 98% of ED treatment is appropriate for anaphylaxis.22 In
Steroid use 3.382 1.682–6.797 0.001 our study, only 10.8% of missed anaphylaxis group received
Epinephrine use 10.121 3.099–33.054 0.000 epinephrine. This might be due to lower severity in children com-
Bronchodilator use 26.250 7.612–90.519 0.000 pared with adults. There was no severe patient in the missed ana-
Diagnostic tests 4.148 1.743–9.873 0.001 phylaxis group. However, patients treated with fluid, steroid, and
epinephrine had higher possibility of having missed diagnosis of
Multivariate logistic regression
anaphylaxis compared with those who did not receive such treat-
History of food allergy 3.375 1.420–8.023 0.006 ment. Because epinephrine injection is the first-line treatment.
Seafood, as allergen 3.931 1.249–12.371 0.019 It is also an important index of care quality,23 and clinicians need
Egg, as allergen 4.387 1.305–14.746 0.017 to consider epinephrine injection when anaphylaxis is suspected.
Cow milk, as allergen 10.782 4.871–23.869 0.000 More cardiovascular symptoms were found in the anaphy-
Fluid administration 3.354 1.102–10.206 0.033 laxis group, whereas more gastrointestinal symptoms were present
Antihistamine use 0.198 0.047–0.824 0.026 in the missed anaphylaxis group. This means that we might need
Steroid use 2.672 1.224–5.832 0.014 to suspect anaphylaxis when patients have cardiovascular symp-
Epinephrine use 4.089 1.004–16.657 0.049 toms. We also need to suspect anaphylaxis when patients present
with gastrointestinal symptoms. Many pediatric patients often
have complaints of gastrointestinal symptoms such as abdominal
anaphylaxis group. Regarding treatment at ED, fluid adminis- pain, nausea, vomit, and diarrhea. Furthermore, many of those
tration, epinephrine use, bronchodilator use, and diagnostic tests complaints are idiopathic. Therefore, physicians in ED should
were used more often in the anaphylaxis group (Table 5). carefully interpret these symptoms and consider that these symp-
toms could be associated with anaphylaxis.
DISCUSSION
Results of this study showed that 3.5% of pediatric urticaria TABLE 5. Characteristics of Patients With Anaphylaxis or Missed
patients at the ED met the anaphylaxis diagnostic criteria. Accord- Anaphylaxis
ing to a previous study, approximately 4% of all ED visiting pa-
tients are anaphylaxis patients.6 Another study on clinical characters Missed
of anaphylaxis patients has reported that there are a substantial Anaphylaxis anaphylaxis
number of anaphylaxis patients among those who are diagnosed (n = 11) (n = 37) P
as urticaria or angioedema.12 If someone only analyzes patients Average age, y 6.6 ± 5.4* 4.1 ± 5.3* 0.104
who are registered as anaphylaxis, there must be unseen and Sex, male, % 5 (45.5) 18 (48.6) 0.852
missed anaphylaxis patients.13 Therefore, physicians at ED must History of atopic dermatitis, % 4 (36.4) 2 (5.4) 0.019
clearly understand the diagnostic criteria and precisely register Symptoms, % 0.000
disease classification codes. In addition, proper physical examina-
Cutaneous 11 (100) 37 (100) NA
tion is crucial along with careful history taking for patients with
risk factors. Respiratory 7 (63.6) 16 (43.2) 0.235
Food, hymenoptera stings (venom), and drugs are common Cardiovascular 5 (45.5) 0 (0.0) 0.000
causes of anaphylaxis in one study.9 Another study has shown that Gastrointestinal 2 (18.2) 24 (64.9) 0.006
milk, egg, and nut are common causes of anaphylaxis.14 Despite Neurologic 1 (9.1) 0 (0.0) 0.229
some differences in details, food was also the most common cause ED treatment, %
of anaphylaxis in the present study. Cow milk (37.8%), seafood Fluid administration 10 (90.9) 6 (16.2) 0.000
(13.5%), and egg (10.8%) were common causes of anaphylaxis Antihistamine use 10 (90.9) 34 (91.9) 1.000
in this study. This result was similar to that of a previous study Steroid use 7 (63.6) 13 (35.1) 0.162
showing that common causes of anaphylaxis are milk (28.4%), Epinephrine use 7 (63.6) 4 (10.8) 0.001
egg white (13.6%), nuts (13.2%), and seafood (7.2%).15 Milk,
Bronchodilator use 6 (54.5) 5 (13.5) 0.010
regardless of age, has been found to be the single most frequent
cause of anaphylaxis, accounting for 28.4% among all food Diagnostic tests, % 10 (90.9) 7 (18.9) 0.000
causes.15 The first anaphylactic attack due to milk mostly *Mean ± standard deviation.
(95.5%) happens to patients who are 1 year or younger.16–18 This NA indicates not available.
could be due to the immature immune system and gastrointestinal

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Missed Anaphylaxis in Pediatric Urticaria
This study only included patients who visited ED. Patients 8. Sclar DA, Lieberman PL. Anaphylaxis: underdiagnosed, underreported,
who visited outpatient department and those who had self-limiting and undertreated. Am J Med. 2014;127:S1–S5.
symptoms were not included in this study. Moreover, this study 9. Bohlke K, Davis RL, DeStefano F, et al. Epidemiology of anaphylaxis
was conducted in only 1 training hospital. The quality for registra- among children and adolescents enrolled in a health maintenance
tion of disease classification codes was not validated before. organization. J Allergy Clin Immunol. 2004;113:536–542.
Therefore, results of this study could not be generalized. Another 10. Simons FE, Ardusso LR, Bilò MB, et al. World allergy organization
limitation was that a high ratio of idiopathic cause of both urticaria guidelines for the assessment and management of anaphylaxis. World
and missed anaphylaxis group due to retrospective chart review. Allergy Organ J. 2011;4:13–37.
11. Brown SG. Clinical features and severity grading of anaphylaxis. J Allergy
CONCLUSIONS Clin Immunol. 2004;114:371–376.
Of all pediatric urticaria patients, 3.5% of patients were not
12. Roh EJ, Chung EH, Lee MH, et al. Clinical features of anaphylaxis in
registered as anaphylaxis although they had anaphylaxis symp-
the middle area of south korea. Pediatr Allergy Respir Dis. 2008;18:
toms. Missed diagnosis of anaphylaxis in pediatric urticaria
61–69.
patients at ED were associated with a history of food allergy with
milk, egg, and seafood as causes of allergy, treated with fluid 13. Simons FE, Sampson HA. Anaphylaxis epidemic: fact or fiction? J Allergy
administration, steroid use, and epinephrine use. Consideration Clin Immunol. 2008;122:1166–1168.
for whether the diagnosis of anaphylaxis is missed in pediatric 14. Lee S. IgE-mediated food allergies in children: prevalence, triggers, and
urticaria patients is necessary to obtain accurate prevalence data management. Korean J Pediatr. 2017;60:99–105.
of pediatric anaphylaxis. 15. Lee SY, Ahn K, Kim J, et al. A multicenter retrospective case study of
anaphylaxis triggers by age in korean children. Allergy Asthma Immunol
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ORIGINAL ARTICLE
Initial Characteristics and Clinical Severity of Hemophagocytic

Lymphohistiocytosis in Pediatric Patients Admitted in
the Emergency Department
Jeong-Yong Lee, MD,* Jung Heon Kim, MD,† Jong Seung Lee, MD,† Jeong-Min Ryu, MD, PhD,†
Jong Jin Seo, MD, PhD,* and Ho Joon Im, MD, PhD*
recognition of the disease and preparations for clinical deterioration

Objectives: The diagnosis and management of children with hemophagocytic may be important in the management in children admitted in the ED.
lymphohistiocytosis (HLH) admitted in the emergency department (ED) However, the diagnosis and management of pediatric pa-
are challenging. The present study aimed at describing the initial character- tients with HLH admitted in the ED are challenging. Pediatric pa-
istics of pediatric patients with HLH upon admission in the ED. Moreover, tients with HLH have various initial manifestations, which may
the clinical severity of the condition was assessed. mimic other clinical conditions, such as sepsis, fever of unknown
Methods: We performed a retrospective study of patients who visited the origin, or acute liver failure.2–4 Furthermore, the diagnosis of
pediatric ED and were newly diagnosed with HLH during hospitalization be- HLH is based on 5 clinical findings (HLH-2004 diagnostic
tween February 2012 and January 2017. The patients were classified in the clin- criteria). The criteria include impracticable laboratory tests (low/
ically unstable group if at least 1 of the following conditions was observed upon absent NK cell activity and elevated level of soluble CD25) and
admission in the ED: hypoxia requiring oxygen supplementation, hypotension a pathologic finding (hemophagocytosis in the bone marrow,
requiring inotropic support, coagulopathy with prothrombin time (international spleen, lymph node, or liver), which makes the diagnosis of pa-
normalized ratio, ≥1.5), and seizures or altered consciousness. tients with HLH who are admitted in the ED challenging.5 In ad-
Results: We enrolled 31 pediatric patients with HLH, with a median age dition, the clinical severity of pediatric patients with HLH who
of 6.53 years (interquartile range, 1.35–13.24 years). Abdominal discom- presented to ED could widely vary, ranging from clinically stable
fort along with fever (74.2%) was the most common presenting symptom to fatal conditions requiring immediate resuscitation.
in patients admitted in the ED. Based on the HLH-2004 diagnostic criteria, Identifying the initial symptoms of patients admitted in the
fever (96.8%), hyperferritinemia (96.8%), splenomegaly (74.2%), hypertri- ED may be important in the systematic approach of managing pe-
glyceridemia and/or hypofibrinogenemia (67.7%), and bicytopenia diatric patients with HLH. However, studies related to this are not
(41.9%) were observed in the patients. However, only 8 patients (25.8%) available. Therefore, the present study aimed at assessing the ini-
met the criteria. Nineteen patients (61.3%) were included in the clinically un- tial characteristics and clinical severity of HLH among pediatric
stable group. This group had lower albumin (2.3 vs 3.3 g/dL, P = 0.002) and patients admitted in the ED. We hypothesized that clinically unsta-
fibrinogen levels and higher ferritin level and neutrophil count than the clin- ble patients may show more distinguishable features than clini-
ically stable group. Meanwhile, the number of clinical findings that met the cally stable ones.
diagnostic criteria was not different between the 2 groups. Lower albumin
level was a significant risk factor in the clinically unstable group (odds ra-
tio, 0.040; P = 0.004). METHODS
Conclusions: Pediatric patients with HLH often have clinically unstable
conditions upon admission in the ED. However, only few patients meet the Study Design
HLH-2004 diagnostic criteria. Lower albumin level may be useful in assessing This retrospective study included children and adolescents
clinically unstable patients and preparing for possible deterioration. younger than 17 years who visited our pediatric ED and were
Key Words: hemophagocytic lymphohistiocytosis, serum albumin, newly diagnosed with HLH during their hospitalization between
severity February 2012 and January 2017. The final diagnosis of HLH
was based on the HLH-2004 diagnostic criteria.5 Our institution
(Pediatr Emer Care 2021;37: 204–207) is one of the largest tertiary university-affiliated hospitals located
in Seoul, Korea, which has a pediatric hemato-oncology depart-
H emophagocytic lymphohistiocytosis (HLH) is more common

in the pediatric population and a rare cause for visiting the
emergency department (ED). Both primary (genetic) and second-
ment and ED that provide care to approximately 35,000 children
annually. Patients were searched from our HLH registration sys-
tem, and data were collected by reviewing the electronic medical
ary HLH are commonly triggered by infection or other alterations in charts. This study was approved by our institutional review board.
immune homeostasis and would rapidly progress to a life-
threatening condition due to excessive immune activation.1,2 Early Patients
Among the 45 pediatric patients with HLH who were initially
From the Departments of *Pediatrics, and †Emergency Medicine, Asan Medi- searched, 14 were excluded. Moreover, 12 patients were trans-
cal Center, University of Ulsan College of Medicine. ferred from another hospital after the initiation of HLH-specific
Disclosure: The authors declare no conflict of interest.
Reprints: Ho Joon Im, MD, PhD, Department of Pediatrics, Asan Medical
treatment and 2 had possible HLH relapse.
Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, The patients were categorized into the clinically unstable or
Songpa-gu, Seoul 05505, Republic of Korea stable group. Patients admitted in the ED were classified in the
(e‐mail: hojim@amc.seoul.kr). clinically unstable group if at least 1 of the following conditions
This study was supported by a grant (2016-E63002-00) from Korea Centers for
Disease Control and Prevention.
was observed: (1) hypoxia (a decrease in peripheral oxygen satu-
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. ration of ≥5% from baseline) and administration of supplemental
ISSN: 0749-5161 oxygen, (2) hypotension (a significant decrease in blood pressure
204 www.pec-online.com Pediatric Emergency Care • Volume 37, Number 4, April 2021

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Pediatric HLH in the ED
or blood pressure below the fifth percentile for age with prolonged
capillary refill, decreased peripheral pulse, or tachycardia) requiring TABLE 1. Initial Characteristics of the Patients Upon Admission
in the ED (N = 31)
inotropic support, (3) coagulopathy with prothrombin time
(international normalized ratio, ≥1.5), and (4) seizures or
n (%) or
altered consciousness.
Characteristics Median (IQR)
Data Analysis Age, y 6.53 (1.35–13.24)
The following patient data were collected: (1) general charac- Males 13/31 (41.9%)
teristics (age and sex); (2) presenting signs (body temperature, periph- Presenting symptoms with fever
eral oxygen saturation, blood pressure, pulse rate, splenomegaly, and Abdominal discomfort 23/31 (74.2%)
conscious state) and symptoms (fever, abdominal distension or pain, Abdominal distension (<3 y) 11/12 (91.7%)
rash, enlarged lymph node, generalized pain, and seizure) in the ED; Abdominal pain (≥3 y) 10/19 (52.6%)
(3) initial laboratory data in the ED (hemoglobin, triglyceride, fibrin- Rash 11/31 (35.5%)
ogen, ferritin, and albumin level; blood leukocyte, neutrophil, and Enlarged lymph node 9/31 (29.0%)
platelet count; and prothrombin time); and (4) supportive care
Generalized pain 4/31 (12.9%)
provided in the ED (oxygen supplementation or inotropic sup-
port), transfer to the intensive care unit (ICU) from ED, and sur- 5 Findings included in the HLH-2004
diagnostic criteria
vival after initial therapy for HLH. The 5 signs and symptoms
included in the HLH-2004 diagnostic criteria were as follows: fe- Fever 30/31 (96.8%)
ver, splenomegaly, bicytopenia, hyperferritinemia, and hypertri- Splenomegaly 23/31 (74.2%)
glyceridemia and/or hypofibrinogenemia.5 Each number of Peripheral blood cytopenia 13/31 (41.9%)
clinical findings that met the criteria was considered. (affecting ≥2 of 3 lineages)
Data were presented as percentage or median with interquar- Hemoglobin <9 g/dL 7/31 (22.6%)
tile range (IQR). The K-sample median test was used to compare Neutrophils <1000/μL 9/31 (29.0%)
the continuous variables of the clinically unstable and stable Platelets <100,000/μL 25/31 (80.6%)
groups. Risk factor analysis of the clinically unstable group was Hypertriglyceridemia and/or 21/31 (67.7%)
conducted using univariate and multivariate logistic regression hypofibrinogenemia
models (forward method). P < 0.05 was considered statistically Triglycerides >265 mg/dL 13/31 (41.9%)
significant. All statistical analyses were performed using SPSS Fibrinogen <150 mg/dL 19/31 (61.3%)
software 20.0 (SPSS Inc, Chicago, Ill). Ferritin >500 μg/L 30/31 (96.8%)
RESULTS No. findings satisfying the diagnostic criteria 4 (3–5)
≤3 findings 12/31 (38.7%)
Initial Characteristics of Pediatric Patients With 4 findings 11/31 (35.5%)
HLH Upon Admission in the ED 5 findings 8/31 (25.8%)
Clinically unstable group 19/31 (61.3%)
We enrolled 31 pediatric patients with HLH with a median
age of 6.53 years (IQR, 1.35–13.24 years). The initial characteris- Hypoxia and oxygen supplement 12/31 (38.7%)
tics of patients upon admission in the ED included the presenting Hypotension requiring inotropic support 6/31 (19.4%)
symptoms and findings included in the HLH-2004 diagnostic Coagulopathy with prothrombin time (INR) ≥1.5 11/31 (35.5%)
criteria (Table 1). Seizure or altered consciousness 4/31 (12.9%)
First, all patients (96.8%) except 1 had fever, and the median Admission to intensive care unit 14/31 (45.2%)
days of fever before admission in the ED visit was 7 days Directly from ED 12/31 (38.7%)
(IQR, 5–8 days). Abdominal discomfort with fever (74.2%) During hospitalization 2/31 (6.5%)
was the common presenting symptom of patients upon admission Expired during initial therapy for HLH 3/31 (9.7%)
in the ED. Abdominal discomfort was characterized by abdominal
pain or distension. Abdominal distension was specifically com- INR indicates international normalized ratio.
mon in patients younger than 3 years (11/12), whereas abdominal
pain was common in patients 3 years and younger (10/19). In
addition, rash (35.5%) or enlarged lymph nodes (29.0%) patients (45.2%) were eventually treated in ICU, and 3 patients
were observed. (9.7%) from the clinically unstable group died during the initial
With regard to the 5 signs and symptoms included in the therapy for HLH in the ED (Table 1).
HLH-2004 diagnostic criteria, fever (96.8%), hyperferritinemia Clinical and laboratory findings of the clinically unstable
(96.8%), splenomegaly (74.2%), hypertriglyceridemia and/or group (19 patients, 61.3%) and the stable group (12 patients,
hypofibrinogenemia (67.7%), and bicytopenia (41.9%) were 38.7%) were compared (Table 2). The clinically unstable group
observed. Only 8 patients (25.8%) presented with the all the had significantly lower albumin (2.3 vs 3.3 g/dL, P = 0.002) and
signs and symptoms upon admission in the ED, whereas most fibrinogen levels and higher ferritin level and neutrophil count
of the patients did not. than the clinically stable group. However, the duration of fever be-
fore admission to ED, hemoglobin and triglyceride levels, and
Clinical Severity of Patients Upon Admission in the platelet count were not significant. The number of clinical find-
ED and Risk Factor Analysis ings that met the HLH-2004 diagnostic criteria between the 2
In total, 19 patients (61.3%) were classified in the clinically groups was not significantly different.
unstable group. Although the patients in this group presented with Risk factor analysis of the clinically unstable group was per-
multiorgan system deterioration, hypoxia was the most common formed using the variables that were different between the clini-
cause (12/19), followed by coagulopathy (11/19). Fourteen cally unstable and stable groups (Table 3). Lower albumin level

Lee et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
TABLE 2. Comparison Between the Clinically Unstable and Stable Groups
Variables Unstable Group (n = 19) Stable Group (n = 12) P

Age, y 5.93 (1.56–13.24) 6.68 (0.99–13.99) 0.715
Days of fever before ED visit 7 (5–8) 6.5 (5.25-8) 0.967
Hemoglobin, g/dL 10.9 (9.1–12.6) 11.7 (9.5–13.1) 0.417
Neutrophils, /μL 3970 (1250–6620) 1450 (411–1770) 0.013
Platelets, 103/μL 66 (21–104) 63 (40–80) 0.887
Triglycerides, mg/dL 271 (168–324) 197 (165–279) 0.301
Fibrinogen, mg/dL 95 (79–172) 167 (128–252) 0.023
Ferritin, μg/L 28040 (2766–60254) 3567 (1681–7171) 0.021
Albumin, g/dL 2.3 (2.1–2.6) 3.3 (2.5–3.4) 0.002
No. findings satisfying HLH-2004 diagnostic criteria 4 (3–5) 4 (3–4.75) 0.882
Data are presented as median (IQR).
was a significant risk factor for the clinically unstable group (odds defining the clinical severity of patients upon admission in the
ratio, 0.040; P = 0.004). Multivariate logistic regression analysis ED. In this study, most of the patients (74.2%) presented with less
(forward method) showed the same results because the variables than 5 signs and symptoms and did not meet the criteria upon ad-
other than albumin were not statistically significant in the mission in the ED. This result could be explained by the fact that
univariate analysis. the criteria contain tests that are difficult to conduct in the ED.
Moreover, patients may present with incomplete clinical features
DISCUSSION but are already in the early stage of HLH. Furthermore, the num-
ber of clinical findings that met the criteria was not different be-
This study investigated pediatric patients with HLH based on
tween the clinically unstable and stable groups, indicating that
the perspective of emergency physicians and demonstrated several
the use of the criteria did not help in identifying the clinical sever-
significant results. First, abdominal discomfort (74.2%) with fever
ity of the condition. Therefore, other effective tools for diagnosing
was the most common presenting symptom of patients admitted in
HLH or defining its clinical severity, such as a recently developed
the ED. Second, only 25.8% of the patients admitted in the ED met
scoring system referred to as HScore,10 should be used and its va-
the HLH diagnostic criteria, and this was not related to clinical
lidity in the ED settings must be investigated.
severity. Third, majority of the patients (61.3%) were clinically
Pediatric patients with HLH should be judiciously monitored
unstable upon admission in the ED, and lower albumin level
and managed because their condition often progresses to
could have been a risk factor.
multiorgan failure.1 We defined the clinically unstable group
Regarding the initial symptoms of pediatric patients with
using the criteria based on the deterioration of organ systems af-
HLH upon admission in the ED, abdominal discomfort is com-
fected by HLH. Our results showed that more than half of the pe-
mon, which may be related to hepatosplenomegaly. This symp-
diatric patients with HLH (61.3%) had clinically unstable
tom, which is a result of direct organ infiltration by the activated
conditions, particularly due to hypoxia (38.7%), during admis-
immune cells, is a cardinal sign of HLH2,6 and is more frequently
sion in the ED. Deteriorating pulmonary functions during admission
observed in pediatric patients.3,7 A previous HLH-94 study of
in the ED may indicate acute respiratory distress-like syndrome due
249 pediatric patients reported that hepatomegaly was observed
to HLH or may be a result of combined respiratory infections. Simi-
in 95% of these patients,8 and a multicenter study conducted in
larly, a previous study on adult patients with HLH showed that pul-
China showed that hepatomegaly and splenomegaly were ob-
monary involvement was frequent (42%), although its definition
served in 86.0% and 73.7% of their 323 pediatric patients with
included common symptoms, such cough, dyspnea, and respiratory
HLH, respectively.9 In our study, abdominal distension was prom-
failure. The laboratory findings of the clinically unstable group (neu-
inent in patients younger than 3 years having relatively small
trophil count and fibrinogen, ferritin, and albumin levels) were differ-
intra-abdominal space, whereas abdominal pain was frequent in
ent from those of the clinically stable group, and lower albumin level
patients 3 years and younger who could adequately express pain.
was considered as a significant risk factor in the clinically unstable
Although the HLH-2004 diagnostic criteria are commonly
group. Data on the factors associated with the clinical severity of
used in clinical practice, the use of the number of clinical findings
HLH among patients admitted in the ED are not available. Mean-
from the criteria may be inadequate in diagnosing HLH or
while, a recent study of 116 pediatric patients with HLH patients re-
ported that hypoalbuminemia (≤2.0 g/dL) upon diagnosis was one of
the risk factors associated with 30-day mortality.11 Hypoalbumin-
TABLE 3. Risk Factor Analysis of the Clinically Unstable Group emia is also observed in individuals with other diseases, including
liver diseases, which may result from a decrease in albumin synthe-
Variables OR (95% CI) P sis or increase in catabolism by IL-6 and other inflammatory cyto-
Neutrophils, 103/μL 1.678 (0.996–2.828) 0.052
kines.12 Excessive cytokine production is the main pathogenesis in
HLH, and this is considered as the cause of multiorgan failure and
Fibrinogen, mg/dL 0.991 (0.982–1.001) 0.065
mortality.2,13 Therefore, lower albumin level in the clinically unsta-
Ferritin, 103 μg/L 1.110 (0.992–1.241) 0.069 ble group may be related to hypercytokinemia and could be used as
Albumin, g/dL 0.040 (0.005–0.352) 0.004 an indicator of the clinical severity of pediatric HLH.
OR indicates odds ratio; CI, confidence interval. The present study has several limitations. This study had a
retrospective design and a relatively small number of patients from

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Pediatric HLH in the ED
a single institution and ethnic group. Thus, this limits the general- 5. Henter JI, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic
izability of the study. There may be more patients with HLH who guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood
were not diagnosed in the ED or even during hospitalization, and Cancer. 2007;48:124–131.
some patients could have died before a confirmative diagnosis 6. Ost A, Nilsson-Ardnor S, Henter JI. Autopsy findings in 27 children
was made. In addition, this study did not include specific treat- with haemophagocytic lymphohistiocytosis. Histopathology. 1998;32:
ment outcomes, and genetic analysis was not conducted. Further 310–316.
studies must be conducted to overcome these limitations. 7. Ramos-Casals M, Brito-Zeron P, Lopez-Guillermo A, et al. Adult
In conclusion, pediatric patients with HLH usually present haemophagocytic syndrome. Lancet. 2014;383:1503–1516.
with abdominal discomfort and fever and are often in clinically
8. Trottestam H, Horne A, Arico M, et al. Chemoimmunotherapy for
unstable conditions upon admission in the ED. However, only
hemophagocytic lymphohistiocytosis: long-term results of the
few patients meet the HLH-2004 diagnostic criteria. Lower albu-
HLH-94 treatment protocol. Blood. 2011;118:4577–4584.
min level may be used in identifying clinically unstable patients
and preparing for possible clinical deterioration. 9. Xu XJ, Wang HS, Ju XL, et al. Clinical presentation and outcome of
pediatric patients with hemophagocytic lymphohistiocytosis in
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1. Filipovich A, McClain K, Grom A. Histiocytic disorders: recent insights
into pathophysiology and practical guidelines. Biol Blood Marrow 10. Fardet L, Galicier L, Lambotte O, et al. Development and validation of
Transplant. 2010;16:S82–S89. the HScore, a score for the diagnosis of reactive hemophagocytic
syndrome. Arthritis Rheumatol. 2014;66:2613–2620.
2. Janka GE, Lehmberg K. Hemophagocytic syndromes—an update. Blood
Rev. 2014;28:135–142. 11. Bin Q, Gao JH, Luo JM. Prognostic factors of early outcome in pediatric
hemophagocytic lymphohistiocytosis: an analysis of 116 cases.
3. Machowicz R, Janka G, Wiktor-Jedrzejczak W. Similar but not the same:
Ann Hematol. 2016;95:1411–1418.
differential diagnosis of HLH and sepsis. Crit Rev Oncol Hematol. 2017;
114:1–12. 12. Arroyo V, Garcia-Martinez R, Salvatella X. Human serum albumin,
systemic inflammation, and cirrhosis. J Hepatol. 2014;61:396–407.
4. Ryu JM, Kim KM, Oh SH, et al. Differential clinical characteristics of acute
liver failure caused by hemophagocytic lymphohistiocytosis in children. 13. Henter JI, Elinder G, Soder O, et al. Hypercytokinemia in familial
Pediatr Int. 2013;55:748–752. hemophagocytic lymphohistiocytosis. Blood. 1991;78:2918–2922.

ORIGINAL ARTICLE
Pediatric Esophageal Foreign Body

Possible Role for Digital Tomosynthesis
Andrew Johansen, MD,* Gregory P. Conners, MD, MPH, MBA,*† Jacob Lee, BA,* Amie L. Robinson, BSRT,†
William L. Chew, BS,† and Sherwin S. Chan, MD, PhD*†
includes an esophagram. An esophagram requires patient co-

Objectives: Foreign body (FB) ingestion is a common reason for operation and radiologist participation and provides a higher
emergency department visits, affecting more than 80,000 children in the radiation dose compared with plain chest radiographs.
United States annually. Whereas most ingested FBs are coins or other Digital tomosynthesis (DTS) is a radiographic technique that
radiopaque objects, some are radiolucent FBs such as food. Digital produces cross-sectional images with in-plane resolution similar
tomosynthesis (DTS) is a radiographic technique that produces cross- to that of traditional radiographs.4 Digital tomosynthesis utilizes
sectional images with in-plane resolution similar to that of traditional a standard x-ray tube that is moved by a motorized tube crane
radiographs. Our pilot study evaluated the sensitivity and specificity of and a flat-panel detector overlaid with an antiscatter grid. A com-
DTS to detect FB in comparison to esophagram and clinical impression. puterized reconstruction algorithm allows for production of multi-
Methods: This was a retrospective review on patients aged 0 to 18 years ple cross-sectional images. Digital tomosynthesis of the chest
with suspected esophageal FB who received an esophagram with DTS at provides a radiation dose that is approximately 5% of that of chest
our institution between January 2014 and June 2016. Digital tomosynthesis computed tomography and approximately twice the dose of a
images were analyzed by 3 readers for identification of FB impaction and 2-view computed chest radiograph.4,5 The typical chest DTS
compared with esophagram and discharge diagnosis. This study was ap- dose ranges from 0.27 to 0.31 mGy, depending on the patient's
proved by our local institutional review board. age and size. Chest DTS is approved by the US Food and Drug
Results: A total of 17 patients underwent an esophagography with DTS Administration for chest imaging and has been used to screen for
for suspected esophageal FB, of which 9 (53%) were suspected of having cystic fibrosis and evaluate small pulmonary nodules.6,7 Digital
an FB on esophagram. Compared with esophagram, DTS had a sensitivity tomosynthesis has not previously been evaluated for detection of
of 44%, specificity of 100%, positive predictive value of 100%, and nega- esophageal FB impaction. We began use of a chest DTS protocol
tive predictive value of 62%. Compared with clinical impression, DTS had as part of our standard esophagram protocol for evaluation of chil-
a sensitivity of 33%, specificity of 100%, positive predictive value of dren with suspected esophageal impaction of a radiolucent FB.
100%, and negative predictive value of 38%. After 2½years of experience, we reviewed the resulting chest
Conclusions: This pilot study showed that chest DTS has a very high DTS images, to determine the sensitivity and specificity of this
positive predictive value, compared with esophagram and clinical im- procedure in identifying radiolucent esophageal FBs, as compared
pression, in detecting radiolucent esophageal FBs in children. Chest with esophagram. We also determined sensitivity and specificity
DTS is a promising modality for ruling in the presence of a radiolucent of chest DTS compared with clinical impression.
esophageal FB.
Key Words: digital tomosynthesis, esophageal foreign body, esophagram, METHODS
radiolucent foreign body This project was performed at a large academic pediatric
(Pediatr Emer Care 2021;37: 208–212) hospital with 2 ED sites. Local institutional review board approval
was obtained for a retrospective cohort analysis of all children
who underwent chest DTS for evaluation of suspected esophageal
F oreign body (FB) ingestion is a common reason for emergency
department (ED) visits, affecting more than 80,000 children in
the United States every year.1 The average age of children affected
impaction of a radiolucent FB between January 1, 2014, and June
30, 2016. Waiver of consent was granted because of the retrospec-
is 6 months to 3 years. Although most ingested FBs traverse the tive nature of the study.
gastrointestinal tract without complication, approximately 10%
to 20% of FB ingestion cases require intervention (endoscopy or Patient Selection
surgery), typically for concern of impaction in the esophagus.1 In a collaboration between radiology, surgery, and emer-
Whereas most ingested FBs are coins or other radiopaque ob- gency physicians, we modified our hospital's conventional
jects,2 some are radiolucent FBs such as food. Typically, patients esophagram protocol for children undergoing evaluation in the
with esophageal food impaction are older in age, averaging ED of suspected esophageal impaction of a radiolucent FB, by
12 years in a retrospective study.3 Evaluation of patients with substituting a chest DTS study for the traditional chest radiograph
suspected esophageal impaction of a radiolucent FB typically scout film for patients who could breath-hold for the 11 seconds
required for performance of the chest DTS (as determined by
From the *School of Medicine, University of Missouri at Kansas City; and ED and radiology staff ).
†Department of Radiology, Children's Mercy Hospital, Kansas City, MO.
Disclosure: S.S.-C.C. received funding from GE Healthcare through an Imaging Protocols
investigator-initiated grant related to optimizing digital tomosynthesis
acquisition in pediatric patients from 2015 to 2016. He has served on the Chest DTS imaging was performed using our standard de-
medical advisory board for Jazz Pharmaceuticals. The other authors declare partmental protocol on DTS-capable radiography machines
no conflict of interest. (Discovery XR650 and Discovery XR656; GE Healthcare,
Reprints: Sherwin Shiu-Cheung Chan, MD, PhD, Children's Mercy Hospital,
2401 Gillham Rd, Kansas City, MO 64108 (e‐mail: sschan@cmh.edu).
Milwaukee, Wis). We used the small or medium pediatric chest
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. VolumeRAD protocol. This protocol is set up with a 0.2-mm
ISSN: 0749-5161 copper filter and automatic exposure control. It consists of an

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Pediatric Esophageal Foreign Body
FIGURE 1. Schematic diagram of DTS acquisition. The patient is supine on the table, and the detector is placed under the patient. The
x-ray tube moves in a cranial-to-caudal direction. Multiple exposures are taken. Depending on the projection, different objects at different
depths are projected onto different parts of the detector. These detector images can then be postprocessed to emphasize different depths
by adding the images with different degrees of relative shift.
initial frontal scout image to set up coverage area and then a was obtained was then independently interpreted by 3 reviewers: a
single linear sweep of the x-ray tube over the table and detector. pediatric radiologist with experience in DTS image interpretation,
Sixty low-dose exposures are taken over the sweep. These pro- a radiologic technologist with experience in DTS image interpre-
jections are then reconstructed into 25 coronal slices (Fig. 1). tation, and a fourth-year radiology resident who was reviewing
Our patients were imaged supine for comfort and to minimize DTS images for the first time. The images were reviewed on a
motion. All patients were instructed to breath-hold during PACS workstation (Inteleviewer 4-14-1, Montreal, Quebec, Canada).
image acquisition. Reviewers were blinded to clinical and esophagram results.
Esophagram procedures were performed and interpreted by For each patient, each reviewer determined whether the DTS
1 of 24 board-certified pediatric radiologists. In each study, the images showed a radiolucent esophageal FB (yes/no). Chest
esophagus was evaluated in 2 orthogonal planes after oral barium DTS results were defined as the consensus of at least 2 of the
administration. Esophagram was performed less than 30 minutes 3 reviewers regarding whether a radiolucent FB was present in
following performance of the chest DTS study. Following the esophagus. Each consensus review was compared with reports
esophagram, patients were admitted to the hospital or discharged from the subsequent esophagram.
from the ED, as per clinical determination.
Clinical Impression
Image Review Consensus chest DTS reviews were also compared with clin-
We identified patients who underwent chest DTS for evalua- ical impression. For patients who underwent upper gastrointestinal
tion of possible esophageal impaction of a radiolucent FB through endoscopy, the clinical impression was determined by whether an
use of a radiology information system. Each chest DTS image that esophageal FB was noted in the procedure note. For patients who
TABLE 1. Patient Characteristics, Chief Complaint, Esophagram Dose, and Clinical Course and Discharge Diagnosis of the
17 Patients Who Underwent DTS Scout Prior to Esophagram Examination
Patient ID Age, y Sex Chief Complaint Esophagram Dose, mGy Clinical Course and Discharge Diagnosis
1 10 F Poor food tolerance 5.72 Passed PO challenge, no FB
2 10 M Sensation of food stuck 1.12 Food spontaneously passed
3 14 F Sensation of food stuck 3.5 Food pushed down during scope
4 13 M Sensation of food stuck 2.13 Food pushed down during scope
5 3 M Swallowed button 0.2 Patient vomited FB
6 15 M Cannot keep down liquids 3.1 Meat bolus stuck in esophagus
7 4 F History of TEF; solids intolerance 0.47 Removed food bolus by scope
8 10 F Sensation of food stuck N/A Impacted esophageal food bolus
9 13 M Choked on food N/A Negative scope, no food bolus
10 12 M Choked on food 1.48 Food bolus passed
11 15 F Sensation of food stuck 1.05 Chest pain not related to food bolus
12 14 M Globus sensation 3.51 Vomited food bolus
13 17 M Sensation of food stuck 0.6 No food bolus
14 17 M Sensation of food stuck 1.41 Scope removed food bolus
15 15 F Problems swallowing 4.7 Gastric ulcer, no food bolus
16 13 F Problems swallowing after eating corn dog 1.01 Esophageal reflux, no food bolus
17 16 M Sensation of food stuck 3.89 Food bolus impaction
F indicates female; M, male; PO, by mouth; TEF, tracheoesophageal fistula.

Johansen et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
RESULTS
TABLE 2. Comparison of Patients With and Without Diagnosis
of FB
Patient Population
Patient Characteristic No FB (n = 5) FB (n = 12) P We performed 17 chest DTS studies from January 1, 2014,
through June 30, 2016 (Table 1). There were 10 boys and 7 girls
Age, y 14.0 ± 2.65 11.75 ± 4.39 0.31
ranging in age from 3 to 17 years. The groups with and without
Sex, % male 20 75 0.10 an esophageal FB were similar in age and sex but did have differ-
Scoped, % of total 0 58.3 0.03 ent rates of endoscopy (Table 2).
Values are presented as mean ± SD.
Chest DTS and Esophagram Images
Chest DTS images were of high diagnostic quality with no
motion or movement artifacts in all 17 patients. In our search
did not undergo endoscopy, we instead used the discharge diagno- through the medical records, we did not find any instances of exam-
sis from the inpatient stay or ED visit. inations being aborted because of technical difficulties associated
with the equipment or patient cooperation. Figure 2 shows sample
images from a chest DTS and a conventional esophagram in a pa-
Statistical Analysis tient with an impacted food bolus at the gastroesophageal junction.
Descriptive statistics are reported as means ± SD for con- Chest DTS Versus Esophagram
tinuous variables and frequency with percentage for categorical Consensus reviews (Table 3) of 4 of the 17 chest DTS images
variables. Sensitivity and specificity for chest DTS consensus were suggestive of the presence of radiolucent esophageal FBs
were compared with esophagram and with each patient's clinical and of no FBs in the remaining 13 patients. All 3 chest DTS re-
impression. We report 95% confidence intervals (CIs) for the viewers were in accordance in their review of 11 of the 17
performance characteristics of DTS. DTS images.
FIGURE 2. A, Chest DTS images from a 17-year-old male adolescent who presented the ED with a chief complaint of sensation of food
stuck in throat. A food bolus at the gastroesophageal junction was shown as a soft tissue density that was outlined by adjacent air on the DTS
image (arrow). B, Esophagram images show the food bolus as a filling defect in the barium column on the conventional esophagram (arrow).
Shortly after the esophagram was performed, the patient vomited a chicken nugget. No endoscopy was performed.

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Pediatric Esophageal Foreign Body
TABLE 3. Blinded Image Interpretation by 3 Readers for Identification of FB in Comparison to Clinical Impression and Esophagram
Endoscopy Clinical Esophagram Chest DTS Chest DTS Chest DTS Chest DTS
Patient ID Performed Impression Result Consensus Reviewer 1 Reviewer 2 Reviewer 3
1* No 0 0 0 0 0 0
2 No 1 0 0 0 0 0
3 Yes 1 1 0 0 0 1
4 Yes 1 1 0 1 0 0
5* Yes 1 1 1 1 0 1
6 No 1 1 0 0 0 1
7* Yes 1 1 1 1 1 1
8 Yes 1 1 0 1 0 0
9 Yes 1 1 0 0 0 0
10 No 1 0 0 0 0 1
11* No 0 0 0 0 0 0
12* No 1 1 1 1 1 1
13* No 0 0 0 0 0 0
14* Yes 1 1 1 1 1 1
15* No 0 0 0 0 0 0
16* No 0 0 0 0 0 0
17 No 1 0 0 0 0 0
1 = FB believed present; 0 = no FB believed present.
*Cases where at least 2 of 3 DTS readers agreed with both esophagram and clinical impression.
Esophagrams of 9 of the 17 patients suggested the presence the presence of a radiolucent esophageal FB, there is sufficient ev-
of radiolucent esophageal FBs. Compared with esophagram, con- idence that the FB is indeed present, suggesting there is little
sensus chest DTS had a sensitivity of 44% (95% CI, 15%–77%), additional benefit from continuing with the esophagram. A
specificity of 100% (95% confidence interval, 60%–100%), pos- positive chest DTS then is sufficient evidence to consider pro-
itive predictive value of 100% (95% CI, 40%–100%), and negative ceeding to esophagoscopy.
predictive value of 62% (95% CI, 35%–85%). Third, the modest sensitivity and negative predictive values
of chest DTS suggest that a negative chest DTS does not effec-
Chest DTS Versus Clinical Impression tively rule out the presence of a radiolucent esophageal FB. When
Forty-seven percent (8/17) of patients underwent upper gas- chest DTS is substituted for conventional scout radiograph before
trointestinalendoscopy. Endoscopy wasperformed10.7 ± 7.8 hours an esophagram in cases where there is high suspicion for the
(mean ± SD, n = 7) after the radiographic studies. All 7 patients presence of a radiolucent esophageal FB, continuing with the
(100%) who underwent endoscopy were found to have an esoph- esophagram may add important additional diagnostic information.
ageal FB. Five patients were diagnosed with an esophageal FB
as a discharge diagnosis without endoscopy. Five patients were Limitations
discharged with an alternative diagnosis. Although these data are promising, they should be consid-
Compared with clinical impression, consensus chest DTS ered preliminary because of limitations of this study. We had
had a sensitivity of 33% (95% CI, 11%–65%), specificity of relatively low patient numbers and therefore wide 95% CIs. The
100% (95% CI, 46%–100%), positive predictive value of 100% study was performed at a single center. The pediatric radiologist
(95% CI, 40%–100%), and negative predictive value of 38% and radiologic technologist who interpreted chest DTS images
(95% CI, 15%–68%). have more experience interpreting DTS images than is typical
for most radiologists, although the senior radiology resident phy-
sician interpreter had no special experience in this area. Finally,
DISCUSSION our determination of clinical impression was based on a retrospec-
Results from this pilot study suggest 3 important conclu- tive review of clinical record, in cases with negative esophagram.
sions. First, chest DTS was able to detect radiolucent esophageal In those patients, there was often a lag between the radiology and
FBs in several patients. This suggests that further study of the role endoscopy, so an FB could have passed in that time. Spontaneous
of DTS, including in the pediatric population, is warranted. This passage of esophageal FBs has frequently been described.8 Also,
would include more precisely determining populations and situa- many of the discharge diagnoses were presumptive diagnoses
tions in which this modality is most efficacious, informing defin- based on clinical presentation.
itive cost-benefit calculations.
Second, the very high specificity and positive predictive
values of chest DTS, compared both with esophagram and clinical CONCLUSIONS
impression, suggest that chest DTS could be an effective substi- This pilot study showed that chest DTS has very high speci-
tute for conventional scout radiograph before an esophagram in ficity and positive predictive value, compared with esophagram
cases where there is high suspicion for the presence of a radiolu- and clinical impression, in detecting radiolucent esophageal FBs
cent esophageal FB, especially food. When chest DTS suggests in children, making chest DTS a promising modality for ruling

Johansen et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
in the presence of a radiolucent esophageal FB. Our pilot study 2. Little DC, Shah SR, St Peter SD, et al. Esophageal foreign bodies in the
with 17 patients indicates that a chest DTS result indicating the pediatric population: our first 500 cases. J Pediatr Surg. 2006;41:914–918.
presence of radiolucent esophageal FB could be an effective substi- 3. Lao J, Bostwick HE, Berezin S. Esophageal food impaction in children.
tute for esophagram. Further, chest DTS does not require radiolo- Pediatr Emerg Care. 2003;19:402–407.
gist participation, and the average radiation dose is less than that 4. Dobbins JT, McAdams HP. Chest tomosynthesis: technical principles and
of conventional esophagram. However, its lower sensitivity and clinical update. Eur J Radiol. 2009;72:244–251.
negative predictive values make chest DTS less effective at ruling
5. Vult von Steyern K, Bjorkman-Burtscher IM, Weber L, et al. Effective dose
out the presence of a radiolucent esophageal FB in children. More from chest tomosynthesis in children. Radiat Prot Dosimetry. 2014;158:
studies are needed to better elucidate the role of chest DTS in the 290–298.
management of children with possible radiolucent esophageal FBs.
6. Jung HN, Chung MJ, Koo JH, et al. Digital tomosynthesis of the chest: utility
for detection of lung metastasis in patients with colorectal cancer. Clin
ACKNOWLEDGMENTS Radiol. 2012;67:232–238.
The authors thank the Children's Mercy Medical Writing
7. Vult von Steyern K, Bjorkman-Burtscher IM, Hoglund P, et al. Description
Center for assisting in manuscript preparation.
and validation of a scoring system for tomosynthesis in pulmonary cystic
fibrosis. Eur Radiol. 2012;22:2718–2728.
REFERENCES 8. Conners GP, Chamberlain JM, Ochsenschlager DW. Symptoms and
1. Wyllie R. Foreign bodies in the gastrointestinal tract. Curr Opin Pediatr. spontaneous passage of esophageal coins. Arch Pediatr Adolesc Med. 1995;
2006;18:563–564. 149:36–39.

ORIGINAL ARTICLE
Radiologic Assessment of Skull Fracture Healing

in Young Children
Nancy S. Harper, MD,* Sonja Eddleman, MSN, RN,† Khushbu Shukla, MD,‡ Maria Veronica Narcise, MD,†
Laura J. Padhye, MD,§ Loralie J. Peterson, MPH,* Michael A. Murati, MD,|| and Caroline L. S. George, MD*
in a study using a US database of hospitalized children, almost all

Background: Skull fractures are commonly seen after both accidental cases of skull fracture were attributable to accidental falls, espe-
and nonaccidental head injuries in young children. A history of recent cially in infants younger than 12 months.3 Infants are more likely
trauma may be lacking in either an accidental or nonaccidental head injury to have skull fractures than toddlers after falls regardless of fall
event. Furthermore, skull fractures do not offer an indication of the stage of height.4,5 Although skull fractures are more commonly identified
healing on radiologic studies because they do not heal with callus forma- after accidental falls than nonaccidental head trauma,6 the linear
tion as seen with long bone fractures. Thus, a better understanding on the parietal skull fracture is the most common fracture type identified
timing of skull fracture resolution may provide guidance on the medical in both types of trauma in children younger than 2 years.7,8 In the
evaluation for accidental or nonaccidental head injury. clinical setting, a skull fracture may be identified in a young child
Objective: The aim of the study was to determine the time required for who presents when scalp swelling is observed by a caregiver with-
radiographic skull fracture resolution in children younger than 24 months. out a reported history of head trauma. Likewise, a young child
Methods: This was a retrospective observational analysis of children may have more than 1 skull fracture identified. In these scenarios,
younger than 24 months referred with skull fractures between January the diagnostic dilemma may lie in how to interpret the skull frac-
2008 and December 2012. Analysis included children with accidental head ture(s) in the context of the child's age and development without a
injuries with a known time interval since injury and a negative skeletal sur- clear timeline of injury and whether to initiate an age-appropriate
vey who underwent serial radiographic studies. Complete healing of a skull evaluation for nonaccidental trauma.
fracture was defined as resolution of fracture lucency by radiograph. A comprehensive medical history and physical examination
Results: Of the 26 children who met inclusion criteria, 11 (42.3%) dem- are important in the determination of accidental versus nonaccidental
onstrated resolution of skull fracture(s) on follow-up imaging. Fracture reso- head trauma. This history includes the mechanism of injury (details
lution on radiologic studies ranged from 2 to 18 weeks. Twelve fractures in of the injury event), the child's developmental abilities, and whether
10 children demonstrated fracture resolution at 10 or more weeks after injury. the injury event was witnessed. Although most childhood frac-
Conclusions: Healing or resolution of a skull fracture can take months in tures occur from a reported fall,9,10 a fall is also the most common
children younger than 24 months. With the high variability in skull fracture history of injury provided in cases of nonaccidental head
presentation and large window to fracture resolution, unexplained or mul- trauma.11,12 Identification of other injuries such as scalp swelling,
tiple skull fractures in children younger than 24 months may be the result of abrasions, bruises, and oral trauma add to the understanding of the
a single or multiple events of head trauma. mechanism and timing of injury. When scalp swelling is noted on
Key Words: child abuse, skeletal survey, skull fracture, fracture healing initial examination and/or radiologic studies with an injury, it can
aid in the assessment of the timing of the injury.13 However, ap-
proximately 10% of children with skull fractures have no clini-
cally appreciable or radiographic evidence of scalp or facial soft
E pidemiologic studies on child maltreatment have shown that
children younger than 2 years have high rates of both
nonaccidental head trauma1 and serious physical abuse.2 The rate
tissue swelling at the time of presentation.4,14 The presence or ab-
sence of signs of skeletal healing on radiographic study may be
useful in the assessment of injury timing. Although there are stud-
of nonaccidental head trauma in infants is more than twice the rate
ies on the radiologic healing of long bone fractures in
of young children between the ages of 1 and 3 years.1,2 However,
children15–20 and clavicular birth injuries,21 there are no published
studies on the healing of skull fractures. Furthermore, the mecha-
From the *Department of Pediatrics, University of Minnesota, University of nism of healing differs between long bones and bones of the cal-
Minnesota Masonic Children's Hospital, Minneapolis, MN; †Driscoll Children's varium, thus studies of long bone healing do not translate to skull
Hospital, Corpus Christi, TX; ‡Cox Medical Center South, Springfield, MO; fractures.22 Our objective was to determine the time to radiologic
§Department of Family Medicine and Community Health, University of
Minnesota, M Health Fairview St. Joseph's Hospital; and ||Department of Radi-
fracture resolution in children younger than 24 months presenting
ology, University of Minnesota, University of Minnesota Masonic Children's with skull fracture(s).
Hospital, Minneapolis, MN.
Disclosure: N.S.H.'s institution has received payment for expert witness court
testimony that has been provided in cases of suspected child abuse in which METHODS
she has been subpoenaed to testify. N.S.H. and S.E. have provided paid
expert testimony in cases of suspected child abuse. The other authors This was a retrospective, single-center study conducted at a
declare no conflict of interest. tertiary pediatric hospital with a multidisciplinary child abuse pro-
Reprints: Nancy S. Harper, MD, Otto Bremer Trust Center for Safe and Healthy gram that included subspecialty trained child abuse physicians,
Children, University of Minnesota, 2512 S 7th St, Suite R107, Minneapolis,
MN 55454 (e‐mail: nsharper@umn.edu).
social workers, pediatric radiology, and neuroradiology. The study
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. was approved by the hospital's institutional review board. Data
This is an open access article distributed under the terms of the Creative were extracted from the child abuse program database on cases
Commons Attribution-Non Commercial-No Derivatives License 4.0 of children younger than 24 months with skull fractures who were
(CCBY-NC-ND), where it is permissible to download and share the work
provided it is properly cited. The work cannot be changed in any way or
evaluated between January 1, 2008, and December 31, 2012.
used commercially without permission from the journal. These children were referred to the child abuse program either be-
ISSN: 0749-5161 cause the skull fracture occurred in an infant younger than
Harper et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
12 months or because the referring emergency department (ED) can occur with instrumented deliveries24,25 and the length of time
physician had a concern for child abuse or neglect. As part of for a birth skull fracture to heal is unpublished), date of presenta-
the consultation for head injury, the child abuse program tion to the ED and consultation with child abuse physician, fall
completed safety education and psychosocial assessments as history, fall height, floor surface, location of skull fracture
well as comprehensive consultations by child abuse physicians if (calvarial), type of fracture (simple vs complex), associated soft
indicated. Inclusion criteria were as follows: (1) younger than tissue swelling on clinical examination and radiography, type of
24 months, (2) identified skull fracture(s), (3) caregiver provided radiologic study completed, and radiologic findings on follow-up
a history of recent head trauma, (4) known time of injury, (5) no skull radiographs. A simple skull fracture was defined as single
additional fractures on skeletal survey, and (6) completion of and linear, whereas complex fractures were defined as being
follow-up skull radiographs. multiple, bilateral, diastatic, depressed, or stellate.26 The pres-
Radiologic imaging at the time of ED presentation was at the ence or absence and resolution of skull fractures were based on
discretion of the ED physician with all children initially imaged by the official reading of pediatric radiologists. Complete healing
head computed tomography (CT) with 3-dimensional (3D) recon- of the skull fracture was defined as resolution of the fracture lu-
struction. Other radiologic studies ordered at the time of initial cency by skull radiograph. Fracture length and width during
presentation included skull radiographs (before head CT) and follow-up imaging were not measured. A child abuse physician
skeletal surveys (after identification of a skull fracture) in some reviewed all imaging with the pediatric radiologists at the time
children. The need for additional follow-up imaging was deter- of the initial consultation and follow-up. Timing of radiographi-
mined clinically, for example, to evaluate for leptomeningeal cyst cally demonstrated fracture resolution was determined in weeks.
formation as recommended by neurosurgery. Follow-up imaging The time interval between initial injury and the fracture resolution
included 2 view skull radiographs (frontal and lateral) offered at on skull radiograph was rounded to the nearest week. Descriptive
2 to 3 weeks (in conjunction with a follow-up skeletal survey) statistics were used in analysis.
and several months after initial injury. Follow-up skeletal surveys
still included skull radiographs as the timing of this study overlap-
ped the American College of Radiology recommendation for RESULTS
elimination of skull radiographs from the follow-up skeletal sur- After reviewing data on 106 children evaluated by the child
vey.23 Follow-up skeletal surveys were recommended but not re- abuse program between January 1, 2008, and December 31,
quired in infants younger than 1 year with isolated skull 2012, 26 children were eligible for inclusion in the study.
fractures at the time of this study. Accidental head injury was de- Figure 1 shows the study subject flow chart. The median age of
fined as a child presenting with a history of witnessed accidental the children was 7 months with a range of 0 to 18 months. The
injury (such as a fall) occurring in the absence of additional con- study population was 80.8% Hispanic, consistent with the popula-
cerning injuries such as nonscalp cutaneous trauma (bruising), tion of the region, and 46.2% of the children were male. Most chil-
oral trauma, or skeletal injury. dren (69.2%) were born by vaginal delivery without instrumentation
Data that were extracted included the child's age in months, (Table 1). A child abuse physician evaluated 50% of the children
sex, ethnicity (Hispanic or non-Hispanic), race, maternal age, in- within 24 hours and 69.2% within 48 hours of injury. The remain-
strumentation used, and mode of delivery (as rarely skull fractures der were seen more than 48 hours after injury as the discovery of
FIGURE 1. Flow chart of subject selection.
214 www.pec-online.com © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.
Pediatric Emergency Care • Volume 37, Number 4, April 2021 Skull Fracture Healing in Young Children
fractures (71%), followed by the occipital bone with 4 fractures

TABLE 1. Population Demographics (12.9%), and the frontal bone with 1 fracture (3.2%). No temporal
bone fractures were seen in our study. Two children (7.7%) did not
Subjects (N = 26), n (%)
have associated soft tissue swelling on clinical examination or ra-
Sex diography. Twenty-five children (96.1%) had initial neuroimag-
Male 12 (46.2) ing, which included 3D head CT. Eleven children (42.3%) had
Female 14 (53.8) intracranial bleeds on CT—10 extra-axial hemorrhages and 1 cor-
Age, mo tical hemorrhage. All intracranial hemorrhages were small, focal,
and associated with the fracture area.
0–3 8 (30.7)
Of the 26 children with 31 skull fractures, skull fracture res-
4–6 1 (3.8) olution occurred for 13 fractures (41.9%) from 11 children
7–9 7 (26.9) (42.3%) on follow-up imaging. The radiologic studies demon-
10–12 9 (34.6) strating fracture resolution ranged from 2 to 18 weeks, as 1 child
>12 1 (3.8) demonstrated resolution of a frontal bone fracture on the initial
Ethnicity 2-week follow-up skeletal survey. Ten children (38.5%) received
Hispanic 21 (80.8) only follow-up imaging at 2 to 3 weeks after injury with 9 of these
Non-Hispanic 5 (19.2) children still demonstrating the presence of a fracture on imaging.
Race Therefore, the follow-up imaging at 2 to 3 weeks demonstrated
White 19 (73.1) persistence of skull fracture(s) in 90% of these studies. The re-
maining 16 children (61.5%) with 20 fractures returned for addi-
Black 1 (3.8)
tional imaging beyond the follow-up skeletal survey. Twelve
Others 4 (15.4) fractures in 10 children demonstrated fracture resolution on
No data 2 (7.7) follow-up imaging between 9 and 18 weeks after injury. One child
Mode of delivery with a bilateral skull fracture did not have resolution of one side of
Vaginal 17 (65.4) the fracture at a final imaging visit at 18 weeks. Eight fractures in
Vaginal with instrumentation (forceps) 1 (3.8) the remaining 6 children did not demonstrate fracture resolution
C-section 6 (23.1) when imaged between 9 and 18 weeks after injury.
No data 2 (7.7)
Fall heights
Unknown 7 (26.9) DISCUSSION
<3 ft 12 (46.2) These results are particularly valuable because there are no
3–6 ft 7 (26.9) published studies on the “healing” of skull fractures. Dating of
skull fractures has been limited to the presence or absence of scalp
Floor surface
swelling indicating a more recent injury, whereas the absence of
Tile/concrete 10 (38.5) scalp swelling is not helpful in timing. It is notable that there is
Other surface flooring/concrete 4 (15.4) high variability in the presentation of skull fractures with both
Carpet/concrete 1 (3.8) simple and complex skull fractures (eg, bilateral skull fractures)
Tile 2 (7.7) occurring in falls of less than 3 feet in this study population.
Dirt 1 (3.8) The small number of complex skull fractures in this series limits
Wood 3 (11.5) further analysis. However, in a case-control study of the biome-
Concrete 2 (7.7) chanical characteristics of falls in children, no association was
Unknown 3 (11.5) seen between fall height and the presence of simple or complex
skull fractures.5 Although it is difficult to date head injuries and
scalp swelling was noted days after the occurrence of a fall. Per in-
clusion criteria, all children had a skeletal survey on presentation. TABLE 2. Comparison of Fall Heights to Type of Fracture
All children were scheduled for a complete follow-up skeletal sur- and Surface
vey at 2 weeks. However, 9 children (34.6%) did not complete a
follow-up skeletal survey at 2 weeks (eg, cancellations, no- Unknown
shows, rescheduling, caregiver preference to limit imaging to <3 ft, n (%) 3–6 ft, n (%) Height, n (%)
skull views) but did return later for follow-up skull imaging.
An estimated fall height was available for 19 children No. patients 12 (46.2) 7 (26.9) 7 (26.9)
(73.1%), 12 (46.2%) with an estimated fall height less than 3 feet Simple fractures 11 (42.3) 4 (15.4) 6 (23.1)
and 7 (26.9%) between 3 and 6 feet. Most falls (17 children or Complex fractures 1 (3.8) 3 (11.5) 1 (3.8)
65.4%) occurred onto a surface involving concrete (uncovered Concrete surface 1 (3.8) 0 1 (3.8)
or with an overlying surface such as linoleum). Simple and complex Tile/concrete surface 5 (19.2) 2 (7.7) 3 (15.4)
skull fractures were seen with both fall heights, but 60% of the Carpet/concrete surface 1 (3.8) 0 0
complex skull fractures occurred between 3 and 6 feet (Table 2). Other/concrete surface 2 (7.7) 2 (7.7) 0
There were 31 skull fractures that occurred in 26 children. Tile surface 0 1 (3.8) 1 (3.8)
Simple fractures were noted in 21 children (80.8%) whereas com-
Dirt surface 0 1 (3.8) 0
plex fractures occurred in 5 children (19.2%). Four (80%) of the 5
complex skull fractures were bilateral parietal fractures with 1 Wood surface 2 (7.7) 1 (3.8) 0
child having a complex fracture of the parietal and occipital bones. Unknown surface 1 (3.8) 0 2 (7.7)
Of the simple fractures, 14 (66.7%) were found on the right side N = 26.
and 7 (33.3%) on the left. The parietal bone was affected in 22
© 2020 The Author(s). Published by Wolters Kluwer Health, Inc. www.pec-online.com 215
Harper et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
fractures in children, determining a window of injury may be help- be feasible to design a study of fracture healing using ultrasonog-
ful in cases where the history is unclear, the history includes mul- raphy as information continues to accrue on this technique for
tiple falls or injury events, or when multiple fractures are present. skull fracture identification in the pediatric population.29,30
This study provides some initial data to aid in that process. Al-
though most children in this case series had scalp swelling at the
time of presentation supporting a recent injury, soft tissue swelling CONCLUSIONS
was not present in all children. There were children without frac- Healing or radiographic resolution of a skull fracture in
ture resolution at follow-up visits between 9 and 18 weeks after in- young children can take months. In this retrospective chart review,
jury. In those children that did demonstrate healing, fracture those skull fractures with follow-up imaging demonstrated radio-
resolution largely occurred 10 or more weeks after injury. There- graphic resolution at or after 10 weeks. Emergency medicine phy-
fore, a skull fracture that presents without soft tissue swelling sicians and multidisciplinary teams should be aware of the high
may be a recent injury or may represent a prior head injury event. variability in skull fracture presentation and the large window to
In addition, with the large window to fracture resolution, unexplained skull fracture resolution when children younger than 24 months
or multiple skull fractures in children younger than 24 months present with unexplained or multiple skull fractures.
may be the result of a single or multiple events of head trauma.
This study used a child abuse program database for data ex-
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CME REVIEW ARTICLE
Recognition, Evaluation, and Management of Pediatric

Hereditary Angioedema
Andrew T. Krack, MD,* Jonathan A. Bernstein, MD,† and Richard M. Ruddy, MD‡
primarily in the prehospital, office, urgent care, or emergency de-

Abstract: Hereditary angioedema (HAE) is a rare, often underrecognized partment setting.
genetic disorder caused by either a C1 esterase inhibitor deficiency (type 1)
or mutation (type 2). This leads to overproduction of bradykinin resulting LEARNING OBJECTIVES
in vasodilation, vascular leakage, and transient nonpitting angioedema occur- After completion of this article, the reader should be better
ring most frequently in the face, neck, upper airway, abdomen, and/or extrem- able to:
ities. Involvement of the tongue and laryngopharynx has been associated with
asphyxiation and death. Hereditary angioedema is an autosomal-dominant 1. Describe the pathophysiologic differences between various
condition; therefore, there is a 50% chance an offspring will inherit this disor- causes of angioedema.
der. Any patient presenting with isolated angioedema should be screened with 2. Identify, evaluate, and manage acute complications of heredi-
a C4 measurement, as 25% of cases have no family history of HAE. All pa- tary angioedema (HAE).
tients with HAE will have a functional deficiency of C1 esterase inhibitor. 3. Explain the natural history, precipitating events, and chronic
Contributors that delay the diagnosis of HAE include recognition delay management of HAE, including short-term and long-term pro-
by clinicians who confuse this condition with histaminergic angioedema, phylactic treatments.
the disease's varied presentations, and limitations to timely testing. Pediat-
ric emergency clinicians should be knowledgeable about how to distin-
guish between bradykinin- and histamine-mediated angioedema, as there BACKGROUND
are significant differences in the diagnostic testing, treatment, and clinical Hereditary angioedema (HAE) is a rare, often underrecognized
response between these 2 different conditions. Evidence indicates that genetic disorder caused by either a C1 esterase inhibitor (C1-INH)
early diagnosis and treatment of HAE reduces morbidity and mortality. deficiency (type 1) or mutation (type 2). This leads to overproduc-
Clinician recognition of the mechanistically different problems will ensure tion of bradykinin resulting in vasodilation, vascular leakage, and
patients are appropriately referred to an expert for outpatient management. transient nonpitting angioedema occurring most frequently in the
Key Words: hereditary angioedema, HAE, angioedema, bradykinin, C1 face, neck, upper airway, abdomen, and/or extremities.1 Involve-
esterase ment of the tongue and laryngopharynx has been associated with
asphyxiation and death.2,3
(Pediatr Emer Care 2021;37: 218–225) Type 1 HAE is an autosomal-dominant condition; therefore,
there is a 50% chance an offspring will inherit this disorder.4 Any
patient presenting with isolated angioedema should be screened
TARGET AUDIENCE with a C4 serum measure because 25% of HAE cases have no
family history. All patients with HAE will have a functional defi-
This CME review is intended for pediatricians, family medicine ciency of C1-INH. Patients with type 1 HAE will also have a de-
physicians, emergency medicine physicians, pediatric emergency crease in quantitative C1-INH, whereas patients with type 2 HAE
medicine physicians, pediatric hospitalists, nurse practitioners, have a normal or increased quantitative C1-INH level.5 Type 1 and
physician assistants, emergency medical services personnel, and Type 2 HAEs are also collectively referred to as HAE-C1-INH. A
other health care workers who care for children and adolescents subtype of HAE with normal complement (HAE-nl-C1-INH),
previously labeled type 3, has been recognized. HAE-nl-C1-INH
From the *Clinical Fellow, Department of Pediatrics, Division of Emergency is associated with Factor XII missense mutations. Mutations in plas-
Medicine, Cincinnati Children's Hospital Medical Center, and University of minogen, kininogenase, or angiopoietin have also been reported.4,6
Cincinnati Department of Pediatrics; †Professor of Medicine, Department of In-
ternal Medicine, Division of Immunology/Allergy, University of Cincinnati
Medical Center; and ‡Professor of Pediatrics, Department of Pediatrics, Divi- PATHOPHYSIOLOGY
sion of Emergency Medicine, Cincinnati Children's Hospital Medical Center,
and University of Cincinnati Department of Pediatrics, Cincinnati, OH.
Acute care clinicians should be knowledgeable regarding the
Disclosure: J.A.B. was a principal investigator, consultant, and speaker for various pathophysiologic mechanisms by which angioedema can
Shire/Takeda, CSL Behring, and Pharming, and a principal investigator and manifest, given that the diagnostic workup, management, and
consultant for Biocryst, Kalvista, and IONIS. prognostic outcome differs widely based on etiology.1 Angioedema,
Lippincott CME Institute has identified and resolved all conflicts of interest
concerning this educational activity.
defined as nonpitting edema of the deep dermis or submucosal or
The remaining authors, faculty, and staff in a position to control the content of subcutaneous tissues is due to different mechanisms of action
this CME activity and their spouses/life partners (if any) have disclosed that resulting in increased vascular permeability and extravasation of
they have no financial relationships with, or financial interest in, any fluid into the interstitium.1,7–9
commercial organizations relevant to this educational activity.
Reprints: Andrew T. Krack, MD, Division of Emergency Medicine, Cincinnati
Acute histamine-mediated (allergic; histaminergic) angio-
Children's Hospital Medical Center (CCHMC), 3333 Burnet Ave, ML edema is an allergen-induced, IgE-mediated (type I hypersensitivity
2008, Cincinnati, OH 45229-3026 (e‐mail: Andrew.Krack@cchmc.org). reaction) form of angioedema secondary to mast cell degranulation,
Supplemental digital content is available for this article. Direct URL citations associated with urticarial wheal-and-flare lesions (ie, hives) in 40%
appear in the printed text and are provided in the HTML and PDF versions
of this article on the journal’s Web site (www.pec-online.com).
of cases. It involves the mid- and papillary dermis and in some cases
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. can progress to anaphylaxis.7 Approximately 20% of patients with
ISSN: 0749-5161 histaminergic angioedema present with isolated angioedema without

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Pediatric Hereditary Angioedema
hives.7,10 Common precipitating allergens include foods, medica- the onset of symptoms in the first decade of life, ~37% in the sec-
tions, pollen, dander, and insect stings.10 ond decade, and the final ~11% sometime thereafter.25 There is
Bradykinin-mediated angioedema results from activation of equal predilection for males and females (Table 1).21
the contact activation system,11–13 which is a complex cascade Pediatric patients diagnosed with HAE C1-INH often mani-
regulated by C1-INH with substrates including Factor XII, high- fest symptomatic attacks requiring acute treatment from puberty
molecular-weight kininogen, prekallikrein, and kallikrein.8 Absence down to as early as 6 months of age.17,27 Diagnosis is frequently
of C1-INH results in an increased production of bradykinin, which delayed because many patients receive repeated treatment of hista-
binds to vascular bradykinin B2 receptors, precipitating vasodilation, minergic angioedema.28,29 Earlier onset of symptoms correlates
and extravasation of fluid causing interstitial edema.1,8,11 The with delays in diagnosis and may predict a more severe disease
bradykinin-mediated angioedema types include HAE, angiotensin- phenotype.30
converting enzyme inhibitor (ACEi)–induced angioedema, and
acquired angioedema, the latter 2 of which are exceedingly rare
CLINICAL CASES
in children.1,9,14 The suspected triggers include stress, trauma, in-
fection, surgery, and medical procedures.14,15 Case 1
In addition to histaminergic angioedema and bradykinin-mediated A 19-month-old girl presented with swelling of her hands
angioedema, non–histamine-/non–bradykinin-mediated angio- and feet and abdominal rash that appeared like “ringworm” to
edema types have been described.16 These include idiopathic her father after amoxicillin treatment for acute otitis media. Her
angioedema and pseudoallergic angioedema (including nonste- examination was notable for being well-appearing with normal vi-
roidal anti-inflammatory drug–induced), which are relatively tal signs and few scattered erythematous blanching macules with
rare in children and adolescents and will not be discussed in central clearing on her abdomen, legs, and inguinal region with
this review.15 swelling of hands and feet bilaterally. A diagnosis of serum sick-
ness like reaction was made. She returned to the emergency depart-
ment (ED) 1 year later with left-hand swelling, and again 3 months
EPIDEMIOLOGY later with a similar rash associated with left hand and ankle swell-
Children and adolescents are affected primarily by type 1 and ing without fever. Swelling with each presentation resolved in 1 to
type 2 HAEs,17–20 with HAE type I accounting for ~85% of cases 3 days. A referral to rheumatology was made, at which time it was
and HAE type II accounting for the remaining ~15%.21–24 The noted that similar episodes occurred 3 to 4 times a year, usually
prevalence of HAE is estimated to affect 1:30,000 to 1:50,000 in- with mild viral-type illnesses. The differential at that time included
dividuals.22,23 In a large case series, the mean ± SD age of symp- drug/viral-induced erythema multiforme minor, serum sickness-like
tom onset was 11.2 ± 7.7 years; approximately 50% experienced reaction and less likely periodic fever syndrome, urticaria vasculitis,
TABLE 1. HAE Pediatric Cohort Epidemiologic Factors and Clinical Characteristics17–20
Farkas et al Nanda et al Bennett and Craig Aabom et al

No. patients 50 21 25 22 (14*)
Sex, % female 54 29 52 36
Race, % White NR 95 NR NR
Family history of HAE, % 84 86 84 NR
Age of symptom onset, median (IQR), y 5 (2.8–10) 5.7 (5–9) 7.7 (NR) 4 (1–11)
Age of diagnosis, median (IQR), y 8 (4.5–11.5) 5.0 (4–8) 7 (NR) 3.4 (1.7–5.7)
With fam Hx NR 5.0 (2.0–7.5) 7.2† NR
Without fam Hx NR 10.0 (5–16) 9.5† NR
HAE type, % Type I (90%) NR Type I (100%) Type I (86%)
Presenting complaint at diagnosis, n/N (%)
Peripheral edema NR NR 14/25 (56) 8/14 (57)
Facial/upper airway edema NR NR 8/25 (32) 0 (0)
Abdominal pain/edema NR NR 9/25 (35) 6/14 (43)
Genitourinary edema NR NR 1/25 (4) NR
None (presymptomatic) NR 5/21 (24) 3/25 (12) 8/14 (36)
Distribution of attack locations‡, n/N (%)
Peripheral edema ~890/1392 (64) 11/15 (73) NR 11/14 (79)
Facial/upper airway edema ~180/1392 (13) 4/15 (27) NR 4/14 (29)
Abdominal pain/edema ~278/1392 (20) 14/15 (93) NR 14/14 (100)
Genitourinary edema ~14/1392 (1) NR NR NR
Adapted from Pattanaik and Leiberman.26
*Only 14 of 22 patients had symptoms at/before the time of diagnosis.
†Reported as mean.
‡Reports varied from the location of total cohort attacks during study period (Farkas et al) to lifetime attacks (Nanda et al) to individual history of personal
attack experiences ever (Aabom et al).
NR indicates not reported; HAE, hereditary angioedema; No, number; IQR, interquartile range; Hx, history.

Krack et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
and juvenile idiopathic arthritis. Care was established at age 3 years

with allergy. During her fourth year of life, symptom frequency TABLE 2. Differentiating Histaminergic from
Bradykinin-Mediated Angioedema15,26
and severity worsened, presenting as monthly episodes of fever
and associated swelling of the extremities and face—periodic fe-
Histaminergic Both Bradykinin-Mediated
ver syndromes were suspected. A serum C4 was obtained and
was decreased at <5.5 mg/dL (normal range, 11.8–39.0 mg/dL). Urticaria Swelling of lip/tongue Erythema marginatum
C3 was normal. Low serum C1-INH quantitative (4.8 mg/dL; nor- Rapid onset Pruritis Subacute prodrome
mal range, 21.0–39.0 mg/dL) and serum C1-INH functional (minutes to hours) Facial swelling (hours to days)
percent (37%; normal value, >67%) were subsequently ob- Response to Laryngeal swelling Abdominal swelling/
tained, establishing the diagnosis of type I HAE. The previous epinephrine obstruction
associated rash was retrospectively believed to have been ery- Hypotension/shock Abdominal pain Peripheral swelling
thema marginatum, which is a prodromal rash seen before Wheeze Nausea Genitourinary swelling
HAE attacks in a large percentage of patients. She was started
Resolution in Vomiting Resolution in several days
on plasma-derived C1-INH (Berinert, King of Prussia, Penn) <12–24 h
as an on-demand therapy for acute attacks. Both parents were
tested for HAE and showed normal results. Because there was Adapted from Bernstein et al.15
no family history of HAE noted, it was believed that this case
represented a de novo mutation.
importance for clinicians to recognize the difference between
Case 2 bradykinin-mediated and histaminergic swelling.3
A 16-year-old boy with a known diagnosis of type I HAE A history of recurrent episodes of angioedema or colicky
presents with allergy during follow-up. Family history was notable abdominal pain should raise suspicion for HAE (Table 1).1,17–20
for the father and multiple relatives having type I HAE. At 5 years Hereditary angioedema can be varied in its initial or recurrent pre-
of age, he began experiencing symptoms of intermittent hand, sentation with significant overlap of signs and symptoms with
feet, and genitalia swelling; abdominal pain and vomiting; and a histamine-mediated angioedema and anaphylaxis (Table 2).15,26
lacy reticular rash. His attacks occurred 4 to 5 times a year. The Prodromal symptoms, present in 50% to 95.7% of cases, can
attacks were triggered by minor physical trauma, and he responded be present hours to days before onset of an angioedema attack.31
well to plasma-derived C1-INH (Berinert). At age 10 years, he was The most common prodromal symptoms include pruritis (42%),
enrolled in a trial for on-demand icatibant, a bradykinin-2 receptor erythema marginatum rash (42%), gastrointestinal pain/pressure
antagonist therapy. At age 12 years, his facial swelling attacks in- (39%), and nausea (33%), and, to a lesser extent, fatigue, extrem-
creased in frequency with 6 episodes in 2 months triggered by ity tingling, anorexia, and myalgias.31
trauma, stress, and weather changes (20°F–30°F swings in either di- Clinical factors more suggestive of histaminergic urticarial/
rection). Each attack had prodromal rash of 24 hours consistent angioedema or IgE-mediated anaphylaxis, respectively, are rapid
with erythema marginatum. His treatment was changed to the onset of hives with angioedema in minutes to hours, without or
on-demand kallikrein inhibitor, ecallantide. His attack frequency with wheezing, hypotension, nausea/vomiting, and response to
continued to progress to monthly episodes at age 13 years, and antihistamines, glucocorticoids, or epinephrine, particularly with
cognitive behavior therapy to reduce stress was initiated. At age exposure to a known trigger with resolution within the first 12 to
14 years, because of the increased attack frequency and waning 24 hours of onset.14 In contrast, HAE attacks tend to peak at up to
response to ecallantide, the patient was enrolled in a trial investi- 12 to 24 hours from onset and may persist up to several days.15
gating lanadelumab (Takhzyro, Lexington, Mass), a long-acting Unlike histamine-mediated angioedema, bradykinin-mediated
kallikrein inhibitor administered subcutaneously every 2 weeks. angioedema is not associated with urticarial lesions; however, ery-
By age 15 years, the patient experienced near-complete resolution thema marginatum, a characteristic nonpruritic prodromal rash eas-
of attacks irrespective of triggers like stress, weather changes, and ily confused with hives, is common as observed in case 1.1,14,15,31
trauma. He was eventually able to space the injections to once a
month per the research protocol. He is now currently enrolled in DIFFERENTIAL DIAGNOSIS
an oral plasma kallikrein inhibitor berotralstat (Biocryst Pharma- Clinician suspicion of primary angioedema will help in re-
ceuticals, Durham, NC; still investigational) study and remains ducing the large differential often associated with upper airway
HAE attack–free. obstruction, abdominal pain syndromes, and joint or extremity
pain, swelling, and rash (Table 3, Supplemental Digital Content 1,
CLINICAL CHARACTERISTICS http://links.lww.com/PEC/A710).33 This is important because
all 3 of those symptoms or signs may not manifest in a single epi-
Severity and frequency of HAE attacks can vary within and
sode of HAE. Differential diagnosis will vary depending on age
between individuals on a spectrum ranging from severe weekly at-
and sex of the patient, geographic location, and presenting signs
tacks to mild annual attacks.28,31 Attacks typically manifest as
and symptoms.
swelling of the face or lips, tongue, larynx, extremities, or genita-
lia and/or painful bowel wall edema that can lead to intestinal
obstruction.15,17–20 Attacks can last several days without treatment DIAGNOSTIC TESTING IN THE ED
and be incapacitating.32 Upper airway angioedema can lead to as- In the ED, children with new-onset or recurrent angioedema
phyxiation and death if the airway is not properly monitored and or unexplained, recurrent abdominal pain should have a screening
secured to prevent deterioration of ventilation. Up to 50% of pa- C4 level to assess for HAE. C4 is typically low during and be-
tients with HAE report at least one laryngeal swelling episode in tween attacks, but normal in HAE-nl-C1-INH, ACEi-induced an-
their lifetime, and a single episode of laryngeal angioedema has gioedema, and histamine-mediated anaphylaxis.1,15 A normal C4
been reported to be fatal in children as young as 9 years.3,25 level in a patient highly suspected to have HAE should be repeated
In contrast to anaphylaxis, HAE attacks do no respond to epi- during an attack. Tryptase has utility only in patients presenting
nephrine, H1-antihistamines, or glucocorticoids, emphasizing the with symptoms suggestive of anaphylaxis.15 Other diagnostic

testing should be dictated by the patient's clinical presentation. Con- postprocedure swelling. A second dose of on-demand therapy
sultation with an allergist with HAE expertise is recommended. should also be available in the event initial STP is ineffective2,14
GENERAL MANAGEMENT Long-Term Prophylaxis

General management strategies for HAE focus on a well- The decision to implement long-term prophylaxis (Table 3)
designed rescue plan for acute attacks with early recognition and should involve individual patient factors including severity, fre-
on-demand rescue treatment. There should be a patient-specific quency, and location of attacks after discussion with patient and
prevention plan with attention to patient education, trigger avoid- family members.14
ance, and care coordination, which should include patient and fam-
ily preferences for both short-term and long-term prophylactic ED MANAGEMENT
treatments.14 Emergency department pharmacies should keep at
least one on-demand therapy like icatibant or C1-INH replacement After assessing the severity of angioedema and ensuring air-
therapy on formulary for emergent treatment of an HAE attack. way patency, the next step is to determine if the swelling is hista-
Effective, targeted therapies developed over the past 2 decades minergic or nonhistaminergic in order to select the appropriate
have reduced morbidity and mortality for patients with HAE. treatment pathway. When nonhistaminergic angioedema is suspected,
Antifibrinolytic therapies (tranexamic acid and ε-aminocaproic workup should be initiated to determine if the patient has HAE. In the
acid) and androgens were historically used for prophylaxis, but ED setting, this workup can be challenging because quantitative C4
have been replaced with safer and more effective therapies.14 is unlikely to result in the time necessary to make management de-
cisions. Institutions may also not have HAE on-demand therapies
on their formularies. Previously diagnosed patients with HAE or
On-Demand Treatment for Acute Attacks
those with a strong family history of HAE should receive
Several Food and Drug Administration (FDA)–approved pe- on-demand therapy as soon as possible after initiation of attack to
diatric HAE therapies are now available (Table 3).1 Onset of treat- stop progression. Rarely, a second on-demand dose may be re-
ment effect may take up to 60 minutes, and complete resolution of quired. In the circumstances of an acute abdominal attack requiring
an attack may take several hours.1,14,36 a second dose, it is recommended to avoid premature diagnostic
closure and to assess for other causes of an acute abdomen. Recom-
Short-Term Prophylaxis mended observation time after medication administration in the
Short-term prophylaxis (STP) is indicated before known ED is between 2 to 6 hours to ensure no further progression.15
“stressors,” including medical, surgical, and dental procedures, given For attacks involving the upper airway, airway management
the increased potential risk of precipitating an attack. Short-term pro- is essential to prevent progression to complete airway obstruction.
phylaxis significantly reduces, but does not eliminate, the risk of In general, angioedema behind the teeth (ie, lingual, posterior oro-
acute attack.2 Plasma-derived C1-INH (Berinert) or recombinant pharyngeal, and laryngeal) is more likely to progress to airway ob-
C1-INH (Ruconest, Leiden, the Netherlands; not FDA labeled for struction than predental angioedema.41 Any evidence of impending
this use) delivered intravenously 1 to 2 hours before the procedure upper airway obstruction, including respiratory distress or failure,
is the preferred STP method.37–39 If these agents are not available stridor, hoarseness, or drooling, should prompt the activation of
and the patient is not old enough for other on-demand therapies, institutional critical/difficult airway teams experienced in fiber
fresh-frozen plasma can be used.1,14,40 Patients without a history optic–guided intubation and surgical airways, where available.15
of angioedema attacks induced by trauma or on prophylactic therapy Because supraglottic devices are unlikely to be successful, 2-hand
that is preventing attacks may not always require short-term prophy- bag-valve-mask ventilation may be required, ideally with in-line
15
laxis, but on-demand therapy should be readily available in case of ETCO2 monitoring. Neuromuscular paralysis should be avoided,
TABLE 3. FDA-Approved Pediatric Therapies for HAE1,15,19,34,35
Approved
Generic Trade FDA Approval Indication Ages Administration
Plasma-derived C1-INH Berinert (King of Prussia, Penn) Acute attacks, short-term All ages Intravenous
(protein replacement) prophylaxis
Recombinant human C1-INH Ruconest (Leiden, the Netherlands) Acute attacks 13 y and up Intravenous
(protein replacement)
Ecallantide Kalbitor (Lexington, Mass) Acute attacks 12 y and up Subcutaneous
(plasma-kallikrein inhibitor)
Icatibant Firazyr (Lexington, Mass) Acute attacks 18 y and up Subcutaneous
(bradykinin-2 receptor antagonist)
Plasma-derived C1-INH Cinryze (Lexington, Mass) Long-term prophylaxis 6 y and up Intravenous
Plasma-derived C1-INH HAEGARDA (King of Prussia, PA) Long-term prophylaxis 12 y and up Subcutaneous
Lanadelumab Takhzyro (Lexington, Mass) Long-term Prophylaxis 12 y and up Subcutaneous
(monoclonal antibody inhibitor of plasma
kallikrein)
Adapted from Bennett and Craig.19
C1-INH indicates C1 esterase inhibitor.

and sedation that allows for intact neuromuscular reflexes and spon- 5. Rosen FS, Pensky J, Donaldson V, et al. Hereditary angioneurotic edema:
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bation is considered the criterion standard of care, but video oral 6. Bork K. Hereditary angioedema with normal C1 inhibitor activity
tracheal laryngoscopy is an acceptable alternative.42–44 Preparation including hereditary angioedema with coagulation factor XII gene
and use of experienced proceduralists is encouraged to avoid multi- mutations. Immunol Allergy Clin North Am. 2006;26:709–724.
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Ensure cessation of offending agents, including exogenous
8. Kaplan AP, Joseph K. Pathogenesis of hereditary angioedema: the role of
estrogens or ACEi therapy, as both can worsen HAE.1 Intestinal
the bradykinin-forming cascade. Immunol Allergy Clin North Am. 2017;37:
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discharge is deemed appropriate, patients should be prescribed re-
fills for their on-demand agent. Referral to an HAE expert is key. 9. Zeerleder S, Levi M. Hereditary and acquired C1-inhibitor-dependent
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died of asphyxiation.45 Despite newer, very effective on-demand 14. Frank MM, Zuraw B, Banerji A, et al. Management of children with
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± 14.3 years (range, 9–78 years).3 Mortality is overall higher in emergency department: a practical guide to differential diagnosis and
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19. Bennett G, Craig T. Hereditary angioedema with a focus on the child.
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the development of several effective on-demand and prophylactic
therapies with improvement of outcomes. Emergency providers 20. Farkas H, Csuka D, Zotter Z, et al. Treatment of attacks with
should be able to distinguish bradykinin-mediated from histamin- plasma-derived C1-inhibitor concentrate in pediatric hereditary
angioedema patients. J Allergy Clin Immunol. 2013;131:909–911.
ergic angioedema, initiate appropriate diagnostic workups and
on-demand therapies for acute attacks, and counsel patients and 21. Bowen T, Cicardi M, Farkas H, et al. 2010 International consensus
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2012;130:692–697. 27. Cancian M, Perego F, Senter R, et al. Pediatric angioedema: essential
4. Bork K, Wulff K, Witzke G, et al. Hereditary angioedema with normal features and preliminary results from the Hereditary Angioedema
C1-INH with versus without specific F12 gene mutations. Allergy. 2015; Global Registry in Italy. Pediatr Allergy Immunol. 2020;31(suppl 24):
70:1004–1012. 22–24.

28. Banerji A, Li Y, Busse P, et al. Hereditary angioedema from the patient's 37. Frank MM. Update on preventive therapy (prophylaxis) of hereditary
perspective: a follow-up patient survey. Allergy Asthma Proc. 2018;39: angioedema. Allergy Asthma Proc. 2011;32:17–21.
212–223.
38. Lumry W, Manning ME, Hurewitz DS, et al. Nanofiltered C1-esterase
29. Otani IM, Christiansen SC, Busse P, et al. Emergency department inhibitor for the acute management and prevention of hereditary
management of hereditary angioedema attacks: patient perspectives. angioedema attacks due to C1-inhibitor deficiency in children. J Pediatr.
J Allergy Clin Immunol Pract. 2017;5:128–134.e4. 2013;162:1017–1022 e1011–1012.
30. Christiansen SC, Davis DK, Castaldo AJ, et al. Pediatric hereditary 39. Schneider L, Hurewitz D, Wasserman R, et al. C1-INH concentrate for
angioedema: onset, diagnostic delay, and disease severity. Clin Pediatr treatment of acute hereditary angioedema: a pediatric cohort from the I.M.P.
(Phila). 2016;55:935–942. A.C.T. studies. Pediatr Allergy Immunol. 2013;24:54–60.
31. Reshef A, Prematta MJ, Craig TJ. Signs and symptoms preceding acute 40. Jaffe CJ, Atkinson JP, Gelfand JA, et al. Hereditary angioedema: the use of
attacks of hereditary angioedema: results of three recent surveys. Allergy fresh frozen plasma for prophylaxis in patients undergoing oral surgery.
Asthma Proc. 2013;34:261–266. J Allergy Clin Immunol. 1975;55:386–393.
32. Kemp JG, Craig TJ. Variability of prodromal signs and symptoms
41. Ishoo E, Shah UK, Grillone GA, et al. Predicting airway risk in
associated with hereditary angioedema attacks: a literature review. Allergy
angioedema: staging system based on presentation. Otolaryngol Head
Asthma Proc. 2009;30:493–499.
Neck Surg. 1999;121:263–268.
33. Shaw KN, Bachur RG. Fleisher & Ludwig's Textbook of Pediatric
42. Driver BE, McGill JW. Emergency department airway management of
Emergency Medicine. 7th ed. Philadelphia, PA: Wolters Kluwer; 2016.
severe angioedema: a video review of 45 intubations. Ann Emerg Med.
34. Aygoren-Pursun E, Soteres DF, Nieto-Martinez SA, et al. A randomized 2017;69:635–639.
trial of human C1 inhibitor prophylaxis in children with hereditary
angioedema. Pediatr Allergy Immunol. 2019;30:553–561. 43. Lewis SR, Butler AR, Parker J, et al. Videolaryngoscopy versus direct
laryngoscopy for adult patients requiring tracheal intubation. Cochrane
35. Busse PJ, Farkas H, Banerji A, et al. Lanadelumab for the prophylactic Database Syst Rev. 2016;11:CD011136.
treatment of hereditary angioedema with C1 inhibitor deficiency: a review
of preclinical and phase I studies. BioDrugs. 2019;33:33–43. 44. Pandian V, Zhen G, Stanley S, et al. Management of difficult airway among
patients with oropharyngeal angioedema. Laryngoscope. 2019;129:
36. Busse P, Bygum A, Edelman J, et al. Safety of C1-esterase inhibitor in acute
1360–1367.
and prophylactic therapy of hereditary angioedema: findings from the
ongoing international Berinert patient registry. J Allergy Clin Immunol 45. Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema: the clinical
Pract. 2015;3:213–219. syndrome and its management. Ann Intern Med. 1976;84:580–593.

CME EXAM
INSTRUCTIONS FOR OBTAINING AMA PRA CATEGORY 1 CREDITSTM
Pediatric Emergency Care includes CME-certified content that is designed to meet the educational needs of its readers. An annual
total of 12 AMA PRA CATEGORY 1 CREDITSTM are available through the twelve 2021 issues of Pediatric Emergency Care. This activity
is available for credit through March 31, 2023. The CME activity is now available online. Please visit http://CME.LWW.com for more
information about this educational offering and to complete the CME activity.
CME EXAMINATION
APRIL 2021
Please mark your answers on the ANSWER SHEET.
Recognition, Evaluation, and Management of Pediatric Hereditary Angioedema, Krack et al
1. A 6-year-old boy presents with his fifth episode of lip and tongue ventilation. While preparing for additional airway manage-
swelling. Family history is notable for a mother with HAE type 1. ment, administration of what is the next best step?
Physical examination is notable for a patent airway without stri- a. IM epinephrine
dor or dyspnea but mild lip, tongue, and right arm edema and a b. Plasma-derived C1-INH replacement protein (Berinert)
clustering of serpiginous, nonpruritic, erythematous lesions with c. FFP
pale centers and rounded margins on the left hip. What patho- d. Plasma-derived C1-INH replacement protein (HAEGARDA)
physiologic derangement is most likely in this patient?
a. Bradykinin deficiency 4. A 9-year-old boy with type II HAE presents to the ED with
b. IgE-mediated mast cell degranulation crown-root fractures of teeth E & F. The on-call dental resident
c. Factor XII deficiency is recommending extraction in the ED. What medication is in-
d. Functional C1-esterase inhibitor deficiency dicated before extraction?
a. FFP immediately before extraction
2. A 3-year-old girl presents with acute onset of severe abdominal b. Berinert at least 1 to 2 hours before extraction
pain, this being the fourth similar episode in the last 12 months c. HAEGARDA at least 2 hours before extraction
without any clear etiology despite extensive workup—you sus- d. Lanadelumab (Takhzyro) immediately before extraction
pect HAE. What ED screening test is indicated?
a. Serum C4 5. A 12-year-old girl with type I HAE presents with stridor after
b. Serum tryptase having received Berinert 3 hours ago. A repeat dose of Berinert
c. Serum C1q is given, but she develops dyspnea and hypercapnea after
d. Genetic sequencing of SERPING1 30 minutes. What is the best next step in airway management?
a. Supraglottic device place with ETCO2 monitoring
3. A 16-year-old girl with a known history of HAE-C1-INH pre- b. Immediate RSI
sents with 18 hours of progressive facial and pharyngeal swell- c. Await response from second dose of Berinert
ing and dyspnea, which is temporized with CPAP via BVM d. Awake fiber optic nasotracheal intubation

ANSWER SHEET FOR THE PEDIATRIC EMERGENCY CARE

CME PROGRAM EXAM
April 2021
Please answer the questions on page 224 by filling in the appropriate circles on the answer sheet below. Please mark the one best
answer and fill in the circle until the letter is no longer visible. To process your exam, you must also provide the following information:
Name (please print): __________________________________________________________________________________________
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Daytime Phone ______________________________________________________________________________________________

Specialty ___________________________________________________________________________________________________
1. A B C D

2. A B C D
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Your completion of this activity includes evaluating them. Please respond to the following questions below.
Please rate this activity (1 - minimally, 5 - completely) 1 2 3 4 5
Was effective in meeting the educational objectives
Was appropriately evidence-based
Was relevant to my practice
Please rate your ability to achieve the following objectives, both before this activity and after it::
1 (minimally) to 5 (completely) Pre Post
1 2 3 4 5 1 2 3 4 5
1. Describe the pathophysiologic differences between various causes of angioedema.
2. Identify, evaluate, and manage acute complications of hereditary angioedema (HAE).
3. Explain the natural history, precipitating events, and chronic management of HAE, including
short-term and long-term prophylactic treatments.
How many of your patients are likely to be impacted by what you learned from these activities?
○ <20% ○ 20%–40% ○ 40%–60% ○ 60%–80% ○ >80%
Do you expect that these activities will help you improve your skill or judgment 1 2 3 4 5
within the next 6 months? (1 - definitely will not change, 5 - definitely will change)
How will you apply what you learned from these activities (mark all that apply):
In diagnosing patients ○ In making treatment decisions ○
In monitoring patients ○ As a foundation to learn more ○
In educating students and colleagues ○ In educating patients and their caregivers ○
As part of a quality or peformance improvement project ○ To confirm current practice ○
For maintenance of board certification ○ For maintenance of licensure ○
To consider enrolling patients in clinical trials ○
Other ______________________________________________________________________________________________________
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ULTRASOUND CASE REVIEW
Associate Editor: J. Kate Deanehan, MD, RDMS
Pediatric Abdominal Tuberculosis With Calcified

Intra-abdominal Lymph Nodes Identified by
Point-of-Care Ultrasound
Vigil James, MD,* John Samuel, MBBS, DMRD, MD,† and Gene Yong-Kwang Ong, MBBS, MRCPCH*
CASE PRESENTATION AND US FINDINGS

Background: Tuberculosis of the abdomen is one of the most common
extrapulmonary manifestations of tuberculosis. Even in areas where tuber- A 13-year-old boy was brought to a PED in South India with
culosis is endemic, intra-abdominal tuberculous can pose a diagnostic and fever for 3 weeks and intermittent abdominal pain for 2 weeks
management challenge because of the lack of presence of overt clinical with loss of appetite. There was no associated cough, vomiting, di-
signs and availability of expertise for point of care diagnostics. Point-of- arrhea, or dysuria. The patient's past medical history was signifi-
care ultrasound (POCUS) of the abdomen performed by emergency physi- cant for previous treatment for pulmonary tuberculosis at the
cians is increasingly being used for a variety of clinical presentations to fa- age of 3 years.
cilitate accurate diagnoses in the emergency department. On examination, he was alert with temperature of 39.1°C,
Case Report: We describe the case of a patient presenting to the pediatric heart rate of 110 beats per minute, blood pressure of 94/64 mm Hg;
emergency department with acute abdominal pain, in whom POCUS capillary refill was less than 2 seconds, and there were no signs of
helped expedite the diagnosis of abdominal tuberculosis. dehydration. The cervical, axillary, and inguinal nodes were not
Conclusions: In the right clinical setting, the concurrent presence of enlarged. The abdomen was not distended, but there was general-
intra-abdominal lymphadenopathy, ascites, mesenteric thickening, ileocecal ized tenderness to palpation with hepatosplenomegaly appreciated.
thickening, and splenic microabscesses on ultrasound imaging should lead The lungs were clear on auscultation. The initial differential diagno-
to consideration of the diagnosis of intra-abdominal tuberculosis. Although sis included infectious etiologies such as enteric fever (typhoid),
typically diagnosed on computed tomography or magnetic resonance im- malaria, and abdominal tuberculosis, as well as oncological condi-
aging, in our case, POCUS helped facilitate the bedside diagnosis of ab- tions like acute leukemia or lymphoma.
dominal tuberculosis in the emergency department. A POCUS examination of the abdomen was performed by
the PED attending physician using both linear (14–5 MHz) and
Key Words: abdominal tuberculosis, tuberculous lymphadenopathy, point- curvilinear (2–5 MHz) transducers to look for intra-abdominal pa-
of-care ultrasound, calcified lymph nodes, pediatric abdominal pain, thology and free fluid. The ultrasound examination revealed a cal-
pediatric emergency, bedside ultrasound, extrapulmonary tuberculosis cified right paracolic lymph node with macrocalcifications and
(Pediatr Emer Care 2021;37: 226–229) dense posterior shadowing (Fig. 1). In addition, there was a distor-
tion of the normal lymph node architecture (Fig. 2) with the ab-
sence of a fatty hilum and hypoechoic cortex. There were no
T uberculosis of the abdomen is one of the most common
extrapulmonary manifestations of tuberculosis. Even in areas
where tuberculosis is endemic, intra-abdominal tuberculous can
signs of free fluid in the abdomen suggestive of ascites, nor was
there any small bowel dilatation, mesenteric thickening, ileocecal
pose a diagnostic and management challenge because of the lack thickening, or focal hypoechoic lesions in the liver or spleen seen
of presence of overt clinical signs and lack of availability of ex- on POCUS.
pertise for point of care diagnostics.1 In a majority of pediatric The POCUS findings of a calcified intra-abdominal lymph
patients, the clinical presentation of abdominal tuberculosis in- node, combined with the past history of tuberculosis, helped nar-
cludes fever, abdominal pain, significant weight loss, or chronic row the differential diagnosis to possible abdominal tuberculosis
diarrhea.2 The abdominal symptoms are usually protracted and secondary to reactivation. The patient was admitted for further
nonspecific and, thus, may be confused with other clinical condi- workup to the inpatient ward. The Tuberculin skin test performed
tions, often resulting in a delay in diagnosis.3 was more than 10 mm. His complete blood count was normal ex-
Abdominal tuberculosis presents with a variable involvement cept for hemoglobin of 7.2 g/dL, human immunodeficiency virus
of intra-abdominal structures, including the gastrointestinal tract, serology was negative, erythrocyte sedimentation rate was 79 mm/h,
lymph nodes, peritoneum, liver, and spleen.3,4 We describe the and C-reactive protein level was 48 mg/L. The patient was diag-
case of a patient who presented to the pediatric emergency depart- nosed with abdominal tuberculosis, based on the clinical history
ment (PED) with acute abdominal pain and in whom point-of-care and laboratory markers, and was commenced on antituberculosis
ultrasound (POCUS) helped expedite the diagnosis of abdominal therapy. On follow-up, 4 weeks after starting the antituberculosis
tuberculosis. therapy, the patient had resolution of fever and abdominal pain
and a marked improvement in his appetite.
From the *Children’s Emergency, KK Women’s and Children’s Hospital, TECHNIQUE

Singapore; and †Department of Radiodiagnosis, Christian Fellowship Hospital,
Oddanchatram, Tamilnadu, India. With the patient lying in the supine position, a low-frequency
Disclosure: The authors declare no conflict of interest. transducer should be used for a FAFF (focused assessment for free
Reprints: Vigil James, MD, Children’s Emergency, KK Women’s And fluid) scan to detect free fluid in the abdomen suggestive of asci-
Children’s Hospital, 100 Bukit Timah Road, Singapore, 229899
(e‐mail: vigiljames@gmail.com).
tes. In smaller patients, the high-frequency linear probe provides
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. better resolution for a thorough interrogation of the large bowel
ISSN: 0749-5161 looking for bowel wall thickening, as well as for evaluation of

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Pediatric Abdominal Tuberculosis
FIGURE 1. Tuberculosis calcified lymph node: calcified right paracolic node showing macrocalcification (long thin arrows) and dense
posterior acoustic shadowing (thick arrows). The abdominal wall muscles (arrowhead) are seen in the upper part of the image, and the
mesenteric fat (star) is seen adjacent to the calcified lymph node. The tuberculous node lacks the normal lymph node architecture.
the mesentery and surrounding lymph nodes. The ultrasound de- abnormal lymph node architecture with calcification. Tuberculous
tection of either abdominal lymphadenopathy or ascites, focal lymph nodes will show suppurative changes in the acute phase.
lesions in the liver, or splenic microabscesses is highly suggestive On ultrasound, central necrosis appears as a hypoechoic, hetero-
of intra-abdominal tuberculosis.2,5 geneous echogenicity with debris, septa, and reduction of the
The central abdominal areas should be scanned to detect ab- hyperechoic fatty hilum. There may also be adjacent perinodal
normal dilatation of the small bowel, mesenteric thickening, and soft tissue edema and matting (clumping of multiple nodes with
FIGURE 2. Normal intra-abdominal lymph node for comparison: well-defined lymph node in the right upper quadrant of the abdomen,
which is reniform in shape with a fatty echogenic hilum (long thin arrow). The hilum is continuous with adjacent soft tissue, and the cortex
(star) is relatively hypoechoic when compared with the surrounding tissues. The abdominal wall muscles (arrowhead) and bowel (thick arrow)
with intraluminal contents are seen adjacent to the intra-abdominal lymph node.

James et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
no normal soft tissue in between).6,7 On color Doppler assessment, Tuberculous lymphadenitis in the abdomen can be a result of
vascular distribution with apparent avascular areas and displaced reactivation of healed foci (which were involved during primary
hilar vascularity can be seen in the lymph node.8 infection) or due to hematogenous spread of the tuberculosis
The most common site of intestinal involvement in abdomi- bacilli. Within the abdomen, the lymph nodes in the small
nal tuberculosis is the ileocecal junction (terminal ileal wall bowel mesentery and retroperitoneum are most commonly in-
thickening) and the cecum.3 “Pseudo-kidney sign” describes volved.3 Additional areas of lymph node involvement can include
the involvement of the ileocecal region, which is pulled up to the periportal, peripancreatic, anterior pararenal space, and upper
a subhepatic position producing a bowel mass with an echogenic para-aortic areas.4
central lumen.9 Involvement of the peritoneum will present most The clinical presentation of abdominal tuberculosis is often
commonly as simple ascites or less frequently as complex fluid nonspecific, with vague abdominal pain and systemic complaints,
with septations.4 Mesenteric involvement in abdominal tuberculo- which can lead to a delayed diagnosis.17 Laboratory tests are often
sis, which appears as thickening of the mesentery, is noticed mainly nonspecific, and the tuberculin skin tests and Ziehl-Neelsen stain-
in the left quadrant and paraumbilical regions of the abdomen. ing might yield negative results.18,19 The condition also mimics
The ultrasound assessment should conclude by scanning the many conditions, including malignancy, inflammatory bowel dis-
hepatic and splenic areas for hypoechoic granulomas, and renal ease, and other infectious diseases.20
parenchyma for echogenic lesions and calcifications. Additional The ultrasound findings in abdominal tuberculosis are diverse
scanning in the subxiphoid window to evaluate for the presence because of the varied extent of involvement of hollow viscus, solid
of a pericardial effusion and in bilateral upper quadrants looking organs, lymph nodes, mesentery, and peritoneum depending on the
for an anechoic area in the supradiaphragmatic area (or the “spine stage of the disease process. However, the presence of sonological
sign” suggestive of a pleural effusion) will help detect the presence findings specific to different stages of abdominal tuberculosis
of pericardial and pulmonary involvement, respectively.5 may help expedite the diagnosis in the appropriate clinical setting.
Genitourinary tuberculosis, a form of secondary tuberculo- The most characteristic sonographic finding in patients with early
sis, is very rare in children.10 The sonographic features of renal tu- abdominal tuberculosis is the combination of mesenteric thicken-
berculosis include renal parenchymal masses, cavities, and renal ing with associated mesenteric lymphadenopathy in the proper
or ureteral calcifications. “Putty-like” kidney, which describes clinical setting.21 As the disease progresses, abdominal lymph-
calcified caseous homogeneous renal tissue with moderately adenopathy and splenic microabscesses are consistent findings
dense echogenic appearance greater than 1 cm in diameter, is also in these patients.22 The notable presence of ascites (especially
a rare presentation in children. with fibrinous stranding) and hepatomegaly on ultrasound are
In patients with advanced tuberculosis, clustered calcifications
in several foci can progress to extensive hyperechoic appearing
nodal calcifications with dense posterior acoustic shadowing in TABLE 1. Summary of Ultrasound Findings in Different
Anatomical Areas in Children With Tuberculosis
the chronic phase (Fig. 1).8,11 Tuberculous calcifications distort
the normal reniform architecture of intra-abdominal lymph nodes
Anatomical Region Sonographic Findings
with loss of the fatty echogenic hilum (Fig. 1, 2). Calcified
tuberculous intra-abdominal lymph nodes are generally located in Peritoneal cavity Ascites
the lower central or right lower paracolic areas of the abdomen. • Clear
The differential diagnosis for intra-abdominal calcified lymph • Loculated (thick septa)
nodes in children includes nontuberculous mycobacterial infections, • Sandwich sign (small amount of ascitic
sarcoidosis, lymphoma, leukemia, inflammatory bowel disease fluid between the bowel loops)
(especially Crohn disease), systemic lupus erythematosus, and Lymph nodes Intranodal cystic necrosis
rheumatoid arthritis.12 Perinodal anechoic areas
Matting
Speckled calcification*
Coarse calcification with posterior
REVIEW OF THE LITERATURE acoustic shadows *
Point-of-care ultrasound of the abdomen performed by emer- Mesentery Mesenteric thickening >15 mm
gency physicians is increasingly being used to evaluate patients Increased echogenicity of mesentery
with a variety of clinical complaints and to facilitate accurate diag- Intestines Ileocecal thickening
noses in the emergency department.13 After a thorough history Pseudo-kidney sign (subhepatic bowel
and clinical examination, POCUS should be considered for the as- mass with echogenic central lumen)
sessment of acute abdominal pain, based on the particular differ- Small bowel dilatation
ential diagnosis. Ultrasound can be a useful adjunct for the Increased peristalsis due to small
bedside diagnosis of a variety of abdominal pathologies including bowel obstruction
appendicitis, small bowel obstruction, and gastrointestinal perfo- Liver Focal hypoechoic lesions
ration.13 In resource-limited settings, POCUS performed by emer- Calcified hyperechoic granulomas
gency physicians has been shown to be associated with a faster Spleen Hypoechoic splenic microabscesses
time to diagnosis for a large variety of conditions.14 Hyperechoic splenic granulomas
Abdominal tuberculosis is a common form of extrapulmonary Heart Pericardial effusion
tuberculosis, with lymph nodes being the most commonly involved Lungs Pleural effusion
site, but involvement of other areas of the gastrointestinal tract in- Genitourinary Focal renal echogenic lesion
cluding the liver, spleen, adrenals, and peritoneum can also be Renal parenchymal hypoechoic cavities
seen.15 Tuberculous bacilli reach the abdomen by three routes of Renal parenchymal echogenic calcifications
transmission: gastrointestinal tract infection by ingestion of contam- Ureteral echogenic calcifications
inated sputum or milk followed by spread into the lymph nodes, “Putty-like” kidney
hematogenous spread from a distant tuberculous focus, and direct *Advanced stages of tuberculosis.
transmission from adjacent infected intra-abdominal organs.16

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Pediatric Abdominal Tuberculosis
consistently detected in patients with advanced abdominal tuber- 9. Kedar RP, Shah PP, Shivde RS, et al. Sonographic findings in
culosis.3 While the presence of an individual sonological finding gastrointestinal and peritoneal tuberculosis. Clin Radiol.
might have limited diagnostic value in the diagnosis of abdominal 1994;49:24–29.
tuberculosis, the confluence of multiple sonological findings 10. Nerli RB, Kamat GV, Alur SB, et al. Genitourinary tuberculosis in pediatric
(Table 1) makes the diagnosis highly likely. urological practice. J Pediatr Urol. 2008;4:299–303.
11. Eisenkraft BL, Som PM. The spectrum of benign and malignant etiologies
CONCLUSIONS of cervical node calcification. AJR Am J Roentgenol. 1999;
In a plausible clinical setting, the concurrent presence of 172:1433–1437.
intra-abdominal lymphadenopathy, ascites, mesenteric thickening, 12. Karmazyn B, Werner EA, Rejaie B, et al. Mesenteric lymph nodes in
ileocecal thickening, and splenic microabscesses on ultrasound children: what is normal? Pediatr Radiol. 2005;35:774–777.
imaging are suspicious for the diagnosis of intra-abdominal tuber-
13. Kameda T, Taniguchi N. Overview of point-of-care abdominal ultrasound
culosis. Although typically diagnosed on computed tomography
in emergency and critical care. J Intensive Care. 2016;4:53.
or magnetic resonance imaging, in our case, POCUS helped facil-
itate the bedside diagnosis of abdominal tuberculosis in a pediatric 14. Stanley A, Wajanga BMK, Jaka H, et al. The impact of systematic
patient presenting to the emergency department. point-of-care ultrasound on management of patients in a resource-limited
setting. Am J Trop Med Hyg. 2017;96:488–492.
REFERENCES 15. Shao H, Yang Z-G, Xu G-H, et al. Tuberculosis in the abdominal
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imaging. Int J Tuberc Lung Dis Off J Int Union Tuberc Lung Dis.
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2013;17:90–95.
2. Heller T, Goblirsch S, Wallrauch C, et al. Abdominal tuberculosis:
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rural South Africa. Int J Infect Dis. 2010;14:e108–e112. gastrointestinal and abdominal tuberculosis. Eur Radiol. 2004;
14(suppl 3):E103–E115.
3. Rathi P, Gambhire P. Abdominal Tuberculosis. J Assoc Physicians India.
2016;64:38–47. 17. Teh LB, Ng HS, Ho MS, et al. The varied manifestations of abdominal
tuberculosis. Ann Acad Med Singapore. 1987;16:488–494.
4. Malik A, Saxena NC. Ultrasound in abdominal tuberculosis. Abdom
Imaging. 2003;28:574–579. 18. Wells AD, Northover JM, Howard ER. Abdominal tuberculosis: still a
problem today. J R Soc Med. 1986;79:149–153.
5. Weber SF, Saravu K, Heller T, et al. Point-of-care ultrasound for
extrapulmonary tuberculosis in India: a prospective cohort study in 19. Uzunkoy A, Harma M, Harma M. Diagnosis of abdominal tuberculosis:
HIV-positive and HIV-negative presumptive tuberculosis patients. experience from 11 cases and review of the literature. World J
Am J Trop Med Hyg. 2018;98:266–273. Gastroenterol. 2004;10:3647–3649.
6. Ying M, Ahuja AT, Evans R, et al. Cervical lymphadenopathy: sonographic 20. Jadvar H, Mindelzun RE, Olcott EW, et al. Still the great mimicker:
differentiation between tuberculous nodes and nodal metastases from abdominal tuberculosis. AJR Am J Roentgenol. 1997;168:
non-head and neck carcinomas. J Clin Ultrasound JCU. 1998;26:383–389. 1455–1460.
7. Ahuja A, Ying M, Evans R, et al. The application of ultrasound criteria for 21. Jain R, Sawhney S, Bhargava DK, et al. Diagnosis of abdominal
malignancy in differentiating tuberculous cervical adenitis from metastatic tuberculosis: sonographic findings in patients with early disease. AJR Am J
nasopharyngeal carcinoma. Clin Radiol. 1995;50:391–395. Roentgenol. 1995;165:1391–1395.
8. Park JH, Kim DW. Sonographic diagnosis of tuberculous lymphadenitis in 22. Bélard S, Heller T, Orie V, et al. Sonographic findings of abdominal
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1619–1626. 2017;36:1224–1226.

SPECIAL FEATURE
Pediatric Emergency Telemedicine

An Untapped Resource for Vulnerable Populations During COVID-19
Joan Bregstein, MD,* Daniel Fenster, MS, MD,* and Maria Lame, MD†
(Pediatr Emer Care 2021;37: 230–231) Medicaid still remains largely within the powers of individual
states, and telehealth implementation varies state to state in terms
of services for which providers will receive reimbursement. Also
B efore COVID-19, our pediatric emergency department (ED)
would have been evaluating and treating close to 180 children
daily. We are a quaternary care, level 1 trauma center, serving as a
at issue is telehealth parity legislation, which addresses whether
telehealth visits should be reimbursed at the same rates as
safety net for Washington Heights/Inwood in NYC, a primarily im- in-person visits for the same complaint.3 Even within New York
migrant, Latino, limited English-speaking population. Over 30% of State, reimbursement policies may differ across telehealth applica-
patients present with mild diseases, including colds, sore throats, tions. Despite efforts in March by the Centers for Medicare and
and rashes, most of which do not require highly specialized care. Medicaid (CMS) to expand the range of telehealth visits federally
COVID-19 has, and continues to affect adults on a much covered, an insurance plan might only cover primary care telehealth
larger scale than it affects children. When coupled with federally visits but not emergency visits. There are still entire markets that
and state-imposed “stay-at-home” orders in March and fear of lack telehealth, because of the lack of reimbursement or reimburse-
nosocomial spread of infection with travel to an ED, we knew ment at lower rates than comparable in-person services.
when COVID hit that our ED volume would fall. We were sur- Technological literacy is a huge barrier because users require
prised, though, that it fell by close to 85% and has remained low. access to a computer, tablet, or smartphone with high-speed Inter-
Before this unprecedented drop in patient volume, there was net. Greater than 40% of low-income New Yorkers lack
emergence of our multicampus pediatric emergency medicine high-speed Internet.4 There have been efforts to increase broad-
telehealth program that encompassed not only the community of band internet in low-income areas, but this issue still remains un-
Washington Heights but also that of Queens, one of the most ethni- resolved. Even if high quality internet is available, there is a price
cally diverse counties in the United States and the “epicenter of the tag associated with this which is a barrier, particularly if the
epicenter” of the US COVID pandemic. This comprehensive pro- telehealth visit is lengthy. The use of text messaging in health care
gram had been launched several years ago, but was still experienc- delivery and outreach has expanded in the last 15 to 20 years but
ing growing pains. Pediatric telehealth generally has blossomed system requirements for telehealth divide the patient population
nationally1 but, because of the nature of emergency medicine, along socioeconomic lines.5
which requires an urgent, hands-on, real-time evaluation of patients, The lack of English language proficiency is a compounding
telehealth in our EDs had not found its comfort zone. It should have barrier impairing access to pediatric emergency telehealth care.
been an efficient option for the 30% of our population experiencing Only half of New Yorkers speak English at home,2 and although
less severe disease. We had piloted a variety of virtual pediatric many EDs have 24-hour interpreter services, this is not yet stan-
emergency programs but provider buy-in and satisfaction was dard of care for telehealth practices. Additionally, there is a lack
limited, and pediatric ED virtual visits were low, approximating of telemarketing in these communities in their native languages.
1.3 calls per day during the winter of 2020. Pediatric ED telehealth Another factor that has likely impacted the recent lack of pe-
was still looking for its purpose. diatric emergency telehealth volume is the overall decrease in the
With Governor Cuomo's “NYS on PAUSE” order issued need for emergency care. Many pediatric visits to our ED are, at
March 20, 2020, and thus the newly imposed barrier to accessing least in part, to obtain school notes to excuse for illness, which
emergency care in an ED, we expected calls to our pediatric emer- is a requirement in NYC public schools. Schools are still primarily
gency telehealth program to soar but, again, they did not. Despite functioning virtually or, in some cases, in a hybrid fashion so
the fact that adult virtual emergency care was booming, calls for school notes are less in demand. Additionally, because children
children totaled fewer than 10 per day across all campuses. That are quarantined indoors, there are fewer opportunities for acciden-
leaves hundreds of patients per day who were missing from the tal injuries and community spread of infections.
emergency health care system, and begs the question, where were From our virtual experiences with the adult population, which
they and why were they not on telehealth? relied highly on telehealth during the COVID pandemic, we have
First, cost is an issue. As much as 27% of the communities realized the enormous capabilities of telemedicine in emergency
we serve lives below the poverty line.2 For this population, an care. In the last 10 months, in addition to hundreds of COVID-
emergency telehealth visit is unaffordable, particularly without in- 19–related concerns, we have addressed a range of clinical issues
surance reimbursement and if payment upfront is requested. in our adults from sore throats to chest pain and congestive heart
failure; we have even diagnosed appendicitis. We have provided a
From the *Department of Emergency Medicine, Columbia University Vagelos platform for follow-up visits, respiratory checks, prescription re-
College of Physicians & Surgeons, New York Presbyterian Morgan Stanley newals, and specialty clinic referrals. Many of these, if not for
Children's Hospital; and †Department of Emergency Medicine, Weill Cornell
Medical College, New York Presbyterian Komansky Center for Children's
telehealth, would have been in-person ED visits.
Health, New York, NY. There are indeed limitations to pediatric emergency telehealth.
Disclosure: The authors declare no conflict of interest. Many say that virtual emergency care reduces the continuity of care
Reprints: Joan Bregstein, MD, Department of Emergency Medicine, Columbia and intimacy that results from the traditional ongoing doctor-patient
University Medical Center, CHN-1, 3959 Broadway, New York, NY 10032
(e‐mail: jsb61@cumc.columbia.edu).
relationship, which develops over time. They also argue that there
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. are privacy issues and risk of hacking and infiltration in the syn-
ISSN: 0749-5161 chronous real-time video. Added to these are the possibility that

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Pediatric Emergency Telemedicine During COVID-19
prescriptions, and possibly antibiotic use, may increase with vir- including how children access emergency medical care in the future.
tual visits. There is also the challenge of evaluating the very young We, as health care providers and policy makers, have a unique oppor-
population in which a hands-on physical examination might give tunity to change the way New Yorkers, and specifically children, use
a provider a better handle on how the patient is doing. However, the ED. With careful foresight and planning, we can effect positive
emergency telehealth provides the opportunity for the patient to change by making pediatric emergency telehealth more accessible
be seen urgently and expeditiously by a provider, virtually, in to all New Yorkers. We must work at the state level to ensure ap-
the privacy of their own home. It allows for a focused one-on- propriate third-party reimbursements and work locally to reduce
one patient to provider encounter and eliminates the inherent dis- language barriers and improve access to technology. These efforts
tractions of a busy ED environment. Additionally, there are oppor- will go a long way in improving access to emergency care for all.
tunities for virtual stethoscopes and otoscopes that can approach
the sophistication of a “live” physical examination, and the possi-
bility of stronger firewalls for protection of privacy. Most impor- REFERENCES
tantly, it has the potential to divert care outside of the ED for 1. Olson CA, McSwain SD, Curfman AL, et al. The current pediatric telehealth
patients who use EDs for less urgent concerns. landscape. Pediatrics. 2018;141:e20172334.
Pediatric emergency telehealth is efficient, time-saving, and 2. https://www.osc.state.ny.us/osdc/rpt2-2016.pdf
cost-saving. It should never replace the general pediatrician's role
in caring for children. However, access to emergency telehealth 3. Yang YT. Telehealth Parity Laws. Health Affairs Health Policy Brief. 2016:
can reduce patient wait times, both at home and in EDs. This will Aug. doi:10.1377/hbp20160815.244795.
go a long way toward decanting our ED waiting rooms, and ulti- 4. https://comptroller.nyc.gov/wp-content/uploads/documents/Census_and_
mately, reducing the spread of infection. The_City_Overcoming_NYC_Digital_Divide_Census.pdf:11-15.
We are hopeful that, with dissemination of the new vaccine, 5. Househ M. The role of short messaging service in supporting the delivery
the COVID-19 pandemic will pass its peak and will soon trend of healthcare: an umbrella systematic review. Health Inform J. 2016;
downward, but we should be mindful of how we resume our lives, 22:140–150.

SPECIAL FEATURE
Risk of Serious Bacterial Infections in Young Febrile Infants

With COVID-19
Alison Payson, MD, Veronica Etinger, MD, Pablo Napky, MD, Stephanie Montarroyos, DO,
Ana Ruiz-Castaneda, MD, and Marcos Mestre, MD, MBA
to 5.4%.3–10 Therefore, the presence of a concomitant viral infec-

Objectives: The purposes of this study were to describe the clinical char- tion can aid in the workup and management of these febrile infants.
acteristics of febrile infants younger than 90 days with severe acute respira- Severe acute respiratory syndrome coronavirus 2 (SARS-
tory syndrome coronavirus 2 (SARS-CoV-2) infections, to investigate the CoV-2) is a novel single-stranded RNAvirus spread by respiratory
prevalence of serious bacterial infections (SBIs) in these infants, and to droplets that originated in Wuhan, China, and has caused a global
compare the risk of SBI in SARS-CoV-2–positive febrile infants with pandemic of coronavirus disease 2019 (COVID-19).11 There have
sex- and age-matched SARS-CoV- 2–negative febrile infants. been case reports of COVID-19 infections in neonates and infants
Methods: This was a retrospective cohort study conducted from March to illustrating a spectrum of disease from asymptomatic positive
November 2020 in a tertiary children's hospital. Patients were identified by cases to severe illness requiring endotracheal intubation and me-
International Classification of Diseases, 10th Revision codes and included chanical ventilation.12–15 Several case series have described the
if age was younger than 90 days, a SARS-CoV-2 test was performed, and at generally benign course of COVID-19 in febrile infants and ob-
least 1 bacterial culture was collected. Positive cases of SARS-CoV-2 were served a low rate of SBI in this population.16–18 The purpose of
age- and sex-matched to negative controls for analysis. Serious bacterial in- this study was to investigate the risk of SBI in febrile infants youn-
fection was defined as a urinary tract infection, bacterial enteritis, bacter- ger than 90 days with a SARS-CoV-2 infection and to compare
emia, and/or bacterial meningitis. this risk of SBI with that of SARS-CoV-2–negative sex- and
Results: Fifty-three SARS-CoV-2–positive infants were identified with a age-matched febrile infants.
higher rate of respiratory symptoms and lower white blood cell and
C-reactive protein values than their SARS-CoV-2 matched controls. The
rate of SBI in the SARS-CoV-2–positive infants was 8% compared with METHODS
34% in the controls; the most common infections were urinary tract infec- This was a retrospective cohort study of febrile infants eval-
tions (6% vs 23%). There were no cases of bacteremia or bacterial menin- uated in the emergency department (ED) of a freestanding pediat-
gitis in the COVID-19 (coronavirus disease 2019) infants and 2 (4%) cases ric hospital in the Southeastern United States who were younger
of bacteremia in the controls. The relative risk of any SBI between the 2 than 90 days and had a documented temperature of 100.4°F or
groups was 0.22 (95% confidence interval, 0.1–0.6; P ≤ 0.001). greater at home or in the ED within the previous 24 hours. The
Conclusions: These results suggest that febrile infants younger than study took place during an 8-month period between March and
90 days with COVID-19 have lower rates of SBI than their matched November 2020. Patients were identified using International
SARS-CoV-2–negative controls. These data are consistent with previous Classification of Diseases, 10th Revision codes for “fever” and
studies describing lower risks of SBI in febrile infants with concomitant vi- “disturbance of temperature regulation of newborn.” Infants born
ral respiratory tract infections. at less than 34 weeks of gestational age and infants with comor-
Key Words: COVID-19, febrile infant, serious bacterial infection bidities placing them at high risk of bacterial infections or compli-
cations from a respiratory infection (including infants with
congenital heart disease, chronic lung disease, and hydrocephalus
with ventriculoperitoneal shunts) were excluded. Patients who did
T he diagnostic evaluation and management of young febrile in-
fants continue to be a highly debated topic within the pediatric
literature. Fever is a nonspecific symptom in this population that is
not have a SARS-CoV-2 polymerase chain reaction (PCR) test
performed or who did not have 1 or more bacterial cultures (from
urine, blood, cerebrospinal fluid [CSF], and/or stool) collected
frequently due to a benign viral process but is feared to be the ini-
were also excluded. There is no standard institutional protocol
tial presentation of serious bacterial infections (SBIs) associated
for the diagnostic evaluation or treatment of this population, so
with high rates of morbidity and mortality. Reported rates of
based on laboratory results and clinical judgment, patients were
SBI in this population vary because of differences in age groups
discharged from the ED or admitted for further management.
and definitions among studies, but generally range from 7.0% to
We classified infants according to their COVID-19 status, ei-
12.5% of low-risk infants with high-risk infants having a rate as
ther positive or negative, based on real-time RT-PCR testing of na-
high as 21%.1–10 Febrile infants with respiratory viral infections,
sopharyngeal specimens performed using one of several platforms
such as respiratory syncytial virus (RSV) and influenza, have sig-
including the BioFire Respiratory 2.1 (RP2.1) Panel (BioFire Di-
nificantly lower risks of SBI with rates of bacteremia of less than
agnostics LLC, Salt Lake City, UT), Xpert Xpress SARS-CoV-2
2% and rates of urinary tract infections (UTIs) ranging from 1.1%
test (Cepheid, Sunnyvale, CA), Simplexa COVID-19 Direct Assay
(DiaSorin Molecular LLC, Cypress, CA), and T2SARS-CoV-2
From the Departments of Pediatric Hospital Medicine and Emergency Medi-
Panel (T2 Biosystems Inc., Lexington, MA). Obtaining a SARS-
cine, Nicklaus Children's Hospital, Miami, FL. CoV-2 PCR test was at the discretion of the physician based on risk
Disclosure: The authors declare no conflict of interest. factors and clinical presentation.
Reprints: Alison Payson, MD, Department of Pediatric Hospitalist Medicine, We used the REDCap electronic database to collect informa-
Nicklaus Children's Hospital, 3100 SW 62nd Ave, Miami, FL 33155
(e‐mail: Alison.Payson@nicklaushealth.org).
tion from the electronic medical record. Data were collected on
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. demographics, preceding signs and symptoms, maximum temper-
ISSN: 0749-5161 ature, disposition from the ED, length of stay if admitted, and

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Bacterial Infections in Infants With COVID-19
treatment with at least 1 dose of antibiotic therapy. Laboratory 141 patients met the inclusion criteria. Fifty-three SARS-CoV-
data collected from initial presentation included complete blood 2–positive infants were age- and sex-matched to 53 SARS-CoV-
count, C-reactive protein (CRP), procalcitonin, blood culture, uri- 2–negative infants (Fig. 1).
nalysis and urine culture, CSF analysis and culture, gastrointesti- Table 1 shows the demographics of the 2 groups. The mean
nal panel by PCR and/or stool culture, respiratory pathogen age of all infants was 44.4 days (range, 6–89 days); 19 (18%) were
panels, and nasopharyngeal SARS-CoV-2 PCR results. 0 to 28 days, 61 (58%) were 29 to 56 days, and 26 (25%) were 57
The primary outcome measure was the presence of an SBI. to 90 days; 62 (58%) were male. Both groups primarily identified
An SBI was defined as the growth of a pathogenic, bacterial organ- with White race and Hispanic ethnicity and had Medicaid insur-
ism in the urine, blood, stool, or CSF. A UTI was defined as 50,000 ance; fewer parents of infants with COVID-19 identified as pri-
colony-forming units/mL or greater of a single known pathogen mary English speakers (45%) than parents of controls (62%).
from a catheterized specimen or greater than 10,000 colony- Thirty-six (68%) SARS-CoV-2–positive infants and 33 (62%)
forming units/mL of a single uropathogen obtained via catheteriza- controls were admitted to general inpatient units; there was no
tion with a positive urinalysis. The urinalysis was considered posi- statistical difference in rate of admissions, median length of stay
tive if there was leukocyte esterase, and/or nitrites, or greater than if admitted, or treatment with antibiotics between the 2 groups.
10 white blood cells (WBCs)/high-power field in an uncentrifuged More SARS-CoV-2–positive infants had chest radiographs per-
specimen.19,20 Although data were collected on whether chest ra- formed (59%) compared with only 21% of negative controls
diographs were obtained, pneumonia was not classified as an SBI (P ≤ 0.0001); none of the radiographs in either group were
because of the difficulty in differentiating between bacterial and interpreted as lobar pneumonia, and no infants were treated for
viral pneumonia based on chest radiographs. clinical pneumonia.
We compared the demographics, clinical characteristics, lab- Infants in the 2 groups had similar clinical presentations with
oratory results, and rates of SBI between infants with and without a mean temperature of 101.0°F for cases and 101.1°F for controls
COVID-19. Controls consisted of infants who were sex- and (Table 2). Compared with controls, SARS-CoV-2–positive infants
age-matched (within 14 days of age) who presented with fever presented more frequently with respiratory symptoms (47% vs
during the same time period but had a negative SARS-CoV-2 23%; P ≤ 0.014) and had lower median WBC counts (8.1 vs
PCR test. Student t tests were used to analyze continuous vari- 11.6; P < 0.0001) and CRP values (0.50 vs 0.85; P ≤ 0.01). There
ables, Fisher exact tests were used to analyze categorical data, were no significant differences between the 2 groups in terms of
and the Wilcoxon rank-sum test for ordinal data. Relative risk constitutional symptoms (including lethargy, irritability, and rash),
(RR) ratios and 95% confidence intervals (CIs) were calculated gastrointestinal symptoms, or median procalcitonin values.
between the 2 populations of interest. All statistical tests were Table 3 shows the rates of SBI between the 2 groups. In the
2-tailed. Statistical significance was designated at a P ≤ 0.05. Sta- COVID-19 group, there were 4 cases of SBI (8%). There were 3
tistical analysis was performed using Prism version 8.0 software (6%) UTIs caused by Escherichia coli, Enterococcus faecalis,
(GraphPad, San Diego, Calif ). The study protocol was approved and Klebsiella aerogenes, all occurring in males younger than
by the hospital's institutional review board. 60 days, and 1 (2%) bacterial enteritis due to Salmonella species.
There were no cases of bacteremia, bacterial meningitis, or addi-
tional respiratory infections in this group. In the control group,
RESULTS there were 18 cases of SBI (34%). There were 12 (23%) UTIs, 4
A total of 220 charts were identified based on International (8%) cases of bacterial enteritis, and 2 (4%) cases of bacteremia.
Classification of Diseases, 10th Revision codes, and a total of Urinary tract infections occurred in 8 males and 4 females; all
FIGURE 1. Patient population.

Payson et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
TABLE 1. Patient Demographics According to COVID-19 Status
COVID-19–Positive COVID-19–Negative Risk Difference

Variable (n = 53) (n = 53) (95% CI) P
Mean age, d 46.5 ± 20.1 46.4 ± 21.6 0.15 (−8.2 to 7.9) 0.97
White race 49 (92%) 45 (85%) 7.5% (−6.4 to 21.6) 0.36
Hispanic ethnicity 47 (89%) 46 (87%) 1.9% (−12.5 to 16.3) >0.99
English as primary language 24 (45%) 33 (62%) −17.0% (−1.5 to 37.2) 0.12
Medicaid insurance 43 (81%) 36 (68%) 13.2% (−4.7 to 30.2) 0.18
Chest radiography obtained 31 (58%) 11 (21%) 37.7% (17.9 to 53.9) 0.0001
Urine culture obtained 50 (94%) 52 (98%) −3.8% (−7.3 to 14.2) 0.62
Blood culture obtained 48 (91%) 50 (94%) −3.8% (−8.9 to 16.2) 0.72
CSF obtained 19 (36%) 23 (43%) −7.5% (−11.3 to 27.2) 0.55
Admitted to general inpatient hospital unit 36 (68%) 33 (62%) 5.7% (−13.5 to 24.3) 0.68
Median length of stay, h 42.3 (29.5–62.1) 45.6 (38.5–66.5) −3.3 (−15.6 to 4.2) 0.28
Patients receiving treatment with antibiotics 25 (47%) 34 (64%) 17.0% (−1.4 to 37.1) 0.12
Values are mean ± SD, median (IQR), or number (%).
12 cases of UTI were caused by E. coli. One case of bacteremia DISCUSSION

was due to group B streptococcus (GBS) in an 18-day-old male in-
fant born to a mother with unknown GBS status. The other bacter- As the febrile infant conundrum continues to evolve, there
emia infection was due to E. coli in a 23-day-old male infant with has been a recent focus on decreasing the costly and invasive eval-
a negative urine culture who was born to a GBS-positive mother uation and management of SBI in febrile infants with a concomitant
adequately treated with intrapartum antibiotics. All 4 cases of en- viral infection.20–23 Multiple studies have investigated the risk of
teritis were due to Salmonella species. There were no cases of SBI in febrile infants with documented RSVand/or influenza infec-
meningitis. There were 7 cases of rhino/enteroviruses identified tions. In 2004, PECARN (Pediatric Emergency Care Applied Re-
by the BioFire Respiratory 2.1 (RP2.1) Panel in the control group; search Network) conducted a prospective cross-sectional study of
none of these patients had an SBI. febrile infants younger than 60 days based on RSV status and the
There was a statistically significant difference in the rates of risk of SBI including UTI, bacteremia, meningitis, and enteritis.
total SBI between the SARS-CoV-2–positive and negative groups The rate of any SBI in the RSV-positive group was 7.0% compared
(8% and 34%) with an RR of 0.22 (95% CI, 0.08–0.57; with 12.5% in the RSV-negative group with a clinically significant
P ≤ 0.001). There was also a significant difference in the rates risk difference of 5.5%. The most common infections were UTIs,
of UTIs between the 2 groups (6% and 23%) with an RR of with a rate of 5.4% in the RSV-positive infants and 10.1% in the
0.25 (95% CI, 0.08–0.76; P ≤ 0.023). There was no significant RSV-negative infants. There was not a statistically significant dif-
difference in invasive bacterial infections (IBIs) between the ference between the 2 groups in terms of bacteremia or meningitis,
groups, with only 2 cases of bacteremia found in the control group as there were no cases of meningitis in the RSV-positive group and
and no cases of meningitis in either group. only a 1.1% rate of bacteremia in this group.4 Similarly, Titus and
Separating the infants by age, overall there were 5 of 19 Wright5 conducted a retrospective cohort study of infants younger
(26%) SBI in infants younger than 29 days of age, 9 of 61 than 8 weeks and found that the risk of SBI (UTI, bacteremia, and
(15%) in infants 29 to 56 days of age, and 8 of 26 (30%) in infants meningitis) in febrile infants with RSV was low compared with
57 to 90 days of age. Comparing SBI rates in the population youn- RSV-negative infants (RR of 0.09). Krief et al6 looked at the rate
ger than 57 days between the SARS-CoV-2–positive and SARS- of SBI (including enteritis) in infants with influenza infections
CoV-2–negative groups (9% vs 28%) also showed a significant and again found that febrile infants younger than 60 days with a
RR of 0.33 (95% CI, 0.12–0.90; P ≤ 0.04). concomitant influenza infection had lower rates of SBI than their
TABLE 2. Patient Clinical and Laboratory Findings According to COVID-19 Status
Variable COVID-19–Positive (n = 53) COVID-19–Negative (n = 53) Risk Difference (95% CI) P

Mean maximum temperature, °F 101.0 ± 0.8 101.1 ± 0.8 −0.1 (−0.4 to 0.2) 0.53
Constitutional symptoms 18 (34%) 20 (38%) −3.8% (−15.0 to 22.9) 0.84
Respiratory symptoms 25 (47%) 12 (23%) 24.5% (5.0 to 41.7) 0.01
Gastrointestinal symptoms 11 (21%) 11 (21%) 0% (−16.7 to 16.7) >0.99
Median WBC, 103/μL 8.1 (6.1–9.8) 11.6 (9.9–13.9) −3.5 (−5.0 to −2.6) <0.0001
Median CRP, 103/μL 0.5 (0.1–0.5) 0.85 (0.1–3.2) −0.35 (−1.3 to 0) 0.01
Median procalcitonin, ng/mL 0.06 (0.05–0.09) 0.05 (0.05–0.14) 0.01 (−0.02 to 0.01) 0.93

TABLE 3. SBI According to COVID-19 Status
Variable COVID-19–Positive (n = 53) COVID-19 Negative (n = 53) Relative Risk (95% CI) P
Any SBI 4 (8%) 18 (34%) 0.22 (0.08 to 0.57) 0.001
UTI 3 (6%) 12 (23%) 0.25 (0.08 to 0.76) 0.02
Enteritis 1 (2%) 4 (8%) 0.25 (0.04 to 1.6) 0.36
IBI (bacteremia/meningitis) 0 2 (4%) 0 0.5
Values are number (%).
influenza-negative counterparts (2.5% vs 13.3% with an RR of CoV-2–positive and negative febrile infants with an RR of 0.22.
0.19), with UTIs being the most common infection. While these Similar to published literature, the most common infections in
individual studies differed in age groups and definitions of SBIs, both groups were UTIs, and there was a statistical difference in
they all documented lower rates of SBI in the viral respiratory UTIs between the 2 groups with an RR of 0.25. There were very
groups (range, 2.5%–7%) compared with RSV/influenza–negative few cases of IBI and no statistical difference between the 2 groups;
counterparts (up to 13%), with statistically significant differences the 2 cases of bacteremia occurred in infants younger than 28 days
in rates of UTIs (the most commonly observed SBI) between the who are generally considered a high-risk population and fre-
groups but no difference in bacteremia or meningitis due to the quently receive a complete evaluation and empiric antibiotic treat-
infrequency of these infections (rates of <2%).3–10 ment solely based on age.
As exemplified by these individual studies, Ralston et al8 an- Compared with the study by Leibowitz et al16 that found in-
alyzed the risk of SBI in febrile infants younger than 90 days with creased lethargy and feeding difficulties in infants with COVID-
bronchiolitis and/or RSV by conducting a meta-analysis of studies 19, we found that infants with COVID-19 had similar clinical pre-
conducted through 2010. Eleven studies were analyzed (using sentations to their negative counterparts except for an increase in
UTI, bacteremia, and bacterial meningitis to define SBI) and respiratory symptoms. On laboratory evaluation, we found
found that the most common infections were UTIs with a weighted SARS-CoV-2–positive infants to have lower WBC and CRP values,
rate of 3.3%; there were very few cases of bacteremia, and there which correlates with the leukopenia and neutropenia documented
were no cases of meningitis reported.8 These results confirm that in other case series.16–18 As there were more cases of SBI in the
febrile infants with viral infections have significantly lower risks control group, the WBC, CRP, and procalcitonin values would be
of SBI, but still have an appreciable rate of UTIs. expected to be higher in this group, although we did not see an ap-
Case reports describe infants with COVID-19 presenting preciable difference in procalcitonin. Although there is no standard
with nonspecific symptoms such as fever, lethargy, poor feeding, protocol for the evaluation and management of febrile infants at our
tachypnea, and diarrhea—similar to the symptoms seen in the institution, there was no statistically significant difference in urine,
general febrile infant population and therefore making them an in- blood, or CSF cultures obtained; the rate of admissions from the
teresting addition to the febrile infant conundrum.12–18 The largest ED; or the number of patients receiving empiric antibiotic therapy
study on neonates with COVID-19 included a sample of 37 neo- between the 2 groups of infants. SARS-CoV-2–positive infants
nates (average age of 15.6 days ±7.7) from Turkey. This study re- did have more chest radiographs performed, likely secondary to
ported that neonates presented more commonly with fever, their increase in respiratory symptoms, but no consolidations sug-
hypoxemia, and cough; 57% required respiratory support with gestive of superimposed pneumonia were identified.
supplemental oxygen or noninvasive ventilation, but only 3% re- Our study had several limitations. Our cohort of infants was
quired mechanical ventilation.14 While this study is informative, relatively small because of the time frame and smaller prevalence
it focused on a younger, not exclusively febrile population and of infants with COVID-19 as compared with other respiratory in-
did not comment on the rates of SBI in these infants. fections. While our rate of SBI in the controls was higher than re-
There have been several small case series focusing on febrile ported rates, our minimal rates of bacteremia and meningitis
infants with COVID-19 in the United States. The largest study had correlate with the literature. Our study also coincided with a Sal-
20 SARS-CoV-2–positive febrile infants younger than 90 days monella outbreak traced to onions and peaches, and we had a high
who were found to have higher rates of lethargy and feeding diffi- rate of Salmonella enteritis. Furthermore, the overall hospital cen-
culties on presentation and lower WBC, neutrophil, and lympho- sus was low during the study period, but there was a higher acuity
cyte counts compared with 81 SARS-CoV-2–negative infants case mix index suggesting a skewed proportion of ill-appearing
from previous years. None of these SARS-CoV-2–positive infants infants presented to the ED. This was a retrospective study; there-
had concurrent SBIs compared with 18 (22%) of the SARS-CoV- fore, the data collected are limited to what is recorded in the elec-
2–negative infants.16 Our study builds off this comparison study tronic medical record. The decision to obtain a SARS-CoV-2 PCR
and case reports by McLaren et al17 and Mithal et al,18 which test was left to the discretion of the physician; therefore, not every
did report UTIs (2 cases and 1 case respectively) in young febrile febrile infant presenting to the ED was tested. These PCR results
infants with concurrent COVID-19 infections but had no reports are also not readily available overnight so diagnostic and manage-
of IBI. ment decisions may have been made without this knowledge. Not
To our knowledge, our study is the largest case series of every infant had cultures from all sources obtained (particularly
COVID-19 infections in febrile infants younger than 90 days of stool cultures, which were obtained based only on clinical suspi-
age and the first study to specifically investigate the rates of SBI cion for enteritis); thus, although unlikely, some infants may have
in these infants compared with age- and sex-matched SARS- had an SBI that was missed because of lack of cultures.
CoV-2–negative febrile infants. Although our overall rates of Our study contributes to the growing literature on the risks of
SBI were higher than previous studies addressing the risk of SBI SBI in febrile infants in the setting of a global pandemic caused by
in infants with respiratory viral infections, there remained a statis- a novel RNA virus. While the risk of SBI was lower in febrile in-
tically significant difference in the rates of SBI between SARS- fants younger than 90 days with COVID-19, the rates of UTI were

not insignificant, making urine studies still a worthwhile diagnos- 11. Centers for Disease Control and Prevention. Coronavirus disease 2019
tic tool. Although a small sample, our data are consistent with pre- (COVID-19). 2020. Available at: https://www.cdc.gov/coronavirus/2019-
vious studies describing lower risks of SBI in young febrile infants ncov/index.html. Accessed October 6, 2020.
with concomitant viral respiratory infections, suggesting that 12. Altendahl M, Afshar Y, de St Maurice A, et al. Perinatal
while COVID-19 may have a variety of clinical presentations maternal-fetal/neonatal transmission of COVID-19: a guide to safe
and courses, in the febrile infant population it appears to be similar maternal and neonatal care in the era of COVID-19 and physical distancing.
to other viral pathogens. As the future of this current pandemic is NeoReviews. 2020;21:e783–e794.
still unknown, larger studies are needed to further assess the risk 13. Zeng L, Xia S, Yuan W, et al. Neonatal early-onset infection with
of SBIs with greater confidence in febrile infants with COVID-19. SARS-CoV-2 in 33 neonates born to mothers with COVID-19 in Wuhan,
China. JAMA Pediatr. 2020;174:722–725.
REFERENCES 14. Kanburoglu MK, Tayman C, Oncel MY, et al. A multicentered study on
1. Bachur RG, Harper MB. Predictive model for serious bacterial infections epidemiologic and clinical characteristics of 37 neonates with
among infants younger than 3 months of age. Pediatrics. 2001; community-acquired COVID-19. Pediatr Infect Dis J. 2020;39:e297–e302.
108:311–316. 15. Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 among children in
2. Baraff LJ, Oslund SA, Schriger DL, et al. Probability of bacterial infections China. Pediatrics. 2020;145:e20200702.
in febrile infants less than three months of age: a meta-analysis. Pediatr 16. Leibowitz J, Krief W, Barone S, et al. Comparison of clinical and
Infect Dis J. 1992;11:257–264. epidemiologic characteristics of young febrile infants with and without
3. Byington CL, Enriquez FR, Hoff C, et al. Serious bacterial infections in severe acute respiratory syndrome coronavirus-2 infection. J Pediatr.
febrile infants 1 to 90 days old with and without viral infections. Pediatrics. 2020;S0022-3476(20)31264-6.
2004;113:1662–1666. 17. McLaren SH, Dayan PS, Fenster DB, et al. Novel coronavirus infection in
4. Levine DA, Platt SL, Dayan PS, et al. Risk of serious bacterial infection in febrile infants aged 60 days and younger. Pediatrics. 2020;146:e20201550.
young febrile infants with respiratory syncytial virus infections. Pediatrics. 18. Mithal LB, Machut KZ, Muller WJ, et al. SARS-CoV-2 infection in infants
2004;113:1728–1734. less than 90 days old. J Pediatr. 2020;224:150–152.
5. Titus MO, Wright SW. Prevalence of serious bacterial infections in 19. Subcommittee on Urinary Tract Infection, Steering Committee on Quality
febrile infants with respiratory syncytial virus infection. Pediatrics. 2003; Improvement and Management, Roberts KB. Urinary tract infection:
112:282–284. clinical practice guideline for the diagnosis and management of the initial
6. Krief WI, Levine DA, Platt SL, et al. Influenza virus infection and the risk UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;
of serious bacterial infections in young febrile infants. Pediatrics. 2009; 128:595–610.
124:30–39. 20. Kuppermann N, Dayan PS, Levine DA, et al. A clinical prediction rule to
7. Melendez E, Harper MB. Utility of sepsis evaluation in infants 90 days of identify febrile infants 60 days and younger at low risk for serious bacterial
age or younger with fever and clinical bronchiolitis. Pediatr Infect Dis J. infections. JAMA Pediatr. 2019;173:342–351.
2003;22:1053–1056. 21. Jaskiewicz JA, McCarthy CA, Richardson AC, et al. Febrile infants at low
8. Ralston S, Hill V, Waters A. Occult serious bacterial infection in infants risk for serious bacterial infection—an appraisal of the Rochester criteria
younger than 60 to 90 days with bronchiolitis: a systematic review. Arch and implications for management. Febrile Infant Collaborative Study
Pediatr Adolesc Med. 2011;165:951–956. Group. Pediatrics. 1994;94:390–396.
9. Hall CB, Powell KR, Schnabel KC, et al. Risk of secondary bacterial 22. Baraff LJ, Bass JW, Fleisher GR, et al. Practice guideline for the
infection in infants hospitalized with respiratory syncytial viral infection. management of infants and children 0 to 36 months of age with fever
J Pediatr. 1988;113:266–271. without source. Agency for Health Care Policy and Research. Ann Emerg
10. Mahajan P, Browne LR, Levine DA, et al, Febrile Infant Working Group of Med. 1993;22:1198–1210.
the Pediatric Emergency Care Applied Research Network (PECARN). 23. Liebelt EL, Qi K, Harvey K. Diagnostic testing for serious bacterial
Risk of bacterial coinfections in febrile infants 60 days old and younger infections in infants aged 90 days or younger with bronchiolitis. Arch
with documented viral infections. J Pediatr. 2018;203:86–91.e2. Pediatr Adolesc Med. 1999;153:525–530.
Acute Hemorrhagic Edema of Infancy With Associated

Hemorrhagic Lacrimation: Erratum
I n the February 2021 issue, the first author was incorrectly identified in "Acute Hemorrhagic Edema of Infancy With Associated
Hemorrhagic Lacrimation."
Carolina Vega, MD, is the correct first author, and the correct order of authors is Vega C, Sneller H, Zemel L, and
Chicaiza HP.
REFERENCE
Sneller H, Vega C, Zemel L, et al. Acute Hemorrhagic Edema of Infancy With Associated Hemorrhagic Lacrimation. Pediatr Emerg Care. 2021;37:e70–e72.

SPECIAL FEATURE
Risk of Serious Bacterial Infections in Young Febrile Infants

With COVID-19
Alison Payson, MD, Veronica Etinger, MD, Pablo Napky, MD, Stephanie Montarroyos, DO,
Ana Ruiz-Castaneda, MD, and Marcos Mestre, MD, MBA
to 5.4%.3–10 Therefore, the presence of a concomitant viral infec-

Objectives: The purposes of this study were to describe the clinical char- tion can aid in the workup and management of these febrile infants.
acteristics of febrile infants younger than 90 days with severe acute respira- Severe acute respiratory syndrome coronavirus 2 (SARS-
tory syndrome coronavirus 2 (SARS-CoV-2) infections, to investigate the CoV-2) is a novel single-stranded RNAvirus spread by respiratory
prevalence of serious bacterial infections (SBIs) in these infants, and to droplets that originated in Wuhan, China, and has caused a global
compare the risk of SBI in SARS-CoV-2–positive febrile infants with pandemic of coronavirus disease 2019 (COVID-19).11 There have
sex- and age-matched SARS-CoV- 2–negative febrile infants. been case reports of COVID-19 infections in neonates and infants
Methods: This was a retrospective cohort study conducted from March to illustrating a spectrum of disease from asymptomatic positive
November 2020 in a tertiary children's hospital. Patients were identified by cases to severe illness requiring endotracheal intubation and me-
International Classification of Diseases, 10th Revision codes and included chanical ventilation.12–15 Several case series have described the
if age was younger than 90 days, a SARS-CoV-2 test was performed, and at generally benign course of COVID-19 in febrile infants and ob-
least 1 bacterial culture was collected. Positive cases of SARS-CoV-2 were served a low rate of SBI in this population.16–18 The purpose of
age- and sex-matched to negative controls for analysis. Serious bacterial in- this study was to investigate the risk of SBI in febrile infants youn-
fection was defined as a urinary tract infection, bacterial enteritis, bacter- ger than 90 days with a SARS-CoV-2 infection and to compare
emia, and/or bacterial meningitis. this risk of SBI with that of SARS-CoV-2–negative sex- and
Results: Fifty-three SARS-CoV-2–positive infants were identified with a age-matched febrile infants.
higher rate of respiratory symptoms and lower white blood cell and
C-reactive protein values than their SARS-CoV-2 matched controls. The
rate of SBI in the SARS-CoV-2–positive infants was 8% compared with METHODS
34% in the controls; the most common infections were urinary tract infec- This was a retrospective cohort study of febrile infants eval-
tions (6% vs 23%). There were no cases of bacteremia or bacterial menin- uated in the emergency department (ED) of a freestanding pediat-
gitis in the COVID-19 (coronavirus disease 2019) infants and 2 (4%) cases ric hospital in the Southeastern United States who were younger
of bacteremia in the controls. The relative risk of any SBI between the 2 than 90 days and had a documented temperature of 100.4°F or
groups was 0.22 (95% confidence interval, 0.1–0.6; P ≤ 0.001). greater at home or in the ED within the previous 24 hours. The
Conclusions: These results suggest that febrile infants younger than study took place during an 8-month period between March and
90 days with COVID-19 have lower rates of SBI than their matched November 2020. Patients were identified using International
SARS-CoV-2–negative controls. These data are consistent with previous Classification of Diseases, 10th Revision codes for “fever” and
studies describing lower risks of SBI in febrile infants with concomitant vi- “disturbance of temperature regulation of newborn.” Infants born
ral respiratory tract infections. at less than 34 weeks of gestational age and infants with comor-
Key Words: COVID-19, febrile infant, serious bacterial infection bidities placing them at high risk of bacterial infections or compli-
cations from a respiratory infection (including infants with
congenital heart disease, chronic lung disease, and hydrocephalus
with ventriculoperitoneal shunts) were excluded. Patients who did
T he diagnostic evaluation and management of young febrile in-
fants continue to be a highly debated topic within the pediatric
literature. Fever is a nonspecific symptom in this population that is
not have a SARS-CoV-2 polymerase chain reaction (PCR) test
performed or who did not have 1 or more bacterial cultures (from
urine, blood, cerebrospinal fluid [CSF], and/or stool) collected
frequently due to a benign viral process but is feared to be the ini-
were also excluded. There is no standard institutional protocol
tial presentation of serious bacterial infections (SBIs) associated
for the diagnostic evaluation or treatment of this population, so
with high rates of morbidity and mortality. Reported rates of
based on laboratory results and clinical judgment, patients were
SBI in this population vary because of differences in age groups
discharged from the ED or admitted for further management.
and definitions among studies, but generally range from 7.0% to
We classified infants according to their COVID-19 status, ei-
12.5% of low-risk infants with high-risk infants having a rate as
ther positive or negative, based on real-time RT-PCR testing of na-
high as 21%.1–10 Febrile infants with respiratory viral infections,
sopharyngeal specimens performed using one of several platforms
such as respiratory syncytial virus (RSV) and influenza, have sig-
including the BioFire Respiratory 2.1 (RP2.1) Panel (BioFire Di-
nificantly lower risks of SBI with rates of bacteremia of less than
agnostics LLC, Salt Lake City, UT), Xpert Xpress SARS-CoV-2
2% and rates of urinary tract infections (UTIs) ranging from 1.1%
test (Cepheid, Sunnyvale, CA), Simplexa COVID-19 Direct Assay
(DiaSorin Molecular LLC, Cypress, CA), and T2SARS-CoV-2
From the Departments of Pediatric Hospital Medicine and Emergency Medi-
Panel (T2 Biosystems Inc., Lexington, MA). Obtaining a SARS-
cine, Nicklaus Children's Hospital, Miami, FL. CoV-2 PCR test was at the discretion of the physician based on risk
Disclosure: The authors declare no conflict of interest. factors and clinical presentation.
Reprints: Alison Payson, MD, Department of Pediatric Hospitalist Medicine, We used the REDCap electronic database to collect informa-
Nicklaus Children's Hospital, 3100 SW 62nd Ave, Miami, FL 33155
(e‐mail: Alison.Payson@nicklaushealth.org).
tion from the electronic medical record. Data were collected on
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. demographics, preceding signs and symptoms, maximum temper-
ISSN: 0749-5161 ature, disposition from the ED, length of stay if admitted, and

treatment with at least 1 dose of antibiotic therapy. Laboratory 141 patients met the inclusion criteria. Fifty-three SARS-CoV-
data collected from initial presentation included complete blood 2–positive infants were age- and sex-matched to 53 SARS-CoV-
count, C-reactive protein (CRP), procalcitonin, blood culture, uri- 2–negative infants (Fig. 1).
nalysis and urine culture, CSF analysis and culture, gastrointesti- Table 1 shows the demographics of the 2 groups. The mean
nal panel by PCR and/or stool culture, respiratory pathogen age of all infants was 44.4 days (range, 6–89 days); 19 (18%) were
panels, and nasopharyngeal SARS-CoV-2 PCR results. 0 to 28 days, 61 (58%) were 29 to 56 days, and 26 (25%) were 57
The primary outcome measure was the presence of an SBI. to 90 days; 62 (58%) were male. Both groups primarily identified
An SBI was defined as the growth of a pathogenic, bacterial organ- with White race and Hispanic ethnicity and had Medicaid insur-
ism in the urine, blood, stool, or CSF. A UTI was defined as 50,000 ance; fewer parents of infants with COVID-19 identified as pri-
colony-forming units/mL or greater of a single known pathogen mary English speakers (45%) than parents of controls (62%).
from a catheterized specimen or greater than 10,000 colony- Thirty-six (68%) SARS-CoV-2–positive infants and 33 (62%)
forming units/mL of a single uropathogen obtained via catheteriza- controls were admitted to general inpatient units; there was no
tion with a positive urinalysis. The urinalysis was considered posi- statistical difference in rate of admissions, median length of stay
tive if there was leukocyte esterase, and/or nitrites, or greater than if admitted, or treatment with antibiotics between the 2 groups.
10 white blood cells (WBCs)/high-power field in an uncentrifuged More SARS-CoV-2–positive infants had chest radiographs per-
specimen.19,20 Although data were collected on whether chest ra- formed (59%) compared with only 21% of negative controls
diographs were obtained, pneumonia was not classified as an SBI (P ≤ 0.0001); none of the radiographs in either group were
because of the difficulty in differentiating between bacterial and interpreted as lobar pneumonia, and no infants were treated for
viral pneumonia based on chest radiographs. clinical pneumonia.
We compared the demographics, clinical characteristics, lab- Infants in the 2 groups had similar clinical presentations with
oratory results, and rates of SBI between infants with and without a mean temperature of 101.0°F for cases and 101.1°F for controls
COVID-19. Controls consisted of infants who were sex- and (Table 2). Compared with controls, SARS-CoV-2–positive infants
age-matched (within 14 days of age) who presented with fever presented more frequently with respiratory symptoms (47% vs
during the same time period but had a negative SARS-CoV-2 23%; P ≤ 0.014) and had lower median WBC counts (8.1 vs
PCR test. Student t tests were used to analyze continuous vari- 11.6; P < 0.0001) and CRP values (0.50 vs 0.85; P ≤ 0.01). There
ables, Fisher exact tests were used to analyze categorical data, were no significant differences between the 2 groups in terms of
and the Wilcoxon rank-sum test for ordinal data. Relative risk constitutional symptoms (including lethargy, irritability, and rash),
(RR) ratios and 95% confidence intervals (CIs) were calculated gastrointestinal symptoms, or median procalcitonin values.
between the 2 populations of interest. All statistical tests were Table 3 shows the rates of SBI between the 2 groups. In the
2-tailed. Statistical significance was designated at a P ≤ 0.05. Sta- COVID-19 group, there were 4 cases of SBI (8%). There were 3
tistical analysis was performed using Prism version 8.0 software (6%) UTIs caused by Escherichia coli, Enterococcus faecalis,
(GraphPad, San Diego, Calif ). The study protocol was approved and Klebsiella aerogenes, all occurring in males younger than
by the hospital's institutional review board. 60 days, and 1 (2%) bacterial enteritis due to Salmonella species.
There were no cases of bacteremia, bacterial meningitis, or addi-
tional respiratory infections in this group. In the control group,
RESULTS there were 18 cases of SBI (34%). There were 12 (23%) UTIs, 4
A total of 220 charts were identified based on International (8%) cases of bacterial enteritis, and 2 (4%) cases of bacteremia.
Classification of Diseases, 10th Revision codes, and a total of Urinary tract infections occurred in 8 males and 4 females; all
FIGURE 1. Patient population.

TABLE 1. Patient Demographics According to COVID-19 Status
COVID-19–Positive COVID-19–Negative Risk Difference

Variable (n = 53) (n = 53) (95% CI) P
Mean age, d 46.5 ± 20.1 46.4 ± 21.6 0.15 (−8.2 to 7.9) 0.97
White race 49 (92%) 45 (85%) 7.5% (−6.4 to 21.6) 0.36
Hispanic ethnicity 47 (89%) 46 (87%) 1.9% (−12.5 to 16.3) >0.99
English as primary language 24 (45%) 33 (62%) −17.0% (−1.5 to 37.2) 0.12
Medicaid insurance 43 (81%) 36 (68%) 13.2% (−4.7 to 30.2) 0.18
Chest radiography obtained 31 (58%) 11 (21%) 37.7% (17.9 to 53.9) 0.0001
Urine culture obtained 50 (94%) 52 (98%) −3.8% (−7.3 to 14.2) 0.62
Blood culture obtained 48 (91%) 50 (94%) −3.8% (−8.9 to 16.2) 0.72
CSF obtained 19 (36%) 23 (43%) −7.5% (−11.3 to 27.2) 0.55
Admitted to general inpatient hospital unit 36 (68%) 33 (62%) 5.7% (−13.5 to 24.3) 0.68
Median length of stay, h 42.3 (29.5–62.1) 45.6 (38.5–66.5) −3.3 (−15.6 to 4.2) 0.28
Patients receiving treatment with antibiotics 25 (47%) 34 (64%) 17.0% (−1.4 to 37.1) 0.12
12 cases of UTI were caused by E. coli. One case of bacteremia DISCUSSION

was due to group B streptococcus (GBS) in an 18-day-old male in-
fant born to a mother with unknown GBS status. The other bacter- As the febrile infant conundrum continues to evolve, there
emia infection was due to E. coli in a 23-day-old male infant with has been a recent focus on decreasing the costly and invasive eval-
a negative urine culture who was born to a GBS-positive mother uation and management of SBI in febrile infants with a concomitant
adequately treated with intrapartum antibiotics. All 4 cases of en- viral infection.20–23 Multiple studies have investigated the risk of
teritis were due to Salmonella species. There were no cases of SBI in febrile infants with documented RSVand/or influenza infec-
meningitis. There were 7 cases of rhino/enteroviruses identified tions. In 2004, PECARN (Pediatric Emergency Care Applied Re-
by the BioFire Respiratory 2.1 (RP2.1) Panel in the control group; search Network) conducted a prospective cross-sectional study of
none of these patients had an SBI. febrile infants younger than 60 days based on RSV status and the
There was a statistically significant difference in the rates of risk of SBI including UTI, bacteremia, meningitis, and enteritis.
total SBI between the SARS-CoV-2–positive and negative groups The rate of any SBI in the RSV-positive group was 7.0% compared
(8% and 34%) with an RR of 0.22 (95% CI, 0.08–0.57; with 12.5% in the RSV-negative group with a clinically significant
P ≤ 0.001). There was also a significant difference in the rates risk difference of 5.5%. The most common infections were UTIs,
of UTIs between the 2 groups (6% and 23%) with an RR of with a rate of 5.4% in the RSV-positive infants and 10.1% in the
0.25 (95% CI, 0.08–0.76; P ≤ 0.023). There was no significant RSV-negative infants. There was not a statistically significant dif-
difference in invasive bacterial infections (IBIs) between the ference between the 2 groups in terms of bacteremia or meningitis,
groups, with only 2 cases of bacteremia found in the control group as there were no cases of meningitis in the RSV-positive group and
and no cases of meningitis in either group. only a 1.1% rate of bacteremia in this group.4 Similarly, Titus and
Separating the infants by age, overall there were 5 of 19 Wright5 conducted a retrospective cohort study of infants younger
(26%) SBI in infants younger than 29 days of age, 9 of 61 than 8 weeks and found that the risk of SBI (UTI, bacteremia, and
(15%) in infants 29 to 56 days of age, and 8 of 26 (30%) in infants meningitis) in febrile infants with RSV was low compared with
57 to 90 days of age. Comparing SBI rates in the population youn- RSV-negative infants (RR of 0.09). Krief et al6 looked at the rate
ger than 57 days between the SARS-CoV-2–positive and SARS- of SBI (including enteritis) in infants with influenza infections
CoV-2–negative groups (9% vs 28%) also showed a significant and again found that febrile infants younger than 60 days with a
RR of 0.33 (95% CI, 0.12–0.90; P ≤ 0.04). concomitant influenza infection had lower rates of SBI than their
TABLE 2. Patient Clinical and Laboratory Findings According to COVID-19 Status
Variable COVID-19–Positive (n = 53) COVID-19–Negative (n = 53) Risk Difference (95% CI) P

Mean maximum temperature, °F 101.0 ± 0.8 101.1 ± 0.8 −0.1 (−0.4 to 0.2) 0.53
Constitutional symptoms 18 (34%) 20 (38%) −3.8% (−15.0 to 22.9) 0.84
Respiratory symptoms 25 (47%) 12 (23%) 24.5% (5.0 to 41.7) 0.01
Gastrointestinal symptoms 11 (21%) 11 (21%) 0% (−16.7 to 16.7) >0.99
Median WBC, 103/μL 8.1 (6.1–9.8) 11.6 (9.9–13.9) −3.5 (−5.0 to −2.6) <0.0001
Median CRP, 103/μL 0.5 (0.1–0.5) 0.85 (0.1–3.2) −0.35 (−1.3 to 0) 0.01
Median procalcitonin, ng/mL 0.06 (0.05–0.09) 0.05 (0.05–0.14) 0.01 (−0.02 to 0.01) 0.93

TABLE 3. SBI According to COVID-19 Status
Variable COVID-19–Positive (n = 53) COVID-19 Negative (n = 53) Relative Risk (95% CI) P
Any SBI 4 (8%) 18 (34%) 0.22 (0.08 to 0.57) 0.001
UTI 3 (6%) 12 (23%) 0.25 (0.08 to 0.76) 0.02
Enteritis 1 (2%) 4 (8%) 0.25 (0.04 to 1.6) 0.36
IBI (bacteremia/meningitis) 0 2 (4%) 0 0.5
Values are number (%).
influenza-negative counterparts (2.5% vs 13.3% with an RR of CoV-2–positive and negative febrile infants with an RR of 0.22.
0.19), with UTIs being the most common infection. While these Similar to published literature, the most common infections in
individual studies differed in age groups and definitions of SBIs, both groups were UTIs, and there was a statistical difference in
they all documented lower rates of SBI in the viral respiratory UTIs between the 2 groups with an RR of 0.25. There were very
groups (range, 2.5%–7%) compared with RSV/influenza–negative few cases of IBI and no statistical difference between the 2 groups;
counterparts (up to 13%), with statistically significant differences the 2 cases of bacteremia occurred in infants younger than 28 days
in rates of UTIs (the most commonly observed SBI) between the who are generally considered a high-risk population and fre-
groups but no difference in bacteremia or meningitis due to the quently receive a complete evaluation and empiric antibiotic treat-
infrequency of these infections (rates of <2%).3–10 ment solely based on age.
As exemplified by these individual studies, Ralston et al8 an- Compared with the study by Leibowitz et al16 that found in-
alyzed the risk of SBI in febrile infants younger than 90 days with creased lethargy and feeding difficulties in infants with COVID-
bronchiolitis and/or RSV by conducting a meta-analysis of studies 19, we found that infants with COVID-19 had similar clinical pre-
conducted through 2010. Eleven studies were analyzed (using sentations to their negative counterparts except for an increase in
UTI, bacteremia, and bacterial meningitis to define SBI) and respiratory symptoms. On laboratory evaluation, we found
found that the most common infections were UTIs with a weighted SARS-CoV-2–positive infants to have lower WBC and CRP values,
rate of 3.3%; there were very few cases of bacteremia, and there which correlates with the leukopenia and neutropenia documented
were no cases of meningitis reported.8 These results confirm that in other case series.16–18 As there were more cases of SBI in the
febrile infants with viral infections have significantly lower risks control group, the WBC, CRP, and procalcitonin values would be
of SBI, but still have an appreciable rate of UTIs. expected to be higher in this group, although we did not see an ap-
Case reports describe infants with COVID-19 presenting preciable difference in procalcitonin. Although there is no standard
with nonspecific symptoms such as fever, lethargy, poor feeding, protocol for the evaluation and management of febrile infants at our
tachypnea, and diarrhea—similar to the symptoms seen in the institution, there was no statistically significant difference in urine,
general febrile infant population and therefore making them an in- blood, or CSF cultures obtained; the rate of admissions from the
teresting addition to the febrile infant conundrum.12–18 The largest ED; or the number of patients receiving empiric antibiotic therapy
study on neonates with COVID-19 included a sample of 37 neo- between the 2 groups of infants. SARS-CoV-2–positive infants
nates (average age of 15.6 days ±7.7) from Turkey. This study re- did have more chest radiographs performed, likely secondary to
ported that neonates presented more commonly with fever, their increase in respiratory symptoms, but no consolidations sug-
hypoxemia, and cough; 57% required respiratory support with gestive of superimposed pneumonia were identified.
supplemental oxygen or noninvasive ventilation, but only 3% re- Our study had several limitations. Our cohort of infants was
quired mechanical ventilation.14 While this study is informative, relatively small because of the time frame and smaller prevalence
it focused on a younger, not exclusively febrile population and of infants with COVID-19 as compared with other respiratory in-
did not comment on the rates of SBI in these infants. fections. While our rate of SBI in the controls was higher than re-
There have been several small case series focusing on febrile ported rates, our minimal rates of bacteremia and meningitis
infants with COVID-19 in the United States. The largest study had correlate with the literature. Our study also coincided with a Sal-
20 SARS-CoV-2–positive febrile infants younger than 90 days monella outbreak traced to onions and peaches, and we had a high
who were found to have higher rates of lethargy and feeding diffi- rate of Salmonella enteritis. Furthermore, the overall hospital cen-
culties on presentation and lower WBC, neutrophil, and lympho- sus was low during the study period, but there was a higher acuity
cyte counts compared with 81 SARS-CoV-2–negative infants case mix index suggesting a skewed proportion of ill-appearing
from previous years. None of these SARS-CoV-2–positive infants infants presented to the ED. This was a retrospective study; there-
had concurrent SBIs compared with 18 (22%) of the SARS-CoV- fore, the data collected are limited to what is recorded in the elec-
2–negative infants.16 Our study builds off this comparison study tronic medical record. The decision to obtain a SARS-CoV-2 PCR
and case reports by McLaren et al17 and Mithal et al,18 which test was left to the discretion of the physician; therefore, not every
did report UTIs (2 cases and 1 case respectively) in young febrile febrile infant presenting to the ED was tested. These PCR results
infants with concurrent COVID-19 infections but had no reports are also not readily available overnight so diagnostic and manage-
of IBI. ment decisions may have been made without this knowledge. Not
To our knowledge, our study is the largest case series of every infant had cultures from all sources obtained (particularly
COVID-19 infections in febrile infants younger than 90 days of stool cultures, which were obtained based only on clinical suspi-
age and the first study to specifically investigate the rates of SBI cion for enteritis); thus, although unlikely, some infants may have
in these infants compared with age- and sex-matched SARS- had an SBI that was missed because of lack of cultures.
CoV-2–negative febrile infants. Although our overall rates of Our study contributes to the growing literature on the risks of
SBI were higher than previous studies addressing the risk of SBI SBI in febrile infants in the setting of a global pandemic caused by
in infants with respiratory viral infections, there remained a statis- a novel RNA virus. While the risk of SBI was lower in febrile in-
tically significant difference in the rates of SBI between SARS- fants younger than 90 days with COVID-19, the rates of UTI were

not insignificant, making urine studies still a worthwhile diagnos- 11. Centers for Disease Control and Prevention. Coronavirus disease 2019
tic tool. Although a small sample, our data are consistent with pre- (COVID-19). 2020. Available at: https://www.cdc.gov/coronavirus/2019-
vious studies describing lower risks of SBI in young febrile infants ncov/index.html. Accessed October 6, 2020.
with concomitant viral respiratory infections, suggesting that 12. Altendahl M, Afshar Y, de St Maurice A, et al. Perinatal
while COVID-19 may have a variety of clinical presentations maternal-fetal/neonatal transmission of COVID-19: a guide to safe
and courses, in the febrile infant population it appears to be similar maternal and neonatal care in the era of COVID-19 and physical distancing.
to other viral pathogens. As the future of this current pandemic is NeoReviews. 2020;21:e783–e794.
still unknown, larger studies are needed to further assess the risk 13. Zeng L, Xia S, Yuan W, et al. Neonatal early-onset infection with
of SBIs with greater confidence in febrile infants with COVID-19. SARS-CoV-2 in 33 neonates born to mothers with COVID-19 in Wuhan,
China. JAMA Pediatr. 2020;174:722–725.
REFERENCES 14. Kanburoglu MK, Tayman C, Oncel MY, et al. A multicentered study on
1. Bachur RG, Harper MB. Predictive model for serious bacterial infections epidemiologic and clinical characteristics of 37 neonates with
among infants younger than 3 months of age. Pediatrics. 2001; community-acquired COVID-19. Pediatr Infect Dis J. 2020;39:e297–e302.
108:311–316. 15. Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 among children in
2. Baraff LJ, Oslund SA, Schriger DL, et al. Probability of bacterial infections China. Pediatrics. 2020;145:e20200702.
in febrile infants less than three months of age: a meta-analysis. Pediatr 16. Leibowitz J, Krief W, Barone S, et al. Comparison of clinical and
Infect Dis J. 1992;11:257–264. epidemiologic characteristics of young febrile infants with and without
3. Byington CL, Enriquez FR, Hoff C, et al. Serious bacterial infections in severe acute respiratory syndrome coronavirus-2 infection. J Pediatr.
febrile infants 1 to 90 days old with and without viral infections. Pediatrics. 2020;S0022-3476(20)31264-6.
2004;113:1662–1666. 17. McLaren SH, Dayan PS, Fenster DB, et al. Novel coronavirus infection in
4. Levine DA, Platt SL, Dayan PS, et al. Risk of serious bacterial infection in febrile infants aged 60 days and younger. Pediatrics. 2020;146:e20201550.
young febrile infants with respiratory syncytial virus infections. Pediatrics. 18. Mithal LB, Machut KZ, Muller WJ, et al. SARS-CoV-2 infection in infants
2004;113:1728–1734. less than 90 days old. J Pediatr. 2020;224:150–152.
5. Titus MO, Wright SW. Prevalence of serious bacterial infections in 19. Subcommittee on Urinary Tract Infection, Steering Committee on Quality
febrile infants with respiratory syncytial virus infection. Pediatrics. 2003; Improvement and Management, Roberts KB. Urinary tract infection:
112:282–284. clinical practice guideline for the diagnosis and management of the initial
6. Krief WI, Levine DA, Platt SL, et al. Influenza virus infection and the risk UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;
of serious bacterial infections in young febrile infants. Pediatrics. 2009; 128:595–610.
124:30–39. 20. Kuppermann N, Dayan PS, Levine DA, et al. A clinical prediction rule to
7. Melendez E, Harper MB. Utility of sepsis evaluation in infants 90 days of identify febrile infants 60 days and younger at low risk for serious bacterial
age or younger with fever and clinical bronchiolitis. Pediatr Infect Dis J. infections. JAMA Pediatr. 2019;173:342–351.
2003;22:1053–1056. 21. Jaskiewicz JA, McCarthy CA, Richardson AC, et al. Febrile infants at low
8. Ralston S, Hill V, Waters A. Occult serious bacterial infection in infants risk for serious bacterial infection—an appraisal of the Rochester criteria
younger than 60 to 90 days with bronchiolitis: a systematic review. Arch and implications for management. Febrile Infant Collaborative Study
Pediatr Adolesc Med. 2011;165:951–956. Group. Pediatrics. 1994;94:390–396.
9. Hall CB, Powell KR, Schnabel KC, et al. Risk of secondary bacterial 22. Baraff LJ, Bass JW, Fleisher GR, et al. Practice guideline for the
infection in infants hospitalized with respiratory syncytial viral infection. management of infants and children 0 to 36 months of age with fever
J Pediatr. 1988;113:266–271. without source. Agency for Health Care Policy and Research. Ann Emerg
10. Mahajan P, Browne LR, Levine DA, et al, Febrile Infant Working Group of Med. 1993;22:1198–1210.
the Pediatric Emergency Care Applied Research Network (PECARN). 23. Liebelt EL, Qi K, Harvey K. Diagnostic testing for serious bacterial
Risk of bacterial coinfections in febrile infants 60 days old and younger infections in infants aged 90 days or younger with bronchiolitis. Arch
with documented viral infections. J Pediatr. 2018;203:86–91.e2. Pediatr Adolesc Med. 1999;153:525–530.
Acute Hemorrhagic Edema of Infancy With Associated

Hemorrhagic Lacrimation: Erratum
I n the February 2021 issue, the first author was incorrectly identified in "Acute Hemorrhagic Edema of Infancy With Associated
Hemorrhagic Lacrimation."
Carolina Vega, MD, is the correct first author, and the correct order of authors is Vega C, Sneller H, Zemel L, and
Chicaiza HP.
REFERENCE
Sneller H, Vega C, Zemel L, et al. Acute Hemorrhagic Edema of Infancy With Associated Hemorrhagic Lacrimation. Pediatr Emerg Care. 2021;37:e70–e72.

SPECIAL FEATURE
Pediatric Emergency Medicine Fellowship Programs
A t the heart of the specialty of pediatric emergency medicine

(PEM) is compassionate, equitable, high-quality, evidence-based
care for ill and injured children. Fundamental to that mission
new programs, however given dynamic changes we recognize
there may be inaccuracies.
This is designed to serve as a quick reference; space limitations
is outstanding training for those who will provide this care. do not permit publication of all details of each program. In the era of
To help meet a growing need, PEM fellowship training pro- COVID, programs have focused on providing expanded information
grams continue to grow in number and size. The following list- through their websites, however applicants are strongly encouraged
ing provides information about each of these programs across to directly contact programs of interest. We would like to extend a
the United States and Canada. The list was compiled from the special thank you to the Pediatric Emergency Care journal staff,
previous year's data, updated with input from program leaders. the PEM Fellowship Directors for their continued support of this
Additional sources of information included the 2020 NRMP PEM Fellowship Program listing, and Kevin Deschenes (PEM
Match Participant List, the ERAS PEM Fellowship List, and at- Fellowship Program Coordinator at the Boston Children's Hospi-
tendees of the 2020 AAP National Conference & Exhibitions tal) for his administrative support in compiling this directory.
Section on Emergency Medicine (SOEM) Subcommittee of
Fellowship Directors (virtual) meeting. The list has been re- Joshua Nagler, MD, MHPEd
vised to reflect current information and expanded to include Chair, AAP SOEM Subcommittee of Fellowship Directors

Nagler Pediatric Emergency Care • Volume 37, Number 4, April 2021
Program Associate/Assistant Program

Program Director PD e-mail Program Director APD E-mail Coordinator PC E-mail
University of Alabama Terri Coco, MD tcoco@peds.uab.edu Christina Cochran, MD ccochran@peds.uab.edu Brittany Appelboom bappelboom@peds.uab.edu
at Birmingham
University of Alberta Stollery Andrew Dixon, MD andrew.dixon@albertahealthservices. Anita Reff pedsemerg@ualberta.ca
Children's Hospital ca
Phoenix Children's Jon McGreevy, jmcgreevy@ Claudia Yeung, cyeung@ Christina Ash cash@phoenixchildrens.com
Hospital MD, MSPH phoenixchildrens.com MD, FAAP phoenixchildrens.com
University of Arkansas Nick Hobart-Porter, porternicholasw@ Amber Morse, MD ammorse@uams.edu Stephanie Veach sveach@uams.edu
Medical Sciences DO uams.edu
Arkansas Children's Hospital
Loma Linda University Tim Young, MD tpyoung@llu.edu Heather Kuntz, MD hkuntz@llu.edu Shelly Nelson sknelson@llu.edu
Medical Center &
Children's Hospital
Children's Hospital Christine Cho, christine.cho@ Danielle Levitt, MD dlevitt@chla.usc.edu Yvette Resendiz yresendiz@chla.usc.edu
Los Angeles MD, MPH, Med chla.usc.edu Cindy Luu, MD ciluu@chla.usc.edu
UCSF Benioff Children's Cornelia (Nel) cornelia.latronica@ Leticia Kerlegan leticia.kerlegan@ucsf.edu
Hospital Oakland Latronica, MD ucsf.edu heidi.
Heidi Werner, werner@ucsf.edu
MD, MSHPEd
University of California, Kathryn Pade, MD kpade@rchsd.org Kaitlin Vallin kvallin@rchsd.org
San Diego Rady
Children's Hospital
Harbor-UCLA Medical Kelly Young, MD kyoung3@ Tim Horeczko, MD thoreczko@ Jeanne Austin jaustin@dhs.lacounty.gov
Center dhs.lacounty.gov dhs.lacounty.gov
Stanford University Andrea Fang, MD andreafang@ Brenda Roth broth2@stanford.edu
stanford.edu
University of Colorado Tien Vu, MD tien.vu@ Jason Woods, MD jason.woods@ Brooke Baker brooke.baker@childrenscolorado.org
Children's Hospital childrenscolorado.org childrenscolorado.org
Colorado
University of Connecticut Matt Laurich, MD mlaurich@ Marianne Custer mcuster@connecticutchildrens.org

Connecticut Children's connecticutchildrens.org
Medical Center
Yale-New Haven Melissa Langhan, melissa.langhan@yale.edu Gunjan Tiyyagura, MD gunjan.kamdar@yale.edu Elizabeth Briggs bett.briggs@yale.edu
Children's Hospital MD
Alfred I. DuPont Andrew adepiero@ Amy Thompson, MD amy.thompson@ Debbie Campbell dcampbell@nemours.org
Hospital for Children DePiero, MD nemours.org nemours.org
Children's National Jennifer jchapman@ Christina Lindgren, MD clindgren@ Hilda Rojas hrojas@childrensnational.org
Hospital Chapman, MD childrensnational.org Sabrina Guse, MD childrensnational.org
sguse@
childrensnational.org
University of Florida Todd Wylie, MD todd.wylie@jax.ufl.edu Debra Eurom debra.eurom@jax.ufl.edu
College of Medicine,
Jacksonville
Nicklaus Children's Vincenzo Maniaci, MD vincenzo.maniaci@ Lisa Howard lisa.howard@nicklaushealth.org
Hospital nicklaushealth.org
Orlando Health Program Efren Salinero, MD, FAAP efren.salinero@ Coleen Scuderi coleen.scuderi@orlandohealth.com
Arnold Palmer Hospital orlandohealth.com
for Children
Emory University Wendalyn K. Little, wendalyn.little@ Sherita Holmes, MD shertia.holmes@emory.edu Donna Stringfellow dstring@emory.edu
School of Medicine MD, MPH emory.edu
Children's Healthcare
of Atlanta
Medical College of Natalie Lane, MD nlane@augusta.edu Aimee Baer abaerellington@augusta.edu Lauren Neely lneely@augusta.edu
Georgia, Augusta Ellington, MD
University Children's
Hospital of Georgia
Ann & Robert H. Lurie Karen Mangold, kmangold@ Priya Jain, MD pgjain@ Neshwa Rajeh nrajeh@luriechildrens.org
Children's Hospital MD, MEd luriechildrens.org luriechildrens.org
University of Chicago Lisa McQueen, MD lmcqueen@peds.bsd. Diana Yan, MD diana.yan@ Kayla Stroner kayla.stroner@peds.bsd.uchicago.edu
Comer Children's Hospital uchicago.edu uchospitals.edu
Indiana University Stephen Cico, sjcico@iu.edu Heather Saavedra, MD hsaavedr@iu.edu Kris Powell krmpowel@iu.edu
Riley Hospital MD, MEd
for Children at IU Health
University of Louisville Danielle Graff, dmgraf02@louisville.edu Johanna Said, MD johanna.said@ Krystal Kaufman krystal.kaufman@louisville.edu
Norton Children's MD, MSc louisville.edu
Hospital
Johns Hopkins Thuy Ngo, thuy.ngo@jhmi.edu Kate Deanehan, MD jdeaneh1@jhmi.edu Laura Gerafentis lgerafe1@jhmi.edu
Children's Center DO, MEd Lauren Kahl, MD lkahl4@jhmi.edu
Boston Medical Center David Dorfman, david.dorfman@bmc.org Ariel Hoch, DO, MPH ariel.hoch@bmc.org Lisa Blake lisa.blake@bmc.org
MD
Boston Children's Hospital Joshua Nagler, MD, joshua.nagler@ Katie Dorney, MD kate.dorney@childrens. Kevin Deschenes kevin.deschenes@childrens.harvard.edu
MHPEd childrens.harvard.edu harvard.edu
UMMS-Baystate Blake Spirko, MD blake.spirko@ Julien Ginsberg- julien.ginsberg-peltz@ Tara Rivest tara.rivest@baystatehealth.org
baystatehealth.org Peltz, MD baystatehealth.org
Helen DeVos Children's Bhawana Arora, bhawana.arora@ Christopher Benner, MD christopher.benner@ Saron Mogos saron.mogos@spectrumhealth.org
Hospital Michigan MD spectrumhealth.org spectrumhealth.org
State University
Continued next page

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Pediatric Emergency Medicine Fellowship Programs
Address 1 Address 2 City State Zip Telephone Fax Website

1600 Seventh Avenue South CPP 1 - Suite #110 Birmingham Alabama 35233-1711 (205) 638-9587 (205) 975-4623 https://www.uab.edu/medicine/peds/education/
fellowships/em-fellows-prog
University of Alberta 3-574D Edmonton Clinic Edmonton Alberta T6G 1C9 (780) 248-5533 https://www.ualberta.ca/pediatrics/pediatric-education-
Health Academcy programs/postgraduate-medical-education/
11405-87 Avenue, emergency-medicine-residency-program
3rd floor
1919 East Thomas Road Phoenix Arizona 85016 (606) 922-1134 (606) 546-1414 https://www.phoenixchildrens.org/graduate-
medical-education/fellowship-programs/
pediatric-emergency-medicine-fellowship
1 Children's Way Slot 512-16 Little Rock Arkansas 72202 (501) 364-1099 (501) 364-6931 https://pediatrics.uams.edu/education/
fellowships/peds-em/
PO Box 2000, 11234 Anderson Street Loma Linda California 92354 (909) 558-7698 (909) 558-7941 https://lluh.org/health-professionals/gme/
MC A-890 resident-fellow/pediatric-emergency-
medicine-fellowship/how-apply
4650 Sunset Boulevard M/S #113 Los Angeles California 90027 (323) 361-2109 (323) 361-3891 https://www.chla.org/fellowship/emergency-
medicine-fellowship
747 52nd Street Oakland California 94609 (510) 428-3259 (510) 450-5836 https://www.childrenshospitaloakland.org/
main/pediatric-emergency-medicine-
fellowship-program.aspx
3020 Children's Way MC 5075 San Diego California 92123 (858) 966-8036 (858) 966-7433 http://www.rchsd.org/pemfellow
1000 West Carson Street Box #21 Torrance California 90509-2910 (424) 306-5400 (310) 212-6101 http://pemsource.org/about/
900 Welch Road, MC 5768 Palo Alto California 94304 (650) 723-6576 (650) 723-0121 https://emed.stanford.edu/fellowships/pediatric.html
Suite 350
13123 East 16th Avenue B-251 Aurora Colorado 80045 (303) 724-2566 (720) 777-7317 http://www.ucdenver.edu/academics/
colleges/medicalschool/departments/
pediatrics/subs/emerg/educat/
fellowship/Pages/fellows.aspx
282 Washington Street Hartford Connecticut 06106 (860) 837-6260 (860) 837-6262 https://health.uconn.edu/graduate-medical-
education/pediatric-fellowships/pediatric-
fellowships/
100 York Street Suite 1F New Haven Connecticut 06511 (203) 737-7440 (203) 737-7447 https://medicine.yale.edu/pediatrics/
sections/emergencymed/fellowship/
1600 Rockland Road PO Box 269 Wilmington Delaware 19899 (302) 651-5860 (302) 651-4227 https://www.nemours.org/education/gme/
fellowships/emergency.html
111 Michigan Avenue NW Washington District of Columbia 20010 (202) 476-4177 (202) 476-3573 http://childrensnational.org/ForDoctors/gme/
fellowship/EmergencyMedicine/
EmergencyMedicine.aspx
UF Department of 655 West Eighth Street Jacksonville Florida 32209 (904) 244-4046 (904) 244-5848 http://www.hscj.ufl.edu/emergency-medicine/
Emergency Medicine fellowship-pediatric-emergency/
3100 SW 62nd Avenue Miami Florida 33155 (786) 624-3588 (305) 662-8291 https://www.nicklauschildrens.org/medical-
professionals/medical-education/graduate-
medical-education-gme/b-gme-fellowship-
training-programs/pediatric-
emergency-medicine-fellowship
92 West Miller Street Emergency Medicine Orlando Florida 32806-2036 (321) 841-7789 (321) 841-4046 orlandohealth.com/pedsem
MP-366
1547 Clifton Road, Atlanta Georgia 30322 (404) 785-7142 (404) 785-7989 https://med.emory.edu/departments/pediatrics/
2nd floor divisions/emergency-medicine/education/
fellow/index.html
1120 15th Street AF2016 Augusta Georgia 30912 (706) 721-5592 (706) 721-7718 https://www.augusta.edu/mcg/em/ed/
fellowships/pediatric/
225 East Chicago Avenue Box #62 Chicago Illinois 60611 (312) 227-6080 (312)227-9475 https://www.pediatrics.northwestern.edu/
education/fellows/emergency/
5721 South Maryland Avenue MC 8016 Chicago Illinois 60637 (773) 702-0432 (773) 834-0748 http://pediatrics.uchicago.edu/education/
fellowship/emergency-medicine
720 Eskenazi Avenue Faculty Office Building, Indianapolis Indiana 46202 (317) 944-1955 (317) 880-0545 https://medicine.iu.edu/emergency-medicine/
3rd floor education/fellowship/pediatrics
Department of Pediatric 571 South Floyd Street, Louisville Kentucky 40202 (502) 629-7212 (502) 629-5991 https://louisville.edu/medicine/departments/
Emergency Medicine Suite 412 pediatrics/divisions/emergency-medicine/
fellowship-program
1800 Orleans Street Bloomberg G1509 Baltimore Maryland 21287 (410) 955-6143 (410) 614-7339 https://www.hopkinsmedicine.org/johns-hopkins-
childrens-center/healthcare-professionals/education/
fellowships/emergency-medicine/
801 Albany Street, 4th floor Boston Massachusetts 02119 (617) 414-5514 (617) 414-4393 https://www.bmc.org/pediatrics-emergency-department/
medical-professionals/fellowship-program
300 Longwood Avenue BCH3066 Boston Massachusetts 02115 (617) 355-6624 (617) 730-0335 https://dme.childrenshospital.org/graduate-medical-
education/trainings-programs/division-of-emergency-
medicine/pem-fellowship-program/
759 Chestnust Street S5427 Springfield Massachusetts 01199 (413) 794-5999 (413) 794-8070 http://www.baystatehealth.org/education-research/
education/fellowships/pediatric-emergency-medicine
100 Michigan Street NE MC 13 Grand Rapids Michigan 49503 (616) 267-1455 (616) 267-0090 https://www.spectrumhealth.org/
medicaleducation/fellowships/pediatric-
emergency-medicine
Continued next page


University of Michigan Michele Carney, mmcarney@ Sarah Tomlinson, shamilt@med.umich. Janene Bondie jbondie@med.umich.edu
MD med.umich.edu MD Emily edu ejmath@med.
Mathias, MD umich.edu
Children's Hospital Katherine McVety, kmcvety@dmc.org Amy Delaroche, MD adelaroc@dmc.org Jasmine Harris jharris6@dmc.org
of Michigan MD
Oakland University Margaret Menoch, margaret.menoch@ Lauren Adams, lauren.adams2@ Melody Cikalo meloday.cikalo@beaumont.edu
William Beaumont School MD beaumont.edu MD Dan beaumont.edu
of Medicine William Nguyen, MD dan.nguyen@
Beaumont Hospital beaumont.edu
Children's Hospitals and Kara Seaton, MD kara.seaton@ Jennifer Argentieri, MD jennifer.argentieri@childrensmn.org Heather Pomeroy heather.pomeroy@childrensmn.org
Clinics of Minnesota childrensmn.org
Health Partners Institute of
Education and Research
University of Mississippi Melissa Frascogna, mfrascogna@umc.edu Matthew Maready, MD mmaready@umc.edu Denise Merideth dmerideth@umc.edu
Medical Center MD
Children's Mercy Hospital Lina Patel, MD lpatel@cmh.edu Frances Turcotte-Benedict fgturcotte@cmh.edu April Gerry algerry@cmh.edu
Saint Louis University Scott Thomas, MD thomassm@slu.edu Kavitha Krishnarao kavitha.krishnarao@health.slu.edu

School of Medicine
Cardinal Glennon
Children's
Medical Center
Washington University Kathryn Leonard, leonardk@wustl.edu Kris Forneris krisforneris@wustl.edu
St. Louis MD
Children's Hospital
University of Nevada Jay Fisher, MD jay.fisher@unlv.edu Ami Shah, MD ami.p.shah@outlook.com Tricia Sarmiento tricia.sarmiento@unlv.edu
Las Vegas School
of Medicine
Newark Beth Israel Catherine Scarfi, cscarfi@barnabashealth.org Cena Tejani, MD ctejani@barnabashealth.org Florence Chase florence.chase@rwjbh.org
Medical Center and MD
The Children's Hospital
of New Jersey
Morristown Medical Christopher christopher.amato@ Mahsa Akhavan, MD mahsa.akhavan@ Scottie Christians wescott.christian@atlantichealth.org
Center Atlantic Amato, MD atlantichealth.org atlantichealth.org
Health System
University of Natasha James, MD ncjames@salud.unm.edu Sara Skarbek-Borowska, MD sskarbek@salud.unm.edu Ryan Van Otten rvanotten@salud.unm.edu
New Mexico
Maimonides Infant Hector Vazquez, hvazquez@ Christine Rizkalla, MD crizkalla@maimonidesmed.org Susan Caliendo scaliendo@maimonidesmed.org
and Children's MD, MSc maimonidesmed.org
Hospital of Brooklyn
New York-Presbyterian Christopher chk9064@nyp.org Adetunbi Ayeni, MD ada9028@nyp.org Brian London bel9052@nyp.org
Brooklyn Methodist Kelly, MD
Hospital
Children's Hospital at Daniel Fein, MD dfein@montefiore.org JoAnne Walters jowalters@montefiore.org
Montefiore Albert
Einstein College
of Medicine
University of Buffalo Heather Territo, hterrito@buffalo.edu Kunal Chadha, MD kchadha@upa.chob.edu Sharon Chodora schodora@upa.chob.edu
John R. Oishei MD
Children's Hospital
Cohen Children's Medical Dave Teng, MD dnateng1999@gmail.com Michael Preis, DO mpreis@northwell.edu Jasmine Lawrence jlawrenc@northwell.edu
Center North Shore-LIJ
Health System
Children's Hospital of Cindy Roskind, cg278@cumc.columbia.edu Lisa Brooks-McDonald lm3451@cumc.columbia.edu
New York-Presbyterian MD
Columbia University
Medical Center
Icahn School of Medicine Lou Spina, MD louis.spina@mountsinai.org Jennifer Sanders, MD jennifer.sanders@mountsinai.org Claribel Velasquez claribel.velasquez@mountsinai.org
at Mount Sinai
New York Presbyterian Yaffa Vitberg, MD ymv9001@med.cornell.edu Yvonne Wright yvw2004@med.cornell.edu

Hospital (Cornell
Campus)
New York University Selin Sagalowsky, selin.sagalowsky@nyulangone.org Joanne Agnant, MD, MSc joanne.agnant@nyulangone.org Meena Casas meena.casas@nyulangone.org
Bellevue MD, MPH
Hospital Center
Golisano Children's Anne Brayer, MD anne_brayer@urmc.rochester.edu Asim Abbasi, MD asim_abbasi@urmc.rochester.edu Jennifer Moffit jennifer_moffit@urmc.rochester.edu
Hospital at Strong
University of Rochester
Albert Einstein College of Stephen Blumberg, MD stephen.blumberg@nychhc.org Abigail Nixon, MD abigail.nixon@nychhc.org Nicole Weinheimer nicole.weinheimer@nychhc.org
Medicine Jacobi
Medical Center
SUNY Downstate Ambreen Khan, ambreen.khan@downstate.edu Aquila Lewis aquila.lewis@downstate.edu
Health Sciences MD
University Kings
County Hospital
SUNY Upstate Erin Hanley, MD hanleye@upstate.edu Andrea Williams willaan@upstate.edu
Medical University
Atrium Health's Carolinas Christyn Magill, MD christyn.magill@atriumhealth.org Amy Puchalski, MD amy.puchalski@atriumhealth.org Asuncion Erikson asuncion.erikson@atriumhealth.org
Medical Center and Levine
Children's Hospital
Continued next page


1500 East Medical Center Taubman Center, Ann Arbor Michigan 48109-5305 (734) 232-6166 (734) 763-9298 https://medicine.umich.edu/dept/emergency-
Drive, SPC 5305 B1 380 medicine/education/fellowships/pediatric-
emergency-medicine-fellowship-pem
3901 Beaubien Boulevard Detroit Michigan 48201 (313) 966-0945 (313) 993-7118 https://www.childrensdmc.org/health-
professionals/just-for-doctors/fellowships/
emergency-medicine
3601 West 13 Mile Road Royal Oak Michigan 48073 (248) 898-2001 (248) 898-2017 https://www.beaumont.edu/graduate-medical-
education/fellowship-programs/pediatric-
emergency-medicine
345 North Smith Avenue Mailstop 70-504 St. Paul Minnesota 55102 (651) 220-6914 (651) 220-6033 https://www.childrensmn.org/careers/
internship-residency-fellowship-
programs/pediatric-emergency-medicine-
fellowship/
Department of Pediatrics 2500 North State Street Jackson Mississippi 39216 (601) 815-6922 (651) 984-2086 https://www.umc.edu/som/Departments%20and%
20Offices/SOM%20Departments/Pediatrics/
Divisions/Emergency%20Medicine/Fellowship/
Fellowship.html
2401 Gillham Road Kansas City Missouri 64108 (816) 302-8420 (816) 559-9520 https://www.childrensmercy.org/professional-
education/fellowships/pediatric-emergency-
medicine-fellowship/
1465 South Grand Boulevard St. Louis Missouri 63104 (314) 577-5360 (314) 268-4116 https://www.slu.edu/medicine/pediatrics/
fellowships/pediatric-emergency-
medicine.php
660 South Euclid Avenue Campus Box 8116 St. Louis Missouri 63110 (314) 454-2558 (314) 454-4345 http://pediatrics.wustl.edu/emergency/fellowship
Department of 901 Rancho Lane, Las Vegas Nevada 89106 (702) 383-7885 (702) 366-8545 https://www.lasvegasemr.com/pem-
Emergency Medicine Suite 135 fellowship.html
201 Lyons Avenue Newark New Jersey 07112 (973) 926-6671 (973) 282-0562 https://www.rwjbh.org/for-healthcare-
professionals/medical-education/newark-
beth-israel-medical-center/pediatric-
emergency-medicine-fellowship/
100 Madison Avenue Box #8 Morristown New Jersey 07960 (973) 971-7926 (973) 290-7202 https://www.atlantichealth.org/morristown/for+
professionals/residents+&+fellows/residency+
programs/emergency+medicine/
fellowships/pediatric+emergency+medicine
1 University of New Mexico MSC11 6025 Albuquerque New Mexico 87131 (505) 272-6052 (505) 272-6503 https://emed.unm.edu/pem/education/
emergency-medicine-fellowship.html
965 48th Street Brooklyn New York 11219 (718) 283-6290 (718) 635-7228 https://www.maimonidesmed.org/emergency-medicine/
fellowships/pediatric-emergency-medicine-
fellowship/overview-pediatric-emergency
506 6th Street Brooklyn New York 11215 (718) 780-5040 (718) 780-3153 https://www.nyp.org/brooklyn/medical-education/
fellowship-training-programs/pediatric-emergency-
medicine-fellowship-program-
111 East 210th Street Bronx New York 10467 (718) 920-5312 (718) 798-6485 https://www.cham.org/specialties-and-programs/
emergency-medicine/education-training https://
virtualtour.montefiore.org/cham-pediatrics-
fellowship?_ga=2.186087136.873230537.
1609787036-1469875961.1609787036
1001 Main Street 5th floor Buffalo New York 14203 (716) 323-0222 (716) 323-0293 http://medicine.buffalo.edu/pediatrics/
education/fellowships/emergency.html
269-01 76th Avenue New Hyde New York 11040 (718) 470-5277 (718) 470-3935 https://professionals.northwell.edu/graduate-medical-
Park education/fellowship-pediatric-emergency-medicine-
cohen-childrens-medical-center
622 West 168th Street PH2-210 New York New York 10032 (212) 305-8536 (212) 305-6792 https://www.emergencymedicine.columbia.
edu/pediatric-emergency-medicine-
fellowship
Department of One Gustave L. Levy New York New York 10029 (212) 241-8069 (212) 241-1946 https://icahn.mssm.edu/education/
Emergency Medicine Place, Box 1149 residencies-fellowships/list/pediatric-
emergency-fellowship
525 East 68th Street Box #179 New York New York 10065 (212) 746-0780 (212) 746-4883 https://pediatrics.weill.cornell.edu/education/
fellowships/pediatric-emergency-medicine-
fellowship
462 First Avenue 8th fllor New York New York 10016 (212) 263-2693 (212) 562-7752 https://med.nyu.edu/emergency/education/
fellowships/acgme-accredited-
fellowships/pem-fellowships
601 Elmwood Avenue Box #655 Rochester New York 14642 (585) 273-4244 (585) 473-3516 https://www.urmc.rochester.edu/education/
graduate-medical-education/prospective-
fellows/pediatric-emergency-medicine.aspx
1400 Pelham Parkway Room 1B-25 Bronx New York 10461 (718) 918-5826 (718) 918-7459 https://jacobipem.org/fellowship/
450 Clarkson Avenue Box #1228 Brooklyn New York 11203-2098 (718) 270-4442 (718) 245-4799 http://pem.clinicalmonster.com/
550 East Genessee Street Syracuse New York 13210 (315) 464-6222 (315) 464-6229 https://www.upstate.edu/emergency/education/
fellowships/peds.php
1000 Blythe Boulevard MEB 3rd Floor, Department Charlotte North Carolina 28203 (704) 355-4212 (704) 355-7047 https://atriumhealth.org/education/graduate-medical-
of Emergency Medicine education/physician-fellowships/emergency-
medicine/pediatric-emergency-medicine
Continued next page


University of North Carolina Courtney Mann, MD courtney.mann@weppa.org Scott Connelly, MD scott.connelly@weppa.org Wynne Sheen wynne.sheen@weppa.org
Hospitals Program
Wake Forest Adam Johnson, MD adajohns@wakehealth.edu Nancy Holliday nhollida@wakehealth.edu
University School
of Medicine Program
Akron Children's Hospital Nirali Patel, MD npatel@akronchildrens.org Sarah Kline-Krammes skline-krammes@akronchildrens.org Carole Holliday cholliday@akronchildrens.org
Cincinnati Children's Michelle Eckerle, michelle.eckerle@cchmc.org Paria Wilson, MD, Med paria.wilson@cchmc.org Amy Flaherty amy.flaherty@cchmc.org
Hospital Medical Center MD, MPH
Rainbow Babies Jerri Rose, jerri.rose@uhhospitals.org Megan Evers, MD megan.evers@uhhospitals.org Maura Dooley maura.dooley@uhhospitals.org
and Children's Hospital MD, FAAP
Nationwide Kristin Stukus, MD kristin.stukus@nationwide Jennifer Mitzman, jennifer.mitzman@ Tammy Reiss tammy.reiss@nationwidechildrens.org
Children's Hospital childrens.org MD Julia Lloyd, MD nationwidechildrens.
org julia.lloyd@
nationwidechildrens.org
University of Oklahoma Amanda Bogie, amanda-bogie@ouhsc.edu Ryan McKee, MD ryan-mckee@ouhsc.edu Karen Willbanks karen-willbanks@ouhsc.edu
College of Medicine MD
Children's Hospital, LHSC at Gurinder Sangha, gurinder.sangha@lhsc.on.ca Sonya Collard sonya.collard@lhsc.on.ca

Western University MD
Children's Hospital Raagini Jain, MD rjain@cheo.on.ca Michael White miwhite@cheo.on.ca

of Eastern Ontario
The Hospital for Iwona Baran, MD iwona.baran@sickkids.ca laura. Ritsa Iriotakis ritsa.irotakis@sickkids.ca
Sick Children Laura Simone, MD simone@sickkids.ca
Oregon Health & Science Jessica Bailey, MD bailejes@ohsu.edu yue@ohsu.edu Arige El-Naser elnaser@ohsu.edu
University Randall Esther Yue, MD
Children's Hospital
St. Christopher's Evan Weiner, MD ejw33@drexel.edu Luis Gamboa, MD llg54@drexel.edu Kim Abrams kimberly.abrams@towerhealth.org
Hospital for Children
Children's Hospital Richard Scarfone, scarfone@email.chop.edu Pamela Fazzio, MD fazziop@email.chop.edu Julia Swanson swansonjl@email.chop.edu
of Philadelphia MD
UPMC Children's Melissa Tavarez, melissa.tavarez2@chp.edu Jane Soung, MD jane.soung@chp.edu Danielle Harvey danielle.harvey3@chp.edu
Hospital of Pittsburg MD
Montreal Children's Hospital Raphael Paquin, MD raphael.paquin@mcgill.ca John Batt pediatricemergencymed@mcgill.ca
CHU Sainte-Justine Hospital Marisol Sanchez soleil.sanchez@gmail.com Julie Korzeniewski julie.korzeniewski@sss.gouv.qc.ca
Montreal University
Hasbro Children's Hospital Elizabeth Jacobs, elizabeth_jacobs@brown.edu Lauren Allister, MD lauren_allister@brown.edu Wendy Wesley wwesley@lifespan.org
Warren Alpert Medical MD
School of Brown University
Medical University of South M. Olivia Titus, MD titusda@musc.edu Ian Kane, MD kanei@musc.edu Ingrid Schneider schneider@musc.edu
Carolina Program
University of Tennessee Le Bonheur Mindy Longjohn, mindylongjohn@gmail.com Rick Hanna, MD rhanna3@gmail.com April Smith asmit359@uthsc.edu
Children's Medical Center MD, MPH
Vanderbilt University Medical Daisy Ciener, daisy.a.ciener@vumc.org Rebekah Shaw rebekah.shaw@vumc.org
Center Monroe Carell Jr. MD, MS
Children's Hospital
at Vanderbilt
The University of Texas Coburn Allen, MD challen@ascension.org Sujit Iyer, MD ssiyer@ascension.org Irene Teeler iteeler@seton.org
at Austin Dell
Medical School
UT Southwestern Medical Jo-Ann jo-ann.nesiama@ Sing-Yi Feng, MD sing-yi.feng@utsouthwestern.edu Kevin Lynch kevin.lynch@utsouthwestern.edu
Center at Dallas Nesiama, MD utsouthwestern.edu
Baylor College of Medicine Esther Sampayo, emsampay@texaschildrens.org Kim Little-Wienert, MD, MEd kjlittle@texaschildrens.org Margo LaTour mlatour@bcm.edu
Texas Children's Hospital MD, MPH Marideth Rus, MD, MEd mcrus@texaschildrens.org
Children’s Memorial Hermann Donna Mendez, donna.mendez@uth.tmc.edu Kandice Kaylor kandic.kaylor@uth.tmc.edu

Hospital McGovern Pediatric MD, EdD McLeod
Emergency Medicine
at UTHealth
Primary Children's Hospital Michael Miescier, MD michael.miescier@hsc.utah.edu Zachary Drapkin, MD zachary.drapkin@ Megan Warren megan.warren@hsc.utah.edu
University of Utah Pediatric Elizabeth Keating, hsc.utah.edu elizabeth.
Emergency Medicine MD (GH Track) keating@hsc.utah.edu
Inova Children's Hospital The Aline Baghdassarian, aline.baghdassarian@inova.org Minal Amin, MD minal.amin@inova.org Shamaila Kausar shamaila.kausar@inova.org
Altieri Pediatric Emergency MD, MPH
Medicine Fellowship
Children's Hospital of the King's Joel M. Clingenpeel, joel.clingenpeel@chkd.org Kimberley Kelly kimberley.kelly@chkd.org
Daughters Eastern Virginia MD, MPH,
Medical School MS.MEdL
Children's Hospital of Richmond Rashida Woods, MD rashida.woods@vcuhealth.org Jonathan Silverman, jonathan.silverman@vcuhealth.org Sharon Fleming sharon.fleming@vcuhealth.org
Virginia Commonwealth MD, MPH
University
Seattle Children's Hosptial Derya Caglar, MD derya.caglar@seattlechildrens.org Tamar Anderson tamar.anderson@seattlechildrens.org
University of Washington
Children's Hospital of Wisconsin Viday Heffner, MD vheffner@mcw.edu Christina Hoppe choppe@mcw.edu
Medical College of Wisconsin


3000 New Bern Avenue 3rd floor MOB, Raleigh North Carolina 27610 (919) 350-7828 (919) 350-8874 https://www.med.unc.edu/emergmed/
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One Perkins Square Akron Ohio 44308 (330) 543-8452 (330) 543-3761 https://www.akronchildrens.org/pages/Pediatric-
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3333 Burnett Avenue MLC 2008 Cicinnati Ohio 45229 (513) 636-7966 (513) 636-7967 http://www.cincinnatichildrens.org/education/
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11100 Euclid Avenue Mailstop RBC-6002 Cleveland Ohio 44106 (216) 844-4853 (216) 844-7166 https://www.uhhospitals.org/rainbow/the-center-of-
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940 NE 13th Street Suite 2G-2300 Oklahoma City Oklahoma 73104 (405) 271-2429 (405) 271-2421 https://www.oumedicine.com/department-of-pediatrics/
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800 Commissioners Room B1-437 London Ontario N6A 5A5 (519) 685-8377 (519) 685-8156 https://www.schulich.uwo.ca/paediatrics/
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Department of Emergency 3181 SW Sam Jackon Portland Oregon 97239 (503) 494-6993 (503) 494-8237 https://www.ohsu.edu/school-of-medicine/
Medicine, CDW-EM Park Road emergency/pediatric-emergency-
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160 East Erie Avenue Philadelphia Pennsylvania 19134 (215) 427-8812 (215) 427-4668 https://www.towerhealth.org/academic-affairs/pediatric-
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Division of Emergency 3401 Civic Center Boulevard, Philadelphia Pennsylvania 19104-4399 (215) 590-3948 (215) 590-4454 https://www.chop.edu/centers-programs/
Medicine CTRB, 9th floor emergency-department/fellowship
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Cote Sainte-Catherine
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125 Doughty Street MSC 561 Charleston South Carolina 29425 (843) 792-0269 (843) 792-3022 https://medicine.musc.edu/departments/
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Emergency Services
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Department pediatric-emergency-medicine-
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Medicine Children's Lane emergency_medicine/
1250 East Marshall Street 2nd floor, Suite 500 Richmond Virginia 23298-0401 (804) 828-5250 (804) 828-4603 https://emergencymedicine.vcu.edu/residency_
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em/index.html
4800 Sand Point Way NE Mailstop MB.7.520 Seattle Washington 98105 (206) 987-7074 (206) 729-3070 http://www.peds.uw.edu/fellowships/
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North 92nd Street emergency-medicine/Fellowship

ORIGINAL ARTICLE
Adverse Drug Event–Related Admissions to a

Pediatric Emergency Unit
Indira Valadê Carvalho, MSc,* Vanessa Marcilio de Sousa, BS,† Marília Berlofa Visacri, PhD,*
Júlia Coelho França Quintanilha, MSc,* Cinthia Madeira de Souza, MSc,*
Rosiane Fátima Lopes Ambrósio, BS,* Marcelo Conrado dos Reis, MD,‡ Rachel Alvarenga de Queiroz, MD,‡
Priscila Gava Mazzola, PhD,† Taís Freire Galvao, PhD,† and Patricia Moriel, PhD*†
caused by a drug,” and the term ADE as “harm caused by the

Objectives: The objectives of this study were to analyze adverse drug use of a drug.” Adverse drug events represent a large cost imposi-
events (ADEs) related to admissions to a pediatric emergency unit and to tion on the health care sector and can cause hospital or emergency
identify the associated risk factors. department admission, prolongation of hospital stays, morbidity,
Methods: This was a prospective study. Demographic data and details of impairment of quality of life, life-threatening conditions, and, in
medications were collected for each patient admitted. Case studies were the worst cases, mortality.4–9
performed by clinical pharmacists and the clinical team to discuss whether Adverse drug event monitoring is extremely important in the
the admission was due to an ADE and to characterize the ADE. Multivar- pediatric population, owing to the scarcity of clinical trials for this
iate logistic regression was used for statistical analysis. population and the lack of knowledge of pediatric pharmacology,
Results: In total, 1708 pediatric patients were included in this study. Ad- resulting in off-label or unlicensed use of medication. These are
verse drug events were the cause of hospital admission in 12.3% of the considerable obstacles for the safe use of medication in children.
studied population. The majority of patients presenting with an ADE were Moreover, the ongoing maturation of their organs, mainly the liver
in the age group of 0 to 5 years (61.6%), had a mean ± SD age of and kidneys, may alter drug disposition and action, and children
4.9 ± 3.9 years, were female (51.2%), were Caucasian (72.0%), and had are not only different from adults in relation to this aspect but also
infectious disorders (49.3%). High frequencies of medication errors differ vastly within their own age group.10
(68.8%), use of drugs to treat respiratory disorders (27.7%), and ADEs It is expected that the rate of ADEs will be higher for children
of mild severity (75.3%) were reported. The risk of being admitted to than for adults, not only due to the previously mentioned aspects
the pediatric emergency unit for any ADE increased in cases of neurolog- but also because pediatric medications involve weight-based dos-
ical (odds ratio [OR], 4.63; 95% confidence interval [CI], 2.38–8.99), der- ing. This requires calculations and often multiple preparations, as
matological (OR, 3.16; 95% CI, 1.93–5.18), and respiratory (OR, 3.02; there is a lack of age-suitable formulations and dosages. The most
95% CI, 1.89–4.83) disorders. preventable ADE in pediatric outpatients is medication adminis-
Conclusions: A high frequency of ADE-related admissions to the pediat- tration error.11 Parents are frequently responsible for these errors,
ric emergency unit was observed. The risk of being admitted to the pediatric especially those with limited literacy.12 It is known that 50% or
emergency unit for any ADE increased in cases of neurological, dermatolog- more of parents make errors when administering liquid medica-
ical, and respiratory disorders. Clinical pharmacists play an important role in tion.13 Prescribing errors, another preventable ADE, are also com-
the identification of ADEs and the education of child caregivers and health mon. Condren et al14 showed that medication errors were found in
care providers concerning pediatric medication. 9.7% of prescriptions in a pediatric clinic and that the most fre-
Key Words: adverse event, pharmacoepidemiology, pharmacovigilance quently occurring errors were incomplete prescriptions and dosing
errors, primarily related to anti-infectives and anti-inflammatory
(Pediatr Emer Care 2021;37: e152–e158)
medications. Both medication errors and other ADEs can cause
severe damage and are the leading cause of pediatric emergency
P harmaceutical drugs are the most commonly prescribed medi-
cal therapy and the most frequent cause of adverse events
(AEs).1 Adverse events are defined by the World Health Organi-
department admissions.
Our study involves ADEs that occurred outside the hospital
and led to pediatric admissions to the emergency unit. Little re-
zation as “any untoward medical occurrence that may present dur-
search has been conducted to determine the frequency, profile,
ing treatment with a pharmaceutical product but which does not
and associated factors of ADE-induced pediatric emergency ad-
necessarily have a causal relationship with this treatment.”2 The
missions. Existing studies usually (1) have a retrospective design;
World Health Organization does not recognize the term adverse
(2) are performed in the United States, Canada, and Australia; and
drug event (ADE); however, Nebeker et al3 define the term AE
(3) mainly study only drug toxicity as adverse drug reactions
as “harm in a patient administered a drug but not necessarily
(ADRs) and overdoses. Therefore, nonadherence and therapeutic
failures are inadequately addressed.15–22
This study therefore aimed to analyze ADE-related admis-
From the *School of Medical Sciences, †Faculty of Pharmaceutical Sciences, sions to a pediatric emergency unit and identify the associated risk
and ‡Pediatric Emergency Unit, Hospital of Clinics, University of Campinas, factors, with the presence of a clinical pharmacist to quantify and
Campinas, São Paulo, Brazil.
characterize the observed ADEs. This study is the first of its kind
This publication was supported by a grant from Brazilian research agency in our country (Brazil) and may contribute to the scientific literature
(CNPq) (grant number 132273/2012-8). to allow better comprehension of the profile of drug usage in pedi-
Reprints: Patricia Moriel, PhD, Faculty of Pharmaceutical Sciences, University atric patients. This study may also support the monitoring, preven-
of Campinas, 200 Cândido Portinari St, Barão Geraldo, 13083-871
Campinas, São Paulo, Brazil (e-mail: patricia.moriel@fcf.unicamp.br).
tion, and quantification of ADE occurrence in phase IV of drug
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. development, known as pharmacovigilance or postmarketing drug
ISSN: 0749-5161 safety surveillance.
e152 www.pec-online.com Pediatric Emergency Care • Volume 37, Number 4, April 2021

Pediatric Emergency Care • Volume 37, Number 4, April 2021 ADE-Related Admissions
METHODS endocrinological, oncological, bone and joint, hematological, gy-

necological, urological, respiratory, dermatological, gastrointesti-
Study Design nal, renal, immunological disorder, congenital disease, fracture,
returns, genetic disease, insertion of foreign bodies into the respi-
This was a prospective study conducted from July 2011 to
ratory tract, ingestion of toxic substances, hernia, and problems
June 2012 in the pediatric emergency unit of a public teaching
with probes. This classification considered the literature as well
hospital in Campinas, São Paulo, Brazil. The Research Ethics
as the hospital epidemiology.26,27
Committee of the institution approved the study, and caregivers
According to Regulation Number 4/2009 of the Brazilian
(father, mother, or other responsible guardian) who agreed to par-
Health Surveillance Agency (ANVISA, Brazil),28 ADE catego-
ticipation signed a consent form authorizing the use of data.
ries may include ADRs, AEs due to medication quality deviations,
ADRs from unapproved use of medication, drug interactions, ther-
Setting apeutic ineffectiveness, drug poisoning, drug abuse, and medication
The pediatric emergency unit works 24 hours a day, 7 days a errors. Based on this statement, when an ADE-related admission
week, and attends to an average of 1655 patients per month. It has was identified (ADE population), it was classified according to
5 consultation rooms, a procedure room, an inhalation room, a the ADE type (each event could be categorized in more than 1
weighing room, a fully equipped emergency room, and 8 observa- classification) shown in Table 1.
tion beds. The emergency team is composed of physicians and Cases of therapeutic ineffectiveness were evaluated only
nurses. Throughout the year of study, 2 clinical pharmacists re- based on caregivers' reports and consultation of the cited bibliog-
lated to this research were present in the pediatric emergency unit, raphies. Adherence data were obtained using the Morisky-Green
working Monday to Thursday, from 8 AM to 5 PM. questionnaire.37 Beyond the cited bibliographies, the online data-
base Micromedex 2.0 was also consulted for cases of suspected
Participants drug interaction.38 If required, the drug concentration was deter-
mined, either in a sample of medicine or in a peripheral venous
The inclusion criteria for the study were as follows: patients
blood sample, for better characterization of the ADE type.39
of either sex, under 15 years old, and admitted to the pediatric
Adverse drug events were also classified according to the
emergency unit between 8 AM and 5 PM between Monday and
drug and therapeutic class responsible for the event, using the
Thursday, regardless of ethnicity and preexisting diseases. The ex-
Anatomical Therapeutic Chemical Classification,40 and classi-
clusion criteria were as follows: patients hospitalized with respira-
fication according to severity was performed as described by
tory and contact isolation (patients with suspected meningitis and
Coêlho et al.41 For ADRs, we classified causality according to
pertussis) and patients whose caregivers did not allow their partic-
the Naranjo Algorithm,42 a scale used to standardize causality as-
ipation in the study.
sessment for ADRs that classifies the ADR as doubtful, possible,
probable, or defined.
Data Sources and Measurement
For each admission to the pediatric emergency unit, a spe- Pilot Study
cific form was completed, using which the pharmacists collected A pilot study was performed at the pediatric emergency unit
data such patient identification, age, sex, ethnicity, weight, and di- over 30 days (July 2011), to allow methodology validation and to
agnosis. After admission, clinical pharmacists attended the medi- establish statistical parameters. During this period, 76 patients
cal appointment and the case discussion with the emergency team, attended, in which 9 admissions (11.8%) were caused by at least
to collect more information about the diagnostic hypothesis. If 1 ADE. The sample size was calculated from a test of the propor-
necessary, pharmacists conducted a brief interview with the staff. tion of individuals in a descriptive study with a qualitative vari-
After the medical appointment and discussion, pharmacists able, by adding a 5% margin of sampling error and a level of
interviewed caregivers to obtain information on the use of drugs bilateral significance of 5%. To obtain reliability in this study,
(posology, dosage, adverse effects, route of administered, and 1560 patients were therefore required.
compliance). Pharmacists then followed the clinical outcome
(immediate patient discharge, referral to other clinics and health Statistical Analysis
services, or hospitalization in the observation room or pediatric
ward) and monitored the evolution of each case. For patients The data were analyzed using Statistical Analysis System
who received medical discharge, pharmacists gave advice on software (SAS, 9.4 version, Cary, NC). To study the influence of
the use of drugs to be administered at home; however, these data patient-related risk factors (age group, sex, ethnicity, and diagnosis)
were not quantified. and therapy-related risk factors (therapeutic class) on ADEs, ADE
During the appointment with the clinical pharmacy team, case severity, different ADE classes, and ADR causality, multivariate
studies were performed with the clinical team to analyze whether logistic regression with stepwise criteria of variable selection
the admission was due to an ADE and to characterize any ADEs. was used, and the odds ratio and 95% confidence interval were
Two clinical pharmacists were the judges, and if their answers were obtained. For this last analysis, the following groupings were
not in alignment, a third clinical pharmacist decided whether admis- made: severity of ADE, moderate plus severe versus mild; causality
sion was due to an ADE or not. If there was a suspicion of ADE- of ADR, doubtful plus possible versus probable plus defined; and
related admission, detailed studies were performed based on at least age group, 6 to 9 years plus 10 to 15 years versus 0 to 5 years (for
3 different bibliographic sources.23–25 Based on the case studies, the some cases only). The significance level was set at 5% (P < 0.05).
patients were divided into 3 groups: general population (all the ad-
mitted patients), ADE population (those whose admission was due RESULTS
to an ADE), and non-ADE population (those whose admission was During the study period, 20,441 patients were admitted to the
not due to an ADE). pediatric emergency unit, of which 1708 (8.3%) were attended by
Patients' primary diagnoses were classified into one of the the clinical pharmacist. Of these 1708 patients, 1334 (78.1%) were
following categories: infectious disease, neurological, psychi- treated and discharged after a medical appointment, 314 (18.3%)
atric, nutritional, cardiovascular, ophthalmic, otolaryngological, were referred to other clinics and health care services, and 60
© 2018 Wolters Kluwer Health, Inc. All rights reserved. www.pec-online.com e153

Carvalho et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
TABLE 1. Classification According to the Type of ADE
Type of Adverse Drug Event Description

Adverse drug reaction A response to a drug that is noxious and unintended and that occurs at doses normally used in man
for the prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function2
Medication errors Noncompliance
Missed doses due to forgetfulness, schedule change, busy lifestyle, discontinuation due to symptomatic
relief, perceived short- or long-term adverse effects, bad taste, complexity, or interference with daily life29
Inappropriate use of drugs
The use of drugs when no drug therapy is indicated; the use of the wrong drug for a specific condition
requiring drug therapy; the use of drugs with doubtful or unproven efficacy; the use of drugs of uncertain
safety status; failure to provide available, safe, and effective drugs; the use of correct drugs with incorrect
administration, dosages, or duration30
Therapeutic ineffectiveness Occurs when drugs do not exhibit the effects expected of them31
Drug interaction This occurs when 2 or more drugs react with each other, when drugs react with foods or beverages, or when an
existing medical condition makes certain drugs potentially harmful. This may make drugs less effective,
cause unexpected adverse effects, or increase the action of a particular drug.32
Drug poisoning When medication is deliberately or accidentally taken in such a dose that a patient's body cannot adequately
metabolize the drug33
Drug abuse Drug abuse is defined as persistent or sporadic excessive drug use, inconsistent with or unrelated to acceptable
medical practice. Thus, the intentional use of excessive doses, or the intentional use of therapeutic doses for
purposes other than the indication for which the drug was prescribed, is drug abuse. Misuse and nonmedical
use are synonyms of drug abuse.34
Quality deviations Package anatomical problems, breaks, splits, or leaks, lack of identification, poor quality information, lack
of product, dirtiness, organoleptic changes, physicochemical changes of solid products, physicochemical
modifications of liquid and semisolid products35
Unapproved use of Unapproved use of medicines is called off-label use. This term can mean that the drug is used for a disease
medicines or medical condition that it is not approved to treat, such as when a chemotherapy is approved to treat one
type of cancer, but health care providers use it to treat a different type of cancer; given in a different way,
such as when a drug is approved as a capsule, but it is given instead in an oral solution; given in a different
dose, such as when a drug is approved at a dose of one tablet every day, but a patient is told by their health
care provider to take 2 tablets every day.36
(3.6%) were hospitalized for observation. It was observed that the drug. Patients receiving 2 or 3 drugs represented 26% of the
cause of emergency admission for 211 patients (12.3%) was at group, whereas 2 patients were receiving 5 or more types of med-
least 1 ADE. Figure 1 shows the process for patient inclusion, icines (1.0%; maximum, 6).
and Table 2 describes the characteristics of the patients studied The therapeutic classes of drugs involved in ADEs are shown
(general population, non-ADE population, and ADE population). in Table 3. The top 5 classes involved in pediatric emergency unit-
The largest number of ADEs occurred in patients who were related ADEs were as follows: respiratory system, nervous system,
in the 0 to 5 years age group, were female, were Caucasian, and anti-infectives for systemic use, dermatological drugs, and alimen-
had infectious disease. The most frequent disorders found in tary tract and metabolism. The main ADE-causing drugs were
children with ADEs were in the respiratory, dermatological, dexchlorpheniramine (5.8%), prednisolone (5.1%), and fenoterol
and neurological categories. (4.1%) in the respiratory system class; metamizole sodium (7.5%)
In this study, 292 events occurred in the 211 patients, related and paracetamol (5.1%) in the nervous system class; amoxicillin
to 292 drugs. Most (72.0%) of the patients were taking only 1 (10.3%) in the anti-infectives for systemic use class; ketoconazole
(2.4%) in the dermatological class; and finally, bromopride (1.0%)
in the alimentary tract class.
Regarding ADE type, medication errors were the most fre-
quent, followed by therapeutic ineffectiveness and ADRs (Table 4).
There were no ADEs due to drug abuse, quality deviations, or ADRs
from unapproved use of medicines.
Forty-seven patients (2.7% of the general population; 22.3%
of the ADE population) were noncompliant, 20 of whom were
noncompliant owing to treatment discontinuation once the patient
felt better. Regarding inappropriate use (98 patients, 5.7% of the
general population; 46.5% of the ADE population), 35 patients
did not need the drug being used and 26 patients used a lower dos-
age than that which was prescribed.
A higher occurrence of ADEs of mild severity was observed
FIGURE 1. Patient inclusion process. *These patients were not
assessed because there was no clinical pharmacist present at the (75.3%), followed by moderate (23.0%) and severe (1.7%). There
time the patient was admitted, or because they were hospitalized at were no detected fatal events. Regarding ADRs, by studying the
respiratory and contact isolation (patients with suspected causality, only 1 case (2.3%) could be considered defined. Most
meningitis and pertussis), or the caregivers did not allow their cases were determined to have probable causality (47.7%), followed
participation in the study. by cases classified as possible (43.2%) and doubtful (13.6%).
e154 www.pec-online.com © 2018 Wolters Kluwer Health, Inc. All rights reserved.

TABLE 2. Demographic and Clinical Data of the Patients Studied
Characteristics General Population (n* = 1708) Non-ADE Population (n* = 1497) ADE Population (n* = 211)
Age, mean ± SD, y 4.6 ± 3.9 4.6 ± 3.9 4.9 ± 3.9
Age group, n* (%), y
0–5 1091 (63.9) 961 (64.2) 130 (61.6)
6–9 354 (20.7) 309 (20.6) 45 (21.3)
10–15 254 (14.9) 218 (14.6) 36 (17.1)
Not informed 9 (0.5) 9 (0.6) 0 (0.0)
Sex, n* (%)
Male 917 (53.7) 814 (54.4) 103 (48.8)
Female 791 (46.3) 683 (45.6) 108 (51.2)
Ethnicity group, n* (%)
Caucasian 1236 (72.4) 1084 (72.4) 152 (72.0)
Non-Caucasian 427 (25.0) 377 (25.2) 51 (24.2)
Not informed 45 (2.6) 36 (2.4) 8 (3.8)
Diagnosis,† n* (%)
Infectious 893 (52.3) 789 (52.7) 104 (49.3)
Gastrointestinal 172 (10.1) 159 (10.6) 13 (6.2)
Respiratory 114 (6.7) 83 (5.5) 31 (14.7)
Dermatological 113 (6.6) 66 (4.4) 27 (12.8)
Neurological 42 (2.5) 26 (1.7) 16 (7.6)
Bone and joint disorders 29 (1.7) 26 (1.7) 3 (1.4)
Renal 15 (0.9) 13 (0.9) 2 (0.9)
Other‡ 295 (17.3) 285 (19.0) 10 (4.7)
*n = absolute number.
†
Only the 8 most common diagnoses were selected. The diagnoses urologic (n = 5), otolaryngological (n = 5), hematologic (n = 5), endocrinologic
(n = 5), psychiatric (n = 3), oncologic (n = 3), immunologic (n = 2), nutritional (n = 2), cardiovascular (n = 2), ophthalmic (n = 2), and gynecologic disorders
(n = 1) do not appear in the table.
‡
Other diseases: congenital diseases, fractures, returns, genetic diseases, insertion of foreign bodies into the respiratory tract, ingestion of toxic sub-
stances, hernias, and problems with probes.
The multiple logistic regression analysis showed that the risk within the Brazilian pediatric population. Moreover, there are no
of some ADEs may have been influenced by factors such as diag- published international papers with designs similar to that of this
nosis and therapeutic class, as shown in Table 5. study, that is, a prospective design, with a clinical pharmacist an-
alyzing several types of ADEs to determine the frequency of pedi-
DISCUSSION atric emergency admissions due to this ADEs. In a literature
The extent of ADE-related emergency unit admission has not review, Zed et al22 evaluated studies of medication-related emer-
been previously described by well-designed studies conducted gency department admissions in pediatric patients: of 7 studies,
only 1 had a prospective design.16 Comparisons with previous lit-
erature are therefore difficult and will here focus on the study by
TABLE 3. Therapeutic Classes Associated With ADE-Induced Easton-Carter et al.16
Admissions to a Pediatric Emergency Unit The results of this study demonstrate that ADEs are common
in pediatric patients. The prevalence of ADEs was 12.3%, which
Therapeutic Classes (ATC) n (%) is higher than previously reported values. Zed et al22 showed that
the incidence of medication-related pediatric emergency department
Respiratory system (R) 81 (27.7) visits ranged from 0.5% to 3.3% of total visits (only the prospective
Nervous system (N) 72 (24.7) study observed that 3.3% of pediatric emergency department visits
Anti-infectives for systemic use (J) 65 (22.3) were medication related).16 This discrepancy seems to be due to the
Dermatologicals (D) 21 (7.2) study design previously described, as well as the presence of a clin-
Alimentary tract and metabolism (A) 15 (5.1) ical pharmacist identifying ADEs.
Others* 38 (13.0) The sex and age profile of the children admitted to the pediatric
Total 292 (100.0) emergency unit (general population) was consistent with the study by
Easton-Carter et al16; the majority of patients were male with a mean
ATC indicates Anatomical Therapeutic Chemical Classification. age of 4 years. However, whereas Easton-Carter et al16 observed a
*Includes M, muscle-skeletal system; S, sensory organs; H, systemic statistically significant prevalence of males in the ADE population,
hormonal preparations—excluding sex hormones and insulins; L, anti- our study showed roughly equal proportions of both sexes in this
neoplastic and immunomodulating agents; B, blood and blood forming
organs; P, antiparasitic products, insecticides, and repellents; G, genito-
population, with a slightly greater frequency of females.
urinary system and sex hormones; C, cardiovascular system. The most frequent ADE observed in this study was medica-
tion error, particularly the inappropriate use of drugs. This mainly

TABLE 4. ADE Classes in Relation to the General Population and the ADE Population, With Case Examples
Absolute % of the General % of the ADE

ADEs Frequency Population Population* Case Examples
Medication errors 145 8.4 68.8 —
Inappropriate use 98 5.7 46.5 Patient with viral infection using antibiotics
Noncompliance 47 2.7 22.3 Patient with persistent infection, whose mother reported
forgetting to administer the antibiotic
Therapeutic ineffectiveness 97 5.7 45.9 Patient with persistent fever after correct use of antipyretic
ADR 44 2.6 20.8 Patient presenting with tachycardia after use of fenoterol
Drug poisoning 3 0.2 1.5 Patient presenting with seizures after high doses of tizanidine
Drug interaction 3 0.2 1.5 Patient presenting with seizures after concomitant use of
clobazam and carbamazepine
*The percentages add to a sum of greater than 100% because some children presented more than 1 ADE.
occurred when patients did not need the drugs being administered showed that compliance was significantly higher (82%) for the
or when patients administered a lower dosage than that which was shorter therapy, compared with the longer course, with only 74%
prescribed. The findings of Zed et al22 and Easton-Carter et al16 compliance. Among children receiving antibiotics for the longer
support our results. Zed et al22 showed that the most common time period, compliance was significantly higher (79%) for days 0
ADE-induced emergency visits and hospital admissions were to 5 compared with days 6 to 10 (57%).44 Compliance with a treat-
due to patients receiving drugs despite having no indication for ment plan is lower still in cases of chronic diseases, such as juvenile
the use of those drugs (17.2–36.2%). Easton-Carter et al16 found diabetes and asthma, that require complex therapy for long time
that the primary cause of ADE-induced pediatric emergency periods.45 Studies show that parents forget around half of the in-
visits was ADRs (42.1%), followed by patients taking drugs for formation provided by 15 minutes after consultation with the doc-
which there was no valid medical indication (accidental or inten- tor, recalling the first third of the guidance and remembering more
tional poisoning, 33.2%). about the diagnosis that the details of the treatment plan.46
There was a high frequency of therapy noncompliance in this For many years, pediatric ADRs have been a significant pub-
study. A systematic review of international pediatric studies from lic health problem.47 These were the third most frequent ADE in
low- and middle-income countries reported variability in the prev- our study, with a count almost half of the number found in the
alence of antiretroviral therapy compliance. Figures ranged between study reported by Easton-Carter et al (42.1%).16 The data found
49% and 100%, with 76% of studies reporting greater than 75% for causality of ADRs using the Naranjo algorithm differ from
adherence.43 Easton-Carter et al16 only observed 8.9% noncom- those found in other studies. Posthumus et al48 found that, although
pliance (patients who experienced an ADE that was the result of 15 patients were admitted owing to ADRs (patients were not ex-
not receiving the prescribed drug), a lower frequency than was ob- posed to chemotherapy), 66.7% of cases were rated as having prob-
served by us. A study of children aged 0.5 to 5 years treated for able causality, 20.0% as possible causality, and 13.3% as defined
pneumococcal infection with amoxicillin for either 5 or 10 days causality: no doubtful ADRs were observed. Easton-Carter et al16
TABLE 5. Influence of Patient and Therapy-Related Risk Factors on ADEs—Only Statistically Significant Results are Shown Here
Odds Ratio
ADE Factor Risk (Covariate) (95% CI) Interpretation
Any ADE Diagnosis Neurological disorder 4.63 (2.38–8.99) The risk of children with neurological disorder
who have an ADE-induced emergency
unit admission is increased 4.63-fold.
Dermatological disorder 3.16 (1.93–5.18) The risk of children with dermatological disorder
who have an ADE-induced emergency unit
admission is increased 3.16-fold.
Respiratory disorder 3.02 (1.89–4.83) The risk of children with respiratory disorder
who have an ADE-induced emergency unit
ADR Diagnosis Dermatological disorder 6.41 (2.48–16.55) The risk of children with dermatological disorder
who have an ADR-induced emergency unit
Therapeutic class Nervous System (N) 68.67 (8.01–588.81) The risk of children using a nervous system drugs
who have an ADR-induced emergency unit
Noncompliance Diagnosis Respiratory disorder 4.71 (1.95–11.38) The risk of children with respiratory disorder who
have a noncompliance-induced emergency unit
CI indicates confidence interval.

used the causality assessment for overall ADEs and not only for committed to information, communication, and education related
ADRs. These researchers observed defined ADEs in 37.9% of to the rational use of drugs in pediatrics. Thus, our study empha-
cases, probable ADEs in 30.4%, and possible ADEs in 31.8%. sizes the importance of action of clinical pharmacists through
Our results for ADE severity were slightly different to those pharmaceutical care and clinical pharmacy practice. Along with
in the studies found by Zed et al.22 We found a prevalence of mild the clinical team, clinical pharmacists should guide and intervene
severity, followed by moderate and severe severity, but in other in the correct use of drugs, report ADEs to health surveillance
studies, approximately one half of ADEs reported were identified groups, detect and solve real ADEs, and prevent possible ADEs,
as being moderate, followed by mild and severe events. For exam- with the aim to improve the welfare of pediatric patients and re-
ple, moderate ADEs were present in 42.1% of cases in the study duce the cost to the public health system.
reported by Easton-Carter et al.16 The present results have limitations, as the study was carried
Respiratory agents are involved in 10.6% to 35.0% of ADE- out at a single center and did not assess other relevant aspects such
induced pediatric hospital admissions and emergency visits17,49 as the preventability of ADEs; costs; licensing status of medicines;
and central nervous system agents in 3.5% to 17.5%.17,18,21,49,50 characteristics of parents or caregivers, including socioeconomic
In the present study, the ADE frequency observed for respiratory status; follow-up of patients who experienced ADEs; and the lack
agents was as expected based on the percentages cited previously, of information about medicines used by the non-ADE population.
and this was the major ADE-inducing therapeutic class. This was Other limitations include the potential bias involved in the phar-
also found by Martínez-Mir et al49 in their study of ADRs leading macist declaring an event an ADE, recall bias of the family, and
to pediatric hospital admission. The anti-allergy drug dexchlorphe- the fact that the sample used was only a subset of the total patients
niramine was the most frequent cause of ADEs in this therapeutic admitted to the pediatric emergency unit.
class. Similarly, Easton-Carter et al16 observed that chlorphenir- The results presented in this study demonstrate a high fre-
amine was 1 of the 12 most frequent causes of ADEs. Nervous quency of ADE-related admissions to the pediatric emergency
system drugs were the second most common cause of ADEs unit in a public teaching hospital of Brazil. The chance of being
and were associated with ADEs at a slightly higher frequency than admitted to the pediatric emergency unit for any ADE increased
those found in other studies. This is because we observed cases in cases of neurological, dermatological, and respiratory disorders.
where ADEs were induced by the analgesic metamizole sodium, Clinical pharmacists play an important role in the identification of
which is banned in many countries. Furthermore, paracetamol ADEs and the education of children's caregivers and health profes-
was also a prevalent cause of ADEs, both here and in the findings sionals about pediatric medication and may be part of the pediatric
of Easton-Carter et al.16 In a review by Smyth et al,51 antiepilep- multidisciplinary team. More information and well-designed pro-
tics and nonsteroidal anti-inflammatory drugs were therapeutic spective studies in pediatric drug safety are essential. These should
classes frequently associated with ADRs causing pediatric hospital be encouraged in Brazil and other countries to portray the situation
admission. For antiepileptics, the studies reported clinical presen- surrounding ADEs, and to draw attention to the adoption of preven-
tations involving ataxia, skin rash, and drowsiness; and for non- tive and resolutive public policies.
steroidal anti-inflammatory drugs, cutaneous reactions, drowsiness,
abdominal pain, and vomiting.51 These symptoms were also present ACKNOWLEDGMENTS
in the pediatric patients observed by us. Care should be taken The authors would like to acknowledge the School of Medi-
with these medications in pediatric settings, mainly owing to cal Sciences and Hospital of Clinics of University of Campinas.
their association with a higher chance of ADR-induced pediatric
emergency visits.
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ORIGINAL ARTICLE
Substance Use in a Domestic Minor Sex Trafficking

Patient Population
Jessica L. Moore, BA,* Amy P. Goldberg, MD, FAAP,*† and Christine Barron, MD, FAAP*†
one of the most prevalently stated reasons by adult survivors for

Abstract: Substance use and abuse have been documented as both a risk entering into commercial sex work.10,11 Alternatively, minors
factor in and consequence of involvement in domestic minor sex traffick- may be introduced to drug use while engaged in DMST to dull
ing (DMST). Domestic minor sex trafficking is defined as the commercial the trauma experienced during their exploitation, while providing
sexual exploitation of children in exchange for money, food, shelter, or any an opportunity for a trafficker (pimp) to generate control over the
other valued entity. The current investigation sought to describe substance victim.11 Subsequent drug abuse and addiction may therefore be a
use in a cohort of DMST patients who present for medical evaluation. Find- consequence associated with DMST involvement.
ings revealed that 68 patients referred for DMST involvement reported Quantitative research is needed on both the reported use of
high rates of alcohol/substance use and parental substance abuse. Further, substances and urine toxicology results of high-risk youth referred
many patients who had a urine toxicology screen had a positive result, most for concern of DMST involvement. The objective of the current
often identifying the presence of cannabinoids. Our data may inform the investigation was to add to the current literature by providing a de-
importance of comprehensive assessments and specialized interventions tailed conceptualization of substance use in a cohort of DMST pa-
for substance abuse in this unique patient population. tients who present for medical evaluation. Our goal was to capture
Key Words: alcohol/substance use, domestic minor sex trafficking, empirical data at both the initial evaluation and referral visit and
substance use also to investigate patient-reported substance and urine toxicology
results. These data may inform the importance of comprehensive
assessments and specialized interventions for substance abuse in
this unique patient population.
D omestic minor sex trafficking (DMST) is defined as the
commercial sexual exploitation of children (aged <18 years)
within US borders in exchange for money, food, shelter, or any METHODS
other valued entity,1 These crimes have become an increasingly The institutional review board approved all research proce-
recognized public health issue with far-reaching social, psycho- dures. Medical records of patients at a child protection medical clinic
logical, and medical consequences.2 While accurate statistics on for concerns of DMST were retrospectively reviewed (n = 68). Sub-
the incidence and prevalence of this issue are unavailable, Estes ject identification was obtained from an electronic record database
et al conservatively estimated that 150,000 to 300,000 American maintained of patients between August 1, 2013, and July 15, 2016.
children are at risk of being victimized each year, and the average Inclusion criteria were all patients younger than 18 years referred
age they are recruited is 12 to 14 years.3 Youth who have histories to a child protection clinic specifically for the evaluation of sexual
of child maltreatment, are socioeconomically disadvantaged, and abuse secondary to DMST involvement. All patients were US citi-
engage in risk-taking behaviors such as substance use are at in- zens or legal residents trafficked as indicated by medical record re-
creased vulnerability to sexual exploitation.2,3 view, thus meeting the definitional criteria of potential DMST
Recent studies have found that victims of DMST often pres- victims. Referrals were made by medical facilities (emergency de-
ent for medical attention because of their complex and multiface- partment, inpatient psychiatry), a parent/guardian, teacher, legal
ted medical and psychiatric needs.4–7 In conjunction with runaway and law enforcement agencies, and state child protective agencies.
behavior, childhood maltreatment, and mental health issues, sub- Included patients were either verified victims through self-disclosure
stance use/abuse may proceed and/or follow the initiation of com- and/or evidence (eg, law enforcement sting operations, pictures
mercial sexual exploitation.4,5,7 High rates of substance use have posted on Backpage.com) that indicated DMST involvement, or
been identified in populations of adults engaged in prostitution,8 suspected involvement. Patients suspected of DMST involvement
and more recently sex-trafficked minors,4–6 and can be under- were referred because of significant concerns that placed them at
stood in several ways. Identifying preexisting substance abuse high risk (eg, had friends who were victimized, high-risk behaviors).
and addiction behaviors may be a recruitment tactic by traffickers An electronic medical record review was conducted by a
promising to supply the victim's addiction.9 In addition, adoles- trained research assistant, and overseen by the principal investigator.
cents engaged in nonaddictive alcohol/substance use as part of ad- Electronic medical records included inpatient, outpatient, and con-
olescent experimentation, or as a means of coping with stress, are sultation patient encounters in the emergency department and other
at increased risk of exploitation due to decreased inhibitions and medical center clinics (eg, adolescent health care center, inpatient
impaired judgment. In previous studies, substance use/abuse was psychiatric). The sources of information consisted of physician
notes documenting patient/guardian interviews, demographics,
From the *Department of Pediatrics, Hasbro Children's Hospital; and †Depart- medical histories, and diagnostic tests within medical encounters
ment of Pediatrics, The Warren Alpert Medical School of Brown University, for the period of 1 year prior to and including their initial referral
Providence, RI. for DMST. All variables were collected from electronic medical re-
All phases of this study were supported by the Fleet Scholarship grant 101-6345. cords when available, and descriptive statistics were calculated.
Reprints: Jessica L. Moore, BA, Lawrence A. Aubin, Sr. Child Protection
Center, Potter Bldg 005, 593 Eddy St, Providence, RI 02903 RESULTS
(e‐mail: Jmoore4@lifespan.org).
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Demographics of the 68 included patients are presented in
ISSN: 0749-5161 Table 1. The majority of patients (76.5%) were 15 to 17 years old,
Pediatric Emergency Care • Volume 37, Number 4, April 2021 www.pec-online.com e159

Moore et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
Additionally, fewer than half of patients (41.8%) were tested

TABLE 1. Demographic Characteristics of Patients Referred for with urine toxicology 1 year prior to their initial evaluation for
DMST Involvement
DMST involvement; of those patients, 63.6% had a positive re-
sult, most often being cannabinoids (73.3%). (Fig. 2B). Further,
n (%)
13 (38.2%) of 34 patients had a negative urine toxicology result
Age, y at their initial presentation for DMST, and slightly fewer than
11–12 1 (1.5) half (13/28 [46.4%]) had a negative urine toxicology result a
13–14 15 (22.1) year prior to their initial evaluation.
15–17 52 (76.5) Moreover, more than half (55%) of patients had a parent
Gender who abused substances through self-report during their initial
evaluation for DMST and/or retrospective chart review of
Female 65 (95.6)
patient encounters.
Male 1 (1.5)
Transgender 2 (2.9)
DISCUSSION
Race/ethnicity
Substance use is a mechanism that may perpetuate the re-
White 33 (48.5)
cruitment and ongoing engagement in sex trafficking for both
African American 25 (36.8) adults and minors. The current study, in conjunction with prior
Asian 3 (4.4) research,3–5 has identified high rates of substance use specifically
Hispanic 2 (2.9) in a patient population of youth referred for DMST involvement.
Unknown 5 (7.4) An overwhelming majority (88%) of our patients reported to a
Living situation physician that they have used alcohol and/or other substances ei-
Home 42 (61.8) ther historically or during their initial evaluation when concern
Group home 26 (38.2) was raised for DMST.
Patients who reported using substances most commonly
disclosed marijuana use (50/59 [or 84.7%]), followed by alcohol
use (35/59 [59.3%]). Patients less frequently reported the use of
drugs such as cocaine (12/59 [20.3%]), MDMA (6/59 [10.2%]),
female (95.6%), and white (48.5%) and/or lived at home (61.8%) and heroin (3/59 [0.05%]). Similarly, a study of New York youth
during the time of their initial evaluation for DMST. found that 54% reported using marijuana on a regular basis,
Further, patients who reported using substances most com- whereas 26% used cocaine and 25% used alcohol. Only 3% used
monly disclosed marijuana use (50/59 [84.7%]), followed by alcohol methamphetamines regularly, and 1% reported using prescription
use (35/59 [59.3%]). Patients less frequently reported the use of drugs painkillers.7 Another study of homeless youth involved in prosti-
such as cocaine (12/59 [20.3%]), methylenedioxymethamphetamine tution found that alcohol (78%) and marijuana (70%) were the
(MDMA) (6/59 [10.2%]), and heroin (3/59 [0.05%]) (Fig. 1). most frequently reported substances.12 Our data confer with these
Urine toxicology testing was obtained during the initial evalu- studies; polysubstance use is common among sex-trafficked
ation for DMST involvement and 1 year prior to that date. As dem- youth, particularly marijuana and alcohol use. (Fig. 1) Thus, pa-
onstrated in Figure 2A, a urine toxicology test was obtained in only tients at risk of or involved in DMST may present for medical at-
half of our patients (50.7%) during their initial evaluation. The ma- tention with positive toxicology results or disclosures of drug use.
jority of patients who were screened had a positive urine toxicology Prior studies have found that patients present frequently for
result (61.8%), most commonly positive for cannabinoids (95.2%). medical attention before being identified as DMST victims. While
FIGURE 1. Patient-reported substance use (MDMA).

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Substance Use in Minor Sex Trafficking Population
parents who abuse substances may also have a genetic disposition

toward substance abuse at a young age. Hence, our finding of pa-
rental substance abuse may further explain the high rate of re-
ported substance use in our cohort of patients referred for DMST.
Several limitations should be considered in the context of
our findings. We included patients presenting to medical providers
in a single New England hospital; therefore, generalizations de-
rived from the data likely cannot be applied to all populations of
sex-trafficked youth. Considering the retrospective study design,
variables cannot be distinguished as occurring prior to or during
the period of exploitation. Casual factors for DMST involvement
such as substance use should be explored in sex-trafficked youth
who present for medical attention. Additionally, future studies
should examine whether there is a change in frequency and type
of drug use from initiation into sex trafficking to their engagement
in DMST. Further research is also needed to examine the efficacy of
substance abuse treatment programs for sexually exploited youth.
CONCLUSION
Patients referred for DMST involvement had high rates of
alcohol/substance use, parental substance use, and/or positive
urine toxicology results yielding several important points. First,
adolescents who use/abuse substances may have a propensity to-
ward risk-taking behaviors such as sex trafficking; thus, substance
use/abuse may be a risk factor for and indicator of sex-trafficking
involvement, which should prompt clinicians to screen for and ed-
ucate about DMST in a substance using patient population. Second,
minors who have parents who abuse substances come from dys-
functional environments and poor support systems and there-
fore may be more susceptible to engage in high-risk behaviors
(eg, sexual exploitation, substance use). Third, a youth's depen-
FIGURE 2. Urine toxicology screen and results. A, Positive and dency on drugs and the perpetuation of addiction may be a
negative results represent the 50.7% of patients who had a urine method in which traffickers maintain control over their victims.
toxicology screening at the initial evaluation for DMST involvement.
B, Positive and negative results represent the 41.8% of patients
Given the link between DMST and substance use, specialized
who had a urine toxicology screening a year prior to their initial substance abuse treatment programs and education should be a
evaluation for DMST involvement. component of the multidisciplinary approach to caring for the
multifaceted needs of these vulnerable youth.
victims rarely self-disclose involvement and do not often present REFERENCES

with confirmatory evidence of DMST involvement, victims 1. Victims of Trafficking and Violence Protection Act of 2000. Public Law
commonly present with multiple risk factors (eg, substance use, 106e386d. October 28, 2000; 114 STAT. 1465.
homelessness) warranting urine toxicology testing. Given our high
2. Institute of Medicine and National Research Council. Confronting
rates of self-reported substance use and positive results from urine
Commercial Sexual Exploitation and Sex Trafficking of Minors in the
toxicology screening, patients who present to medical providers United States: A Guide for Providers of Victim and Support Services.
with reported substance use/addiction or observable intoxication Washington, DC: The National Academies Press; 2013.
necessitate screening for possible sex-trafficking victimization. At
3. Estes RJ, Weiner NA, The commercial sexual exploitation of children in the
the same time, patients who present for concern of DMST involve-
US, Canada and Mexico. Available at: http://www.gems-girls.org/Estes%
ment should prompt clinicians to screen for substance use/abuse
20Wiener%202001.pdf. Accessed November 14, 2015.
and obtain urine toxicology.
In addition to substance use, adverse childhood experiences 4. Goldberg AP, Moore JL, Houck C, et al. Domestic minor sex trafficking
such as abuse and family dysfunction are often linked to sex- patients: a retrospective analysis of medical presentation. J Pediatr Adolesc
trafficking involvement.13 Our data found that more than half Gynecol. 2017;30:109–115.
(55%) of patients had a parent who abused substances through 5. Varma S, Gillespie S, McCracken C, et al. Characteristics of child
self-report during their initial evaluation for DMST and/or retro- commercial sexual exploitation and sex trafficking victims presenting for
spective chart review of patient encounters. Parental substance medical care in the United States. Child Abuse Negl. 2015;44:98–105.
abuse often creates a foreground of family dysfunction and de- 6. Lederer L, Wetzel CA. The health consequences of sex trafficking and their
creased support (eg, inadequate parental supervision). The resultant implications for identifying victims in healthcare facilities. Ann Health Law.
traumatic developmental experience weakens a child's resiliency, 2014;23:61–91.
and parental substance abuse may therefore create susceptibility 7. Curtis R, Terry K, Dank M, et al. The Commercial Sexual Exploitation of
to engage in risk-taking behaviors such as sex trafficking.2 Fur- Children in New York City: Volume 1: The CSEC Population in New York
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guardians, such as the abuse of substances, creating a propensity National Institute of Justice, US Department of Justice; 2008: Available at:
toward using and abusing drugs at an early age. Children of www.ncjrs.gov/pdffiles1/nij/grants/225083.pdf. Accessed October 2, 2015.

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8. Raymond JG, Hughes DM. International and Domestic Trends in Sex 11. Edwards JM, Iritani BJ, Hallfors DD. Prevalence and correlates of
Trafficking of Women in the United States, 1999–2000. Ann Arbor, MI: exchanging sex for drugs or money among adolescents in the United States.
Inter-university Consortium for Political and Social Research [distributor]; Sex Transm Infect. 2006;82:354–358.
2006. Available at: https://doi.org/10.3886/ICPSR03438.v1. 12. Yates GL, MacKenzie RG, Pennbridge J, et al. A risk profile comparison of
9. Kennedy MA, Klein C, Bristowe JTK, et al. Routes of recruitment into homeless youth involved in prostitution and homeless youth not involved.
prostitution. J Aggression Maltreat Trauma. 2007;15:1–19. J Adolesc Health. 1991;12:545–548.
10. Stoltz JA, Shannon K, Kerr T, et al. Associations between childhood 13. Violence Prevention. Centers for Disease Control and Prevention. Available
maltreatment and sex work in a cohort of drug-using youth. Soc Sci Med. at: https://www.cdc.gov/violenceprevention/acestudy/index.html.
2007;65:1214–1221. Published April 1, 2016. Accessed January 16, 2018.

ORIGINAL ARTICLE
Do Social and Environmental Factors Affect the Emergency

Service Admission Characteristics of
Preschool-Aged Pediatric Trauma Patients?
A Prospective Study
Ekim Saglam Gürmen, MD,* Serkan Doğan, MD,† and Tarık Ocak, MD‡
predictable and preventable. Documenting and investigating the

Objective: Studies related to the epidemiology of trauma play a major occurrences of various trauma types enable us to apprehend the
role in determining the health status of the communities living in the vicinity characteristics of this significant problem.2 When cause-specific
of the centers that they are conducted. We have found no epidemiological mortality and nonfatal health outcomes in 195 countries from
study related to emergency service admission conducted only on preschool- 1995 to 2015 were analyzed, it was determined that reductions in
aged children in the literature. Our aim was to determine characteristics of rates of other disorders have led to the relatively increased importance
trauma in this age group, to analyze encountered trauma types, and to inves- of noncommunicable diseases and injuries.3
tigate possible associations among epidemiological factors, characteristics We have found no epidemiological study related to emergency
of the trauma victims, and trauma itself in pediatric patients admitted to our service admission conducted only on preschool-aged children in
emergency service. the literature. The aim of our study was to determine the character-
Methods: We conducted a prospective study with patients aged 66 months istics of the trauma in this age group, to analyze the encountered
and younger, admitted to Emergency Service of Istanbul Kanuni Sultan trauma types, and to investigate the possible associations among
Suleyman Training and Research Hospital between July 1, 2015, and the epidemiological factors, the characteristics of the trauma
December 31, 2015. Data related to age, sex, occupational status of parents, victims, and the trauma itself in pediatric patients admitted to the
number of siblings, Glasgow coma scale score, transport mode, admission emergency service.
time period of the day, general health status, type of trauma, the trauma site,
involved body regions, radiologic imaging and laboratory results, consul-
tations, clinical diagnosis and outcome, duration of emergency service stay,
METHODS
and treatment cost were collected and statistically analyzed.
Results: A total of 688 preschool-aged cases were admitted owing to Study Setting, Patients, and Data
trauma. The major mode of transport was a private vehicle (98.3%), and Recording Collection
the major cause was falling (64.0%). The major traumatized body region This prospective study was conducted between July 1, 2015,
was head and neck (51.0%), and the major diagnosis was soft tissue trauma and December 31, 2015, with patients admitted to the Emergency
(90.1%). The average duration of stay was 122.01 minutes and affected by Service of Istanbul Kanuni Sultan Suleyman Training and Re-
sibling number, trauma type, and employment status. The total service fee search Hospital. It is the largest training-research hospital of the
was interrelated with the type of trauma and the site that trauma occurred; it Küçükçekmece-Avcılar District. The daily admission rate of its
also was strongly correlated with duration of emergency service stay. emergency department, which includes a 3-bed resuscitation
Conclusions: Our results suggest that both in-hospital and social/ room, a 10-bed red treatment area, and a 40-bed yellow treatment
environmental aspects should be improved to reduce the clinical and social area, is approximately 2000 patients.
burden of trauma. The inclusion criteria of the study were (a) being preschool
Key Words: pediatric trauma, trauma epidemiology, cost analysis aged (<66 months of age, the age that primary education starts
in Turkey) and (b) being admitted to the emergency service with
(Pediatr Emer Care 2021;37: e163–e169) the diagnosis of trauma. The study was approved by the Hospital's
Ethics Committee for Clinical Research. Informed consent of the
D uring the last 50 years, a significant reduction in child mortality

has occurred, mainly through achievements in the prevention
of communicable diseases. However, the worldwide efforts to reduce
parents was obtained before the inclusion of their children into the
study. Data related to age, sex, the occupational status of the parents,
the number of siblings, Glasgow coma scale score, the transport
the morbidity, disability, and mortality due to trauma in the pediatric mode of the patient to the emergency service, the admission time
age group have not provided satisfactory achievement yet. Approx- period of the day to the emergency service, general health status of
imately 830,000 children die from unintentional or accidental injuries the patient, the patient's place in triage categorization, the type of
every year, the vast majority of which occur in low-income and trauma, the location that trauma occurred, the body locations involved
middle-income countries.1 in the traumatic event, the radiologic imaging study results, the
Trauma, described as the physical injury due to the exposure to laboratory results, the type of consultations, the clinical diagnosis,
intolerable force or the lack of adequate heat or oxygen, is generally the clinical outcome, the duration of emergency service stay, and
the treatment cost, which were recorded by the staff of the emergency
From the *Department of Emergency Medicine, Salihli State Hospital, Manisa; service in charge at the time of admission of the patient, were col-
†Department of Emergency Medicine, Kanuni Sultan Süleyman Research and lected and analyzed.
Training Hospital, İstanbul, Turkey; and ‡Department of Emergency Medicine,
Bagcilar Medilife Hospital, İstanbul, Turkey.
Disclosure: The authors declare no conflict of interest. Statistical Analysis
Reprints: Ekim Saglam Gürmen, MD, Department of Emergency Medicine, Power analysis was performed using G*Power (version 3.1.7)
Manisa Celal Bayar University, Medical Faculty Hospital, 45030 Manisa,
Turkey (e‐mail: ekimdr@hotmail.com).
software to determine the sample size. The power of the study is
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. expressed as 1 − β (β = probability of error type II), and the studies
ISSN: 0749-5161 are needed to have a power of 99% in general. According to Cohen's

Saglam Gürmen et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
The causes of trauma were falling in 64.0% (440), crash/

TABLE 1. The Distribution of the Demographic Characteristics collision in 24.7% (170), traffic accident in 2.2% (15), burns
of the Cases
in 3.6% (25), and other causes in 5.5% (38) of the cases. Among
the patients who had encountered trauma due to falling, 9.5%
n %
(42) had fallen from high places, 2.7% (12) from the bicycle,
Sex Male 286 41.6 8.4% (37) from the stairs, 51.4% (226) from the bed, and 28.0%
Female 402 58.4 (123) had encountered falling in other forms. The accident had oc-
Employment status of the parent Yes 513 74.6 curred at home in 76.5% (526), at a nursery in 1.7% (12), on the
No 175 25.4 street or at the playground in 16.4% (113), and at other places in
No. siblings Single child 69 10.0 5.4% (37) of all cases who had encountered trauma. When the trau-
matized regions were analyzed, it was determined that head and
1 Sibling 223 32.4
neck trauma was present in 51.0 (351) of the cases. The other trau-
2 Siblings 227 33.0 matized regions of the body were thorax in 10.9 (75), abdomen in
3 Siblings 101 14.7 9.3% (64), pelvis in 3.8% (26), upper extremities in 30.2% (208),
4 Siblings 43 6.3 and lower extremities in 19.2% (132) of the cases. The diagnosis
≥5 Siblings 25 3.6 was soft tissue trauma in 90.1% (620), superficial head injury in
6.1% (42), burn in 2.8% (19), and out-of-vehicle traffic accident
in 1.0% (7) of the patients. When the clinical outcomes were ana-
effect size coefficients, in the performed preliminary group study, lyzed, the rates of discharge from the emergency service, hospitali-
the correlation between the duration of emergency service stay zation, and transfer to another medical facility were found as 97.2%
and the total service fee was determined to have a moderate effect (669), 2.2% (15), and 0.6% (4), respectively. Table 2 shows the data
size (r = 0.300); it was calculated that a minimum of 188 subjects related to the characteristics and outcome of trauma.
should be included in the study to have a 99% power at the level of Regarding the use of radiologic imaging techniques, direct
α = 0.05. All cases admitted to the emergency service and who x-ray was obtained in 55.1% (379), tomography was performed
met the inclusion criteria were included in the study. in 39.0% (268), and ultrasonography was performed in 11.2% (77)
Number Cruncher Statistical System 2007 (Kaysville, Utah) of the patients. Regarding the use of laboratory investigations,
software program was used for statistical analysis. During making hemogram was performed in 8.4% (58), biochemical tests were
the comparisons of the quantitative data, in addition to the descriptive
statistical methods (mean, standard deviation, median, frequency, ratio,
minimum, and maximum), Mann-Whitney U test was used for com- TABLE 2. The Distributions Related to the Characteristics of the
parison of the parameters that did not show normal distribution. Trauma and Its Outcome
Kruskal-Wallis test was used for comparing three or more
groups, which did not have a normal distribution, and Bonferroni- n %
corrected Mann-Whitney U test was used to determine the group
causing the difference. The Fisher-Freeman-Halton test was used The type of trauma Falling 440 64.0
to compare qualitative data. Spearman correlation analysis was From a high place 42 9.5
used to evaluate the interparameter relationships. Significance was From the bicycle 12 2.7
considered at p levels of <0.05. From the stairs 37 8.4
From the bed 226 51.4
Other 123 28.0
RESULTS Crash/collision 170 24.7
A total of 688 preschool-aged pediatric cases (402 [58.4%] Traffic accident 15 2.2
females, 286 [41.6%] males) were admitted to the emergency service Burn 25 3.6
owing to trauma during the study period. The mean ± SD age of the
Other 38 5.5
patients was 29.41 ± 17.63 months and within the range between
1 month and 66 months. It was determined that the ratios of the The place where accident Home 526 76.5
occurred Day nursery 12 1.7
employed and unemployed parents were 74.6% (513) and 25.4%
(175), respectively. Whereas 10.0% of the cases was a single child, Street/playground 113 16.4
32.4% (223) had 1 sibling, 33.0% (227) had 2 siblings, 14.7% (101) Other 37 5.4
had 3 siblings, 6.3% (43) had 4 siblings, and 3.6% (25) had 5 or The body region exposed to trauma
more siblings. Table 1 shows the demographic characteristics of Head and neck 351 51.0
the patients. Thorax 75 10.9
When the ways of the arrival of the patients to the emergency Abdomen 64 9.3
service were analyzed, it was determined that 1.7% (12) of the cases Pelvis 26 3.8
were delivered via 112 emergency health care services and 98.3%
Upper extremity 208 30.2
(676) were brought by private vehicles. The admission rates of the
patients to the emergency service was 38.4% (264) between 08:00 Lower extremity 132 19.2
A.M. and 03:59 P.M., which is the day shift, 53.6% (369) between Diagnosis Soft tissue injury 620 90.1
04:00 P.M. and 11:59 P.M. (the evening shift), and 8.0% (55) between Superficial head trauma 42 6.1
00:00 A.M. and 07:59 A.M. (the night shift). Whereas the general Burn 19 2.8
status of 99.64% (684) of the patients was well, 0.3% (2) was Out-of-vehicle traffic accident 7 1.0
moderate, and 0.3 (2) was poor. The median Glasgow coma scale Clinical outcome Discharged 669 97.2
score was 15, ranging between 1 and 15. When the triage categories Hospitalized 15 2.2
were analyzed, the ratios were determined as 1.3% (9) for the green, Transferred 4 0.6
98.4% (677) for the yellow, and 0.3% (2) for the red codes.

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Emergency Service Admission of Preschool-Aged Patients
FIGURE 1. The distribution of the duration of stay in the emergency service according to the number of siblings.
made in 8.1% (56), coagulation tests were made in 5.5% (38), and the stay durations of the cases who had no or only 1 sibling were
identification of the blood group was made in 0.6% (4) of the statistically significantly higher when compared with 5 or more
cases. When the consulted departments were investigated, it was siblings (P = 0.044, P = 0.015, respectively). The duration of stay
found that the most frequently consulted department was the Depart- of the cases with 1 sibling was statistically significantly higher
ment of Orthopedics and Traumatology with the rate of 33.0% (P < 0.05) than that of cases with 5 or more siblings (P = 0.015).
(227). The rates of consultations of other departments were 6.0% The results of the statistical analysis were shown in Figure 1.
(41) for neurosurgery, 3.6% (25) for pediatric surgery, 2.3% (16) The duration of stay in the emergency service showed statis-
for pediatrics, 1.2% (8) for otorhinolaryngology, and 0.3% (2) for tically significant difference regarding the trauma types (P = 0.001,
ophthalmology departments. P < 0.01). According to the results of Bonferroni-corrected Mann-
The mean ± SD duration of stay in the emergency service Whitney U paired comparisons made for identifying the group
was found as 122.01 ± 141.44 minutes, ranging from 1 to 1620 mi- that generated the difference, the average duration of stay of the
nutes, and the average fee for the total of provided services cases who had encountered a traffic accident was statistically sig-
was found as 85.48 ± 150.08 Turkish Lira (TL), ranging from 0 to nificantly increased (P < 0.01) when compared with the cases who
3438 TL. The duration of stay in the emergency service showed had encountered falling (P = 0.001), crash/collision (P = 0.001),
statistically significant differences regarding the number of the burn (P = 0.001), and other accidents (P = 0.001). The average du-
siblings (P = 0.001, P < 0.01). According to the paired compari- ration of stay of the cases who had presented to the emergency service
sons made for identifying the group that generated the difference, due to falling was statistically significantly increased (P < 0.01) when
FIGURE 2. The distribution of the duration of stay in the emergency service according to the trauma types.

FIGURE 3. The distribution of the trauma types according to the accident occurrence sites.
compared with the cases who had encountered crash/collision accident had occurred (P = 0.001, P < 0.01). According to the
(P = 0.002), burn (P = 0.001), and other accidents (P = 0.001). paired comparisons made for identifying the group that generated
The average duration of stay of the cases who had been admitted the difference, statistically significant increases in the rates of fall-
to the emergency service owing to crash/collision was statistically ing at other accident sites (P = 0.024), of crash/collision at the in-
significantly increased (P < 0.01) when compared with the cases house or street/playground accidents (P = 0.012), of traffic acci-
who had been admitted owing to burn trauma (P = 0.002) and dents at the street/playground accidents (P = 0.001), and of burns
other causes (P = 0.001). The results of the statistical analysis were at the in-house accidents (P = 0.038) were determined (P < 0.05).
shown in Figure 2. The results of the statistical analysis were shown in Figure 3.
The average duration of stay of the cases whose parents were The total service fees have statistically significant differences
unemployed was determined to be statistically significantly in- when compared regarding the trauma types (P = 0.009, P < 0.01).
creased when compared with those who had working parents According to the results of Bonferroni-corrected Mann-Whitney
(P = 0.001, P < 0.01). U paired comparisons made for identifying the group that gener-
Statistically significant differences were determined between ated the difference, the average total service fee of the cases who
the trauma types when compared regarding the sites in which had encountered traffic accidents and had been admitted to the
FIGURE 4. The distribution of total service fees according to trauma types.

FIGURE 5. The distribution of the average total service fee according to the occurrence sites of accidents.
emergency service was found to be statistically significantly the level of 40.2% (r = 0.402, P = 0.001, P < 0.01). Figure 6 shows
higher (P < 0.05) than of those who had encountered falling this positive correlation.
(P = 0.006), crash/collision (P = 0.005), burns (P = 0.043), and
other traumas (P = 0.010). The results of the statistical analysis LIMITATIONS
were shown in Figure 4. Total service fees show statistically signif- This study involved 2 major limitations. The first limitation
icant differences regarding the occurrence sites of the accident was that, although the sample size was quite large, it was possible
(P = 0.021; P < 0.05). According to the results of Bonferroni- to convey the results of the population living in the vicinity of our
corrected Mann-Whitney U paired comparisons made to identify hospital only. Because great variations are possible to occur among
the groups that created the difference, the average total service fees regions of a large city and country, we are unable to comment on the
of traumas occurring at home were found to be statistically signifi- pediatric trauma epidemiology in Istanbul and Turkey.
cantly lower when compared with traumas occurring at nurseries, The second limitation involved the health status of the
street/playground, and the other sites (P = 0.041, P < 0.05). The re- cases in the sample. Almost all patients were well regarding
sults of the statistical analysis were shown in Figure 5. A statistically their overall health status (99.4%) (only 4 patients had either
significant positive correlation was determined between the duration moderate or poor health status). This ratio was surprisingly
of stay in the emergency service and total service fee (increasing ser- high when trauma was considered as the diagnosis. However,
vice fee with increasing duration of stay in the emergency service) at it can also be considered that, because our emergency service
FIGURE 6. The correlation of total service fee with the duration of stay in the emergency service.

works with the policy of admitting every patient from its prox- children, our result was correlated to some degree with the result
imity, any child with a medical history of trauma presented of Claudet et al.12
even when no symptom or sign was present. There still may The trauma types in our series consisted mainly of falling
be doubt that our emergency service was used inappropriately from various places (64%). This result was consistent with most of
by the parents. This issue was emphasized by Chamberlain the studies published in the literature.6,10,13,14 However, there are
and Pollack4 in 1998, in their article on developing a method also studies having contradictory results when compared with ours.
for assessing emergency department performance. They found One study, conducted in 2002 in our country, found the highest rated
that 24% of their patients (including those with trauma) were trauma type as traffic accidents (46%),15 whereas Kundal et al16 also
inappropriately admitted. determined that the highest score (60%) belonged to road traffic ac-
cidents in males. One thing worth mentioning in Kundal's study16
was that, although more rarely met, the trauma seen in females
DISCUSSION was owing to falling in their series (52%). In 99.4% of the cases
Considering trauma as a coincidental event is not adequate (n = 684), there was a traumatized body region. Head and neck re-
from the epidemiological point of view. It should be considered gion was the most commonly affected site (51.0%). This result
as a condition created by various causing agents, showing variations was consistent with other published studies in which falls were
related to the causation between the agent, the host, and the environ- the dominant trauma type.17,18 However, in some studies in which
ment, thus necessitating investigation of the epidemiologic aspects.5 traffic accidents were rated higher, polytrauma injuries (involve-
We have found no epidemiological study related to emergency ment of more than 2 organ systems) and abdominal/extremity inju-
service admission conducted only on preschool-aged children in ries were determined to have higher incidences when compared
the literature, and the aim of our study was to determine the epide- with head trauma.16
miologic features of preschool-age trauma in an emergency service The most frequently used imaging technique was obtaining
and to investigate the interactions of the epidemiological factors direct x-ray images, and the second most commonly used technique
with the characteristics of the trauma victims and the trauma. was computed tomography. Surprisingly, ultrasonographic exami-
The results of our study revealed that females outnumbered nation, although easily available, was performed only in 11.2% of
males by a ratio of 1.4:1. cases. The reason for this order of imaging techniques might be
This result was not consistent with various epidemiologic the types of trauma encountered in our emergency service. In the
studies in the medical literature. Sharma et al6 reported a male/female study conducted by Güzel et al18 to evaluate their fall-related trauma
ratio of 1.9:1, and Aluisio et al7 reported the same ratio as 2.0:1. cases, their imaging techniques were reported to be in a similar order;
The cause of this inconsistency might be the difference in the however, their direct x-ray and ultrasonographic examination rates
age range between our study and the studies published in the medical were higher than ours (81% and 32%, respectively). These differ-
literature. While our study sample consisted of preschool-aged ences might have originated from their study sample being consti-
children, 52% of children in Sharma et al's study6 were attending tuted from only the cases who had encountered falling.
the school, and the age range in Aulisio et al's study7 was 6 to The average duration of emergency service stay was 122 mi-
13 years. We were unable to find any study investigating the par- nutes in our series. The statistically significant increase observed
ents' employment status of pediatric trauma victims in the literature. in the duration of stay of the patients having unemployed parents
A considerably low employment rate was found (74.6%) among in the emergency service can be explained by the time man-
parents of child trauma victims. The rate of unemployment was agement problem encountered by the working parents. Be-
calculated as 25.4%. The district that our emergency service was cause unemployed parents have less concern about the time
located was Istanbul, and the 2016 unemployment rate in Istanbul spent in the emergency service, they might not have felt obliged
was reported as 13.5% by Turkish Statistical Institute.8 Although to leave the emergency service early. The other statistically signifi-
the unemployment rate was not mentioned in the study conducted cant finding was related to the number of the siblings. The patients
by Marcin et al, 9 their result was quite supportive of ours. had most commonly either 2 or 3 siblings (33% each). We were un-
They investigated the socioeconomic disparities in morbidity and able to find any study investigating the number of the siblings of
mortality related to pediatric trauma and found that children child trauma patients. The significant reductions determined in
from communities with lower socioeconomic status had higher the duration of emergency service stay with 5 siblings or less can
injury hospitalization rates. A similar conclusion was reached by be explained with concerns of the parents about their children left
Fiorentino et al10; they concluded that socioeconomic factors such at home or elsewhere. They might have been unwilling to spend
as poverty, lack of health insurance, or poor maternal education time away from their other children and might have requested to
might be associated with a higher risk of trauma. In our series, leave the hospital if the absolute necessity for staying in the emer-
the high unemployment rate might have led to a lower income, gency service was not present when the number of their siblings
leading to disturbance in taking preventive measures against was 5 or more. The determined differences in stay duration regard-
trauma for children with unemployed parents. ing different types of trauma revealed that stay duration varied ac-
Almost all trauma patients were delivered to the emergency cording to the concerns of the emergency service staff and the
service by private vehicles (98.3%). A total of 112 emergency parents about the seriousness of the trauma. Although much rarer,
health care services has been used very rarely; 1.7% was a quite traffic accident as the cause of admission to the emergency service
surprisingly low rate because the inappropriate use of 112 emer- had led to a significant increase. This might have originated from
gency health care service system is very common in our country the time spent with consultations, investigations, and legal pur-
as indicated by a very recently conducted study by Kaynak et al.11 poses. It can be suggested that the number of consultations, inves-
In another study conducted by Claudet et al,12 the rate of transport tigations, and legal procedures can affect the duration of stay in
other than with the use of private vehicle was 47%. In that study, an the emergency service.
interesting point was that, although the overall use of ambulance The average total service fee was 85.48 TL. The significantly
had a high rate, as the patients' ages got smaller, the rate of delivery increased total service fee in traffic accidents when compared with
by private vehicles, driven by parents mostly, increased (76% of the other trauma types can be explained by an increased number of
the children younger than 2 years old vs 35% of those older than consultations, investigations, and legal procedures performed in
10 years old). Because our sample consisted of preschool-aged pediatric patients who have encountered traffic accidents. The site

that the trauma occurred was determined to have an impact on total 5. Hollwarth ME. Prevention of unintentional injuries: a global role for
service fee; the significantly lower fees in in-house traumas, when pediatricians. Pediatrics. 2013;132:4–7.
compared with the other sites, can be explained by the variations 6. Sharma M, Lahoti BK, Khandelwal G, et al. Epidemiological trends of
and distribution differences in the trauma types according to the pediatric trauma: a single-center study of 791 patients. J Indian Assoc
site of the accident. The statistically significant positive correlation Pediatr Surg. 2011;16:88–92.
determined between total service fee and the duration of emergency 7. Aluisio AR, Umuhire OF, Mbanjumucyo G, et al. Epidemiologic
service stay can be explained by investigations, consultations, and characteristics of pediatric trauma patients receiving prehospital care in
procedures requiring both time and money simultaneously; usually, Kigali, Rwanda. Pediatr Emerg Care. 2017; doi: 10.1097/
the more extensive the procedures, the more time and money they PEC.0000000000001045.
necessitate, increasing both in correlation. 8. Karakaş M. Labour force Statistics, 2016. Ankara: Turkish Statistical
Our discharge rate (97.2%) was similar to the result of the Institute; 2017.
study conducted by Tambay et al14 in another Training and Research
9. Marcin JP, Schembri MS, He J, et al. A population-based analysis of
Hospital, located in Adana, Turkey (96%). However, the rates of
socioeconomic status and insurance status and their relationship with
transfer to another facility and hospitalization showed minor dis-
pediatric trauma hospitalization and mortality rates. Am J Public Health.
crepancies, such as 0.6% versus 0.1% for transfer and 2.2% versus 2003;93:461–466.
4.3% for hospitalization. These minor discrepancies can be explained
by variations in the admission and transfer policies of the hospitals, 10. Fiorentino JA, Molise C, Stach P, et al. Pediatric trauma. Epidemiological
study among patients admitted to Hospital de Niños “Ricardo Gutiérrez”.
although they follow similar rules under the supervision of the
Arch Argent Pediatr. 2015;113:12–20, I-V.
Turkish Ministry of Health.
In conclusion, the clinical and social epidemiology of pediat- 11. Kaynak MF, Gafurogullari S, Deniz ZE, et al. The analysis of the patients
ric trauma has not been thoroughly investigated throughout the taken to emergency service by 112 emergency healthcare services: a
world. When compared with several published studies performed prospective clinical study. Eur Res J. 2017; Early Online System.
on this subject, some of our results were consistent, whereas some 12. Claudet I, Bounes V, Federici S, et al. Epidemiology of admissions
issues such as the number of siblings have not been previously in a pediatric resuscitation room. Pediatr Emerg Care. 2009;25:
studied in detail. Both the in-hospital and the social aspects of 312–316.
the environment should be improved to reduce the clinical and social 13. Kiser MM, Samuel JC, McLean SE, et al. Epidemiology of pediatric injury
burden related to trauma, keeping in mind that the best approach to in Malawi: burden of disease and implications for prevention. Int J Surg.
trauma is prevention. Further detailed multicenter clinical and social 2012;10:611–617.
epidemiological studies will shed light on the trauma problem and 14. Tambay G, Satar S, Kozaci N, et al. Retrospective analysis of pediatric
augment the efforts for reduction of its severity and prevention. trauma cases admitted to the emergency medicine department. JAEM.
2013;12:8–12.
15. Gurses D, Sarioglu-Buke A, Baskan M, et al. Epidemiologic evaluation of
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1. Peden M, Oyegbite K, Ozanne-Smith J, et al World Report on Child Injury 2002;8:156–159.
Prevention. Geneva: WHO; 2008. 16. Kundal VK, Debnath PR, Sen A. Epidemiology of pediatric trauma and its
2. Kemp A, Sibert J. Childhood accidents: epidemiology, trends, and pattern in urban India: a tertiary care hospital-based experience. J Indian
prevention. J Accid Emerg Med. 1997;14:316–320. Assoc Pediatr Surg. 2017;22:33–37.
3. Kassebaum N, Kyu HH, Zoeckler L, et al. Child and adolescent health from 17. Alyafei KA, Toaimah F, El Menyar A, et al. Analysis of pediatric trauma
1990 to 2015: findings from the global burden of diseases, injuries, and risk data from a hospital based trauma registry in Qatar. Int J Crit Illn Inj Sci.
factors 2015 study. JAMA Pediatr. 2017;171:573–592. 2015;5:21–26.
4. Chamberlain JM, Pollack MM. A method for assessing emergency 18. Guzel A, Karasalihoglu S, Kucukugurluoglu Y. Evaluation
department performance using patient outcomes. Acad Emerg Med. of the fall-related trauma cases applied to our pediatric emergency
1998;5:986–991. department. Ulus Travma Acil Cerrahi Derg. 2007;13:211–216.

ORIGINAL ARTICLE
Decline in Pediatric Emergency Department Behavioral Team

Activations After Institution of an Agitation Protocol
Hannah Pavlov, BS,* Genevieve Santillanes, MD,† and Ilene Claudius, MD‡
restraint.4 Voluntary administration of medications orally is preferred

Objective: Aggressive behavior among pediatric patients with psychiat- when possible5 and has a lower risk of adverse outcomes when
ric complaints in emergency departments is a growing problem. An agita- compared with intramuscular administration of medications.6
tion protocol was instituted in 1 pediatric emergency department to provide For more severely agitated patients, appropriate choices, combi-
scaled recommendations for differing levels of aggression. The study nations and doses of medications as well as use and monitoring
objective was to determine if the frequency of activation of an emergency of physical restraints may be necessary to avoid injury to patients
behavioral response team changed after protocol initiation. and staff.7 However, the training required for a scaled response
Methods: A protocol for escalating management of agitation in pediatric could present a challenge, both to high volume centers with mul-
patients was introduced in February 2016. The electronic medical record tiple providers and lower volume centers with encounters too in-
was queried for subsequent behavioral response team activations over the frequent to allow skill maintenance.
next 16 months. Patient demographics and specific features surrounding Currently, an accepted practice of emergency response to
the activation were retrospectively recorded from the medical record, includ- youth agitation does not exist.8,9 Introduction of treatment pathways
ing length of stay, medications administered, and documented deescalation has improved different aspects of care in a number of pediatric
techniques. Frequency and features of behavioral team activations were com- diseases.10–13 Whether used as a surrogate or a complement to
pared with activations from a period before the planning and implementation full-scale training in management of agitated pediatric patients in
of the protocol (May 2014 to May 2015). the emergency department (ED), development of a clinical pathway
Results: Twenty-one patient visits were found to require behavioral focused on early and escalating management may decrease the need
response team activation over 16 months, compared with 31 for the for more invasive interventions in PED patients.
13-month preprotocol period. Attempts at verbal/ environmental redirec- Prior research in our PED identified 31 patients who required
tion were seen in 77% and deescalation by medication administration be- a total of 41 activations of a behavioral response team for severe
fore the activation occurred in 14% of patients. During the behavioral agitation or elopement over a 13-month period, with suboptimal
team activation, 81% of the patients were given psychiatric medications documentation of deescalation attempts.14 The objective of this
and 81% were placed in physical restraints. study was to determine if implementation of an intervention
Conclusions: A decrease from a baseline of 2.4 to 1.3 behavioral re- targeting treatment of pediatric agitation is associated with a
sponse team activations per month, or a 46% decline, was noted following decrease in the frequency of activation of an emergency behav-
the institution of a clinical protocol for pediatric agitation. ioral response team in the PED.
Key Words: behavioral response team, agitation, deescalation
(Pediatr Emer Care 2021;37: e170–e173) METHODS
Patients and Setting

M anagement of patient agitation is an increasing necessity in
pediatric emergency departments (PEDs), and frequently
outstrips provider training and resources. Although a recent PED
The study was conducted at an urban tertiary care hospital
with a dedicated PED (annual census of ~20,000). Medical patients
survey found that 28% of staff experience fear for their personal are seen in the PED through age 20 years and psychiatric patients
safety while at work several times per month,1 most emergency through age 17 years. A pediatric psychiatry team is available for
medicine residencies and pediatric emergency medicine fellow- consultation Monday through Friday 8 AM-5 PM; general psychi-
ships do not provide formal psychiatric training.2 Pediatric emer- atrists perform consults during other hours. A behavioral response
gency departments are experiencing an increasing burden, but team consisting of nurse managers, psychiatric nursing staff and
with insufficient training on how to properly deal with agitated pa- county sheriffs is available 24 hours per day for patients with se-
tients safely and in the least invasive manner possible.3 vere agitation, violence toward self or others, or active elopement
Optimal intervention would include a scaled response to ag- attempts. Each activation that occurs in the PED is recorded in
itation when appropriate, targeting lower levels of agitation with the electronic medical record (EMR). This was queried from
more basic interventions. Early identification of agitated patients February 2015 through May 2016 for a patient list, which was ver-
can allow time for environmental interventions, utilization of re- ified through assessment of the full medical record. All patients
sources (eg, child life specialists), and verbal deescalation and po- with a verified behavioral response team activation from the
tentially avoid escalation to involuntary chemical and physical PED were included. For patients requiring multiple activations,
only the initial activation was counted, to prevent a single patient with
From the *Department of Emergency Medicine, University of Southern refractory agitation from skewing the results. However, subsequent
California, and †Department of Emergency Medicine, Keck School of Medicine activations are also reported. Institutional review board approval
of USC, Los Angeles; and ‡Department of Emergency Medicine, Harbor-UCLA, was obtained for this research with wavier of informed consent.
West Carson, Torrance, CA.
Reprints: Ilene Claudius, MD, Harbor-UCLA Department of Emergency Intervention
Medicine D9, 1000 West Carson Blvd, Torrance, CA 90501
(e‐mail: iaclaudius@gmail.com).
An agitation protocol was introduced in February 2016 (Fig. 1).
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. This protocol was created jointly by 2 PED physicians and 3 child
ISSN: 0749-5161 and adolescent psychiatrists, and based in part on the best practices

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Institution of an Agitation Protocol
Data Collection
The EMR (Cerner) was queried for each patient requiring a
behavioral response team activation in the postprotocol period
for the following information:
Patient information
Demographics: sex, age, ethnicity, primary residence

Known psychiatric illness: outpatient psychiatric medications,
prior diagnoses
Presence of a caregiver in the ED
Patient care information
Involuntary hold details (if relevant): location of hold place-

ment, reason for hold
ED visit details: length of ED stay, ED disposition
Deescalation: attempts at verbal deescalation, medications (type,
time, route)
Behavioral team activation details: time from patient arrival

to team activation, medications given during behavioral team arrival in-
cluding route and type, physical restraints utilized, number of activa-
tions per visit, time to subsequent team activations, adverse outcomes.
Timing of activation is recorded in the EMR, and was con-
firmed by orders and nursing/ physician documentation surrounding
the event. A data dictionary was created before data abstraction and
data was collected in using standardized data collection tool. Data
collection was performed primarily by 1 investigator (H.P.) after train-
ing by the principal investigator (PI) (I.C.). The PI, an attending
pediatric emergency medicine physician reviewed all data col-
lected by H.P., a student researcher. These results were then com-
pared to previously collected data for behavioral team activations
that occurred in patients younger than 18 years before the imple-
mentation of the protocol during the period from May 2014
through May 2015, also verified by the PI.14
Definitions
Any attempt at environmental or verbal calming was termed
“verbal deescalation.” This includes verbally attempting to calm
patient, changing environment, caregiver if needed, contacting re-
sources, such as recreational therapy, and so on. “Oral medications
administered” indicates that a patient voluntarily took oral medica-
tions targeting psychiatric symptoms or agitation (eg, olanzapine,
benzodiazepines, etc.). Medications, which were ordered, but re-
fused by the patients, were not counted.
Statistics
Descriptive statistics were performed. The difference in over-
all behavioral team activations, verbal deescalation and voluntary
pharmacologic deescalation attempts was compared between the
preprotocol period and the postprotocol period using the χ2 test.
The University of Southern California Institutional Review
Board approved this study with waiver of consent.
FIGURE 1. Guideline for management of agitation/aggression in
psychiatrically ill patients in the pediatric ED.
RESULTS
publications of Project BETA.15–17 The clinical pathway was pre- During the 13-month preprotocol period, there were 1465 total
sented to all attending ED physicians at faculty meeting, to nurses patients seen monthly in the PED and 31 patients (2.4 patients per
by the medical area director, and was made available to all providers month) requiring behavioral response team activations. During the
on the department “wiki” on all computer workstations at all times. 16-month postprotocol period, there were 1545 total patients seen
There were no additional changes made regarding acceptance, no monthly in the PED and 22 patients requiring behavioral team activa-
additional protocols, and no additional educational sessions regard- tions. Upon chart review, no notation or indication for a behavioral
ing psychiatric patients in the PED between the periods. team activation was noted in one patient. The 21 remaining

Pavlov et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
patients (1.3 patients per month) were included in the final analysis.
There was a significant decrease in activations following introduction TABLE 2. Features of the Behavioral Team Activations
of the protocol (P = 0.03). Demographic information about the
Postintervention Preintervention
preintervention and postintervention groups is presented in Table 1.
During the preprotocol period, verbal deescalation was doc- Activation within 1 h of 33.3% 50%
umented in 53% and voluntary pharmacologic in 3.2%. In the ED arrival
postprotocol period, verbal deescalation was attempted in 77.3% Verbal deescalation attempts 77.3% 53%
(P = 0.04) and voluntary pharmacologic in 14.3% (P = 0.18). In- Oral medication administered 14.3% 3.2%
formation about documented deescalation attempts and the behav- Physical restraints 81% 87.1%
ioral team activations is presented in Table 2. No adverse events to Patients with more than 1 team 7 6
the medications or restraints were noted. activation
Medications administered during 81% 74.2%
DISCUSSION team activation
The literature on safe and effective management of acute agi-
tation in the PED is nascent. Oral olanzapine and risperidone have
been shown to be as effective at agitation control as intramuscular decreased and verbal deescalation increased in the postprotocol
haloperidol,18,19 and olanzapine has been associated with minimal period, recurrent activations and percentage of patients requiring
adverse events.20 These studies support the safety and efficacy of physical restraint did not. Although literature on physical restraint
individual medication options in pediatric patients. However, to of pediatric patients is not extensive, both adverse physical and
our knowledge, this is the first study of the utility of a protocol ad- psychologic effects are associated with their use in patients over-
dressing different levels of agitation and emphasizing early admin- all, and experts advocate for less restrictive means when possi-
istration of oral medications. In this study, there was a 46% lower ble.21 Further interventions are required to target these areas.
rate of behavioral team activation in the postprotocol period. There are several limitations to the study. There is no institu-
Although an association between the initiation of the proto- tional policy providing oversight as to when the behavioral response
col and a reduction in behavioral response team activations does team should be activated; however, the provider-dependent nature
not prove causality, there were no other changes in providers or of activation applied similarly to each period. The retrospective de-
medication availability between the periods included. There are sign limits availability of information to the documentation in the
a number of potential benefits to protocol creation and availability. medical record. It is possible that non-pharmacologic interventions
Providers may be less comfortable with the dosing, safety in dif- (“verbal deescalation”) were performed without documentation.
ferent ages, and medication interactions of psychiatric medica- Because of the change in EMR between the prephase and postphase
tions than those used for other medical conditions, and pathways of the study, there was a change in the recording of behavioral team
can be used to avert potential errors. Additionally, not all providers activations from manual transcribing in a notebook to electronic re-
are aware of institutional resources, such as child life, to assist cording via the EMR. It is possible that there is a difference in com-
with lower levels of agitation. The PED staff member who initially pleteness of recording. Additionally, the numbers are small and
notes signs of early agitation may not be the primary physician. represent an urban population at a center, which receives a substan-
Having protocols in place may empower nursing attendants provid- tial number of police transports of patients placed on mental health
ing 1:1 supervision and other staff members to more easily recognize holds in the prehospital setting, often without presence of care-
early signs of agitation and either report to the primary provider or givers. In centers with greater family presence and more outpatient
offer non-pharmacologic deescalation. Finally, recommending the resources, strategies involving the family and outpatient mental
use of pediatric doses of medication and use of oral medications health providers may prove more effective than uniform application
early may not only minimize adverse events, but also decrease seda- of an agitation protocol. Alternatively, other centers may not have
tion time, allowing earlier evaluation by psychiatry and transfer to services, such as child life, and these recommendations would
definitive care. Although frequency of behavioral team activation require alteration for generalizability.
TABLE 1. Characteristics of Pediatric Patients Requiring a Behavioral Team Activation
Feature Postintervention Preintervention

Sex Female 42.9% 45.2%
Male 57.1% 54.8%
Mean age, y 15.4 14.3
Ethnicity White 0% 13%
Black 24% 32%
Hispanic/Latino 57% 48%
Other or Unknown 19% 7%
Residence Foster or Group Care 38.1% 32.3%
Prehospital hold 42.8% 64.5%
Disposition Discharge home/foster care 28.6% 32.3%
Transfer to a psychiatric hospital/urgent care 61.9% 64.5%
Other 9.5% 3.2%
Mean length of stay 20 h 17 min 24 h 22 min
Caregiver present in ED 38.1% 41.9%

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Institution of an Agitation Protocol
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clinical decision rule and staged imaging protocol for diagnosis of
1. Shaw J. Staff perceptions of workplace violence in a pediatric emergency appendicitis. Value Health. 2016;19:28–35.
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13. Fallon SC, Delemos D, Akinkuotu A, et al. The use of an institutional
2. Santucci KA, Sather J, Baker MD. Emergency medicine training programs' pediatric abdominal trauma protocol improves resource use. J Trauma
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current perspective. Pediatr Emerg Care. 2003;19:154–156.
14. Wang C, Santillanes G, Kearl YL, et al. Emergent medication
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15. Holloman GH, Zeller S. Overview of Project BETA: best practices in
4. Chun TH, Katz ER, Duffy SJ. Pediatric mental health emergencies and evaluation and treatment of agitation. West JEM. 2012;13:1–2.
special health care needs. Pediatr Clin N Am. 2013;60:1185–1201. 16. Richmond JS, Berlin JS, Fishkind AB, et al. Verbal de-escalation of the
5. Allen MH, Currier GW, Hughes DH, et al. The expert consensus guideline agitated patient: consensus statement of the American Association for
series. Treatment of behavioral emergencies. Postgrad Med. 2001 (Spec): Emergency Psychiatry Project BETA De-escalation Workgroup. WestJEM.
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6. Adimando A, Poncin Y, Baum C. Pharmacological management of the 17. Wilson MP, Pepper D, Currier GW, et al. The psychopharmacology of
agitated pediatric patient. Pediatr Emerg Care. 2010;26, 861–863. agitation: consensus statement of the American Association for Emergency
Psychiatry Project BETA De-escalation Workgroup. WestJEM. 2012;13:
7. Chun T, Mace S, Katz E. Execuative summary: evaluation and
26–34.
management of children and adolescents with acute mental health or
behavioral problems. Part 1: common clinical challenges of patients with 18. Villari V, Rocca P, Fonzo V, et al. Oral risperidone, olanzapine and
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8. Janssens A, Hayen S, Walraven V, et al. Emergency psychiatric care for
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20. Cole JB, Klein LR, Strobel AM, et al. The use, safety, and efficacy of
10. Hu F, Zhang J, Shi S, et al. Fever management in the emergency department olanzapine in a level I pediatric trauma center emergency department over a
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ORIGINAL ARTICLE
Current Practices in Pediatric Emergency Medicine

Fellowship Trauma Training
Diana T. Fleisher, MD,* Rachel J. Katz-Sidlow, MD,† and James A. Meltzer, MD, MS‡
To meet this challenge, the PEM Fellowship Directors' Writ-

Objective: The management of injured children is a required element of ing Group in 2016 recommended “alternative educational oppor-
pediatric emergency medicine (PEM) fellowship training. Given the relatively tunities,” including simulation, web-based resources, innovative
infrequent exposure of trainees to major trauma, it is important to understand didactic approaches, and formalized evaluation.8 Although multi-
how programs train fellows and assess their competency in pediatric trauma. ple tools and courses exist to teach PEM fellows how to manage
Methods: An online survey was sent to 84 PEM fellowship program di- pediatric trauma, they have not been coordinated into a standard-
rectors (PDs). Program directors were asked to describe their program's ized curriculum that is universally recommended in the face of in-
characteristics, the degree of fellow independence, educational techniques frequent first-hand clinical exposure.
used to train fellows in trauma, and their expectation of fellows' compe- Defining the state of current practice and expectations in PEM
tency in 14 core trauma-related skills upon graduation. Program directors fellowship trauma training may aid efforts to design a universal
were classified as having high expectations if they anticipated that graduat- PEM trauma curriculum. The primary objective of this study was
ing fellows could perform 12 trauma skills or more independently. to describe the current clinical settings, educational techniques,
Results: Fifty-nine programs (70%) responded. Although most programs and expectations for trauma training in PEM fellowship.
(55, 93%) identified as pediatric trauma centers, fellows at the majority of pro-
grams (41, 69%) spent some or all of their trauma experience at an outside
hospital. Only a minority of programs (17, 29%) allowed fellows to lead pedi- METHODS
atric trauma resuscitations as independent attendings without precepting. Pro-
grams used over a dozen different educational methods to varying degrees. Study Design and Population
Less than half of programs (28, 47%) used a formal trauma curriculum. We conducted a cross-sectional survey of PEM fellowship
Whereas 33 PDs (56%) had high expectations, only 9 (15%) expected fellows program directors (PDs) in the Unites States and Canada from
to be able to perform all 14 skills. April to June 2016. Program directors were identified using both
Conclusions: There is considerable variability in how PEM fellows are published listings9 and the American Medical Association's Fel-
trained to care for injured children. Most PDs do not realistically expect fellowship and Residency Electronic Interactive Database Access.10
lows to be able to perform all recommended trauma skills after graduation. Active PD status was verified by individual phone calls. The survey
Our findings highlight the need for further research and efforts to standard- was distributed via surveymonkey.com (SurveyMonkey, Palo Alto,
ize the training of PEM fellows in pediatric trauma. Calif ) to 84 PDs representing 81 PEM fellowships programs. Email
Key Words: autonomy, competency, expectation, fellowship, reminders to complete the survey were sent monthly for 2 months,
independence, trauma and a final phone call was made 3 months after initial distribution.
The Institutional Review Board of the Albert Einstein College of
(Pediatr Emer Care 2021;37: e174–e178) Medicine evaluated the study protocol and deemed this study ex-
empt from further review.
E ach year, approximately 8 million injured children present to

emergency departments across the United States.1 To care for
these patients, well-trained pediatric emergency experts are needed.
Instrument
To design the online survey, we first conducted a review of
Since the inception of accredited pediatric emergency medicine
the literature using Pubmed.gov and the following search terms:
(PEM) fellowships, leaders in PEM have worked to develop guide-
traumatology, education, medical, graduate, competency-based
lines to train fellows in the management of acutely injured chil-
education, pediatrics, clinical competence, and emergency medi-
dren.2,3 Accreditation Council for Graduate Medical Education
cine. This search yielded a bibliography with a comprehensive list
(ACGME) standards require that PEM fellows attain competency
of methods used to teach trauma to surgical, emergency medicine
in trauma resuscitation for children of all ages, as well as in specific
(EM), and PEM trainees. To ensure that the list of educational and
trauma-related skills.4 Despite our country's large volume of injured
assessment methods was exhaustive and included the most feasible
children, very few present with critical injuries.1 Consequently, a
teaching methods, a 2-round modified Delphi process was con-
major challenge to achieving proficiency in the management of in-
ducted. A panel of 7 PEM and trauma education experts was iden-
jured children is the relative infrequency of opportunities for PEM
tified through a comprehensive literature review and responded to
fellows to participate in pediatric trauma resuscitation and perform
participate in the Delphi process. These experts contributed to the
critical procedures.5–7
list of educational and assessment methods and ranked all methods
using a 3-point Likert scale for effectiveness and feasibility. Teach-
From the *Division of Pediatrics, Department of Emergency Medicine, Kings ing and assessment methods deemed both ineffective and unfeasi-
County Hospital Center, SUNY Downstate College of Medicine, Brooklyn;
†Department of Pediatrics, and ‡Division of Emergency Medicine, Department
ble by more than 50% of participants were excluded.
of Pediatrics, Jacobi Medical Center, Albert Einstein College of Medicine, Using the most recently published ACGME Program Require-
Bronx, NY. ments for Graduate Medical Education in Pediatric Emergency
Disclosure: The authors declare no conflict of interest. Medicine,4 this group of experts was next asked to identify the
Reprints: James A. Meltzer, MD, Jacobi Medical Center, 1400 Pelham Parkway
S, 1B25, Bldg 6, Bronx, NY 10461 (e‐mail: james.meltzer@nychhc.org).
trauma skills that a PD might realistically expect fellows to perform
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. independently by the completion of fellowship. Three respondents
ISSN: 0749-5161 offered supplemental skills to add to the ACGME requirements.

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Practices in PEM Fellowship Trauma Training
The final list of 14 core trauma-related skills included 11 skills consis- 26 [44%]; Level 2, 3 [5%]). Fellows at most programs (41, 69%)
tent with the ACGME requirements: arterial catheterization, central spent some or all of their trauma experience at an outside hospital.
venous catheterization, cricothyrotomy-translaryngeal intubation, Trauma resuscitation efforts at most programs (54, 92%) were led
endotracheal intubation, external cardiac pacing, intraosseous ac- by PEM: PEM alone (9, 15%) or PEM as part of a multidisciplinary
cess, tube thoracostomy, pericardiocentesis, nasal packing, the team (45, 76%). Surgery led trauma resuscitation alone at only 5
ability to perform a primary and/or secondary survey, and the abil- (8%) programs. In a minority of programs (17, 29%), PEM fellows
ity to serve as a team leader.4 Our panel added 3 supplemental led trauma resuscitations autonomously as independent attendings
skills to this list, including needle thoracostomy, crowd control/ without precepting. Of these, 1 program (6%) granted autonomy
family liaison, and FAST/eFAST (ie, Focused Assessment with to fellows in their first year, 4 (24%) in their second year, and 12
Sonography for Trauma/extended Focused Assessment with (71%) in their third year.
Sonography for Trauma) examination.
The survey was piloted with non-PD PEM faculty, PEM fel- Educational Design
lows, and EM faculty and was revised for clarity. The final survey Only 28 (47%) PEM fellowship programs used a formal
invited PDs to describe their program's (1) characteristics and trauma curriculum. Of these, 27 (96%) delivered this material in
clinical setting, and the degree of fellow independence, (2) educa- the first year of fellowship, 22 (79%) delivered this material in
tional and assessment techniques used to train fellows in trauma, the second year, and 20 (71%) delivered this material in the third
and (3) their expectation of graduating fellows' competency in year. Forty-two programs (71%) provided different trauma educa-
the 14 core trauma-related skills. The total number of questions tion materials to each year of fellowship. Specific instructional
varied according to the PDs response; the maximum number of methods used to teach and assess trauma management are pre-
questions was 34. Participants were allowed to write-in additional sented in Table 1. Surgeons contributed to PEM fellow trauma educa-
responses when a particular method or skill was not specifically tion in a majority of the programs (38, 64%). However, PDs reported
listed in the question. We anticipated the final survey would take that surgeons taught their fellows components of trauma training with
5 to 10 minutes to complete. variable frequency: weekly, 1 (3%); monthly, 9 (24%); quarterly,
9 (24%); biannually, 8 (21%); yearly, 5 (13%); other, 6 (16%).
Definitions Almost all programs required that their fellows certify in Pe-
We defined a formalized simulation center as one that contained diatric Advanced Life Support (PALS)12 (58, 98%) and Advanced
the presence of a mock trauma bay, separate control room, debriefing/ Trauma Life Support (ATLS)13 (58, 98%). Some programs (12,
conference room, and videotaping capabilities, or some portion
thereof.11 Multidisciplinary mock traumas were defined as those TABLE 1. Methods Used by PEM Fellowships to Train Their
practiced with other services (eg, surgery, nursing, orthopedics). Five Fellows in the Management of Pediatric Trauma
educational methods were considered as a means of fellow assess-
ment: debriefing, video recording of trauma or mock trauma resus- Training Methods n (%)
citations, checklists to evaluate trauma resuscitations, required
procedure logs, and clinical case logs. Predidactic self-assessment, Education
initially included on the survey as an educational method, was cat- ACLS 1 (2)
egorized as an additional assessment method for the purpose of Podcasts 6 (10)
the data analysis. Finally, PDs were classified as having high ex- Computer modules 11 (19)
pectations if they anticipated graduating fellows could perform Formal skills courses (other than PALS/ATLS) 12 (20)
12 (80%) or more of the core trauma skills independently. Trauma journal club 14 (24)
Asynchronous learning material 16 (27)
Statistical Analysis Academic writing by fellows 22 (37)
All statistical analyses were performed using STATA version Textbooks 25 (42)
14.1 (StataCorp, College Station, Tex). Continuous data were de- Small groups 27 (46)
scribed using medians (interquartile ranges [IQRs]), and categor-
Trauma grand rounds 27 (46)
ical data were described using frequencies (percentages).
Workshops 27 (46)
Cognitive theory training 30 (51)
RESULTS Formal education by surgeons 38 (64)
Multidisciplinary mock trauma 42 (71)
Program Characteristics, Clinical Setting, and Fellows teach trauma to nurses, residents, others 49 (83)
Fellow Independence Lectures 54 (92)
Fifty-nine PDs (70%) responded, each representing an indi- Simulation 57 (97)
vidual program. Four participants responded twice, and only the PALS 58 (98)
first response was analyzed. The median number of fellows per ATLS 58 (98)
program was 6 (IQR, 4–8; max, 18). One of the 59 programs Assessment
was planning to accept their first fellowship class at the time of sur- Predidactic self-assessment 3 (5)
vey and offered a response based on their anticipated program. The Checklists 16 (27)
median yearly pediatric emergency department census for respon- Videotaping real time and/or simulated trauma 17 (29)
dents was 54,000 (IQR, 33,000–70,000) with a median admission
Required procedures for competency 28 (47)
rate of 12% (IQR, 10%–17%). Fifty-seven (97%) programs ac-
cepted both pediatric and EM residency graduates, although Case logs 37 (63)
2 (3%) accepted only pediatric residency graduates. Formal debriefing after trauma 46 (78)
Most programs identified as pediatric trauma centers (Level 1, ACLS indicates advanced cardiac life support.
50 [85%]; Level 2, 5 [8%]), but not as adult trauma centers (Level 1,

Fleisher et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
20%) used at least 1 additional third-party skills course including

Advanced Pediatric Life Support,14 4 (7%); Trauma Evaluation TABLE 2. Frequency of PDs' Expectation of Competency in 14
Core Trauma-Related Skills for Graduates of PEM Fellowship
and Management,15 6 (10%); Emergency Management of Severe
Burns,16 1 (2%); Advanced Cardiovascular Life Support,17 1 (2%);
Trauma Skill n (%)
and a disaster life support course, 1 (2%). No program reported
using the Rural Trauma Team Development Course18 or the Arterial line placement 23 (39)
Trauma Resuscitation in Kids Course.19 Cricothyrotomy/translaryngeal ventilation 34 (58)
Simulation and multidisciplinary mock trauma were widely Pericardiocentesis 35 (59)
used. Simulation was used by almost all programs (57, 97%) External cardiac pacing 39 (66)
and most reported using a formalized simulation center (56, Nasal packing 41 (69)
95%). The frequency of simulation center use was as follows:
Central venous line placement 50 (85)
monthly, 14 (25%); quarterly, 28 (50%); biannually, 7 (13%); and
yearly, 7 (13%). Forty-two programs (71%) reported conducting FAST/eFAST examination* 53 (90)
multidisciplinary mock traumas with 5 (12%) performing them un- Tube thoracostomy 54 (92)
announced, 20 (48%) announced in advance, and 17 (40%) used Needle thoracostomy* 56 (95)
a mixture of announced and unannounced events. The frequency Crowd control/family liaison* 56 (95)
of multidisciplinary mock traumas was as follows: monthly, Intubation/airway management 58 (98)
18 (43%); quarterly, 13 (31%); biannually, 9 (21%); yearly, Primary and/or secondary survey 59 (100)
1 (2%); and other, 1 (2%). Intraosseous line placement 59 (100)
At least 1 formal cognitive training technique was used in Team leader 59 (100)
about half (30, 51%) of programs. Methods included the following:
TeamSTEPPS,20 15 (50%); SBAR,21 12 (40%); situation aware- *Not required by ACGME but recommended by expert panel.
ness,22 15 (50%); stepping back,23 6 (20%); and cognitive dispo- (e)FAST indicates (extended) focused assessment with sonography for
sitions to respond,24 1 (3%). trauma.
Most PDs (49, 83%) reported that their fellows teach trauma
skills to other providers, such as medical students and nurses. In ad-
dition, fellows in some programs (22, 37%) engaged in trauma- experience. Little is known, however, regarding external rotators'
related academic writing, such as research or book chapter writing. attainment of competency in trauma skills and how well they
Forty-six programs (78%) used 2 or more tools to assess maintain those acquired skills once the external rotation is com-
competency in trauma, with debriefing after trauma resuscitation plete. We also found that, although all 59 PDs expected their fel-
as the most commonly used assessment technique (Table 1). Of lows after graduation to function as a team leader during trauma
those that used debriefing, only 23 (50%) debrief after trauma re- resuscitation, most fellows (70% of programs) never lead trauma
suscitations most or all of the time. resuscitation autonomously during fellowship. Although granting
trainee independence in high acuity settings while maintaining pa-
PD Expectations tient safety can be challenging,28,29 many PEM fellows may be ex-
Approximately half of all PDs surveyed (33, 56%) were clas- pected after graduation to perform in a supervisory role for which
sified as having high expectations of their graduating fellows. they are not prepared. Further research is needed to determine the
However, only 9 (15%) expected their fellows to perform all optimal amount and timing of autonomy in trauma management
14 core trauma skills listed in Table 2. that will adequately prepare fellows to lead trauma management
as future attendings in a variety of practice settings.28
Pediatric emergency medicine fellowship programs were
DISCUSSION also found to vary considerably in the educational methods they
The impetus to develop the ATLS course came from Dr use to teach and assess trauma management. Although the major-
James Styner's experience witnessing unprepared providers per- ity of programs lack a formal trauma curriculum, formal skills
form inadequately in the resuscitation of his children after a plane courses remain the foundation of trauma training for PEM fellows,
crash.25 Central to the motivation to develop this and other critical with almost all programs requiring PALS and ATLS training. Nei-
care courses is the idea that standardized approaches to learning ther PALS nor ATLS, however, address the full breadth of pediat-
critical care medicine can allow those who infrequently treat se- ric trauma beyond the initial patient evaluation and treatment.27
verely ill or injured patients to perform well. Trauma is the leading Although the Trauma Resuscitation in Kids course19 has been de-
cause of death for children in the United States,26 and having well- veloped to improve hands-on experience with uncommon life-
trained emergency physicians capable of caring for injured chil- saving procedures for injured children, none of the PDs in our
dren is of paramount importance. Training PEM fellows requires study reported using it. Formal skills courses may be important
addressing the intersection between the expectation that PEM tools for training PEM fellows, but they do not adequately address
practitioners should be experts in the field of pediatric trauma gaps in first-hand clinical exposure. Moreover, prior studies have
and the rare opportunities to acquire that expertise. Although there shown that skills learned in these courses decline over time30,31
is some consensus as to the material that should be covered in a particularly when exposure to critically injured patients is low.32
trauma curriculum,27 there is no agreement on how best to deliver After PALS and ATLS, survey respondents identified simu-
it. This survey describes the current landscape for PEM fellowship lation as the next most common educational method used to teach
trauma education in the United States and Canada, and the compe- trauma management to PEM fellows. Simulation has been exten-
tency expectations PDs have for their fellows upon graduation. sively studied and shown to be an effective means of acquiring and
Overall, we found that clinical exposure to trauma resuscita- assessing trauma and acute care skills.11,33–37 Through simulation,
tion for PEM is variable. Although the majority of programs sur- PEM fellows can become familiar with equipment they infre-
veyed identified themselves as pediatric trauma centers, our quently have an opportunity to use (eg, thoracostomy tubes, rapid
results show that most PEM fellowships require trainees to rotate infuser). Several investigations have demonstrated that scenario-
out of their home institution to improve their hands-on trauma based simulation training is effective at improving teamwork

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Practices in PEM Fellowship Trauma Training
and clinical performance, not only in simulated patients but also in requesting specific data regarding the competency level of the pro-
actual patient scenarios.38,39 In a study of PEM simulation experi- gram's graduating fellows. Nevertheless, this surrogate measure is
ence, Cheng et al36 described their fellowship program's longitudi- in line with the ACGME's approach, which requires PD affirmation
nal simulation-based acute care curriculum. This program allowed of fellow competence based on the ACGME Milestones, rather than
PEM fellows to participate in simulation-based scenarios at least a standardized assessment to document competence.4,7
6 times per year.36 Although the optimal frequency for PEM fel-
low exposure to simulation-based training has not been estab-
lished, most programs that we surveyed train their fellows in a CONCLUSIONS
simulation center 1 to 4 times per year. Potential barriers to imple- This survey demonstrated great variability in the PEM fel-
menting a PEM simulation-based training program include a lack lowship trauma experience and that the opportunity for fellow au-
of financial support, simulator equipment, dedicated space, and tonomy in trauma resuscitation is uncommon. With infrequent
experienced simulation faculty.11 exposure to major trauma, alternative educational methods are es-
We found that lectures continue to be among the most com- sential. Although PALS, ATLS, simulation training, and lectures
monly used methods for teaching trauma to PEM fellows, with are used by more than 90% of PEM fellowships programs, over
92% of programs using this educational method. This finding is a dozen other methods are also used to varying degrees. Less than
interesting given the current trend in medical education toward ac- half of PEM programs have a formal curriculum to teach pediatric
tive learning formats and “flipped classrooms.”40 We also ob- trauma, and few PDs realistically expect fellows to achieve com-
served that, despite the increasing availability of online medical petency in all 14 core trauma-related skills. Our findings support
educational resources,41,42 less than a third of PEM fellowships re- the need for a validated, standardized educational approach to en-
ported incorporating asynchronous learning into their trauma ed- sure that PEM fellows learn, and attain competency in, pediatric
ucation program. Asynchronous learning is trainee-centered and trauma management.
uses online resources to enable the learner to acquire knowledge
without being limited to a particular time or place. This method
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ORIGINAL ARTICLE
Care Coordination in Emergency Departments for Children

and Adolescents With Behavioral Health Conditions
Assessing the Degree of Regular Follow-up After Psychiatric
Emergency Department Visits
Sean Lynch, PhD, LCSW,* Whitney Witt, PhD,† Mir M. Ali, PhD,* Judith L. Teich, MSW,* Ryan Mutter, PhD,*
Brent Gibbons, PhD,† and Christine Walsh, BA†
to behavioral health services at the time it is needed continues to

Background: Increasing numbers of children are receiving care for be- present serious challenges, making EDs sometimes the most acces-
havioral health conditions in emergency departments (EDs). However, sible resource in the community for health care.3
studies of mental health–related care coordination between EDs and pri- However, follow-up behavioral health care after an ED visit
mary and/or specialty care settings are limited. Such coordination is impor- is typically provided by primary care or specialty behavioral
tant because ED care alone may be insufficient for patients' behavioral health providers in outpatient settings that are not connected to
health needs. the ED.4 The ability to coordinate care is dependent on resources
Methods: We analyzed claims during the year 2014 from Truven Health in the community, and some EDs (eg, pediatric EDs) may be better
Analytics MarketScan Medicaid and Commercial databases for outpatient equipped for care coordination than EDs that serve all ages. We
services and prescription drugs for youth 2 to 18 years old with continuous should not expect people to be seen again in the ED, so this service
enrollment. We applied a standard care coordination measure to insurance delivery pattern raises the question of how well care is coordinated
claims data in order to examine whether youth received a primary care or between the ED and outpatient settings such as these; because
specialty follow-up visit within 7 days following an ED visit with a psychi- some patients and ED providers may lack awareness of commu-
atric diagnosis. We calculated descriptive statistics to evaluate differences nity mental health resources, they may have limited access to psy-
in care coordination by enrollees' demographic, insurance, and health- chiatrists or social workers, and so interventions are needed to
related characteristics. In addition, we constructed a multivariate logistic re- increase coordination between the ED and the behavioral health
gression model to detect the factors associated with the receipt of system.5 While research suggests that approximately 65% of
care coordination. youth who made more than 1 behavioral health–related ED visit
Results: The total percentages of children who received care coordination were also being cared for by an outpatient behavioral health pro-
were 45.8% (Medicaid) and 46.6% (private insurance). Regardless of in- vider,6 another report suggests that ED staff need training on the
surance coverage type, children aged 10 to 14 years had increased odds provision of appropriate discharge instructions for youth with be-
of care coordination compared with youth aged 15 to 18 years. Children havioral health conditions.7
aged 2 to 5 years and males had decreased odds of care coordination. Care coordination is an established means of improving
Conclusions: It is of concern that fewer than half of patients received quality of care and patient health outcomes.8 Care coordination
care coordination following an ED visit. Factors such as behavioral health may support more efficient use of health care services by preventing
workforce shortages, wait times for an appointment with a provider, and possibly avoidable, high-cost utilization, such as ED visits.9 For the
lack of reimbursement for care coordination may help explain these results. purposes of this study, care coordination is defined as “the deliber-
Key Words: adolescents, behavioral health, care coordination ate organization of patient care activities between 2 or more partic-
ipants (including the patient) involved in a patient's care to facilitate
the appropriate delivery of health care services.”10
The topic of pediatric behavioral health–related care coordi-
T he percentage of children in the United States who are diag-
nosed with a behavioral health disorder in any particular year
is approximately 13% to 20%, suggesting that these conditions are
nation between the ED and outpatient settings has seldom been
studied. A recent national report indicated that the overall quality
of care coordination was mixed between 2007 and 2011.11 How-
common.1 Increasing numbers of children are receiving treatment
ever, this report measured ED visits with a first-listed diagnosis re-
for these conditions in emergency departments (EDs) with a na-
lated to mental health or alcohol or substance abuse, defined these
tional study suggesting a 26% increase in psychiatric visits from
visits as preventable, and did not measure follow-up care in outpa-
491,000 in 2001 to 619,000 in 2010.2 In many communities, access
tient settings. The degree to which children with behavioral health
conditions receive care coordination in EDs is unknown, and also
From the *Center for Behavioral Health Statistics & Quality, Substance Abuse it is unclear which demographic, insurance type (public vs pri-
& Mental Health Services Administration, US Department of Health & Human
Services, Rockville, MD; and †IBM Watson Health, Durham, NC.
vate), plan type (eg, health maintenance organization [HMO], pre-
Disclosure: The authors declare no conflict of interest. ferred provider organization [PPO]), and other factors, such as
The views expressed here are those of the authors and do not necessarily reflect physical health comorbidities, are associated with the receipt of
the views of the Substance Abuse and Mental Health Services care coordination.
Administration or the US Department of Health and Human Services.
Reprints: Sean Lynch, PhD, LCSW, Center for Behavioral Health Statistics &
This study has several objectives. There are no child-
Quality, Substance Abuse & Mental Health Services Administration, 5600 specific, behavioral health–related care coordination measures
Fishers Lane, Rockville, MD 20857 (e‐mail: sean.lynch@samhsa.hhs.gov). for use with the ED setting, so we applied a National Quality Fo-
Supplemental digital content is available for this article. Direct URL citations rum (NQF)–endorsed measure of follow-up care after psychiatric
ED visits for adults 18 years or older to children and adoles-
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. cents.12,13 We used this standard measure of behavioral health care
ISSN: 0749-5161 coordination and operationalized it using insurance claims data to

Lynch et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
determine the extent to which children (with Medicaid or private range of care coordination in this study among children and youth
insurance) receive care coordination related to their behavioral by age group. Comorbidity status was defined by 2 types of co-
health conditions when they present in the ED. A limitation of this morbidity variables, other behavioral health comorbidity, and
approach is that we are unable to know for sure whether care co- physical health comorbidity. Other behavioral health comorbidity
ordination was deliberate because insurance claims codes for this was separated into 2 variables, mental health comorbidity and sub-
activity are infrequently used; however, this strategy provides re- stance use comorbidity, with each variable defined as 1 if an addi-
searchers with a good proxy for this activity, and defining care co- tional mental health and/or substance use diagnosis was present,
ordination in this way for other health conditions has been taking into account the diagnosis used to identify the behavioral
supported by the NQF.14 The study then identified key factors as- health ED visit. For physical health comorbidity, we used the
sociated with that care coordination. Healthcare Cost and Utilization Project Single-Level Clinical
Classifications Software (CCS) (see Supplemental Material 3,
METHODS http://links.lww.com/PEC/A285 for CCS categories).17 Individ-
uals with any listed diagnosis from the ED visit record that met
Data Source, Subject Selection, and Study Period these physical health comorbidity CCS classifications were posi-
Using the Truven Health Analytics MarketScan Multi-State tively coded for a condition.
Medicaid Database and the Commercial Claims and Encounters There were 2 possible Medicaid insurance plan types, com-
Database, we extracted claims for all outpatient services and en- prehensive and HMO, with large enough numbers to permit anal-
rollment information for children and adolescents aged 2 to ysis. In the Medicaid data, we excluded high-deductible health
18 years with continuous enrollment during calendar year plans (HDHPs) and consumer-directed health plans (CDHPs) be-
2014.15 The Commercial database is proprietary and includes cause of low frequencies of enrollees. For the same reason, in the
deidentified insurance claims from employees and dependents, commercial data, we excluded capitated or partially capitated
which are provided by large, self-insured employers and re- point-of-service (POS) plans. For private insurance, in addition
gional health plans who participate in the database. The Medic- to comprehensive and HMO, other possible plan types were HDHPs,
aid database is also proprietary, and it includes deidentified CDHPs, exclusive provider organizations (EPOs), noncapitated
claims from beneficiaries in 11 Medicaid states. We created sep- POS plans, and PPOs. We combined the HDHPs and CDHPs
arate Medicaid and private insurance data sets for analysis pur- for private insurance into an HDHP category and combined
poses. In 2014, the Commercial database contained claims EPO, PPO, and POS into “other managed care.”
records for more than 47 million individuals from approximately Additional individual characteristics were available for
350 payers, and the Medicaid database contained claims records MarketScan Commercial data only, including region (Northeast,
for more than 11 million individuals.15 North Central, South, West, and other) and primary beneficiary
employee status (active, disabled, retired, other). Region was
Outcome Measure: Follow-up Care After an categorized as “other” when the variable was missing. The pri-
mary beneficiary of the insurance coverage was defined as “ac-
ED Visit With a Behavioral Health Diagnosis
tive” if the beneficiary was currently employed, “disabled” if
We used an NQF-endorsed care coordination measure ap- the beneficiary was on disability, “retired” if the beneficiary
plied to health insurance claims as a framework for our assessment was retired but still receiving benefits, and “other” if employee
of care coordination following a mental health– or substance use– status was missing.
related ED visit.13 Children and adolescents were selected if they
had an ED encounter during the 11-month period from January 1, Analytic Approach
2014 through November 30, 2014, with any listed behavioral
health diagnosis (see Supplemental Material 1, http://links.lww. In order to evaluate the frequency distributions of enrollees'
com/PEC/A278 for complete list of International Classification demographic, insurance, and health-related characteristics by care
of Diseases, Ninth Revision, Clinical Modification codes). The coordination status, we calculated descriptive statistics. χ2 tests
measure uses primary diagnosis (ie, first-listed) to identify behav- were used to assess the statistical significance of associations with
ioral health ED visits, but we selected any listed diagnosis, follow- the measure of care coordination. When we found significant
ing the Agency for Healthcare Research and Quality approach, to differences in the overall χ2 tests (P < 0.05), we then tested each
be more inclusive given that there is no primary diagnosis field for subgroup for significance relative to all other subgroups. These
ED visits.16 We examined follow-up care from the first identified additional tests permitted us to determine which subgroup(s) in-
behavioral health ED visit during the period and used the dis- fluenced the overall group significance.
charge date of the ED visit as the anchor date for the episode of We performed multivariate logistic regression analyses to
care. The binary care coordination measure then was defined as identify the factors associated with the binary outcome variable,
1 if the patient had a follow-up visit with either a primary care receipt of care coordination. Because we utilized 2 different insur-
or a specialty mental health provider (see Supplemental Material ance type–specific data sets for the analysis, logistic regression
2, http://links.lww.com/PEC/A284, for provider type codes) in models were performed separately for enrollees with Medicaid in-
the 7 days after the ED visit discharge.13 Emergency department surance and those who were privately insured. All independent
visits that resulted in an inpatient admission were excluded from variables were categorical in nature, and a reference category was
this study. omitted for each independent variable.
Independent Variables RESULTS

Individual characteristics of enrollees available in both the
MarketScan Medicaid and Commercial data were sex, age (2–5, Descriptive Analyses
6–9, 10–14, and 15–18 years), and comorbidity status from the Table 1 contains results of descriptive analyses for the ED
identified ED visit. Although children aged 2 to 5 and 6 to 9 years care coordination measure. We report column percentages to show
may represent a small proportion of behavioral health–related ED enrollee characteristics and row percentages for the percentage of
visits, the authors believed it was important to represent the full enrollees who received care coordination.

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Care Coordination in Emergency Departments
TABLE 1. Percentage of Behavioral Health–Related ED Visits That Resulted in a Follow-up Visit With a Health Provider in 7 Days After
Discharge, by Sociodemographic Characteristics and Payer Type, Column Percentages
Medicaid (n = 29,102) Commercial (n = 24,066)

Had CC Had CC
Total Measure χ2 Individual Total Measure χ2 Individual
(Column (Row Category vs (Column (Row Category vs
Percentage) Percentage) χ2 All Others Percentage) Percentage) χ2 All Others
Patient and Payer
Characteristics n % n % P P n % n % P P
Total 29,102 100 13,335 45.8 24,066 100 11,216 46.6
Age, years <0.0001 <0.0001
2–5 925 3.2 277 29.9 <0.0001 221 0.9 58 26.2 <0.0001
6–9 3384 11.6 1550 45.8 0.9824 1129 4.7 463 41.0 0.0001
10–14 13,209 45.4 6398 48.4 <0.0001 8032 33.4 4222 52.6 <0.0001
15–18 11,584 39.8 5110 44.1 <0.0001 14,684 61.0 6473 44.1 <0.0001
Sex 0.0001 <0.0001
Male 13,700 47.1 6113 44.6 10,658 44.3 4663 43.8
Female 15,402 52.9 7222 46.9 13,408 55.7 6553 48.9
Comorbidities
Mental health 5553 19.1 3101 55.8 <0.0001 3378 14.0 1823 54.0 <0.0001
condition
Substance use disorder 1503 5.2 682 45.4 0.7218 1358 5.6 547 40.3 <0.0001
Physical health 9439 32.4 4759 50.4 <0.0001 7635 31.7 3894 51.0 <0.0001
condition
Type of insurance <0.0001 <0.0001
Comprehensive 5986 20.6 2472 41.3 242 1.0 125 51.7 0.1139
HMO 23,086 79.3 10,860 47.0 3397 14.1 1423 41.9 <0.0001
HDHP 3348 13.9 1629 48.7 0.0105
Other managed care 14,794 61.5 7025 47.5 0.0006
Unknown 2279 9.5 1012 44.4 0.0267
Employee status 0.0727
Active 13,145 54.6 6209 47.2 0.0317
Retired 423 1.8 194 45.9 0.7575
Disability 32 0.1 19 59.4 0.1473
Other 10466 43.5 4794 45.8 0.0291
Region <0.0001
Northeast 7958 33.1 2944 37.0 <0.0001
North Central 5277 21.9 2961 56.1 <0.0001
South 7665 31.8 3839 50.1 <0.0001
West 2873 11.9 1324 46.1 0.5509
Other 293 1.2 148 50.5 0.1774
Other managed care plans include EPOs, PPOs, and POS plans. For this measure, individuals in missing/unknown plans (n = 30) were not included in the
Medicaid data because cell sizes were considered too few to permit analyses. Individuals in POS with capitation plans (n = 6) were also not included in the
commercial data because cell sizes were considered too few to permit analyses. Commercial data for this measure are limited to cases where the insured was
a dependent of the primary beneficiary. No cases were found where the insured was an employee (n = 0) or spouse (n = 0) of the primary beneficiary.
CC indicates care coordination.
Children and Adolescents Covered by Medicaid aged 2 to 5 years had a markedly lower than average care
There were 29,102 children and adolescents with Medicaid coordination (29.9%).
coverage who had a behavioral health–related ED visit. From re-
ported column percentages, the largest age category of enrollees
was 10 to 14 years (45.4%). A higher proportion of enrollees were Children and Adolescents Covered by
female (52.9%), and comorbid physical health conditions were Private Insurance
most common (32.4%). From reported row percentages, fewer There were 24,066 children and adolescents with private
than half of Medicaid patients (45.8%) had a follow-up visit with health insurance coverage who had a behavioral health ED visit.
a primary or specialty care provider within 1 week (7 days) fol- The largest age group was children aged 15 to 18 years (61.0%).
lowing the ED visit. Children aged 10 to 14 years had slightly There were more females (55.7%) than males. From reported
higher than average care coordination (48.4%), and children row percentages, fewer than half (46.6%) had a follow-up visit

with a primary or specialty care provider within 1 week (7 days) Medicaid and private insurance results were similar for co-
following the ED visit. Similar to Medicaid descriptive results, morbidity variables. Children with a mental health comorbidity
children aged 2 to 5 years had much lower than average care co- had 1.77 higher odds (Medicaid) and 1.59 higher odds (private
ordination (26.2%), whereas adolescents aged 10 to 14 years had insurance) of care coordination than children without a mental
higher than average care coordination (52.6%). health comorbidity. Similarly, children with a physical health
comorbidity had 1.25 higher odds (Medicaid) and 1.22 higher
odds (private insurance) than children without a physical health
Multivariate Regression Analyses comorbidity. Having a substance use comorbidity was not sta-
Multivariate regression results for the factors associated with tistically significant for children covered by Medicaid (AOR,
the ED care coordination measure are presented in Table 2. Re- 0.92; CI, 0.83–1.02) but was associated with lower odds of care
gression results, which control for multiple patient and payer char- coordination for children with private insurance (AOR, 0.77;
acteristics, are consistent with descriptive findings. CI, 0.60–0.87).
Under both Medicaid and private insurance, children aged 10 Children with comprehensive coverage under Medicaid had
to 14 years had higher odds of receiving care coordination than the decreased odds of care coordination (AOR, 0.79; CI, 0.75–0.84).
reference group (adolescents aged 15–18 years). Children aged 2 Under private insurance, odds of care coordination were not
to 5 years had lower odds of care coordination (Medicaid adjusted different for children covered by comprehensive coverage (ref-
odds ratio [AOR], 0.61; confidence interval [CI], 0.53–0.70; erence = HMO), whereas children with HDHP (AOR, 1.14; CI,
private AOR, 0.45; CI, 0.33–0.60). For Medicaid and private 1.04–1.27) and other managed care plan (AOR, 1.18; CI, 1.09–
insurance, males have slightly lower odds of care coordination 1.27) types had increased odds of care coordination.
(Medicaid AOR, 0.93; CI, 0.89–0.98; private AOR, 0.82; CI, For the region variable that was available only in the private
0.77–0.86) than females. insurance data, the results do suggest an association between
TABLE 2. Adjusted Odds of Post–Emergency Room Visit Care Coordination Among Children With Behavioral Health Conditions, by
Payer Type
Medicaid N = 29,072 Commercial N = 24,060

Patient and Payer Characteristic AOR 95% CI AOR 95% CI
Age, years
2–5 0.61 0.53–0.70* 0.45 0.33–0.60*
6–9 1.11 1.02–1.20* 1.05 0.93–1.19
10–14 1.21 1.15–1.27* 1.44 1.36–1.53*
15–18 Reference Reference Reference Reference
Sex
Male 0.93 0.89–.98* 0.82 0.77–0.86*
Female Reference Reference Reference Reference
Comorbidities
Mental health condition 1.77 1.67–1.88* 1.59 1.47–1.72*
Substance use disorder 0.92 0.83–1.02 0.77 0.60–0.87*
Physical health condition 1.25 1.19–1.32* 1.22 1.15–1.29*
Type of insurance
Comprehensive plan 0.79 0.75–0.84* 1.141 0.87–1.50
HMO Reference Reference Reference Reference
HDHP† 1.14 1.04–1.27*
Other managed care plan 1.18 1.09–1.27*
Unknown 1.29 1.15–1.44*
Employee status
Active Reference Reference
Retired 1.02 0.83–1.24
Disability 1.32 0.64–2.74
Other 1.00 0.95–1.06
Region
Northeast Reference Reference
North Central 2.04 1.90–2.20*
South 1.51 1.42–1.61*
West 1.44 1.32–1.58*
Other‡ 1.76 1.39–2.25*
*P < 0.05.
†
Including CDHPs.
‡
Other managed care plans include EPOs, PPOs, and POS plans.

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Care Coordination in Emergency Departments
region and care coordination. All region odds ratios for North young children, in which case care coordination may not be neces-
Central, South, West, and other (ie, missing) were statistically sig- sary. Although the number of young children aged 2 to 5 years was
nificant (greater than 1), indicating children in those regions have small relative to the other age groups, it is of concern that some
increased odds of care coordination compared with the reference care coordination following psychiatric-related ED visits may be
category, Northeast. left undone or not completed in a timely manner. Although we
did not have data on behavioral health providers who are trained
and certified in the provision of care to young children, this study
DISCUSSION finding raises the issue of the shortage of these clinicians.29–31
This study was a preliminary step toward measuring Even though an ED physician may make a referral that the care-
ED-related behavioral health care coordination. Its purposes were givers of a young child seek behavioral health care, there may be
to adapt an existing care coordination measure for ED visits con- no provider nearby who could provide such care. As a result, it
nected with behavioral health and to evaluate the degree to which may not be possible for care coordination to be completed for this
care coordination may be occurring. Study findings suggest that age group because of workforce shortages. Efforts to address this
fewer than half of children and youth with behavioral health– gap would mean that problems could be identified and interven-
related ED visits may be receiving care coordination as defined tions could be implemented when children are younger, possibly
by a follow-up visit with a primary or specialty care provider preventing symptoms from worsening or mitigating their effects
within 7 days. There are several possible explanations that may so that behavioral health outcomes improve and ED utilization
clarify this outcome including the following: (1) the ED physician is minimized.
made a referral for follow-up care, but the caregiver did not com- This study found lower odds of care coordination for male
plete the referral; (2) the caregiver tried to complete the referral children compared with females, and this finding is consistent
but was unable to schedule an appointment within 7 days or was with studies of follow-up care for adults that have also resulted
unable to schedule a visit at all with a provider; (3) the presenting in similar findings for male patients.32 Regardless of age, lower
problem was deemed to be resolved during the ED visit, and no odds of care coordination for male children and youth compared
care coordination was thought to be needed; or (4) the ED phy- with females following a behavioral health–related ED visit may
sician did not make a referral. A potential solution to the first 2 be associated with societal expectations regarding emotional be-
possibilities is ED-based care coordination provided by a medi- havior connected with sex.33 Behavioral health problems in fe-
cal social worker or other professional, such as a nurse case males may be more widely recognized than in males because
manager.18–20 However, many EDs lack these resources. Con- Western society associates emotions with the feminine, and so
nected with this matter is wait times, especially for specialty care emotional disorders may be deemed a higher priority when some
behavioral health providers such as psychiatrists, which can be caregivers or clinicians observe these conditions in females com-
as long as 50 days in some states.21 Finally, related to the third pared with males.34 As a result, some behavioral health problems
possibility, the ED can be a source of emergent behavioral health in males may be deemphasized or overlooked. Consequently,
care for some families when they cannot access care in the com- completing referrals for this group may not be considered a prior-
munity in either primary or specialty care settings when they ity and so care coordination may happen at lower rates for males
need it.22–25 For example, consider the anecdotal case of a care- than for females.
giver who took his/her child to the ED for care because the child Because many providers have not been able to bill for care
was sent home from school for attention-deficit/hyperactivity coordination and the cases when they could were limited, clini-
disorder–related behaviors and was advised that the child would cians rarely submit reimbursement requests to insurance compa-
not be permitted to return to class until his/her behavior avoided nies for this activity.35 In place of using an analysis strategy
disrupting the class. These terms may have led the caregiver to go based on a specific care coordination billing code, the approach
to the ED in order to seek a prescription for stimulants for his/her for this study was to use inference. However, some observers
child that had perhaps lapsed or expired, possibly because he/she may deem this design to be a limitation of this study. Future re-
had no regular relationship with a primary care provider. search that is conducted after 2017 might take a billing code–
Children aged 10 to 14 years had increased odds of receiving focused approach with insurance claims data once providers begin
care coordination compared with older youth, suggesting that billing for care coordination using a new rule for Medicare that
school-related concerns connected with the child's age may be would reimburse providers for certain behavioral health services
a factor in the receipt of care. Some teachers may require that a when they are provided within a collaborative care model.36 Per-
child's behavioral health problem be adequately addressed with a haps other payers will follow Medicare's lead in this area. Another
psychopharmacological or psychosocial intervention before he/ limitation may be that the rate of care coordination that we found
she returns to the classroom. Children aged 10 to 14 years may in this study was an underestimate, given the possibility that the
be more compliant with treatment than older teenagers, and this behavioral health care some youth received after follow-up from
characteristic may explain why this group had increased odds of a specialty provider was paid for out of pocket.
care coordination. Other studies have found a temporal effect of
the school year related to trends in behavioral health–related ED
visits among children.26,27 Although our data did not directly ex-
amine this factor, care coordination may be more likely to occur in CONCLUSIONS
order to facilitate a child's immediate return to school following an Care coordination by primary care and/or specialty care pro-
ED visit. viders following a behavioral health–related ED visit by children
However, this factor may be less of a concern for younger and youth is important because few EDs are equipped to fully
children (aged 2–5 years old) because they spend less time in handle these matters beyond addressing the presenting problem
school (or may not be in school at all) compared with older chil- without assistance from behavioral health clinicians, and EDs
dren, and young children's behavioral health conditions may be are not intended to provide behavioral health care on an ongoing
different than those of adolescents who may experience more sui- basis.32,37 Emergency departments are an important component
cidal ideation or substance use.28 Emergency department physi- of medical neighborhoods that comprise primary and specialty
cians may be more likely to suggest watchful waiting for certain care providers. Medical neighborhoods with adequate behavioral

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ORIGINAL ARTICLE
Elevated Heart Rate and Risk of Revisit With Admission in

Pediatric Emergency Patients
Carrie Daymont, MD, MSCE,* Fran Balamuth, MD, PhD, MSCE,†‡ Halden F. Scott, MD,§
Christopher P. Bonafide, MD, MSCE,†|| Patrick W. Brady, MD, MSc,¶
Holly Depinet, MD, MPH,# and Elizabeth R. Alpern, MD, MSCE**
with an elevated heart rate (HR).2 Such policies may prompt ther-
Objective: The aim of this study was to identify emergency department apy to reduce HR, such as fluid boluses or antipyretics, and may
(ED) heart rate (HR) values that identify children at elevated risk of ED re- delay or prevent discharge.
visit with admission. The clinical utility of discharge HR-based reevaluation strat-
Methods: We performed a retrospective cohort study of patients 0 to egies has not been demonstrated. If these strategies are effective at
18 years old discharged from a tertiary-care pediatric ED from January identifying children in need of additional care, they should be
2013 to December 2014. We created percentile curves for the last recorded more widely implemented. However, even interventions with
HR for age using data from calendar year 2013 and used receiver operating strong face validity may be ineffective. Implementation of ineffec-
characteristic (ROC) curves to characterize the performance of the percen- tive strategies may reduce time and resources available for more
tiles for predicting ED revisit with admission within 72 hours. In a held-out high-yield activities or may lead to unintended negative conse-
validation data set (calendar year 2014 data), we evaluated test characteris- quences. The choice of HR cut points may impact the effective-
tics of last-recorded HR-for-age cut points identified as promising on the ness of discharge HR–based interventions. In practice, most HR
ROC curves, as well as those identifying the highest 5% and 1% of last re- cut points for children are based on expert opinion and are not em-
corded HRs for age. pirically derived.3–8 One recent publication identified an associa-
Results: We evaluated 183,433 eligible ED visits. Last recorded HR for tion between a prespecified measure of elevated HR for age
age had poor discrimination for predicting revisit with admission (area un- (>99th percentile for healthy outpatients) and a small increased risk
der the curve, 0.61; 95% confidence interval, 0.58–0.63). No promising cut of revisit (risk ratio, 1.3) but no increased risk in a composite out-
points were identified on the ROC curves. Cut points identifying the come of revisit with clinically important intervention or admission.9
highest 5% and 1% of last recorded HRs for age showed low sensitivity We sought to empirically identify cut points for discharge
(10.1% and 2.5%) with numbers needed to evaluate of 62 and 50, respec- HR that would identify children at high risk of revisit with admis-
tively, to potentially prevent 1 revisit with admission. sion after ED discharge using a large electronic health record data
Conclusions: Last recorded ED HR discriminates poorly between chil- set. We also aimed to identify alternate measures of HR that may
dren who are and are not at risk of revisit with admission in a pediatric be more effective and subsets of patients for whom evaluation of
ED. The use of single-parameter HR in isolation as an automated trigger for discharge HR may be particularly useful.
mandatory reevaluation prior to discharge may not improve revisit outcomes.
Key Words: discharge, quality improvement, readmissions, vital signs
MATERIALS AND METHODS
R apidly distinguishing between children who are dangerously

ill and children who are ill but will recover with minimal or
no intervention is one of the key challenges of pediatric emer-
Study Design and Setting
We performed a retrospective study of children visiting the
gency care. In order to avoid discharging children with dangerous Children's Hospital of Philadelphia ED in calendar years 2013
illnesses (including, notably, sepsis),1 some emergency depart- and 2014. This ED is a large, urban, academic, tertiary-care pedi-
ments (EDs) have sought to use discharge vital signs as an adjunct atric ED with approximately 90,000 visits per year.
to clinical judgment, often by mandating reevaluation of patients
Selection of Participants
We extracted demographic and clinical data from the elec-
From the *Departments of Pediatrics and Public Health Sciences, Penn State tronic (Epic) health record. We evaluated all children younger than
College of Medicine, Hershey; and †Center for Pediatric Clinical Effectiveness 18 years during the study period with at least 1 index ED visit. An
and ‡Division of Emergency Medicine, Children's Hospital of Philadelphia,
Philadelphia, PA; §Department of Pediatrics, Section of Emergency Medicine, index visit was defined as any ED visit with at least 1 HR that
University of Colorado School of Medicine, Aurora, CO; ||Division of General ended in a disposition of discharge and was not preceded by an-
Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; Divisions of other ED visit within 7 days. We included all eligible visits for pa-
¶Hospital Medicine and #Emergency Medicine, Cincinnati Children's Hospital tients with multiple visits.
Medical Center, Cincinnati, OH; and **Division of Emergency Medicine, De-
partment of Pediatrics, Ann & Robert H. Lurie Children's Hospital, Northwest-
ern University Feinberg School of Medicine, Chicago, IL. Measurements
Reprints: Carrie Daymont, MD, MSCE, Penn State College of Medicine, Mail
Revisits were defined as any visit to the ED within 72 hours
Code H085, 500 University Dr, Hershey, PA 17033 of discharge from an index visit. Revisit with admission was de-
(e‐mail: cdaymont@pennstatehealth.psu.edu). fined as any revisit within 72 hours of discharge that ended in a
Supplemental digital content is available for this article. Direct URL citations disposition of admission to the hospital, admission to the observa-
tion unit, or death. We evaluated the last recorded HR prior to ED
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. discharge, even when only 1 HR was recorded. Triage HR, max-
ISSN: 0749-5161 imum HR, body temperature at the time of triage HR and last

Daymont et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
recorded HR, medications given during the visit, and ED disposi- and alternate outcomes. For each sensitivity analysis, only the pa-
tion were also extracted. rameter(s) indicated were changed; otherwise, the inclusion criteria
(all discharged visits in 2014), HR cut point (last-recorded HR-for-
Outcome age percentiles), and outcome (revisit with admission within
Our primary outcome was the proportion of index ED visits 72 hours) of the primary analysis were used. The sensitivity anal-
followed by an ED revisit with admission within 72 hours. Revisit yses are detailed below:
with admission was chosen as the primary outcome because it was
considered more likely to identify children with serious unrecognized Additional HR Types and Temperature-Adjusted HR
illness at the initial visit. Alternate outcomes were evaluated, includ- We created percentiles for triage for age and maximum HR
ing any revisit, as described further in the Sensitivity Analyses. for age (the maximum HR observed during the ED visit) using
2013 data. We also created and evaluated HR-for-age percentiles
Analysis Overview adjusted for body temperature for last HR and triage HR by
Our primary analysis was performed in 3 steps. First, we de- subtracting 10 beats/min for each degree Celsius above 37°C and
veloped percentile curves for last recorded HR for age, which adding 10 beats/min for each degree Celsius below 37°C.12–14
would allow us to evaluate the relationship between vital signs When a simultaneously recorded temperature was not available,
and outcomes across ages. Second, we used data from 2013 to cre- we used the HR without adjustment. For each set of percentiles,
ate receiver operating characteristic (ROC) curves to identify can- we evaluated discrimination with ROC curves and determined
didate cut points for last recorded HR using an outcome of ED the cut points that identify the highest 5% and 1% of HRs for age.
revisit with admission within 72 hours. Finally, we used data from
2014 to evaluate the performance of candidate HR-for-age cut Restricted Inclusion Criteria
points. Details of these steps are presented below. Last recorded HR may be related to outcomes differently in
visits with certain characteristics, either because of true physio-
Percentile Creation logic differences or altered clinician behavior related to HR.
We used HR data from visits in 2013 ending in discharge, ad- Therefore, we evaluated the test characteristics of candidate last-
mission, or observation to create the percentiles. A random subset recorded HR-for-age cut points in 3 restricted groups. First, we re-
(40%) of the data was used to generate the curves, and the remain- stricted the sample to visits in which albuterol had not been given,
ing 60% was used to evaluate the fit of the percentiles overall and because of the effect of β-agonist medications on HR. Second, we
within 5 age groups: younger than 1 year, 1 to younger than restricted the sample to visits in which 1 or more boluses of intra-
3 years, 3 to younger than 6 years, 6 to younger than 12 years, venous fluid had been given, because HR is often a factor consid-
and 12 years or older. We initially used the GAMLSS package ered when determining the need for an intravenous bolus and
in R software to create a last-recorded HR-for-age percentile refer- assessing the adequacy of the response to a bolus. We used logistic
ence that would allow conversion of HRs to z scores.10 However, regression to compare the risk of revisit for visits with and without
the distribution of last recorded HRs differed from a normal distri- albuterol administration and with and without bolus administration.
bution in a manner that could not be modeled well using the Finally, we restricted the sample to visits in which the last HR was
GAMLSS framework, and the fit of the upper centiles in the val- recorded 30 minutes or less before discharge, as these HRs are
idation data set was poor. Therefore, we created a last-recorded more likely to be representative of the HR at the time of discharge.
HR-for-age percentile reference using quantile regression with cu-
bic splines, a method that does not require any assumptions about Varied Outcomes
the underlying distribution of data.11 We created multiple upper We evaluated the predictive value and test characteristics of
centile curves (12 levels ≥90th percentile) to allow identification selected cut points above for the following alternate outcomes:
of the level best associated with the outcomes of interest. any ED revisit, ED revisit with intensive care unit (ICU) admis-
sion, and ED revisit with admission within 1 or 7 days.
Cut Point Identification
For the primary analysis presented here, we generated ROC Resolution of Tachycardia
curves examining the relationship between last-recorded-HR per- We identified visits in which any HR, starting at triage, was
centile and our primary outcome in discharged patients in 2013. above the highest 5% cut point for last recorded HR for age.
We considered 5% and 1% to be the upper and lower bounds of Among those visits, we considered visits in which the last re-
the proportion of ED visits for which it may be feasible to delay corded HR was less than this cut point to have resolved tachycar-
discharge in order to perform some degree of further observation, dia and used logistic regression to evaluate whether resolved
evaluation, or treatment, ranging from a single set of repeat vital tachycardia was associated with a change in risk of ED revisit,
signs to admission. Therefore, we chose to examine cut points with or without admission, within 72 hours.
for the highest 5% and 1% of discharge HR among discharged pa- Statistical analyses were done using Stata 14.2 (StataCorp,
tients using 2014 data, in addition to any promising cut points College Station, Tex). The study was designated not human sub-
identified from the ROC curves. jects research by the institutional review board at Penn State College
of Medicine and met criteria for not human subjects research set by
Performance of Candidate Cut Points the Children's Hospital of Philadelphia institutional review board.
We calculated standard test characteristics for candidate HR
percentile cut points.
RESULTS
Sensitivity Analyses There were 183,433 visits by 104,159 patients in 2013 and
The primary analysis included all index visits. After the pri- 2014 (Fig. 1). Visit data from 2013 and 2014 showed generally
mary analysis, we performed sensitivity analyses using 2014 data similar demographic and visit characteristics, including a similar
to evaluate alternate HR measures, restricted inclusion criteria, prevalence of ED revisits with admission (0.8%; Table 1). The

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Elevated Heart Rate and Risk of Revisit
FIGURE 1. Flowchart of visit exclusions and included data.
proportion of visits with an HR within 30 minutes of discharge 50 and 62 children with high last recorded HRs would need to
was higher in 2014 than in 2013 (P < 0.001). be evaluated to potentially prevent 1 revisit with admission.
The median number of HRs recorded for discharged visits
was 2 (interquartile range, 1, 3), with 33% of discharged visits
having only 1 recorded HR.
Sensitivity Analyses
HR-for-Age Percentiles Maximum HR had a higher AUC than last recorded HR (0.66;
95% CI, 0.64–0.68). The AUC for triage HR (0.63; 95% CI,
The last-recorded HR-for-age percentiles (Supplemental File
0.61–0.66) and the sensitivity, PPV, and positive likelihood ratios
1, http://links.lww.com/PEC/A283) demonstrated good fit in the
all had overlapping CIs with those for last recorded HR (Table 3).
validation subset. Among 5 age groups, the proportions of HRs
No other modifications, including using temperature-
above the 95th percentile ranged from 4.8% to 5.5%, and the pro-
adjusted HR, restricting the type of analyzed visits, and using al-
portions above the 99th percentile ranged from 0.7% to 1.4%.
ternate outcomes, resulted in improved test characteristics. The
risk of revisit with admission was higher for visits in which albu-
Primary Analysis terol was given (odds ratio [OR], 2.2; 95% CI, 1.7–2.7) compared
The area under the curve (AUC) for predicting revisit with with when it was not given and higher for visits in which intrave-
admission using last recorded HR was 0.61 (95% confidence in- nous boluses were given (OR, 2.3; 95% CI, 1.7–3.2) compared
terval [CI], 0.58–0.63) (Fig. 2). Because no promising cut points with visits in which no bolus was given. Test characteristics in
were identified on the ROC curves, only cut points for the highest these restricted visit groups were not improved compared with
5% and 1% of HR for age were evaluated further. These cut points the primary analysis including all index visits (Table 3).
corresponded to the 91st and 97th percentiles of last recorded HR Visits in which tachycardia resolved were more likely to end
among all ED patients, because higher last recorded HRs were in discharge (OR, 2.4; 95% CI, 2.3–2.6) compared with visits in
more prevalent among visits ending in admission. These cut which tachycardia was present and was not resolved at the last re-
points had low sensitivity and positive predictive value (PPV), corded HR. Among visits that ended in discharge, resolution of
with likelihood ratios (positive) of 2.0 and 2.4, respectively, and tachycardia was not associated with a significant change in risk
likelihood ratios (negative) of 0.95 and 0.99 (Table 2). Between of revisit with admission (OR, 1.4; 95% CI, 0.97–1.9) and was

TABLE 1. Demographic and Clinical Information, by Visit
2013 2014
n % n %
Total included visits 81,350 82,823
Distinct patients 61,949 59,367
Age
0 to <1 y 13,058 16% 12,958 16%
1 to <4 y 24,882 31% 24,954 30%
4 to <12 y 28,437 35% 29,345 35%
12 to <18 y 14,973 18% 15,566 19%
Race
American Indian or Alaska Native 51 0.06% 57 0.07%
Asian 2523 3% 2466 3%
Black or African American 50,308 62% 50,630 61%
Native Hawaiian or other Pacific Islander 70 0.09% 86 0.1%
White 19,511 24% 20,088 24%
Multiple races 1225 2% 1367 2%
Other 7629 9% 8083 10%
Unknown 33 0.04% 46 0.06%
Ethnicity
Hispanic or Latino 6118 8% 6337 8%
Not Hispanic or Latino 75,191 92% 76,409 92%
Unknown 41 0.05% 77 0.09%
Chief complaint*
Fever 13,501 17% 13,091 16%
Respiratory distress 16,315 20% 17,238 21%
Trauma 13,251 16% 13,395 16%
Discharged visits 66,081 81% 67,659 82%
Distinct patients for discharged visits 49,366 50,533
Of discharged visits
Any revisit (3 d) 1821 2.8% 1873 2.8%
Revisit with admission (3 d) 557 0.8% 552 0.8%
Revisit with ICU admission (3 d) 32 0.05% 22 0.03%
Received albuterol 6025 9% 6371 9%
Received ≥1 boluses 2317 4% 2127 3%
Last HR ≤30 min before discharge 12,278 19% 17,394 26%
*Most common chief complaints presented; visits may have more than one chief complaint.
associated with an increased, rather than a decreased, risk of any revisit with admission. For example, if reevaluation were triggered
revisit (OR, 1.3; 95% CI, 1.1–1.6). for an HR in the highest 5% of all discharged ED patients,
62 patients would require reevaluation to potentially prevent 1 re-
visit with admission, and the vast majority (90%) of revisits with
CONCLUSIONS admission would be preceded by a discharge HR that would not
Multiple prior studies in children and adults have shown as- have triggered any reevaluation. This estimation presumes that re-
sociations between abnormal vital signs and more serious illness evaluation would be able to prevent subsequent revisit with admis-
or poorer outcomes,15–24 and clinicians already consider HR in sion; however, it is likely that some of these revisits with
decisions regarding therapy and admission. Our study design did admission were not preventable, and the true number needed to
not directly measure the association between HR and outcomes evaluate would actually be higher.
because, in many cases, HR would have already been incorpo- Clinicians are often advised to follow changes in vital signs
rated into therapy decisions and the decision to admit or discharge. or of scores derived from vital signs.6,25 However, evidence for
Our study evaluated the potential additional benefit of a focused whether and how changes in vital signs or vital sign scores are as-
look at the last recorded HR to avoid poor outcomes after dis- sociated with outcomes is lacking. Among discharged visits with
charge. While we found a weak association between the last re- an elevated HR at any time during the ED visit, resolution of
corded HR and subsequent ED revisit with admission, a detailed tachycardia was associated with an increase in risk of revisit,
analysis and sensitivity analyses did not identify HR cut points rather than a decrease in risk. One possible explanation for this un-
that discriminated well between children at high and low risk of expected finding is ascertainment bias; the decision to wait for

been explored in prior research. We developed validated HR-for-

age percentiles specific to the ED setting, which may be of use
to researchers or those developing clinical tools. We used these
percentiles and ROC curves to identify cut points with the best
discrimination, rather than determining HR cut points a priori.
Ensuring that clinicians are aware of tachycardia prior to dis-
charge is an intervention with strong face validity. Our findings
and those of Wilson et al9 do not support the use of the last re-
corded HR as a trigger to prevent or delay discharge, but our work
is not definitive. Given the uncertain benefit, it is especially im-
portant to consider the risks of HR-based triggers. The biggest risk
may be that clinicians could be inappropriately reassured by a
nonelevated HR. The negative likelihood ratios of last recorded
HR for age were extremely weakly informative (0.95–0.99).
Therefore, when clinicians have other reasons to be concerned
about a patient, a nonelevated HR should not be used in isolation
as justification for being less concerned. The diversion of time
FIGURE 2. Receiver operating characteristic curves for discharge, and resources from more high-yield activities and the risks from
triage, and maximum HR-for-age percentiles identifying unnecessary testing or admission in tachycardic patients are 2
discharged visits with a return admission within 72 hours.
other important potential risks that should be balanced against
uncertain benefit.
resolution of tachycardia, or to repeat measurements of HR, may The most important limitation of this study is our inability to
reflect increased concern on the part of the clinician that is associ- directly measure the outcome of interest: harm due to inadequate
ated with more serious illness. In addition, the documentation of a care or inappropriate discharge at the index visit. We used ED re-
single HR in the typical range just prior to discharge may some- visit with admission as a proxy for this outcome, but the relationship
times reflect variability in HR or a transient decrease in HR rather between revisit with admission and both harm and appropriate-
than a true resolution of the process causing tachycardia and may ness of care is unclear.27–30 Despite their limitations, revisits, with
therefore be inappropriately reassuring in certain patients. The or without admission, are often used as quality indicators by hos-
finding that resolution of tachycardia is associated with increased pitals and other groups. Therefore, in the absence of other options
risk of revisit counters the clinical practice of observing and that are measurable on a large scale, we believe that revisit with
watching for normalization of vital signs at the end of a visit to de- admission is an appropriate outcome for an initial evaluation of
termine suitability for discharge. We also found that maximum the clinical value of last recorded HR–based reevaluation strate-
HR had the largest AUC for predicting revisit with admission. If gies. Revisit with admission likely overestimates the frequency
these findings are confirmed in other ED populations, it may be of harm due to inadequate care; therefore, its use as an outcome
advisable for clinicians to consider maximum HR more heavily measure would likely result in falsely decreased sensitivity and
in their decision making than a final HR. This finding is supported falsely elevated PPV. Because the sensitivity and PPV in this study
by research in adult patients admitted to the hospital, for whom vi- were so low, it seems unlikely that desirable test characteristics
tal sign abnormalities in the 24 hours preceding discharge, but not would be achieved even with a relatively large increase in sensitiv-
necessarily occurring just prior to discharge, were associated with ity and a small decrease in PPV.
an increased likelihood of death or readmission within 30 days.26 The study was retrospective, and the frequency and timing of
Test characteristics were not improved when we adjusted HR HR measurement and recording were likely impacted by disease
for body temperature. Although many children with a very high severity, patient characteristics, and provider characteristics. Some
fever do not have a dangerous illness, the lack of improved test elevated HR observations would not have been included in our
characteristics when adjusting for body temperature may reflect evaluation because they caused the clinical team to admit the child
some association between increased body temperature and more or recheck the HR, which would bias toward the null. The similar
severe illness. results of our evaluation limited to HRs done 30 minutes or less
Strengths of this study included the large population and sev- before discharge provide some reassurance that confounding by
eral novel sensitivity analyses that, to our knowledge, have not factors that influence the timing of the discharge HR did not
TABLE 2. Test Characteristics for Identifying Discharged Visits Followed by Revisit and Admission Within 3 Days Using Cut Points
Selecting Visits With the Highest 5% and 1% of Last Recorded HRs for Age
Highest 5% Highest 1%
Point Estimates 95% CIs Point Estimates 95% CIs
Test + 5.2% 5.0%–5.3% 1.0% 1.0%–1.1%
Sensitivity 10.1% 7.8%–13.0% 2.5% 1.4%–4.2%
Specificity 94.9% 94.7%–95.1% 99.0% 98.9%–99.0%
Positive predictive value 1.6% 1.2%–2.1% 2.0% 1.1%–3.3%
Negative predictive value 99.2% 99.2%–99.3% 99.2% 99.1%–99.3%
Likelihood ratio (+) 2.0 1.5–2.6 2.4 1.4–4.2
Likelihood ratio (−) 0.95 0.7–1.3 0.99 0.6–1.7
Number needed to evaluate 62 48–82 50 30–91

TABLE 3. Selected Test Characteristics for Sensitivity Analyses of Alternate HR Cut Points, Restricted Inclusion Criteria, and Alternate
Outcomes
Highest 5% Highest 1%
Analysis Sensitivity PPV LR (+) Sensitivity PPV LR (+)
Primary 10.1% 1.6% 2.0 2.5% 2.0% 2.5
Alternate HR types
Triage HR 15.9% 2.2% 2.7 4.3% 2.7% 3.4
Maximum HR 14.9% 2.3% 2.9 4.9% 3.2% 3.9
Temperature-adjusted HR
Adjusted last recorded HR 9.2% 1.5% 1.8 1.6% 1.3% 1.6
Adjusted triage HR 13.5% 1.9% 2.5 3.4% 2.8% 3.4
Restricted inclusion criteria
No albuterol 4.9% 1.2% 1.6 1.1% 1.9% 2.6
Bolus 10.5% 4.3% 2.4 — 0 —
Last HR ≤30 min before discharge 10.6% 2.1% 2.0 2.2% 2.7% 2.6
Alternate outcomes
Any return (3 d) 7.1% 3.8% 1.4 1.5% 4.0% 1.4
Return with ICU admission (3 d) 13.6% 0.1% 2.7 — 0 —
Return admission (1 d) 10.6% 0.5% 2.0 1.7% 0.4% 2.1
Return admission (7 d) 11.1% 2.8% 2.2 3.2% 4.0% 3.2
LR (+) indicates likelihood ratio positive.
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17. Berger T, Green J, Horeczko T, et al. Shock index and early recognition of on discharge and the risk of post-discharge adverse outcomes. J Gen Intern
sepsis in the emergency department: pilot study. West J Emerg Med. 2013; Med. 2017;32:42–48.
14:168–174. 27. Sabbatini AK, Kocher KE, Basu A, et al. In-hospital outcomes and costs
18. Considine J, Thomas S, Potter R. Predictors of critical care admission in among patients hospitalized during a return visit to the emergency
emergency department patients triaged as low to moderate urgency. J Adv department. JAMA. 2016;315:663–671.
Nurs. 2009;65:818–827. 28. Pham JC, Kirsch TD, Hill PM, et al. Seventy-two-hour returns may not be a
19. Hong W, Earnest A, Sultana P, et al. How accurate are vital signs in good indicator of safety in the emergency department: a national study:
predicting clinical outcomes in critically ill emergency department patients. 72-hour returns are not a good ED safety indicator. Acad Emerg Med. 2011;
Eur J Emerg Med. 2013;20:27–32. 18:390–397.
20. Horeczko T, Wintemute GJ. Asthma vital signs at triage: home or 29. Abualenain J, Frohna WJ, Smith M, et al. The prevalence of quality issues
admission (ASTHmA). Pediatr Emerg Care. 2013;29:175–182. and adverse outcomes among 72-hour return admissions in the emergency
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emergency department patients. J Intern Med. 2004;255:579–587. general emergency departments. Pediatr Emerg Care. 2007;23:94–102.

ORIGINAL ARTICLE
Prognostic Factors of Children Admitted to a Pediatric

Intensive Care Unit After an Episode of Drowning
Alberto Salas Ballestín, MD,*† Juan Carlos de Carlos Vicente, MD,* Guillem Frontera Juan, MD,‡
Artur Sharluyan Petrosyan, MD,*† Cristina M. Reina Ferragut, MD,* Amelia González Calvar, MD,*
Maria del Carmen Clavero Rubio, MD,* and Andrea Fernández de la Ballina, MD*†
Evidence pertaining to survival following a submersion in-

Objective: The aim of this study was to evaluate the prognostic factors of jury is limited. The following factors at presentation have been as-
patients admitted to a pediatric intensive care unit (PICU) after drowning. sociated with a poor prognostic: length of immersion longer than
Methods: Retrospective observational study from January 1992 to 5 minutes, time longer than 10 minutes to initiation of basic car-
December 2004 and prospective study from January 2005 to December diopulmonary resuscitation (CPR), resuscitation time exceeding
2015 were conducted in a tertiary children's hospital PICU. The data ana- 25 minutes, Glasgow Coma Scale (GCS) score of 5 or less, persis-
lyzed refer to the patient, event, type of resuscitation performed, and clini- tent apnea requiring CPR on admission to hospital, and arterial
cal situation after resuscitation and at arrival to the PICU; results of blood pH of less than 7.10 upon presentation.5–13
additional tests; and clinical evolution and neurological status at discharge The aim of this study was to evaluate these and other prog-
from the PICU (categorized as death, severe encephalopathy, or normal). nostic factors through analyzing the characteristics and clinical
The considered potential prognostic factors were whether drowning was course of patients admitted in a pediatric intensive care unit
witnessed, the type of initial resuscitation, Glasgow Coma Scale score at (PICU) after an episode of drowning over the past 24 years.
admission, pupil status and reactivity, and pH.
Results: One hundred thirty-one patients were registered. Mortality was
16.7%, and 8.3% had significant neurological sequelae. The clearest factor METHODS
associated with poor outcome was the type of initial resuscitation per- This is an observational study in the referral hospital of the
formed. All patients who did not require cardiopulmonary resuscitation Balearic Islands (Spain), the only PICU of the community, and
(CPR), or only basic CPR, had good outcomes; 96.3% of those who re- it receives all children younger than 15 years who require inten-
quired advanced CPR with epinephrine administration had poor outcomes. sive care in the islands. It is a community with a large tourist pop-
Patients who needed advanced resuscitation with administration of epi- ulation during the summer months.
nephrine had lower temperature, Glasgow Coma Scale score, pH, and bi- The study was approved by the institutional review board of
carbonate at admission and higher level of glucose. In this group, there Hospital Universitario Son Espases with the code number
was also a higher incidence of seizures, acute respiratory distress syn- CI-77-15. The study was conducted retrospectively from 1992
drome, hemodynamic compromise, and acute renal failure. to 2004 and prospectively from 2005 to 2015. Retrospective data
Conclusions: The need for advanced CPR with epinephrine administra- were collected from medical records that were not computerized.
tion on the scene predicts poor neurological outcome (severe encephalop- Prospective data were collected from a questionnaire prepared
athy or death) in drowned children. for the study. All children admitted to the PICU after an episode
Key Words: arrest, cardiopulmonary resuscitation, drowning, of drowning were included, besides those who did not require ad-
hypothermia, intensive care units, neurologic outcome mission to the PICU and those who died in the prehospital phase.
The data analyzed refer to the patient (age, sex), event (fresh-
water or saltwater, drowning witnessed or not), type of resuscita-
tion performed (not accurate, basic, advanced with or without
D rowning is one of the most frequent unintentional injuries in
the world. It occurs from primary respiratory impairment due
to submersion in a liquid medium and is followed by breath-holding
epinephrine), clinical situation after resuscitation and admission
to the PICU (temperature, GCS score, condition of the pupils), re-
sults of additional tests (blood gases with pH and bicarbonate, blood
and involuntary laryngospasm that leads to hypercapnia, hypox-
tests with biochemistry), clinical evolution (seizures, hemodynamic
emia, and, if prolonged, respiratory or cardiorespiratory arrest.
instability requiring inotropic support or volume expansion, acute
According to the World Health Organization, it was the third lead-
respiratory distress syndrome [ARDS] or kidney failure), and neu-
ing cause of death from unintentional injury in 2014 and accounts
rological status at discharge from the PICU, categorized as death; se-
for 7% of all injury-related deaths. It is estimated that 359,000
vere encephalopathy (severe disability or coma/vegetative state) by
people die of drowning worldwide each year. Children are a pop-
Pediatric Cerebral Performance Categories (>3), recording data
ulation at risk to suffer such injuries. It is the fifth leading cause of
according to the pediatric Utstein-Style recommendations; or
death in children aged 5 to 14 years and the 11th one among chil-
good outcome (Pediatric Cerebral Performance Categories ≤3).2
dren younger than 5 years.1–4
The data of the patients who underwent therapeutic hypothermia
were also collected.
From the *Pediatric Intensive Care Unit, †Pediatric Transport Unit, and ‡Clin- The considered potential prognostic factors were whether
ical Research Unit, Hospital Universitario Son Espases, Palma de Mallorca,
Islas Baleares, Spain.
drowning was witnessed, type of initial resuscitation after the
Disclosure: The authors declare no conflict of interest. event (not accurate, basic, advanced with or without epinephrine),
Reprints: Alberto Salas Ballestín, MD, Pediatric Intensive Care Unit, Hospital GCS score, and pupil status and reactivity at the first clinical ex-
Universitario Son Espases, Carretera de Valldemossa 79, 07120 Palma de ploration and blood pH at admission.
Mallorca, Islas Baleares, España
(e‐mail: albertosalasballestin@gmail.com).
Descriptive analysis and calculation of mean, median, and
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. SD for continuous variables and proportions for categorical ones
ISSN: 0749-5161 were performed. To test differences between the groups, Student

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Prognostic Factors After an Episode of Drowning
Glasgow Coma Scale score was a good prognosis factor if it

TABLE 1. Retrospective Versus Prospective Period was greater than 5 (only 3 deaths of 81 patients), but with a lower
score, it was not a reliable factor.
1992–2004 2005–2015
The state of the pupils predicted a good outcome if they were
(n = 82) (n = 49) P
not mydriatic and were reactive at the first neurological exploration
Age 5.18 y 5.43 y 0.69 (90.2% of these patients had a good course) and predicted a bad
Male 68.2% 79.5% 0.23 course in 87% of patients when they were mydriatic and nonreactive.
Freshwater 89.0% 89.8% 0.88 The pH was a good prognostic factor if it was 7.1 or greater
Not witnessed drowning 78.9% 75.5% 0.83 at admission, with 91.3% of patients with good outcomes. Of
those patients with pH of less than 7.1 at admission, only 33.3%
Advanced CPR 33.3% 46.9% 0.18
had a good outcome.
GCS score ≤5 60.0% 68.8% 0.42 Among the factors analyzed, the one most clearly associated
Mydriatic, nonreactive pupils 23.4% 10.4% 0.11 with a poor outcome was the type of initial resuscitation per-
pH 7.21 7.16 0.13 formed after drowning. All patients who did not require CPR, or
Temperature 36.0°C 35.5°C 0.13 required basic CPR (without endotracheal intubation or intrave-
nous administration of epinephrine), had a good course, whereas
t test and analysis of variance were used for continuous variables, 96.2% of those who required advanced CPR with epinephrine ad-
and χ2 or Fisher exact test was used for categorical variables. Cal- ministration had poor outcomes (Table 2).
culations were performed with IBM SPSS Statistics for Windows, Given these obvious results, other factors were analyzed
version 20.0 (IBM Corp, Armonk, NY). regarding the type of CPR performed. Patients who needed ad-
Retrospective and prospective groups were also compared to vanced resuscitation with administration of epinephrine had
check that both groups were similar. lower temperature, lower GCS score at admission, lower pH
and bicarbonate at admission, and a higher level of glucose
(Table 3). This group also experienced a higher incidence of
RESULTS seizures, ARDS, hemodynamic compromise (considered as
During the past 24 years, 131 patients were registered and ad- needing volume expansion or vasoactive drug administration),
mitted to our PICU after an episode of drowning, with a mean of and acute renal failure (with elevated creatinine for their age) than
5.5 (SD, 2.7) patients per year, although there is a great interan- the other groups (Table 4).
nual variability (range, 2–11 per year). This represents 1.9% of In recent years, therapeutic hypothermia was applied for
our PICU total admission. Males predominated at 95 (72.5%) 8 patients who underwent CPR (maintained at 32°C with thermal
compared with females (36 [27.4%]). The mean age was 5 years blanket for 48 hours with subsequent gradual warming of 0.2°C
3 months (SD, 3 years 3 months). Of the children, 63.3% were per hour to recover normothermia). Two (25%) of them required
younger than 6 years. Drowning occurred in freshwater at 89.3% CPR intubation without epinephrine, both without sequelae, and
of the time, whereas only 10.6% occurred in saltwater. 6 (75%) required CPR with epinephrine, all with poor outcome
No significant differences were found between both periods (4 deaths and 2 severe encephalopathies).
(Table 1), so only the global results are presented. Data missing
from the medical records were less than 10% in every category.
Mortality was 16.7% (22 patients), and 8.3% (11 patients) DISCUSSION
had significant neurological sequelae at discharge of PICU with In our series, the most important factor predicting poor out-
severe encephalopathy. Therefore, the outcome was classified as come was the need for advanced CPR on the scene, especially
poor (death or severe encephalopathy) in 25.1% (33 patients). when intravenous administration of epinephrine was required.
The first analyzed factor was whether drowning was All patients in the groups with no need of CPR or basic CPR
witnessed; we found that all but 1 witnessed drowning had good without advanced maneuvers had good clinical course, with no
outcomes (96.4%), whereas only 69.1% of unwitnessed drowning significant neurological sequelae at discharge from intensive care
had good outcomes. in any of them.
TABLE 2. Prognostic Factors Analyzed
Prognostic Indicators Normal or Mild Disability Severe Disability or Vegetative State Deaths P
Witnessed drowning 27 (96.4%) 0 1 (3.6%) 0.024
Unwitnessed drowning 67 (69.1%) 10 (10.3%) 20 (20.6%)
No CPR 18 (100%) 0 0 <0.001
Basic CPR 58 (100%) 0 0
Advanced CPR (intubation only) 17 (81.0%) 2 (9.5%) 2 (9.5%)
Advanced CPR (intubation and epinephrine) 1 (3.7%) 8 (29.6%) 18 (66.7%)
GCS score ≤5 19 (40.4%) 10 (21.3%) 18 (38.3%) <0.001
GCS score >5 78 (96.3%) 0 3 (3.7%)
Mydriatic, nonreactive pupils 3 (13.0%) 4 (17.4%) 16 (69.6%) <0.001
Nonmydriatic, reactive pupils 92 (90.2%) 5 (4.9%) 5 (4.9%)
pH <7.1 9 (33.3%) 3 (11.1%) 15 (55.6%) <0.001
pH ≥7.1 84 (91.3%) 7 (7.6%) 1 (1.1%)

Salas Ballestín et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
TABLE 3. Values of Temperature, GCS Score, pH, Bicarbonate, and Glucose, Depending on the Type of CPR
Clinical Situation and No CPR Basic CPR Advanced CPR Advanced CPR (Intubation and
Additional Tests at Admission (n = 18) (n = 58) (Intubation Only) (n = 21) Epinephrine) (n = 27) P
Temperature, mean (SD), °C 36.4 (0.9) 36.4 (0.8) 35.6 (1.6) 34.0 (1.8)* <0.001
GCS score, median (SD) 14 11 5* 3* <0.001
pH, average (SD) 7.27 (0.09) 7.26 (0.1) 7.19 (0.17) 6.94 (0.21)* <0.001
Bicarbonate, average (SD), mmol/L 21.1 (4.1) 19.9 (6.9) 18.4 (4.9) 12.1 (4.9)* 0.001
Glucose, mean (SD), mg/dL 152.6 (65.1) 188.9 (81.0) 230.5 (80.0) 295.7 (127.3)† 0.001
*P < 0.003 for comparison with other variables.
†
P < 0.001 versus no CPR and versus basic CPR.
In the group of patients who needed advanced CPR with en- higher had a better prognosis compared with those with a pH be-
dotracheal intubation (but without administering epinephrine), low 7.10 (good course in 91.3% of patients with pH ≥7.1), but this
19% had poor outcomes. It was not possible to differentiate other factor has a less strong association with prognosis than the type of
factors of poor prognosis because of the sample size in this group CPR. Bicarbonate values were also lower in more severe patients
(21 patients). That requires a larger sample of patients who need than in patients without sequelae. Lower pH and bicarbonate
endotracheal intubation without intravenous administration of epi- could be due to poor tissue perfusion because of long immersion
nephrine to analyze the factors of good or poor prognosis for or to prolonged ischemia during resuscitation.
this subgroup. In the group of more severely affected patients, in which ad-
Finally, in patients who required advanced CPR with epi- vanced CPR maneuvers were performed, higher blood glucose
nephrine administration, poor outcomes were observed in all but levels were also observed. In previous studies, higher blood glu-
one. Therefore, the need for such maneuvers very clearly predicts cose levels had been suggested as a factor of severity at admission
poor outcome. to the PICU. In this group, more complications in their clinical
Recently, Mtaweh and colleagues,1 with a 60-case series, course, such as seizures, ARDS, hemodynamic compromise,
also reported good outcomes in patients with only respiratory ar- and kidney failure, were registered.14,15
rest and poor outcome in patients with cardiac arrest. It is doubtful whether patients who drowned in cold water
The variable of immersion duration is difficult to measure have a better prognosis because of a neuroprotective effect of hy-
because data at the event location are often confused. In our study, pothermia. In our environment (the Mediterranean Sea), the water
we collected data to whether drowning was witnessed, accepting is warm; therefore, initial hypothermia usually indicates pro-
that at witnessed drowning immersion time is lower. It seems ob- longed immersion time. This is confirmed by the fact that the tem-
vious to assume that children with lower immersion time would perature recorded was significantly lower in those patients who
have better neurological status and better prognosis. In our series, required advanced CPR with epinephrine administration than in
prognosis was good in cases of witnessed drowning. It was found other groups.12,13
that when drowning was not witnessed, more important resuscita- Therapeutic hypothermia is described as a neuroprotective
tion measures were applied, and the prognosis was worse.14 therapy in patients who suffer a cardiac arrest. There are some
Neurological examination following an event should initially published cases of good neurological outcome after performing
assess GCS score and the status of pupils. A worse GCS score, 3 to therapeutic hypothermia in patients with cardiac arrest who re-
5 out of 15, is described in the literature as a poor prognostic fac- quired advanced CPR after drowning. In our study, hypothermia
tor. Our series confirmed that patients with low GCS values had was applied to a few patients, with no improved prognosis of those
worse prognoses, and patients with GCS values higher than who required advanced CPR, although the number of cases was
5 had a good prognosis (96.3%). By matching GCS and the type not enough to draw conclusions from. A longer sample would
of resuscitation, we concluded that in the patients who required be necessary to confirm these data, but it seems that in patients
advanced CPR GCS values were lower than those in the other with a poor initial neurological prognosis (those who required ad-
groups. The same applies to the size and reactivity of the pupils, vanced CPR with intravenous administration of epinephrine) it
with the worst prognosis in patients with unreactive mydriatic pu- may be unnecessary to take such measures.16
pils at the initial examination (good course in 90.2% of patients The relevance of this study is a possibility to predict with
who did not exhibit mydriatic, nonreactive pupils at admission). high reliability the neurological outcome in a child who has suf-
A pH below 7.10 has also been suggested as a poor prognos- fered an episode of drowning. It can be helpful for the information
tic factor. Our study confirmed that patients with a pH of 7.10 or to the family and to guide treatment after initial resuscitation.
TABLE 4. Events During Evolution by Type of CPR
No CPR Basic CPR Advanced CPR Advanced CPR

Events (n = 18) (n = 58) (Intubation Only) (n = 21) (Intubation and Epinephrine) (n = 27) P
Seizures 11.1% 19.0% 19.0% 25.9% 0.065
ARDS 0 3.4% 19.0% 25.9% 0.006
Hemodynamic compromise 5.6% 12.1% 57.1% 81.5% <0.001
Renal insufficiency 0 0 14.3% 40.7% <0.001

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Prognostic Factors After an Episode of Drowning
Because these patients are potential organ donors, all intensive 3. Ahogamientos. Nota descriptiva N°347 Abril de 2014. WHO. Available at:
support despite the prognosis should be initially managed to as- http://www.who.int/mediacentre/factsheets/fs347/es/. Accessed November
sess this possibility with the family. 9, 2015.
In this study, a prospective cohort of patients was grouped 4. Water Sanitation Health. Water-related Diseases. WHO. Available at: http://
with a retrospective one. Because they were admitted to an inten- www.who.int/water_sanitation_health/diseases/drowning/en/. Accessed
sive care unit, data were collected systematically in graphic and November 9, 2015.
medical records, so few data about patients from the retrospective 5. Orlowski JP. Prognostic factors in pediatric cases of drowning and
group were lost (<10% in every category). This allows for analysis near-drowning. JACEP. 1979;8:176–179.
of a greater number of patients by minimizing the potential of error 6. Biggart MJ, Bohn DJ. Effect of hypothermia and cardiac arrest on outcome
in analyzed variables. Recruiting 131 patients from the same center of near-drowning accidents in children. J Pediatr. 1990;117:179–183.
eliminates differences in treatments between hospitals.
7. Dean JM, Kaufman ND. Prognostic indicators in pediatric near-drowning:
Our study has some limitations. We did not dispose data from
the Glasgow Coma Scale. Crit Care Med. 1981;9:536–539.
those patients who suffered drowning and, after initial resuscita-
tion, improved enough to decline an admission to intensive care. 8. Lavelle JM, Shaw KN. Near drowning: is emergency department
The other group of patients who could not be analyzed is that of cardiopulmonary resuscitation or intensive care unit cerebral resuscitation
those who died before hospital admission. indicated? Crit Care Med. 1993;21:368–373.
Because of the limited number of patients per year, it was not 9. Bierens JJ, van der Velde EA, van Berkel M, et al. Submersion in the
possible to check whether changes in care practices over time or in Netherlands: prognostic indicators and results of resuscitation. Ann Emerg
CPR recommendations improved neurological outcome. A multi- Med. 1990;19:1390–1395.
center study would be needed. 10. Suominen P, Baillie C, Korpela R, et al. Impact of age, submersion time and
water temperature on outcome in near-drowning. Resuscitation. 2002;52:
CONCLUSIONS 247–254.
The need for advanced CPR on the scene with epinephrine 11. Habib DM, Tecklenburg FW, Webb SA, et al. Prediction of childhood
administration in drowned children predicts poor neurological drowning and near-drowning morbidity and mortality. Pediatr Emerg Care.
outcome (severe encephalopathy or death) with great reliability. 1996;12:255–258.
Other prognostic factors associated with poor neurological out- 12. Tipton MJ, Golden FS. A proposed decision-making guide for the search,
come depend on the type of resuscitation required. rescue and resuscitation of submersion (head under) victims based on
It is confirmed that the sickest patients, who required more expert opinion. Resuscitation. 2011;82:819–824.
intensive resuscitation measures, had lower temperature, GCS 13. Quan L, Mack CD, Schiff MA. Association of water temperature and
score, and bicarbonate and pH values and higher blood glucose submersion duration and drowning outcome. Resuscitation. 2014;
levels. They also had a higher incidence of seizures, ARDS, he- 85:790.
modynamic impairment, and kidney failure. 14. Blasco Alonso J, Moreno Pérez D, Milano Manso G, et al. Ahogamientos y
casi ahogamientos en niños. An Pediatr (Barc). 2005;62:20–24.
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1. Mtaweh H, Kochanek PM, Carcillo JA, et al. Patterns of multiorgan children and adolescents: a succinct review for emergency physicians and
dysfunction after pediatric drowning. Resuscitation. 2015;90:91–96. nurses. Pediatr Emerg Care. 2005;21:610–616.
2. Idris AH, Berg RA, Bierens J, et al. Recommended guidelines for uniform 16. Aronovich DM, Ritchie KL, Mesuk JL. Asystolic cardiac arrest from near
reporting of data from drowning: the “Utstein style”. Resuscitation. 2003; drowning managed with therapeutic hypothermia. West J Emerg Med.
59:45–57. 2014;15:369–371.

ORIGINAL ARTICLE
Epidemiology of Critical Interventions in Children With

Traumatic Intracranial Hemorrhage
Pradip P. Chaudhari, MD,*† Jose Pineda, MD, MSCI,†‡
Richard G. Bachur, MD,§ and Robinder G. Khemani, MD, MSCI†‡
children with intracranial hemorrhage are considered at high risk

Objective: To estimate rates of critical medical and neurosurgical inter- of neurologic deterioration and need for critical interventions,
ventions and resource utilization for children with traumatic intracranial they are often monitored in the intensive care unit (ICU) and un-
hemorrhage (ICH). dergo serial neuroimaging. However, low-risk children might be
Methods: This was a retrospective study of children younger than safely monitored in a non-ICU setting and may not require serial
18 years hospitalized in 1 of 35 hospitals in the Pediatric Health Informa- neuroimaging unless there is clinically important neurologic
tion System from 2009 to 2019 for ICH. We defined critical intervention deterioration.1–3
as a critical medical (hyperosmotic agents and intubation) or neurosurgical Determining the risk of neurologic deterioration at the point of
intervention. We determined rates of critical interventions, intensive care clinical decision making is complex as it balances provider-level
unit (ICU) admission, and repeat neuroimaging. We used hierarchical lo- factors (such as clinician perspective and risk tolerance for the
gistic regression to identify high-level factors associated with undergoing risk of hemorrhage progression or clinical deterioration) with
critical interventions, controlling for hospital-level effects. patient-level factors (such as actual risk of clinical deterioration
Results: There were 12,714 children with ICH included in the study. Me- and need for critical medical and neurosurgical interventions). Prior
dian (interquartile range) age was 4.3 (0.7–11.0) years. Twelve percent studies describing children with acute traumatic intracranial hemor-
(n = 1470) of children underwent a critical clinical intervention. Critical rhage report varying rates of critical care and neurosurgical inter-
medical interventions occurred in 10% (n = 1219), and neurosurgical interventions due to varying inclusion criteria, such as TBI severity or
ventions occurred in 3% (n = 419). Intensive care unit admission occurred hemorrhage type, and sample sizes.1–13 Ultimately, identifying chil-
in 44% (n = 5565), whereas repeat neuroimaging occurred in 40% dren at low risk of neurologic deterioration would reduce resource
(n = 5072). Among ICU patients, 79% (n = 4366) did not undergo a critical utilization including serial neuroimaging and intensive care moni-
intervention. Of the 11,244 children with no critical interventions, 39% toring, but first requires a better understanding of the overall rates
(n = 4366) underwent ICU admission, and 37% (n = 4099) repeat neuroim- of critical interventions in a large sample of children with intracra-
aging. After controlling for hospital, children with isolated subdural nial hemorrhage.
(P = 0.013) and isolated subarachnoid (P < 0.001) hemorrhage were less Therefore, we aimed to estimate rates of critical medical and
likely to receive critical interventions. neurosurgical interventions for children with traumatic intracra-
Conclusions: Critical medical interventions occurred in 10% of children nial hemorrhage using a large administrative database of US pedi-
with ICH, and neurosurgical interventions occurred in 3%. Intensive care atric medical centers. We hypothesized that critical medical and/or
unit admission and repeat neuroimaging are common, even among those neurosurgical interventions occur infrequently in children with in-
who did not undergo critical interventions. Selective utilization of ICU ad- tracranial hemorrhage, while ICU admissions and repeat neuroim-
mission and repeat neuroimaging in children who are at low risk of requir- aging are used in the majority of children.
ing critical interventions could improve overall quality of care and decrease
unnecessary resource utilization.
Key Words: critical intervention, intracranial hemorrhage, traumatic brain
injury
METHODS
(Pediatr Emer Care 2021;37: e196–e202) Design and Data Source
Data for this study were obtained from the Pediatric Health
M uch of the morbidity, mortality, and resource utilization in
children with traumatic brain injury (TBI) occur in children
with intracranial hemorrhage. The patient's clinical status and re-
Information System (PHIS), an administrative database that con-
tains inpatient, emergency department (ED), ambulatory surgery,
and observation encounter-level data from tertiary care pediatric
sults of neuroimaging determine the need for critical medical in-
hospitals in the United States. These hospitals are affiliated with
terventions, such as administration of hyperosmotic agents and
the Children's Hospital Association (Lenexa, Kan). Data quality
intubation, and neurosurgical interventions. Furthermore, because
and reliability are ensured through a joint effort between the
Children's Hospital Association and participating hospitals. Por-
From the *Division of Emergency and Transport Medicine, Children's Hospital
Los Angeles; †Keck School of Medicine of the University of Southern
tions of the data submission and data quality processes for the
California; ‡Department of Anesthesia and Critical Care Medicine, Children's PHIS database are managed by Truven Health Analytics (Ann
Hospital Los Angeles, Los Angeles, CA; and §Division of Emergency Medi- Arbor, Mich). For the purposes of external benchmarking, partic-
cine, Boston Children's Hospital and Harvard Medical School, Boston, MA. ipating hospitals provide discharge or encounter data including
Reprints: Pradip P. Chaudhari, MD, Division of Emergency and Transport
demographics, diagnoses, and procedures. Hospitals also submit
Medicine, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mail Stop resource utilization data (eg, pharmaceuticals, imaging, and labo-
113, Los Angeles, CA 90027 (e‐mail: pchaudhari@chla.usc.edu). ratory) into PHIS. Timing of resource utilization data is limited to
Supplemental digital content is available for this article. Direct URL citations day of service performed. Data are deidentified at the time of sub-
mission and are subjected to reliability and validity checks before
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. being included in the database. Hospitals with unreliable data were
ISSN: 0749-5161 excluded from the study using standard PHIS reliability checks.

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Critical Interventions in Traumatic ICH
All statistical analyses were performed using Stata/SE ver- We limited outcomes to acute hospitalization from the index
sion 16.0 (Stata Corp, College Station, Tex). The study was deter- ED visit, defined as the first 4 days of the encounter. We defined a
mined to be exempt by our institutional review board. The study critical intervention as an encounter with a critical medical and/or
was approved by the administrators of the PHIS database. In ac- neurosurgical intervention. We defined critical medical interven-
cordance with PHIS policies, the identities of the institutions were tions as hyperosmotic agent administration and/or nonoperative
not reported. endotracheal intubation. We defined repeat neuroimaging as either
a brain CT scan or magnetic resonance imaging (MRI) in addition
to the initial brain CT scan. We recorded demographic factors,
trauma center designation, freestanding versus nonfreestanding
Study Population, Definitions, and Assumptions children's hospital, hospital length of stay, ICU admission,
All children younger than 18 years with an ED encounter hyperosmotic agent (hypertonic saline or mannitol) administration,
from January 1, 2010, through June 30, 2019, who were hospital- nonoperative endotracheal intubation, neurosurgical procedures
ized for a principal diagnosis of intracranial hemorrhage and had (operations, external ventricular drains, or intracranial monitors),
at least 1 brain computed tomography (CT) scan performed on the and hemorrhage subtype. We identified hemorrhage subtypes by
day of their index ED visit were eligible for inclusion. We used the billing codes and grouped them into 7 categories: intraparenchymal,
principal diagnosis code to define intracranial hemorrhage. We in- cerebellar or brainstem, other, mixed (subarachnoid and/or subdural
cluded only children hospitalized during the ED encounter and and/or epidural), isolated subdural, isolated subarachnoid, and iso-
who had a brain CT scan performed on the day of their index lated epidural (full list of billing codes outlined in Supplemental
ED visit to capture the target sample of children with acute intra- Digital Content 1, http://links.lww.com/PEC/A680).
cranial hemorrhage, as hospitalization and CT as the initial neuro-
imaging modality are standard practice.
The unit of analysis was the ED encounter, which was classi- Analysis
fied as a case with intracranial hemorrhage if any International Our primary goal was to estimate rates of critical medical and
Classification of Diseases (ICD) Ninth Revision (ICD-9) or 10th neurosurgical interventions for children with traumatic intracra-
Revision (ICD-10) codes for intracranial hemorrhage were nial hemorrhage. We hypothesized that critical interventions occur
assigned as the principal diagnosis from the index ED visit. The infrequently in children with intracranial hemorrhage, whereas the
full list of diagnostic codes used for case ascertainment is listed ICU and repeat neuroimaging are used frequently. In order to ex-
in Supplemental Digital Content 1 (http://links.lww.com/PEC/ plore high-level factors in children with intracranial hemorrhage
A680). We defined hospitalization by inpatient or observation who did not undergo a critical intervention, we examined
codes. We excluded children with any complex chronic condi- hospital- and encounter-level demographic and diagnostic factors,
tions, including those with malignancy and hematologic disorders, independent of institution, which were associated with critical
based on ICD-9 and ICD-10 codes defined by Feudtner et al,14 be- interventions.
cause the risk of neurologic deterioration and ability to monitor We calculated frequencies and proportions for categorical
clinically may be different in these children. For patients with mul- variables and analyzed them with χ2 tests of homogeneity. We de-
tiple ED encounters, we included only the first ED visit for intra- scribed continuous variables as medians with interquartile ranges
cranial hemorrhage during the study period in order to best (IQRs) and analyzed them with the Mann-Whitney U test. We de-
capture the care provided during acute hospitalization. termined the rates of critical interventions, ICU admission, and
FIGURE 1. Study flowchart.

Chaudhari et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
repeat neuroimaging. Hospital day of service of critical interven- covariates that were significantly associated (P < 0.1) with undergo-
tions performed was analyzed. In order to explore demographic ing a critical intervention in univariable analysis and retained those
and diagnostic factors associated with critical interventions, we that remained associated with the outcome in multivariable modeling
created logistic regression models to determine whether each fac- (P < 0.05) or were confounders (>10% change in association between
tor retained an independent association with critical interventions, covariates and critical interventions regardless of P value) in the final
our primary outcome. To account for potential nonindependence model. For sensitivity analyses, we refit the model among the subset
among encounters at each hospital because of institutional similarities of children admitted to the ICU and for the outcome of neurosurgical
in practice patterns, we used hierarchical multivariable logistic regres- intervention. We calculated the final model area under the curve of
sion models with the institution as the random effect.15–17 We first the receiver operating characteristic plot with 95% confidence inter-
constructed a baseline, encounter-level model without covariates vals (CIs).
using the institution as the grouping variable. We chose covariates a
priori based on published literature, our hypothesis, and after examin-
ing both the clinical and the statistical significance from the RESULTS
univariable analysis. The initial set of covariates entered into the
model were two hospital-level factors based on the literature: level Study Sample
1 trauma center designation and whether the hospital was a freestand- The study flowchart is depicted in Figure 1. For this study,
ing children's hospital. We then sequentially entered encounter-level data from 35 hospitals with complete demographic and billing
TABLE 1. Hospital- and Encounter-Level Characteristics, Stratified by Critical Intervention, of Children With Intracranial
Hemorrhage in US Pediatric Hospitals From 2010 to 2019
No Critical Intervention Critical Intervention All

Hospital- and Encounter-Level Characteristics (n = 11,244) (n = 1470) (n = 12,714) P*
Hospital-level characteristics
Level I trauma center designation 9602 (85.4) 1290 (87.8) 10,892 (85.7) 0.015
Freestanding children's hospital 10,361 (92.2) 1355 (92.2) 11,716 (92.2) 0.968
Encounter-level characteristics
Median age in years 3.8 [0.6–10.6] 8.0 [3.2–12.9] 4.3 [0.7–11.0] <0.001
Sex (female) 4327 (38.5) 475 (32.3) 4802 (37.8) <0.001
Race
White 7412 (65.9) 920 (62.6) 8332 (65.5) 0.011
Black 1635 (14.5) 297 (20.2) 1932 (15.2) <0.001
Asian 324 (2.9) 30 (2.0) 354 (2.8) 0.065
Other 1310 (11.7) 168 (11.4) 1478 (11.6) 0.803
Missing 563 (5.0) 55 (3.7) 618 (4.9) 0.034
Ethnicity
Non-Hispanic/Latino 8174 (72.7) 1066 (72.5) 9240 (72.7) 0.884
Hispanic/Latino 2215 (19.7) 248 (16.9) 2463 (19.4) 0.010
Other 855 (7.6) 156 (10.6) 1011 (8.0) <0.001
Source of payment
Private 4739 (42.2) 536 (36.5) 5275 (41.5) <0.001
Public 5538 (49.3) 781 (53.1) 6319 (49.7) 0.005
Other 967 (8.6) 153 (10.4) 1120 (8.8) 0.021
Median calendar year 2013 [2011–2015] 2013 [2011–2016] 2013 [2011–2015] <0.001
Median hospital length of stay 3 [2–4] 6 [4–11] 3 [2–4] <0.001
ICU admission 4366 (38.8) 1199 (81.6) 5565 (43.8) <0.001
Mortality 38 (0.3) 66 (4.5) 104 (0.8) <0.001
Repeat neuroimaging 4099 (36.5) 973 (66.2) 5072 (39.9) <0.001
Hemorrhage subtype
Intraparenchymal 1004 (8.9) 172 (11.7) 1176 (9.3) 0.001
Cerebellar or brainstem 63 (0.6) 4 (0.3) 67 (0.5) 0.151
Other 1135 (10.1) 115 (7.8) 1250 (9.8) 0.006
Mixed† 4721 (42.0) 597 (40.6) 5318 (41.8) 0.315
Isolated subdural 2060 (18.3) 260 (17.7) 2320 (18.3) 0.554
Isolated subarachnoid 1277 (11.4) 118 (8.0) 1395 (11.0) <0.001
Isolated epidural 984 (8.8) 204 (13.9) 1188 (9.3) <0.001
Values in the table represent median [interquartile range] or frequency (percent). Proportions might not sum to 100% because of rounding.
*P values are χ2 or Mann-Whitney U test between critical intervention and no critical intervention.
†
Subarachnoid and/or subdural and/or epidural.

TABLE 2. Frequency of Critical Medical and Neurosurgical Interventions, ICU Admission, and Repeat Neuroimaging in Children
With Intracranial Hemorrhage, by Hemorrhage Type
Critical Intervention (% Hemorrhage Type)

Medical Intervention
All Any Medical or
Hemorrhage n (%, Hyperosmotic Nonoperative Neurosurgical Neurosurgical ICU Repeat
Type Column) Agent* Intubation Intervention Intervention Admission Neuroimaging†
Isolated epidural 1188 (9.3) 111 (9.3) 45 (3.8) 100 (8.4) 204 (17.2) 639 (53.8) 605 (50.9)
Isolated subdural 2320 (18.3) 142 (6.1) 121 (5.2) 68 (2.9) 260 (11.2) 974 (42.0) 985 (42.5)
Isolated 1395 (11.0) 62 (4.4) 60 (4.3) 19 (1.4) 118 (8.5) 468 (33.6) 406 (29.1)
subarachnoid
Mixed‡ 5318 (41.8) 317 (6.0) 263 (5.0) 168 (3.2) 597 (11.2) 2422 (45.5) 2110 (39.7)
Intraparenchymal 1176 (9.3) 94 (8.0) 83 (7.1) 45 (3.8) 172 (14.6) 560 (47.6) 532 (45.2)
Cerebellar or 67 (0.5) 2 (3.0) 1 (1.5) 1 (1.5) 4 (6.0) 18 (26.9) 28 (41.8)
brainstem
Other 1250 (9.8) 57 (4.6) 60 (4.8) 18 (1.4) 115 (9.2) 484 (38.7) 406 (32.5)
Total 12,714 785 (6.2) 633 (5.0) 419 (3.3) 1470 (11.6) 5565 (43.8) 5072 (39.9)
Values in table represent frequency (percent). Percentages in columns are out of total number of each hemorrhage type, rather than the sum total from the
row or column. Proportions may not sum to 100% because of rounding.
*Hyperosmotic agent defined as hypertonic saline or mannitol administered.
†Repeat CT or repeat MRI.
‡
Multiple hemorrhage types (subarachnoid and/or subdural and/or epidural).
information during the study period were eligible for inclusion in Critical Interventions, ICU Admission, and Repeat
the analysis. During the study period of January 1, 2010, through Neuroimaging
June 30, 2019, 29,978 ED visits for intracranial hemorrhage were
identified from 35 pediatric hospitals. After eliminating cases based Rates of critical interventions, ICU admission, and repeat
on a priori exclusions, 12,714 encounters of children admitted neuroimaging stratified by hemorrhage subtype are outlined in
through the ED with intracranial hemorrhage constituted the study Table 2. We found that rates of all 3 outcomes varied by hemor-
sample. Hospital- and encounter-level characteristics are displayed rhage subtype, with each occurring most in children with isolated
in Table 1. The sample was predominantly male (62.2%) with a me- epidural hemorrhage (17.2% critical intervention, 53.8% ICU ad-
dian (IQR) age of 4.3 (0.7–11.0) years. Median (IQR) length of stay mission, and 50.9% repeat neuroimaging). Overall, we found that
was 2 (1–3) days. Mortality was 0.8% (n = 104). 11.6% (n = 1470) of children underwent a critical medical or
FIGURE 2. Hospital day of service for critical medical and neurosurgical interventions in subgroup of children with intracranial hemorrhage
who underwent critical interventions.

neurosurgical intervention. Critical medical interventions oc- CI, 0.92–0.99), isolated subarachnoid hemorrhage (OR, 0.91;
curred in 9.6% (n = 1219) of children with intracranial hemor- 95% CI, 0.88–0.95), and other hemorrhage subtypes (OR, 0.89;
rhage, and neurosurgical interventions occurred in 3.3% 95% CI, 0.83–0.96) were less likely to undergo a critical intervention.
(n = 419). The majority of critical medical and neurosurgical inter- Epidural hemorrhage (OR, 1.03; 95% CI, 1.00–1.06) was indepen-
ventions were performed on hospital day 1 (Fig. 2). dently associated with undergoing a critical medical and/or neurosur-
Forty-four percent (n = 5565) were admitted to the ICU dur- gical intervention and with undergoing a neurosurgical intervention
ing the study period. Of the children admitted to the ICU, 78.5% (OR, 1.10; 95% CI, 1.06–1.15; Supplemental Digital Content 2,
(n = 4366) did not undergo a critical intervention. Repeat neuroim- http://links.lww.com/PEC/A681). The final random-effects model
aging (either repeat CT or MRI) was performed in 39.9% for critical interventions had an area under the curve of 0.66 (95%
(n = 5072), of which 67.6% (n = 3429) were a CT scan, and CI, 0.65–0.67). Results were similar in the sensitivity analysis of chil-
32.4% (n = 1643) were an MRI. Of the 11,244 children who did dren admitted to the ICU (Table 3, Fig. 3).
not receive a critical medical or neurosurgical intervention, 38.8%
(n = 4366) underwent ICU admission, and 36.5% (n = 4099)
underwent repeat neuroimaging. Repeat neuroimaging occurred DISCUSSION
on the day of hospital discharge in 10.6% (n = 1349) of children. In a large sample of children hospitalized at US pediatric
medical centers for intracranial hemorrhage, we found that
nearly half of children were admitted to the ICU and underwent re-
Factors Associated With Critical Interventions peat neuroimaging, whereas critical medical interventions oc-
Results of the final hierarchical multivariable logistic regres- curred in 10% of children, and neurosurgical interventions
sion model are detailed in Table 3 and displayed in Figure 3. In occurred in 3%. Most children who were admitted to the ICU
multivariable modeling, among hemorrhage subtypes, children and/or underwent repeat neuroimaging did not undergo critical
with isolated subdural hemorrhage (odds ratio [OR], 0.96; 95% interventions.
TABLE 3. Final Random-Effects Model for Critical Intervention* in Children With Intracranial Hemorrhage and Among the Subset of
Children Admitted to the ICU
All ICU
Factors OR (95% CI) P OR (95% CI) P
Encounter-level factors
Age 1.00 (1.00–1.00)† <0.001 1.00 (1.00–1.00)‡ <0.001
Female sex 0.86 (0.76–0.97) 0.011 0.85 (0.73–0.97) 0.020
Race
White Reference group — Reference group —
Black 1.30 (1.11–1.53) 0.001 1.41 (1.16–1.70) <0.001
Asian 0.81 (0.55–1.20) 0.301 1.15 (0.73–1.80) 0.555
Other 0.98 (0.80–1.19) 0.826 0.91 (0.71–1.17) 0.452
Missing 0.67 (0.48–0.93) 0.018 0.62 (0.42–0.92) 0.016
Ethnicity
Non-Hispanic/Latino Reference group — Reference group —
Hispanic/Latino 0.97 (0.81–1.16) 0.715 0.96 (0.77–1.20) 0.742
Other 1.69 (1.32–2.17) <0.001 1.62 (1.21–2.17) 0.001
Insurance
Private Reference group — Reference group —
Public 1.34 (1.17–1.52) <0.001 1.27 (1.09–1.48) 0.002
Other 1.29 (1.06–1.59) 0.013 1.30 (1.02–1.65) 0.032
Calendar year 1.06 (1.04–1.09) <0.001 1.10 (1.07–1.14) <0.001
Hemorrhage subtype
Mixed§ Reference group — Reference group —
Intraparenchymal 1.11 (0.92–1.34) 0.276 1.24 (0.99–1.55) 0.062
Cerebellar or brainstem 0.61 (0.37–1.02) 0.060 0.65 (0.31–1.37) 0.259
Other 0.89 (0.83–0.96) 0.002 0.96 (0.89–1.05) 0.376
Isolated subdural 0.96 (0.92–0.99) 0.013 0.95 (0.92–1.00||) 0.028
Isolated subarachnoid 0.91 (0.88–0.95) <0.001 0.94 (0.90–0.99) 0.014
Isolated epidural 1.03 (1.00–1.06) 0.024 0.99 (0.96–1.03) 0.618
*Hyperosmotic agent administration (mannitol or hypertonic saline) and/or neurosurgical intervention.
†
1.000189 (1.000161–1.000216).
‡
1.000134 (1.000100–1.000167).
§
Multiple hemorrhage types (subarachnoid and/or subdural and/or epidural).
||
0.9951.

We found that both ICU admission and repeat neuroimaging We also identified specific hemorrhage subtypes that were
are utilized in a large percentage of children with intracranial hem- associated with whether a child underwent a critical intervention.
orrhage, even among children who did not undergo any critical Children with isolated subdural and isolated subarachnoid hemor-
medical or neurosurgical intervention. The proportion of children rhage, which are generally lesions that are less severe and/or non-
with intracranial hemorrhage who undergo repeat neuroimaging operative, were less likely to undergo a critical medical and/or
in published literature varies from 40% to 88%.1,4–11 In our sam- neurosurgical intervention. We found that children who did not
ple, we found the proportion was 40%. The lower rates in our large undergo critical interventions underwent ICU admission and re-
sample were likely due to inclusion of less severe children with in- peat neuroimaging at similar numbers as the entire cohort. In
tracranial hemorrhage compared with previous literature,4–11 but our sample, there were 4366 children admitted to the ICU and
one that is more reflective of the heterogeneous nature and range 4099 children who underwent repeat neuroimaging who did not
of severity of traumatic intracranial hemorrhage in children. We undergo critical interventions, suggesting a number of children
found that 10% of children received either a critical medical or with intracranial hemorrhage undergo potentially avoidable ICU
neurosurgical intervention. We also found that most children admissions and repeat neuroimaging. Admittedly, the decision to
who were admitted to the ICU and who underwent repeat neuro- admit to the ICU for closer monitoring and obtain repeat neuroim-
imaging did not undergo a critical medical or neurosurgical inter- aging may have also prevented the need for critical intervention;
vention. Although clinical data are not available regarding however, our findings highlight the variability and challenges as-
neurologic status for these children, previous literature highlights sociated with identifying disease severity and risk of hemorrhage
that acute intervention is rare after routine repeat neuroimaging in progression. Whereas Greenberg et al1 derived a clinical risk score
the absence of clinically important neurologic deterioration2,3 and to predict need for ICU admission for children with mild TBI,
that ICU admission may not be necessary for lower-risk children.1 Flaherty et al5 found that even among the more severe epidural
The risk of missing a child with progressive hemorrhage or hemorrhage subtype, utilizing clinical and radiographic predictors
increased intracranial pressure presents a diagnostic challenge can improve risk stratification for these children. From the per-
for clinicians and often leads to routine ICU admission and spective of the treating clinician, targeting the decision for ICU ad-
reimaging and substantial practice variation.18 Because many mission and repeat neuroimaging based on risk stratification
children requiring critical interventions display symptoms to could eliminate unnecessary resource utilization for a large num-
inform the decision, targeting the decision to admit to the ber of children at low risk of critical interventions.
ICU and reimage can decrease unnecessary neuroimaging Our investigation has several important limitations. We lever-
and additional resource utilization, especially for lower-risk le- aged a large administrative database, which allows for a high-level
sions. Furthermore, nonactionable findings on routine repeat examination of resource utilization in children with intracranial
neuroimaging can lead to additional unnecessary scans, inter- hemorrhage but does not allow patient-level review for clinical
ventions, and resource utilization without benefit.9 Better risk characteristics such as severity of injury or the appropriateness
stratification1 would aid clinicians making decisions at the of clinical and imaging decisions. Although we were able to ob-
bedside, improve overall quality of care in these children, and tain estimates of rates of critical interventions, neuroimaging,
decrease unnecessary resource utilization. and ICU admissions, because of limitations of the database, we
FIGURE 3. Final random-effects model for critical intervention in all children with intracranial hemorrhage and among the subgroup of
children with intracranial hemorrhage admitted to the ICU.

were unable to characterize the timing of these outcomes or dis- 3. Hollingworth W, Vavilala MS, Jarvik JG, et al. The use of repeated head
cern whether a patient was transferred from the floor to the ICU. computed tomography in pediatric blunt head trauma: factors predicting
Additionally, the diagnosis of intracranial hemorrhage was based new and worsening brain injury. Pediatr Crit Care Med. 2007;8:348–356.
on diagnostic codes, rather than clinical data, and coding differ- 4. Howe J, Fitzpatrick CM, Lakam DR, et al. Routine repeat brain computed
ences exist between ICD-9 and ICD-10. Also, to better identify tomography in all children with mild traumatic brain injury may result in
our target sample, we included those who were admitted with a unnecessary radiation exposure. J Trauma Acute Care Surg. 2014;76:
principal diagnosis of intracranial hemorrhage and had at least 1 292–295.
CT scan obtained. Because of our inclusion criteria, children 5. Flaherty BF, Moore HE, Riva-Cambrin J, et al. Repeat head CT for
who died in the ED prior to admission or who had billing codes expectant management of traumatic epidural hematoma. Pediatrics. 2018;
for polytrauma were not included, and because of the low mortal- 142:e20180385.
ity rate, we were unable to meaningfully examine mortality data 6. Dawson EC, Montgomery CP, Frim D, et al. Is repeat head computed
stratified by hemorrhage subtype. Although it is likely that we in- tomography necessary in children admitted with mild head injury and
cluded some encounters that were not our target sample, we fo- normal neurological exam? Pediatr Neurosurg. 2012;48:221–224.
cused on high-level outcomes to assess for overall rates in
7. Aziz H, Rhee P, Pandit V, et al. Mild and moderate pediatric traumatic brain
critical interventions, ICU admission, and repeat neuroimaging. injury: replace routine repeat head computed tomography with neurologic
For generalizability, we aimed to identify an otherwise examination. J Trauma Acute Care Surg. 2013;75:550–554.
healthy population of children presenting with intracranial hemor-
8. Murray BL, Mitchell AM, Scarboro SC. Do repeat head CT scans after
rhage. Although we excluded patients with a chronic comorbid
blunt head trauma change management in the pediatric patient? Ann Emerg
condition, we were unable to exclude all possible comorbidities
Med. 2013;62:S67.
that could influence clinical decisions. However, with our exclu-
sion criteria and large sample of patients, the rates observed likely 9. Hill EP, Stiles PJ, Reyes J, et al. Repeat head imaging in blunt pediatric
reflect rates in our target sample. Our sample represents children trauma patients: is it necessary? J Trauma Acute Care Surg. 2017;82:
at major US pediatric hospitals, and our results might not be gen- 896–900.
eralizable to other settings. Because encounters are tracked longi- 10. Patel SK, Gozal YM, Krueger BM, et al. Routine surveillance imaging
tudinally at a single institution, we do not know whether any following mild traumatic brain injury with intracranial hemorrhage may not
children presented to a different institution for follow-up. More- be necessary. J Pediatr Surg. 2018;53:2048–2054.
over, we cannot comment on other important clinical outcomes 11. Bata SC, Yung M. Role of routine repeat head imaging in paediatric
for this sample. traumatic brain injury. ANZ J Surg. 2014;84:438–441.
12. Kochanek PM, Tasker RC, Carney N, et al. Guidelines for the Management
of Pediatric Severe Traumatic Brain Injury, third edition: update of the
CONCLUSIONS Brain Trauma Foundation guidelines. Pediatr Crit Care Med. 2019;20:
In a large sample of children with intracranial hemorrhage, S1–S82.
we found that ICU admission and repeat neuroimaging were com- 13. Tabori U, Kornecki A, Sofer S, et al. Repeat computed tomographic scan
mon, even among those who did not undergo critical medical or within 24–48 hours of admission in children with moderate and severe head
neurosurgical interventions. Critical medical interventions oc- trauma. Crit Care Med. 2000;28:840–844.
curred in 10% of children with intracranial hemorrhage, whereas
14. Feudtner C, Feinstein JA, Zhong W, et al. Pediatric complex chronic
neurosurgical interventions occurred in 3%. Further understand-
conditions classification system version 2: updated for ICD-10 and
ing is needed on how to best implement selective utilization of in- complex medical technology dependence and transplantation.
tensive care monitoring and repeat neuroimaging among children BMC Pediatr. 2014;14:199.
with intracranial hemorrhage who are at low risk of critical
15. Wong GY, Mason WM. The hierarchical logistic regression model for
interventions.
multilevel analysis. J Am Stat Assoc. 1985;80:513–524.
16. Epstein D, Wong CF, Khemani RG, et al. Race/ethnicity is not associated
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Pediatr Surg Int. 2006;22:215–218. J Neurosurg Pediatr. 2018;23:227–235.

ILLUSTRATIVE CASE
A Traumatic Quinceañera
Acute Superior Mesenteric Artery Syndrome in an Adolescent Girl
Eric A. Russell, MD,* Richard M. Braverman, MD,† Sanjeev A. Vasudevan, MD,‡ and Binita Patel, MD*
On physical examination, the patient's vital signs were as

Abstract: A 15-year-old girl presented with 3 days of progressive abdom- follows: weight, 37.6 kg (first percentile); temperature, 36.3°C;
inal distention, pain, and bilious hematemesis. Her symptoms began after heart rate, 173 beats/min; blood pressure, 117/75 mm Hg; and
her quinceañera, during which she wore a tight corset. On examination, respiratory rate, 28 breaths/min. Her height was 153 cm and
she was thin and had significant abdominal distention and pain. A computed body mass index was 16.7 kg/m2 (third percentile). The patient
tomography revealed a massively dilated stomach and proximal duodenum appeared very uncomfortable, anxious, pale, and clammy. Her
to the region of the superior mesenteric artery (SMA) with distal decompres- cardiac examination was notable for her tachycardia and a delayed
sion. An upper gastrointestinal fluoroscopy demonstrated marked dilation of capillary refill of 4 to 5 seconds. Her abdomen was distended and
the stomach through the mid third portion of the duodenum with distal de- diffusely tender.
compression and an associated linear compression on her duodenal wall. The patient's electrolytes demonstrated a carbon dioxide
We believe that she developed acute SMA syndrome. Superior mesenteric level of 17 mmol/L and blood urea nitrogen 28 mg/dL. The remain-
artery syndrome is a partial bowel obstruction caused when the third por- der of her electrolytes and liver function test results were normal.
tion of the duodenum is compressed as it passes between the SMA and The patient's lipase was elevated at 1463/L. Her complete blood
the aorta. Although the SMA syndrome is most commonly described as count demonstrated a white blood cell count of 18.55, hemoglobin
a condition associated with chronic, severe weight loss resulting in a of 16.1 g/dL, hematocrit of 45.6%, and platelet count of 306.
narrowing of the SMA to aorta angle and subsequent duodenal compres- Her abdominal x-ray demonstrated a markedly dilated stom-
sion, it can present acutely from causes such as a postoperative complica- ach, an air-fluid level within the stomach, and multiple posterior
tion, blunt trauma, or external compression. Previously described acute air-fluid levels, likely corresponding to her duodenum. A com-
SMA syndrome from external compression has been the result of medi- puted tomography revealed a massively dilated stomach and prox-
cally necessary causes, such as body casting. In this case, the tight gown imal duodenum with decompression distal to the superior
was likely the inciting factor for her development of SMA syndrome; how- mesenteric artery (SMA) (Fig. 1). A subsequent upper gastrointes-
ever, she was placed at high risk for the condition by being underweight at tinal (GI) fluoroscopy confirmed dilation of the stomach and
baseline and experiencing food restriction for several days preceding her duodenum through the level of its mid third portion with distal
quinceañera. She was treated conservatively with nasogastric decompres- decompression and an associated linear compression on the
sion and parenteral nutrition, and has since completely recovered. duodenal wall (Fig. 2). No evidence of malrotation or gastric
Key Words: superior mesenteric artery syndrome, volvulus was seen.
superior mesenteric artery, partial bowel obstruction The patient was given a total of 80 mL/kg of normal saline
with improvement in her perfusion and tachycardia. A nasogastric
tube was placed, which resulted in 2 L of grossly bloody gastric
contents and significant symptomatic improvement. She was
given antibiotics, a proton pump inhibitor, and subsequently
CASE admitted to the pediatric intensive care unit for hypovolemic
shock and GI bleeding.
A 15-year-old, previously healthy girl presented to a pediatric
emergency department with 3 days of hematemesis, worsening
abdominal distention, and diffuse abdominal pain. Initially, she DISCUSSION
had nonbloody, nonbilious emesis; however, over the past 2 days,
Superior mesenteric artery syndrome is an uncommon but
it progressed to become bilious and grossly bloody. She had well-described condition where the third part of the duodenum
no bowel movement and no known flatus for 2 days. Of note,
is compressed between the SMA and the aorta causing a proximal
1 week before her presentation, the patient had celebrated her
bowel obstruction and associated symptoms. It is typically de-
quinceañera, where she reported wearing a very tight corset and
scribed as a complication of chronic weight loss, where intraperi-
restricting her diet before the party. The patient believed that her
toneal fat is diminished and the angle of the SMA, as it branches
abdominal discomfort started after her party and had gradually
off of the aorta, is reduced, causing compression on the duode-
worsened. She denied any recent trauma, infectious symptoms,
num. Under normal physiologic conditions, the SMA branches
fever, or previous abdominal pain or food intolerance. She had off of the abdominal aorta at an approximate angle of 38 to
no previous abdominal surgeries or hospital admissions. There
65 degrees.1 The third portion of the duodenum passes in be-
was no relevant personal or family history.
tween the SMA and the aorta at the SMA origin. In patients
with SMA syndrome, there is a significant decrease in this angle
From the Departments of *Pediatrics, Sections of Emergency Medicine, †Radi-
to approximately 6 to 22 degrees, which causes compression on
ology, and ‡Surgery, Baylor College of Medicine/Texas Children's Hospital, the duodenum (Fig. 3).1–3 The SMA syndrome is most commonly
Houston, TX. observed in female adolescents and young adults. In 2 pediatric
Disclosure: The authors declare no conflict of interest. studies, the mean ages were reported at 13 and 11.77 years.4,5 In
Reprints: Eric Russell, MD, 6621 Fannin St, Suite A2210, Houston, TX 77030
(e‐mail: earussel@texaschildrens.org).
a case series by Murthi and Raine,6 they report SMA syndrome
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. in a 5-year-old boy. The diagnosis of SMA syndrome is often de-
ISSN: 0749-5161 layed because it is an uncommon diagnosis, symptoms are typically

Russell et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
FIGURE 1. Computed tomographic scan showing a distended

stomach (S) and a distended proximal duodenum (D), narrowing
at the level of the SMA (S) and aorta (Ao).
FIGURE 3. Computed tomographic scan showing a decreased
SMA-aorta angle (10 degrees; normal range, 38–65 degrees) and
nonspecific, and it should be a diagnosis of exclusion. Patients typ- SMA-aorta distance (7 mm; normal range, 13.4–34.3 mm).2
ically present with early satiety or food intolerance, abdominal pain,
postprandial pain, vomiting, and weight loss. Although SMA syn-
drome has classically been described as a chronic illness, it can be often successful through conservative measures, such as decom-
quite acute, with some patients only experiencing symptoms for a pression through a nasogastric tube and nutritional support. In re-
few days before their presentation.1,2,4,5 Diagnosis is typically made fractory cases, surgical correction can have successful outcomes.
through upper GI radiographic series or computed tomography. The SMA syndrome is most commonly described in con-
Various diagnostic criteria have been proposed, but these imaging ditions of significant weight loss, such as after burn injuries or
modalities will typically demonstrate some combination of a nar- chronic wasting conditions. Patients subsequently experience
row SMA angle, shortened SMA to aorta distance, diminished food intolerance, exacerbating their weight loss. It is also a
intra-abdominal fat, and proximal gastric and duodenal dilation known postoperative complication and has been described after
with distal decompression. One may also see an indentation on spinal surgery, scoliosis correction, bariatric surgery, or Nissen
the affected duodenum.2,3 Treatment of SMA syndrome is most fundoplication or as a complication of intraperitoneal adhesions.
Congenital anatomic abnormalities may also predispose someone
to developing SMA syndrome.2,4,5,7,8 The SMA syndrome also
has been described after blunt abdominal trauma.2–11 Falcone
and Garrett reported a case of a 22-year-old man who developed
acute SMA syndrome after significant blunt epigastric trauma
during a basketball game.9 Lastly, SMA syndrome can be caused
by external compression, most commonly associated with body
casting. To our knowledge, this is the first reported case of SMA
syndrome after external compression for nonmedical purposes.
In our case, the patient was well until she had significant ex-
ternal abdominal compression caused by her corset. She subse-
quently developed symptoms of an intestinal obstruction. Her
imaging revealed significant gastric duodenal distention to the
level of the SMA with distal decompression. It is important to note
that there was no other apparent etiology such as malrotation or
gastric volvulus. Her symptoms were greatly improved through
gastric decompression. She continued to have bilious output for
several days, but this gradually diminished and she had a return
of normal bowel function. She was started on peripheral parenteral
nutrition during this time. At the time of discharge, she had no
pain and no vomiting, and was tolerating oral intake. It was felt
that she had developed acute SMA syndrome secondary to
the external compression caused by her corset. This occurred in
the context of her baseline low weight. At the time of her initial
FIGURE 2. Upper GI showing a distended second portion of the presentation, her weight and body mass index were in the first
duodenum (D) with scant contrast reaching nondilated proximal and third percentiles, respectively. She likely was at risk for
jejunum (J). SMA syndrome due to her low weight and developed clinical

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Acute SMA Syndrome in an Adolescent Girl
be debilitating. Diagnosis can be difficult, especially in those with

significant comorbidities such as cerebral palsy or recent trau-
matic injury. The SMA syndrome should be considered in patients
presenting with signs and symptoms of an acute or chronic upper
intestinal obstruction, especially in those that may have a predisposi-
tion for SMA syndrome such as a recent surgery, acute or chronic
weight loss, abdominal trauma, or extrinsic abdominal compression.
REFERENCES
1. Merrett ND, Wilson RB, Cosman P, et al. Superior mesenteric artery
syndrome: diagnosis and treatment strategies. J Gastrointest Surg. 2009;13:
287–292.
2. Welsch T, Büchler MW, Kienle P. Recalling superior mesenteric artery
syndrome. Dig Surg. 2007;24:149–156.
3. Unal B, Aktas A, Kemal G, et al. Superior mesenteric artery syndrome:
CT and ultrasonography findings. Diagn Interv Radiol. 2005;11:90–95.
4. Shiu JR, Chao HC, Luo CC, et al. Clinical and nutritional outcomes in
children with idiopathic superior mesenteric artery syndrome. J Pediatr
Gastroenterol Nutr. 2010;51:177–182.
5. Biank V, Werlin S. Superior mesenteric artery syndrome in children:
a 20-year experience. J Pediatr Gastroenterol Nutr. 2006;42:522–525.
FIGURE 4. Upper GI performed 15 days after presentation 6. Murthi GV, Raine PA. Superior mesenteric artery syndrome in children.
showing the second portion of the duodenum to be nondilated Scott Med J. 2001;46:153–154.
(D) and abundant material reaching nondilated jejunum (J).
7. Desai MH, Gall A, Khoo M. Superior mesenteric artery syndrome—a rare
symptoms with her additional intentional weight loss before her presentation and challenge in spinal cord injury rehabilitation: a case report
party and external compression. She was readmitted 2 days later and literature review. J Spinal Cord Med. 2015;38:544–547.
for 4 days, again with vomiting and epigastric abdominal pain. 8. Keskin M, Akgül T, Bayraktar A, et al. Superior mesenteric artery
She was treated conservatively through gastric decompression. syndrome: an infrequent complication of scoliosis surgery. Case Rep Surg.
During this admission, she had an upper endoscopy that demon- 2014;2014:263431.
strated gastritis but was otherwise unremarkable. A repeat upper 9. Falcone JL, Garrett KO. Superior mesenteric artery syndrome after blunt
GI showed normal gastric emptying and peristalsis (Fig. 4). Since abdominal trauma: a case report. Vasc Endovascular Surg. 2010;44:
discharge, she has been followed up by pediatric gastroenterology 410–412.
and surgery and has had no further symptoms. 10. Kepros JP. Superior mesenteric artery syndrome after multiple trauma.
J Trauma. 2002;53:1028.
CONCLUSIONS 11. Smith BM, Zyromski NJ, Purtill MA. Superior mesenteric artery
Superior mesenteric artery syndrome is an infrequent but syndrome: an underrecognized entity in the trauma population. J Trauma.
well-described condition. The symptoms are nonspecific but can 2008;64:827–830.

ILLUSTRATIVE CASE
“That's Not His Regular Formula”

A Case of Organophosphate Poisoning in an Infant
Jeannette Dodson, MD, Sing-Yi Feng, MD, and David Rodriguez, MD
Organophosphates as a means of suicide pose a significant prob-

Introduction: Organophosphates (OPs) are the basis of many insecti- lem in certain countries such as China, Sri Lanka, Pakistan, and
cides and herbicides and are also used as nerve agents. Approximately India.1 Compared with a number of cases worldwide, pesticide
1 million unintentional and 2 million suicidal poisonings as well as more poisoning in the pediatric population is relatively rare. In 2016,
than 300,000 fatalities that are reportedly due to OPs are reported each year there were 33,458 single agent cases of pesticide poisoning in
worldwide. The mortality rate from OP toxicity is reported as approxi- children less than 5 years of age reported to the poison center.3
mately 20%. We present a rare pediatric exposure to OPs. There are various exposure routes including dermal, gastrointesti-
Case: This is an unintentional OP poisoning in an infant who presented to nal, inhalational, and intravenous. Here we report an unusual case
a pediatric emergency department with obtundation, respiratory dis- of OP poisoning in an infant.
tress, and copious secretions. The infant was intubated, treated with at-
ropine and pralidoxime after resuscitation, and eventually recovered with
no neurologic sequelae. CASE
Discussion: Symptoms from OP toxicity are secondary to effects on A 6-month-old male infant who was born prematurely at an
muscarinic and nicotinic cholinergic receptors in the autonomic and central estimated gestational age of 34 weeks presented after ingestion
nervous systems. Symptoms include diaphoresis, diarrhea, urination, mio- of the commercial ant killer, acephate (Orthene). He had cough
sis, bradycardia, bronchospasm, bronchorrhea, emesis, lethargy, lacrima- and rhinorrhea for several weeks before presentation owing to a vi-
tion, and salivation. Treatment starts with titrated doses of atropine and ral upper respiratory infection, but otherwise he had been in his
oximes (eg, pralidoxime) after resuscitation and decontamination. Severity usual good health. A relative was caring for the child and fed
of toxicity and recovery can be monitored via plasma and whole blood ace- him a 4-ounce bottle she had prepared from an old formula can
tylcholinesterase levels, respectively. Once aging has occurred, oximes will that she did not know was being used to store ant killer. Approx-
not be able to reverse acetylcholinesterase inhibition. Despite early treat- imately 45 minutes after feeding, the patient became inconsolable,
ment, rare cases may result in delayed neurologic complications associated agitated, and irritable, followed by staring spells. He also devel-
with sensory and motor axonal degeneration of the peripheral nerves and oped significant nasal congestion, rhinorrhea, and persistent
spinal cord known as OP-induced delayed neuropathy. drooling. The family called for help, and emergency medical ser-
Conclusions: This case highlights the importance of safety education for vices arrived at the home soon after the call. He was immediately
families. It also demonstrates how to recognize and treat OP toxicity in an transported to the nearest pediatric emergency department.
infant. It emphasizes starting treatment early to avoid complications sec- During emergency medical service transport, the patient was
ondary to aging. started on an albuterol nebulizer treatment and supplemental ox-
Key Words: organophosphate, pesticide, toxicity, poisoning, infant, ygen for wheezing, hypoxia, and acute respiratory distress. On
acetylcholine, pralidoxime, ageing, muscarinic, toxidrome, atropine, arrival to the emergency department, his vital signs were temper-
OPIDN ature of 35.9°C, heart rate of 160 beats/min, respiratory rate of
49 breaths/min, blood pressure of 104/69 mm Hg, and oxygen
saturation of 100% while on 2 L/min of oxygen by nasal cannula.
His physical examination was remarkable for miosis, copious
O rganophosphates (OPs) are esters of phosphoric acid that
were first produced during the 1930s and originally
marketed as insecticides. The German military started to develop
frothy oral secretions, tachycardia with no murmurs, respiratory
distress with intercostal and suprasternal retractions, tachypnea,
wheezing and rhonchi, and hypotonia with decreased spontaneous
OPs as chemical agents of warfare, although they were not used as
movements of his upper and lower extremities. Laboratory evalu-
such until the Iran-Iraq war.1 Currently, OPs are used as insecti-
ation was remarkable for a negative standard immunoassay drugs
cides and as nerve agents; an example is sarin, the nerve gas used
of abuse screen in the urine, normal serum electrolytes, and a re-
in a terrorist action in Tokyo in 1995 by the Aum Shinriku cult
spiratory viral panel, which was positive for rhino/enterovirus.
and by the Syrian military in northern Syria in April 2017.1,2
His chest x-ray demonstrated a normal cardiac silhouette and no
Commercially, OPs replaced organochlorines (eg, Dichlorodi-
lobar infiltrate. Because the patient was exhibiting signs of the
phenyltrichloroethane) as pesticides.
muscarinic toxidrome (diarrhea, urination, miosis, bronchorrhea,
Worldwide, there are approximately 1 million unintentional
bronchospasm, emesis, lacrimation, salivation), he was started
and 2 million suicidal poisonings with organophosphorus insecti-
on atropine (0.02 mg/kg) and pralidoxime (0.25 g). This was then
cides reported per year, and the fatality rate is estimated at 20%.
followed by a second increased dose of 0.05 mg/kg of atropine
owing to persistent respiratory secretions. He was intubated with-
From the Division of Emergency Medicine, Department of Pediatrics, UT
out difficulty via rapid sequence intubation with fentanyl, mid-
Southwestern Medical Center at Dallas, Dallas, TX. azolam, and rocuronium to protect his airway. After intubation,
Disclosure: The authors declare no conflict of interest. he was given a third and again increased dose of atropine
Reprints: Jeannette Dodson, MD, Division of Emergency Medicine, Department (0 .1 mg/kg) for continued bronchorrhea.
of Pediatrics, UT Southwestern Medical Center at Dallas, 5323 Harry Hines
Blvd, Dallas, TX 75390 (e‐mail: jeannette.dodson@utsouthwestern.edu).
After stabilization, the patient was transferred to the pediatric
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. intensive care unit, where he was started on infusions of atropine
ISSN: 0749-5161 at 20% of loading dose per hour and pralidoxime at 10 mg/kg

Pediatric Emergency Care • Volume 37, Number 4, April 2021 OP Poisoning in an Infant
studies have shown that children, particularly of younger age, have

TABLE 1. Examples of OPs and Carbamates higher rates of hand to mouth behaviors than adults. Children also
have higher frequency of contact with their environment and have
OPs Carbamates
decreased hand washing before eating and playing outdoors,
Diazinon Aldicarb allowing for greater opportunities for contact with contaminants.
Chlorpyrifos Carbofuran These factors pose a greater risk for both dermal and oral exposure
Disulfoton Carbaryl to pesticides than adults.4 Furthermore, diet delivers the majority
Azinphos-methyl of exposure to pesticides in children.5 Children have a greater in-
take of food or fluids per body weight resulting in higher systemic
Fonofos
levels of OP than in adults.6,7
Case reports of infant OP poisoning have shown clinical
manifestations simulating sepsis, complicating the picture, such
per hour for continued bronchorrhea and excessive secretions. He as copious secretions, apnea, lethargy, and seizures. Parvez et al8
was weaned from the pralidoxime and atropine infusions after reported a neonate with recurrent OP poisoning that presented
2 days; however, he redeveloped excessive secretions and so was with hypotonia, lethargy, apnea and miosis. Another report by
restarted on the pralidoxime infusion for a total of 4 days. His re- Sofer et al9 presented 25 case reports of infants and young children
spiratory course was complicated by a rhinovirus/enterovirus and with OP poisoning that revealed signs and symptoms related to severe
Moraxella infections. He was intubated for a total of 8 days during central nervous system depression, coma and stupor, dyspnea, and
which he had multiple desaturations and episodes of agitation. He flaccidity. Reviews have shown that pediatric patients with OP intox-
was eventually extubated to high heated flow oxygen by nasal can- ication present with more central nervous system symptoms such as
nula and transferred to the inpatient unit where he was weaned to altered mental status and hypotonia (as in our case) than in adults who
room air. Because of his prolonged intubation and problems with may have primarily classic nicotinic and muscarinic symptoms.7,10
gastrointestinal motility, he required a nasoduodenal tube for feeds. Organophosphates and carbamates (structurally different
He then developed oral aversion. Thus, much of his inpatient unit organic compounds derived from carbamic acid) are widely
course was for occupational therapy to improve his oral intake used in agriculture and as household pesticides and can pose
and weaning him from dependence on medications he had devel- significant health risks to those exposed to them. A list of com-
oped from being sedated for his prolonged intubation. He was mon OPs and carbamates is presented in Table 1. This infant
discharged home on hospital day 28 without neurological sequelae. had altered mental status, copious secretions, respiratory distress
The patient's plasma cholinesterase levels and red blood cell secondary to bronchorrhea, miosis, and hypotonia, 45 minutes
acetylcholinesterase (AChE) levels were sent to a reference lab. after orally ingesting the insecticide. The history of insecticide
His initial plasma cholinesterase level from hospital day 2 was ingestion and presentation of symptoms is consistent with the
118 IU/L (normal, 2900–7100 IU/L), and red blood cell AChE cholinergic toxidrome.
level from hospital day 3 was 10.7 IU/L (normal, 31.2–61.3 IU/L). Organophosphates and carbamates function by binding to
His plasma cholinesterase levels from hospital days 4 and 5 were AChE and rendering the enzyme inactive. The OP phosphorylates
2149 IU/L and 2412 IU/L, respectively. the serine hydroxyl moiety in the enzyme's active site (Fig. 1). The
AChE inhibition results in the accumulation of acetylcholine
(ACh), which overwhelms ACh receptors at the synapses of the
DISCUSSION neuromuscular junction as well as autonomic and central nervous
This is a case of an infant suffering from OP toxicity after be- systems. Organophosphate poisoning has effects on muscarinic
ing unintentionally poisoned. Children are at particular risk for and nicotinic ACh receptors, which results in a constellation of
unintentional ingestion with greater adverse effects owing to their clinical signs and symptoms (diaphoresis and diarrhea, urina-
unique physiology, behavior, and diet. Specifically, observational tion, miosis, bradycardia, bronchospasm, bronchorrhea, emesis,
FIGURE 1. Acetylcholinesterase (AChE) inhibition. Organophosphates function by binding to AChE in nerve cells and rendering this enzyme
inactive. The OP phosphorylates the serine hydroxyl moiety in the enzyme's active site. Aging is a process when the phosphorylated
cholinesterase undergoes a dealkylation reaction; loss of 1 of the 2 alkyl groups attached to the bound phosphate. The enzyme then
undergoes conformation and stability changes, which converts the irreversibly inhibited enzyme to one that is inactive. Once aging
has occurred, the enzyme is refractory to oxime. Oximes reverse the inhibition of AChE by dephosphorylating the serine moiety (figure
from Gonçalves et al11).

Dodson et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
used as confirmation of toxicity and regeneration after symp-

TABLE 2. Nerve Agents Cholinesterase Aging Half-Lives tomatic management.
Organophosphate-induced delayed neuropathy is a rare com-
Nerve Agent Aging Half-Life
plication of severe OP toxicity that can occur 1 to 5 weeks after ex-
Tabun (GA) 46 h posure.13,22,23 Although the etiology of OP-induced delayed
Sarin (GB) 5.2–12 h neuropathy is unknown, it is associated with sensory and motor
Soman (GD) 40 s to 10 min axonal degeneration of the peripheral nerves and spinal cord.
VX 50–60 h Symptoms start distally and progress proximally. This can begin
as cramping in the extremities and can rapidly progress to pares-
thesia followed by muscle weakness, ataxia, suppression of deep
lethargy, excess lacrimation, and salivation, diaphoresis, mydriasis, tendon reflexes, and symmetric flaccid paralysis. Upper and lower
tachycardia, hypertension, and effects on skeletal muscle such as extremities may be affected.22 Currently, there is no specific
fasciculation, weakness, paralysis).12,13 treatment for this complication. Patients with mild symptoms
In this case, the patient developed prolonged symptoms due to may recover in 12 to 15 months. However, motor neuron in-
OP toxicity requiring multiple doses of atropine and pralidoxime, volvement may be permanent in severe cases, and recovery de-
eventually needing infusions of both to control his excessive pends on degree of pyramidal involvement with persistent
bronchorrhea. Atropine is a competitive muscarinic ACh recep- ataxia and paralysis. Fortunately for our patient, he did not de-
tor antagonist, which blocks the effects of excess ACh at musca- velop any neurologic sequelae from his intoxication.
rinic cholinergic synapses. Atropine dosing is 1 to 2 mg
(0.05 mg/kg in pediatrics) and administered intravenously. It is
CONCLUSIONS
redosed every 5 minutes and titrated until tracheobronchial se-
cretions are dry.14 Oximes (eg, pralidoxime) are synergistic to at- Although a relatively common toxicity, this case highlights
ropine. They can remove OPs from the AChE enzyme if aging (a OP toxicity in an infant. It demonstrates the importance of accu-
process whereby the phosphorylated cholinesterase undergoes a rate labeling of products and need for safety education with fam-
dealkylation reaction and converts the irreversibly inhibited en- ilies. Because pediatric patients present with more muscarinic
zyme to an inactive form) has not yet occurred. This will regen- symptoms than nictonic (as in our case), OP toxicity should be
erate and reactivate the AChE enzyme owing to the removal of considered as an etiology for pediatric patients with altered mental
the phosphate group.15 Treatment with pralidoxime prevents ag- status, hypotonia, and significant cholinergic symptoms. Pediatric
ing from occurring if given early enough (Fig. 111). Aging times patients referred for OP toxicity often have an incorrect prelimi-
between the various nerve agents are presented in Table 2.16,17 nary diagnosis because most pediatric cases of OP toxicity are
Pralidoxime is administered as a 1 to 2 g (20–40 mg/kg in pedi- due to unintentional poisoning with little exposure history in com-
atrics) intravenous load over 15 to 30 minutes to avoid vomiting, parison with adults.6,7 Therefore, high clinical suspicion and de-
tachycardia, and diastolic hypotension. The loading dose is tailed exposure history are important for diagnosis of OP toxicity.
followed by another dose 1 hour later. Subsequent doses are
given every 4 to 8 hours for the next 24 to 48 hours.14 REFERENCES
Unlike OPs, carbamates do not undergo aging. Thus, treat- 1. Shadnia KSS. History of the use and epidemiology of organophosphorus
ment with pralidoxime is not needed in the treatment of carbamate poisoning. In: Balali-Mood MA, Abdollahi M, eds. Basic and Clinical
poisoning. Carbamate toxicity is also generally of shorter duration Aspects of Organophosphorus Compounds Vol XII. London: Springer; 2014.
owing to reversible inhibition and rapid metabolism.18 A case se-
2. Syria chemical ‘attack’: What we know: BBC; 2017Available at: https://
ries determined that, although treatment with oximes in carbamate
www.bbc.com/news/world-middle-east-39500947. Accessed April 26, 2017.
toxicity was not beneficial, there appeared to be no harmful effects
of the reversal agent.19 Thus, in cases where it is unknown if the 3. Gummin DD, Mowry JB, Spyker DA, et al. 2016 Annual Report of the
insulting agent is a carbamate or an OP, it may be reasonable to American Association of Poison Control Centers' National Poison Data
give pralidoxime. System (NPDS): 34th annual report. Clin Toxicol (Phila). 2017;55:1072–1254.
Laboratory confirmation of OP poisoning includes plasma 4. Freeman NC, Jimenez M, Reed KJ, et al. Quantitative analysis of children's
AChE levels and red blood cell AChE levels. In our patient, both microactivity patterns: the Minnesota Children's Pesticide Exposure Study.
plasma and red blood cell (RBC) AchE levels were low, with J Expo Anal Environ Epidemiol. 2001;11:501–509.
progressively improving plasma AchE levels throughout his ad- 5. Lu C, Toepel K, Irish R, et al. Organic diets significantly lower children's
mission. Plasma cholinesterase levels measure the level of inhi- dietary exposure to organophosphorus pesticides. Environ Health Perspect.
bition of butyrylcholinesterase, an enzyme generated in the liver. 2006;114:260–263.
Organophosphates inhibit butyrylcholinesterase at much lower 6. Roberts JR, Karr CJ, Council on Environmental Health. Pesticide exposure
levels. Therefore, plasma cholinesterase is not a good indicator in children. Pediatrics. 2012;130:e1765–e1788.
of severity but can be used as an indicator of AChE regeneration 7. Levy-Khademi F, Tenenbaum AN, Wexler ID, et al. Unintentional
and OP elimination.20 Red blood cell AChE assays measure AChE organophosphate intoxication in children. Pediatr Emerg Care. 2007;23:
inhibition on the surface of RBCs in whole blood and can help de- 716–718.
termine the severity of the toxicity because enzyme activity can
8. Parvez Y, Mathew A, Kutti SK. Recurrent neonatal organophoshorus
only improve via erythropoiesis.20 Acetylcholinesterase regenera-
poisoning. Indian Pediatr. 2012;49:752–753.
tion rates in neuron synapses are unclear; therefore, it can be diffi-
cult to ascertain AChE activity during recovery with RBC AChE 9. Sofer S, Tal A, Shahak E. Carbamate and organophosphate poisoning in
assays. Another caveat with cholinesterase testing is that the sam- early childhood. Pediatr Emerg Care. 1989;5:222–225.
ple must be cooled immediately to prevent ongoing interac- 10. Lifshitz M, Shahak E, Sofer S. Carbamate and organophosphate poisoning
tions between organophosphorus, AChE, and oximes, which in young children. Pediatr Emerg Care. 1999;15:102–103.
may alter levels making the results unreliable.21 Because 11. Gonçalves AdS, França Tanos CC, Figueroa-Villar José D, et al.
plasma and RBC AChE levels are tests that need to be sent to Conformational Analysis of Toxogonine, TMB-4 and HI-6 using PM6 and
another institution, in our case, these laboratory values were RM1 methods. J Braz Chem Soc. 2010;21:179–184.

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12. Holstege CP, Dobmeier SG, Bechtel LK. Critical care toxicology. Emerg 18. King AM, Aaron CK. Organophosphate and carbamate poisoning. Emerg
Med Clin North Am. 2008;26:715–739, viii-ix. Med Clin North Am. 2015;33:133–151.
13. Jamal GA. Neurological syndromes of organophosphorus compounds. 19. Lifshitz M, Rotenberg M, Sofer S, et al. Carbamate poisoning and oxime
Adverse Drug React Toxicol Rev. 1997;16:133–170. treatment in children: a clinical and laboratory study. Pediatrics. 1994;93:
14. Rotenberg JS, Newmark J. Nerve agent attacks on children: diagnosis and 652–655.
management. Pediatrics. 2003;112:648–658. 20. Eddleston M, Roberts D, Buckley N. Management of severe
15. Farrar HC, Wells TG, Kearns GL. Use of continuous infusion of organophosphorus pesticide poisoning. Crit Care. 2002;6:259.
pralidoxime for treatment of organophosphate poisoning in children. 21. Eddleston M, Buckley NA, Eyer P, et al. Management of acute
J Pediatr. 1990;116:658–661. organophosphorus pesticide poisoning. Lancet. 2008;371:597–607.
16. Leikin JB, Thomas RG, Walter FG, et al. A review of nerve agent 22. Jokanovic M, Stukalov PV, Kosanovic M. Organophosphate induced
exposure for the critical care physician. Crit Care Med. 2002;30: delayed polyneuropathy. Curr Drug Targets CNS Neurol Disord. 2002;1:
2346–2354. 593–602.
17. Walter FG, Klein R, Thomas RG: Advanced hazmat life support provider 23. Clegg DJ, van Gemert M. Expert panel report of human studies on
manual. 2nd ed. Tucson, AZ: Arizona Board of Regents, 2000; chlorpyrifos and/or other organophosphate exposures. J Toxicol Environ
pp 279–304. Health B Crit Rev. 1999;2:257–279.

ILLUSTRATIVE CASE
Lazarus Syndrome — Challenges Created by

Pediatric Autoresuscitation
Stephen Mullen, MB, BAO, BCH,* Zöe Roberts, MBBS, MRCPCH,†
David Tuthill, MB, BCh, FRCPCH,‡ Laura Owens, MBBCh, MRCEM,† Johann Te Water Naude,‡
and Sabine Maguire, MBBCh, MRCPI, FRCPCH§
After stopping resuscitation, the medical team left the room,

Abstract: Pediatric autoresuscitation is extremely rare, with only 4 docu- and the family remained with the child accompanied by a staff
mented cases in the literature. The longest recorded time between stopping nurse. The monitors were turned off and the patient remained on
cardio pulmonary resuscitation (CPR) and return of spontaneous circulation the bed. The parents noted a small movement approximately
is 2 minutes. We report a previously well 18-month-old who attended the 6 minutes later. A further movement was noted prompting a reassess-
emergency department after an unexplained cardiac arrest. After 10 cycles ment at which time a pulse was palpable. The team was recalled,
of CPR, resuscitation was stopped; 6 minutes later, the patient had a return resuscitation recommenced with the patient in sinus at a rate of
of spontaneous circulation and was transferred to the pediatric intensive care 70 beats per minute. The patient was transferred to pediatric inten-
unit. The patient remains alive but with significant neurological impairment. sive care unit.
There are a variety of theories regarding the pathology of pediatric auto-
resuscitation. The most commonly accepted model is that there is a degree
of autopositive end-expiratory pressure impending venous return as a conse-
INVESTIGATIONS
quence of vigorous ventilation during CPR. This case challenges clinicians No conclusive etiology for cardiac arrest was identified, al-
to reassess our current definition of death and reaffirms the need for clearer though respiratory compromise was suspected. Before the cardiac
guidelines surrounding the certification of death. arrest, the patient was sitting in their car seat, and the parents
commented on a choking event occurring. Furthermore, the pa-
Key Words: ethics, general pediatrics, intensive care, neurology, tient was an ex-preterm, born at 24 weeks. They had a relatively
resuscitation uneventful neonatal course with no chronic lung disease or appar-
(Pediatr Emer Care 2021;37: e210–e211) ent neurological impairment. The patient had previously been
seen by ears, nose and throat as an outpatient owing to noisy
CASE breathing and diagnosed with mild laryngomalacia. Thirteen days
postarrest, the patient had a microlaryngobronchoscopy due to dif-
An 18-month-old male boy attended the emergency department ficulty in extubation. Granulation tissue was noted in the glottic
(ED) after an unexplained collapse. Cardiopulmonary resuscitation and subglottic area. The subglottic granulation tissue was causing
(CPR) was started at the scene and continued by the paramedic a mild stenosis and was excised.
crew and subsequently ED staff. The rhythm was asystole before The initial venous blood gas identified an elevated potassium
changing to pulseless electrical activity (broad complex bradycar- (6.7 mmol/L), but it was a difficult sample to obtain and was ac-
dia with the trace monitored through defibrillation pads and elec- quired at over 30 minutes from the initial collapse (this was treated
trodes). Resuscitation followed current resuscitation guidelines and subsequent levels were normal). Inflammatory markers, renal
(Paediatric Advanced Life Support, Resuscitation Council UK) function, liver function, and the remainder of the electrolytes were
with consideration given to potential reversible causes (ie, hypother- normal. Toxicology investigations were all negative. Computed
mia, hypoxia, hypotension, hypo/hyperkalaemia, toxins, tension tomography brain was performed an hour after admission and
pneumothorax, cardiac tamponade, thromboembolic). Pupils were did not identify any significant abnormalities. Magnetic resonance
size 3 and unreactive on arrival to ED. The patient was intubated imaging brain on day 3 postarrest identified significant changes
and ventilated using a bag-valve mask with pressure blow-off in keeping with a hypoxic-ischemic event.
valve with end tidal CO2 monitoring. After 10 cycles of CPR with A child protection evaluation did not identify any concerns:
5 doses of intravenous adrenaline, CPR was ceased with the investigations were normal, and there was no prior involvement
agreement of the entire resuscitation team (including 3 consul- by Children's Social Services.
tants) in keeping with current guidelines. No echocardiography
was performed during the resuscitation. There was no sign of life,
no palpable pulse (carotid or femoral), no response to painful
OUTCOME
stimulus, and no pupillary response to light. Corneal reflex or The patient survived, although with significant cerebral im-
gag reflex was not assessed at this time. pairment and was extubated on day 4. The child has significant
hypertonia, has seizures, and is unable to communicate or swal-
low. The family has reviewed this article before publication.
From the *Paediatric Emergency Department, Royal Belfast Hospital for
Sick Children, Belfast, N. Ireland; †Paediatric Emergency Department, DISCUSSION
and ‡Noah's Arc Children's Hospital, University Hospital of Wales; and §Divi-
sion of Population Medicine, School of Medicine, Cardiff University, Cardiff,
Lazarus syndrome, named from the biblical story, or
Wales, United Kingdom. autoresuscitation, is defined as a delayed return of spontaneous
Disclosure: The authors declare no conflict of interest. circulation (ROSC) after cessation of CPR.1 This phenomenon
Reprints: Stephen Mullen, MB, BAO, BCH, Paediatric Emergency Department, is rare, with 49 cases documented in a literature review in 20142
University Hospital of Wales, Cardiff, Wales, United Kingdom
(e‐mail: smullen001@gmail.com).
and a further 10 noted in an updated review in 2018.3 Four pedi-
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. atric cases have been published.4–6 Of the 4 cases, ROSC returned
ISSN: 0749-5161 between 30 seconds to 2 minutes after stopping CPR.4–6 In our

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Lazarus Syndrome
case, the time frame of 6 minutes would make this the longest doc- 6 minutes postterminating CPR, a palpable pulse and movements
umented pediatric case. Adult cases have been reported to have were noted. The clinical question turns significantly at this point
ROSC up to 10 minutes after CPR.3 and in this scenario becomes “when is someone deemed alive fol-
None of the previously reported pediatric cases had a favor- lowing a cardiac arrest?” Does a palpable pulse in isolation signify
able outcome. For 3 patients, care was withdrawn either immedi- life? When combined with movement, despite no response to
ately or within the first few days postarrest. The fourth survived painful stimulus or pupillary response, is this enough to warrant
for approximately 5 months but passed away in the setting of di- recommencing active support? Are these movements a sign of life
lated cardiomyopathy. In our case, the child is alive 1 year after or simply a feature of spinal reflexes?
this event but has been left with severe neurological sequelae, with In this case, the actions taken followed current resuscitation
a significant effect on both his and his family's quality of life. guidelines; CPR was started in a bid to regain a cardiac output
The role of bedside ultrasound or cardiac echo in pediatric and signs of life, which when obtained were acted upon. The fam-
cardiac arrests remains unclear. Supporters would suggest that it ily was consulted, and a decision was reached for intensive care,
has the potential to rapidly identify tamponade, tension pneumo- with the patient remaining alive to date, although with a poor neu-
thorax, thromboembolism, and hypovolemia using predominantly rological outcome. However, this is not a universally held view,
adult studies to back up their conclusions.7 The evidence in pediat- with those supporting a more neurological certification of death
ric cardiac arrest is lacking and limited to case series and reports.8 stating their belief that death is not a singular event but a process.
To date, neither Advanced Paediatric Lift Support, the European This debate highlights the need for revisiting the national policy
Resuscitation Council Guidelines, or the American Heart Associa- on certification of death, which includes rare and challenging scenar-
tion Guideline suggests the use of bedside echo in pediatric ios like the one encountered in this case. Furthermore, as mentioned
cardiac arrest.9,10 in previous publications on the same topic, consideration should be
The physiological theories surrounding autoresuscitation vary given to how these cases may impact on organ donation protocols.6
with no universally accepted mechanism. Adult physicians postu-
late a role for hyperkalemia, myocardial stunning postinfarction,
or hyperventilation. For those cases involving children, hyperven-
tilation appears to be the most consistent etiology proposed. The REFERENCES
hyperventilation hypothesis is based on a degree of autopositive 1. Adhiyaman V, Adhiyaman S, Sundaram R. The Lazarus Phenomenon.
end-expiratory pressure, as a result of vigorous ventilation during J R Soc Med. 2007;100:552–557.
CPR. The resulting increase in intrathoracic pressure compresses 2. Ballesteros PS, Aedo IF, Palomino SL. Spontaneous return of circulation
the vena cava and other large thoracic vessels, reducing venous re- after termination of cardiopulmonary resuscitation maneuvers: a systematic
turn, and thus cardiac output. This may also impact the distribu- review of cases of Lazarus phenomenon. Emergencias. 2014;26:307–316.
tion and thus the effect of resuscitation drugs. When CPR is
3. Hornby L, Dhanani S, Shemie SD. Update of a systematic review of
terminated, the reduction in intrathoracic pressure allows venous
autoresuscitation after cardiac arrest. Crit Care Med. 2018;46:e268–e272.
return and potentially ROSC.
The most profound question this case raises surrounds the 4. Cummings BM, Noviski N. Autoresuscitation in a child: the young
definition of death. There is no internationally accepted diagnosis Lazarus. Resuscitation. 2011;82:134.
of death. In the United Kingdom, guidance was issued in 2008 by 5. Duff JP, Joffe AR, Sevcik W, et al. Autoresuscitation after pediatric cardiac
the Academy of Medical Royal Colleges.11 In this document, arrest: is hyperventilation a cause? Pediatr Emerg Care. 2011;27:208–209.
death is defined as “the irreversible loss of those essential charac- 6. Tretter JT, Radunsky GS, Rogers DJ, et al. A pediatric case of
teristics which are necessary to the existence of a living human autoresuscitation. Pediatr Emerg Care. 2015;31:138–139.
person and, thus, the definition of death should be regarded as the 7. Doniger SJ. Bedside emergency cardiac ultrasound in children. Journal
irreversible loss of the capacity for consciousness, combined with of Emergencies, Trauma and Shock. 2010;3:282–291.
irreversible loss of the capacity to breathe.”
8. Marin JR, Abo AM, Arroyo AC, et al. Pediatric emergency medicine
The document addresses many key principles surrounding
point-of-care ultrasound: summary of the evidence. Crit Ultrasound J.
the process of death. 2016;8:16.
It acknowledges that, although there is no legal definition of
death, the courts have adopted the brain-stem death criteria into 9. Maconochie IK, Bingham R, Eich C, et al. European Resuscitation Council
law. In the case of cardiopulmonary arrest, death can be confirmed Guidelines for Resuscitation 2015. Paediatric life support. Resuscitation.
2015;95:223–248.
if irreversible cessation of neurological (pupillary), cardiac, and
respiratory activity has occurred. 10. Atkins DL, Berger S, Duff JP, et al. Part 11: Pediatric Basic Life Support
The guidelines further state that the individual should be ob- and Cardiopulmonary Resuscitation Quality: 2015 American Heart
served by the person responsible for confirming death for a mini- Association Guidelines Update for Cardiopulmonary Resuscitation and
mum of 5 minutes to establish that irreversible cardiorespiratory Emergency Cardiovascular Care. Circulation. 2015;132(18 suppl 2):
arrest has occurred, although it fails to clarify the manner in which S519–S525, originally published October 14, 2015.
the patient is observed. If there is a spontaneous return of a pulse 11. Academy of Medical Royal Colleges. A Code of Practice for the Diagnosis
or respiratory effort, a further 5-minute period of observation and Confirmation of Death. Published Online on October 8, 2010.
should occur. It is unclear from the passage whether this 5-minute Available at: http://aomrc.org.uk/wp-content/uploads/2016/04/Code_
period is only for observation or active resuscitation. After a further Practice_Confirmation_Diagnosis_Death_1008-4.pdf. Accessed
5-minute period of cardiopulmonary arrest, the patient should be February 2018.
reassessed for pupillary response, corneal reflex, and response 12. Maleck WH, Piper SN, Triem J, et al. Unexpected return of spontaneous
to supraorbital pain. Death is then confirmed if all remain absent. circulation after cessation of resuscitation (Lazarus phenomenon).
Other guidelines recommend a 10-minute period before reassess- Resuscitation. 1998;39:125–128.
ment and confirmation of death.1,12,13 13. Kuisma M, Salo A, Puolakka J, et al. Delayed return of spontaneous
From the definition of death noted previously, our patient circulation (the Lazarus phenomenon) after cessation of out-of-hospital
may have met the legal criteria to be certified as dead. However, cardiopulmonary resuscitation. Resuscitation. 2017;118:107–111.

ILLUSTRATIVE CASE
UnBeelievable
A Case of Pediatric Myocarditis After Insect Envenomation
Simon Chi, DO and Jacqueline Le, MD
additionally felt a sensation of “coldness” in his chest when

Abstract: There are numerous case studies describing myocarditis lying down. On the morning of presentation to the emergency
and cardiac events in adults after insect envenomation. To our knowledge, department, he woke up with diffuse, constant, stabbing chest
there are no similar cases documented in children. We report a unique case pain that radiated to his bilateral arms. The chest pain improved
of a 14-year-old adolescent boy who developed acute myocarditis after a with lying flat but was worse with deep breaths, walking, and
bee sting. The pathophysiology involving envenomation and myocarditis standing. The patient denied any fevers, cough, vomiting, dizziness,
remains poorly understood. or syncope.
Key Words: arthropod envenomation, honeybee sting, myocarditis, On presentation, his vital signs were as follows: temperature,
pericarditis, perimyocarditis, anaphylaxis, hypersensitivity, hymenoptera, 37.3°C; blood pressure, 134/88 mm Hg; heart rate, 105 beats
Kounis syndrome per minute; respiratory rate, 16 beats per minute; and oxygen
saturation, 100% on room air. Physical examination revealed
a nontoxic, age-appropriate male in no acute distress. His cardiac
examination was tachycardic without murmurs or rubs, and chest
CASE wall was tender to palpation. Lungs were clear without retractions
A 14-year-old previously healthy Hispanic adolescent boy or accessory muscle use. His extremities were nonedematous with
presented to the emergency department with chief complaint of normal radial and dorsalis pedis pulses. He had no rashes or other
bee sting to the left scalp 2 days ago. He described a constella- abnormal findings on examination.
tion of symptoms as a result of the envenomation. One day ago, Initial electrocardiogram (ECG) was significant for sinus
he experienced stabbing pain in his left knee and thigh. He tachycardia and ST segment elevation in the anterolateral and
FIGURE 1. Initial ECG obtained at 1025 hours, demonstrating sinus tachycardia and ST segment elevation in the anterolateral and inferior
leads, diffuse PR segment depression, PR segment elevation in lead aVR, and ST segment depression in lead V1.
inferior leads, diffuse PR segment depression, PR segment ele-

From Desert Regional Medical Center, Palm Springs, CA. vation in lead aVR, and ST segment depression in V1 (Fig. 1).
Disclosure: The authors declare no conflict of interest. These findings prompted laboratory testing and urgent cardiol-
Reprints: Simon Chi, DO, Desert Regional Medical Center, 1150 North Indian
Canyon Dr, CA, 92262 (e‐mail: simon.chi.86@gmail.com).
ogy consult. The pediatric cardiologist interpreted the ECG as
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. early repolarization and recommended 2 sets of cardiac bio-
ISSN: 0749-5161 markers, C-reactive protein, erythrocyte sedimentation rate, and

Pediatric Emergency Care • Volume 37, Number 4, April 2021 UnBeelievable
FIGURE 2. Subsequent ECG obtained at 1207 hours, demonstrating new absence of ST segment depression in lead V1, and new abnormality
of ST segment elevation in V2.
acetaminophen for pain control. Laboratory data revealed ele- Our patient developed acute myocarditis after a bee sting.
vated troponin of 5.39 ng/mL, creatine kinase MB isoenzyme of The pathophysiology behind insect envenomation and myocar-
21.6 ng/mL, and myoglobin of 207.5 ng/mL. Erythrocyte sedi- ditis is unclear.3 Several sources hypothesize cardiotoxicity
mentation rate was 2 mm/h and C-reactive protein was elevated from envenomation, Kounis syndrome (cardiovascular event
at 29.2 mg/L. Complete blood count showed the following: white from allergy or anaphylaxis), Takotsubo cardiomyopathy, or
blood cell count, 16.1 109/L; hemoglobin, 15.6 g/L; hematocrit, any combination of these events. 4–6 A literature search for
46.6%; and platelets, 256 109/L. Basic metabolic panel and instances of cardiac events after insect envenomation yielded
urine drug screen was unremarkable. Chest radiography was nor- only adult cases of cardiac pathology after envenomation, in-
mal without cardiomegaly. A repeat ECG performed 90 minutes cluding type I atrioventricular block, myopericarditis, and
later was similar to the first, except that the ST segment depres- myocardial infarction.3–5,7–9 The most comparable cases reported
sion in lead V1 was no longer present and new ST segment eleva- in the pediatric population were not of insect envenomation but
tion was seen in lead V2 (Fig. 2). Our overall concern for possible involved arachnid envenomation and M. pneumoniae
acute myopericarditis prompted us to transfer the patient to a infection.6,10–12 Although our patient had a positive Mycoplamsa
tertiary care pediatric facility for admission and further evaluation pneumoniae antibody screen, he did not acutely present with any
and treatment. infectious complaints.
The patient underwent a 5-day hospital course. His echo-
cardiogram showed mild left ventricular dilatation and dimin- CONCLUSIONS
ished left ventricular ejection fraction (50%) and systolic function This is the first reported pediatric case of insect envenom-
(26%). Subsequent cardiac magnetic resonance imaging dem- ation triggering subsequent cardiac pathology. The patient's
onstrated mild myocardial edema involving the apical segments clinical presentation and results of his diagnostic studies were
with corresponding hyperemia, suggestive of acute myocarditis. consistent with acute myocarditis. Given the close proximity
Infectious work-up revealed positive titers for Mycoplasma in time of the bee sting to the presenting chest pain, we believe
pneumoniae IgM and IgG antibodies. He was started on a that the envenomation was the key inciting event for his
milrinone infusion and intravenous immunoglobulin. His chest acute myocarditis.
pain resolved shortly after admission, and he was eventually
discharged on a medication regimen of azithromycin, carve-
REFERENCES
dilol, spironolactone, enalapril, aspirin, and ibuprofen.
1. Ghelani SJ, Spaeder MC, Pastor W, et al. Demographics, trends, and
outcomes in pediatric acute myocarditis in the United States, 2006 to 2011.
DISCUSSION Circ Cardiovasc Qual Outcomes. 2012;5:622–627.
Myocarditis is a rare condition in the pediatric population.1 2. Canter CE, Simpson KE. Diagnosis and treatment of myocarditis in
The most common causes of myocarditis are infectious in etiology children in the current era. Circulation. 2014;129:115–128.
and include coxsackie B, adenovirus, influenza, hepatitis B virus, 3. Vishwanath P, Adhikari D, Akila P, et al. Myocarditis and mobitz type I
β-hemolytic streptococcus, M. pneumoniae, mumps, cytomegalo- heart block following wasp sting. Internet J Cardiol. 2009;8.
virus, Toxoplasma, Chagas disease, Trichinella, Corynebacterium 4. Aminiahidashti H, Laali A, Samakoosh AK, et al. Myocardial infarction
diphtheriae, and Lyme disease.2 Drug etiologies include doxoru- following a bee sting: a case report of Kounis syndrome. Ann Card
bicin and cocaine. Anaesth. 2016;19:375–378.

Chi and Le Pediatric Emergency Care • Volume 37, Number 4, April 2021
5. Scherbak D, Lazkani M, Sparacino N, et al. Kounis syndrome: a stinging 9. Yang HP, Chen FC, Chen CC, et al. Manifestations mimicking acute
case of ST-elevation myocardial infarction. Heart Lung Circ. 2015;24: myocardial infarction after honeybee sting. Acta Cardiol Sin. 2009;25:31–35.
e48–e50. 10. Formosa GM, Bailey M, Barbara C, et al. Mycoplasma pneumonia – an
6. Yaman M, Mete T, Ozer I, et al. Reversible myocarditis and pericarditis unusual cause of acute myocarditis in childhood. Images Paediatr Cardiol.
after black widow spider bite or Kounis syndrome? Case Rep Cardiol. 2006;8:7–10.
2015;2015:768089. 11. Park IH, Choi DY, Oh YK, et al. A case of acute myopericarditis associated
7. Dinamithra NP, Sivansuthan S. Giant Asian honeybee stings induced acute with Mycoplasma pneumonia infection in a child. Korean Circ J. 2012;42:
myocarditis: a case report. Anuradhapura Medical Journal. 2013;7:12–15. 709–713.
8. Puvanalingam A, Karpagam P, Sundar C, et al. Myocardial infarction 12. Agarwala BN, Ruschhaupt DG. Complete heart block from mycoplasma
following bee sting. J Assoc Physicians India. 2014;62:738–740. pneumonia infection. Pediatr Cardiol. 1991;12:233–236.

ILLUSTRATIVE CASE
Coccygodynia Due to a Sacrococcygeal Anomaly

A Rare Cause of Constipation
Paula García Sánchez, MD,* María de Ceano Vivas la Calle, MD,* Julia Martín Sánchez, MD,*
Miguel Ángel Molina Gutiérrez, PhD,* Ana Pérez Vigara, MD,† and Leopoldo Martínez Martínez, PhD‡
abnormalities. In the first years of life, she was diagnosed with relative
Abstract: We report a case of an uncommon sacrococcygeal anomaly in a anal stenosis, which was treated with Hegar dilators until she was
healthy girl initially presenting to the emergency department with coccygodynia 3 years old without improvement. Percentiles of weight and height
and a past history of longstanding constipation. The clinical evolution was were stable in p25-p50 during infancy. Afterward, the diagnosis of
satisfactory once the bony anomaly was removed (coccygectomy). This functional constipation was established according to the Roma III
unusual case exemplifies the importance of the medical history and phys- criteria, as the patient reported 3 defecations per week, straining
ical examination to make an accurate diagnosis. An inadequate interven- in >25% of defecations, hard stools in >25% of defecations, sensa-
tion may result in persistent pain, worsening longstanding constipation, tion of anorectal obstruction in >25% of defecations, and some ep-
and psychosocial and medical consequences. isodes of mild rectal bleeding.
Key Words: coccygodynia, sacrococcygeal anomaly, coccygectomy, Physical examination revealed a well-appearing girl with nor-
organic constipation mal vital constants, a weight of 50 kg (p42), and a height of 1.61 m
(p65). Her abdomen was soft, nondistended, with palpable stool.
She referred pain when coccyx was examined, but there were no
local skin lesions. The digital anorectal examination revealed a
C occygodynia is defined as the presence of pain in the coccyx.
It is also referred to as coccydynia or tailbone pain. It exacer-
bates with any increase of pressure, such as defecation, sexual ac-
slightly patulous rectum full of stool with an adequate anal tone
and the coccyx clearly protruding in the posterior wall just above
dentate line. No abdominal or pelvis masses were palpable, and no
tivity, sitting position, or transitioning from sitting to standing.
anorectal malformations were found.
The etiology is broad, with the most common causes being related
Anteroposterior and lateral sacrococcygeal radiographs were
to trauma. Rare abnormalities of the sacrum and coccyx may ex-
obtained, showing an angular coccyx of almost 90 degrees (Fig. 1).
plain some cases of coccygodynia.1–3
Considering this abnormality, the patient was referred to the
Constipation represents a common problem throughout child-
pediatric surgery department. A magnetic resonance imaging (MRI)
hood and a frequent symptom in those visiting the emergency depart-
was performed to rule out any other abnormalities. The MRI showed
ment (ED).4–6 Although functional constipation represents more than
an anterior curvature of the fifth sacrum vertebra and confirmed an
95% of cases, organic causes like endocrine and metabolic diseases,
angle of almost 90 degrees in the first coccygeal vertebra. The rest
neurologic disorders, or anorectal or anatomic anomalies must be
of vertebrae were normal. Presacral or pelvic masses were not present
recognized by ED pediatricians. A focused history and a physical
(Fig. 2).
examination are essential at the first evaluation.7–10
The patient was admitted for schedule surgery, and the coc-
We describe a case of a 13-year-old girl who presented to the
cygeal bone was removed without incidents (coccygectomy).
ED with coccygodynia and a past history of longstanding constipa-
After a follow-up period of 1½ year, she referred a complete
tion. Imaging examinations revealed a sacrococcygeal anomaly.
resolution of coccygodynia and constipation (she reported a bowel
The patient was referred to the department of pediatric surgery,
habit of 1–2 soft stools daily).
and she experienced a noticeable improvement after coccygectomy.
CASE DISCUSSION
A 13-year-old girl presented to the ED with 7-day history of This case illustrates how a rare sacrococcygeal anomaly may
worsening coccygodynia. She referred pain since she was 11 years be responsible of coccygodynia and may explain a longstanding
old, that had got much worse during the last week. She reported in- constipation. Similar cases have not been reported in the literature.
creased pain with defecation and in the seated position. No traumatic It also exemplifies the fact that a focused history and an exhaus-
antecedent was referred. She denied fever or urinary infections. tive physical examination remain key for the accurate diagnosis.
Her past medical history included a delayed passage of meco- Our patient presented to the ED with two symptoms: first, a
nium and a history of chronic constipation treated by her pediatrician, worsening coccygodynia, which increased with defecation and in
the gastroenterology department, and the pediatric surgery department. the seated position, and second, a persistent constipation despite
She was treated with different laxatives with partial improvement dur- different treatments. The digital anorectal examination revealed a
ing her childhood. Initially, a contrast enema was performed with no coccyx clearly protruding in the posterior wall. Clinical suspicion
of a bony abnormality was essential to stablish the final diagnosis.
In the literature, several authors have reported sacrococcygeal
From the *Pediatric Emergency Department, †Pediatric Department of Radi-
ology, and ‡Department of Pediatric Surgery, La Paz University Hospital,
anomalies responsible for coccygodynia, such as sacrococcygeal
Madrid, Spain. ribs, human pseudotails, or excessive curvature of the coccyx.11–13
Disclosure: The authors declare no conflict of interest. Some of them could be explained by failure of formation or seg-
Reprints: Paula García Sánchez, MD, Pediatric Emergency Department, La Paz mentation of coccygeal vertebrae.12
University Hospital, Paseo de la Castellana 261, 28046, Madrid, Spain
(e‐mail: paula.garsa@gmail.com).
Referred to the configuration of the coccyx, Postacchini and
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. Massobrio14 classified the coccygeal bone in 4 types, being types
ISSN: 0749-5161 II to IV more prone to become painful:

García Sánchez et al Pediatric Emergency Care • Volume 37, Number 4, April 2021
– Type I: the coccyx is curved slightly forward, with its apex

pointing caudally.
– Type II: the coccyx is pointing straight forward, and the curve
is more marked.
– Type III: the coccyx is sharply angulated forward between the
first and second or the second and third segments.
– Type IV: the coccyx is subluxated anteriorly at the level of the
sacrococcygeal joint or at the level of the first or second
intercoccygeal joints, like in our patient.
Constipation occurs when there is an abnormally delayed or
infrequent passage of hard stools accompanied by excessive straining
or pain.9 The diagnosis supposes a challenge to ED pediatricians, par- FIGURE 2. Abdominal and pelvic MRI (sagittal and axial planes):
ticularly when constipation is persistent or it is accompanied by other anterior curvature of the fifth sacrum vertebra with an angle of
symptoms; in these cases, the possibility of organic causes, such as almost 90 degrees in the first coccygeal vertebra. The rest of
endocrine and metabolic diseases, neurologic disorders, or anorectal vertebrae are normal. No presacral or pelvic masses are identified.
or anatomic anomalies, should be taken into consideration.6,8,9 Rectum presents a disposition similar to coccyx.
Although functional constipation is responsible for more than
95% of cases of constipation in children and additional examina- In our case, surgical resection of the whole coccyx was suc-
tions are seldom necessary, all patients should be examined to cessful and all symptoms of the patient disappeared. An inadequate
identify those few with an organic etiology.7 intervention may result in persistent coccygodynia, worsening con-
Once again, a focused history and physical examination are stipation, and psychosocial and medical consequences.2,19
essential at the first evaluation.7,9,10 The main data that should be
collected are age at presentation, passage of meconium, frequency,
consistency and size of stools, medications, usual diet, family and CONCLUSIONS
psychosocial history, and presence of alarm signs (rectal bleeding, A focused history and an exhaustive physical examination
vomiting, weight loss, urinary incontinence, extraintestinal symp- are essential to make a proper diagnosis. Coccygodynia may be
toms…). Important aspects of the physical examination include explained by sacrum or coccyx anomalies, and surgical interven-
the abdominal examination, perianal inspection, anorectal digital tion could be necessary for resolution. Although most cases of
examination, and an exhaustive neurological examination. constipation in children are functional, there is a small percentage
In summary, our patient presented a longstanding constipa- of organic causes which should be identified to prevent complica-
tion probably due to a sacrococcygeal anomaly responsible for tions. An inadequate intervention may result in persistent pain, wors-
coccygodynia with a complete resolution after surgical intervention ening constipation, and psychosocial and medical consequences.
(coccygectomy). In this particular case, it is interesting to underline
the ability of the ED pediatrician to request for a sacrococcygeal REFERENCES
radiograph, suspecting a bony malformation or a presacral mass
1. Foye PM. Coccydynia: tailbone pain. Phys Med Rehabil Clin N Am. 2017;
after anorectal digital examination. Other anomalies associated
28:539–549.
to Currarino syndrome,15–18 a triad composed by sacral malfor-
mation, presacral mass, and anorectal malformation, were later 2. Pennekamp PH, Kraft CN, Stütz A, et al. Coccygectomy for coccygodynia:
discarded by MRI. does pathogenesis matter? J Trauma. 2005;59:1414–1419.
3. Baba-Rasul I, Hama Ameen HM, Khazendar A, et al. A rare case of isolated
lower segment transverse sacral fracture in a 12-year-old girl and its management
by fixation with K-wire. World Neurosurg. 2017;97:758.e1–758.e5.
4. Freedman SB, Thull-Freedman J, Rumantir M, et al. Pediatric constipation
in the emergency department: evaluation, treatment, and outcomes.
J Pediatr Gastroenterol Nutr. 2014;59:327–333.
5. McBride D. Childhood constipation in the emergency department.
J Pediatr Nurs. 2013;28:502–503.
6. Chumpitazi C, Rees CA, Camp EA, et al. Diagnostic approach to
constipation impacts pediatric emergency department disposition. Am J
Emerg Med. 2017;35:1490–1493.
7. Sood MR. Constipation in infants and children: evaluation. Up to Date,
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Gastroenterology, Hepatology, and Nutrition; North American Society for
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in infants and children: evidence-based recommendations from ESPGHAN and
NASPGHAN. J Pediatr Gastroenterol Nutr. 2014;58:258–274.
9. Madani S, Tsang L, Kamat D. Constipation in children: a practical review.
Pediatr Ann. 2016;45:e189–e196.
10. Montgomery DF, Navarro F. Management of constipation and encopresis in
children. J Pediatr Health Care. 2008;22:199–204.
FIGURE 1. Anteroposterior and lateral radiographs of the
sacrococcygeal area demonstrating a 90-degree anterior 11. Miyakoshi N, Kobayashi A, Hongo M, et al. Sacral rib: an uncommon
curvature of coccyx. congenital anomaly. Spine J. 2015;15:e35–e38.

Pediatric Emergency Care • Volume 37, Number 4, April 2021 Coccygodynia Due to a Sacrococcygeal Anomaly
12. Hamoud K, Abbas J. A tale of pseudo tail. Spine (Phila Pa 1976). 2011;19: 16. Vargas-González R, Paniagua Morgan F, Victoria G, et al. Currarino
E1281–E1284. syndrome. A rare cause of severe constipation. Case report and literature
13. Turk CC, Kara NN, Bacanli A. The human tail: a simple skin appendage or review. Rev Gastroenterol Mex. 2008;73:80–84.
cutaneous stigma of an anomaly? Turk Neurosurg. 2016;26:140–145. 17. Calleja Aguayo E, Estors Sastre B, Bragagnini Rodríguez P, et al. Currarino
14. Postacchini F, Massobrio M. Idiopathic coccygodynia. Analysis of triad: different forms of presentation. Cir Pediatr. 2012;25:155–158.
fifty-one operative cases and a radiographic study of the normal coccyx. 18. Phipps KD, Wrogemann J, El-Matary W. A rare cause of chronic
J Bone Joint Surg Am. 1983;65:1116–1124. constipation. Gastroenterology. 2016;150:1090–1091.
15. Duru S, Karabagli H, Turkoglu E, et al. Currarino syndrome: report of five 19. Tobias N, Mason D, Lutkenhoff M, et al. Management principles of organic
consecutive patients. Childs Nerv Syst. 2004;30:547–552. causes of childhood constipation. J Pediatr Health Care. 2008;22:12–23.

LETTER TO THE EDITORS
Statistics Should Be associated with COVID-19. In the absence Children’s Hospital

of effective antivirals, corticosteroids have Hong Kong
Carefully Interpreted a role to play in the treatment of critically ehon@hotmail.com
Vitamin K for Newborn ill patients, namely, to ameliorate the inflam-
Hemorrhages and Steroids matory response and possibly decrease the
progression to fibrosis in those who develop
for COVID-19 acute respiratory distress syndrome. Disclosure: The authors have no con-
During this COVID-19 pandemic, the flicts of interest to disclose. All authors
sheer number of research generated has been have full access to the data, contributed to
To the Editors: increasing exponentially and there are the study, approved the final version for
publication, and take responsibility for its
P ediatricians vividly remember the chaos
caused by the 1992 article that vitamin
K injections to newborns were statistically
now more than 35,000 academic articles
on COVID-19 in less than 6 months.8 With
the intention to publish potentially ground-
accuracy and integrity.
All authors contributed to the follow-
associated with later childhood cancers. breaking findings as soon as possible, some ing items (1) concept or design, (2) acquisi-
Vitamin K is known to be effective in results and conclusions are published online tion of data, (3) analysis or interpretation
preventing both early hemorrhagic disease and cited by other researchers before the peer of data, (4) drafting of the manuscript,
in neonates and late-onset bleeding in young review process. There have been a number of and (5) critical revision for important intel-
infants, whereas intramuscular injection is retracted COVID-19 publications, including lectual content.
more effective than oral administration.1,2 2 articles from 2 prestigious peer-reviewed
Concerns about the administration of intra- journals, which were published by the same
muscular vitamin K were raised by Golding research group using the same international
et al3 associating intramuscular, but not oral, registry.9 Although the articles were subse- REFERENCES
vitamin K with childhood leukemia. Since quently retracted, inevitably, there have been 1. Zipursky A. Prevention of vitamin K deficiency
then, most research has failed to find any unintended consequences, because clinical bleeding in newborns. Br J Haematol. 1999;104:
statistically significant associations that neo- trials were temporarily halted, some of the 430–7.
natal vitamin K administration, irrespective patients might already have lost trust in 2. Controversies Concerning Vitamin K and the
of the route of administration, influences these treatments, and the clinical decisions Newborn. American Academy of Pediatrics
the risk of childhood leukemia or cancer.1,4 and outcomes of COVID-19 patients may Committee on Fetus and Newborn - PubMed.
Now with COVID-19, scientists are have been altered. Available at: https://pubmed.ncbi.nlm.nih.gov/
working hard to find a cure and contain The vitamin K saga in 1992 caused 12837888/. Accessed June 23, 2020.
the pandemic.5 In the early innings of the major issues worldwide because pediatri- 3. Golding J, Greenwood R, Birmingham K, Mott
pandemic, Russell et al6 tabulated a number cians did not know what to give and how M. Childhood cancer, intramuscular vitamin K,
of irrelevant observational clinical studies to advise new mothers how they could pro- and pethidine given during labour. BMJ. 1992;
and ill-founded statistics, cautioning that tect their newborns from the potentially 305:341–6.
corticosteroids would cause more harm than deadly but easily preventable condition,
benefit. Without strong clinical and statisti- 4. Roman E, Fear NT, Ansell P, et al. Vitamin K and
all because of a published report based on
cal evidence to support their use then, the childhood cancer: analysis of individual patient
ill-founded statistics. After 28 years, the en- data from six case-control studies. Br J Cancer.
World Health Organization issued a state- during effects of this research finding are 2002;86:63–9.
ment against corticosteroid usage amidst still influencing parents' decision on the ad-
escalating mortality. Although we acknowl- ministration of vitamin K to their newborn 5. Hon KLE, Leung KKY. Pediatric COVID-19:
edge the potential risks of the high-dose what disease is this? World J Pediatr. 2020;16:
babies. Then and now, the evidence for
corticosteroids when treating COVID-2019 323–5.
the beneficial effects of steroids for severe
pneumonia and agree that corticosteroids cases came perhaps too late, whereas con- 6. Leung KKY, Hon KL, Qian S, et al. Contrasting
should be used judiciously, a short course jecture and poor statistics came too soon. evidence for corticosteroid treatment for
of corticosteroids at a low-to-moderate dose As humble clinicians, we remind enthusi- coronavirus-induced cytokine storm. Hong Kong
is probably justifiable for critically ill patients astic researchers and journal editors to be Med J. 2020;26:269–271.
with hyperinflammation.6 Recently, the latest cognizant of unintended real-world conse- 7. Horby P, Lim WS, Emberson J, et al.
clinical evidence suggests that corticosteroids, quences that come with publications and Effect of dexamethasone in hospitalized
the panacea for severe autoinflammatory cyto- handle the double-edged sword of statistics patients with COVID-19: preliminary.
kine release syndrome (which is probably with extreme care. Report medRxiv. 2020.
similar to the pathophysiological mecha- This research received no specific grant 8. World Health Organisation. COVID-19 Global
nism for COVID-19) can improve survival from any funding agency in the public, com- literature on coronavirus disease. 2020. Available
and reduce deaths by up to one third in ven- mercial, or not-for-profit sectors. at: https://search.bvsalud.org/global-literature-
tilated patients.7 on-novel-coronavirus-2019-ncov/. Accessed
In the absence of randomized clinical June 24, 2020.
trials, intensivists can either provide sup- Karen Ka Yan Leung, MBBS 9. Mehra MR, Desai SS, Kuy S, et al. Retraction:
portive treatment (almost none of which MRCPCH cardiovascular disease, drug therapy, and
are supported by randomized controlled trials), Kam Lun Ellis Hon, MBBS, MD mortality in Covid-19. N Engl J Med.
or treat patients on the basis of the patho- Department of Paediatrics and Adolescent DOI: 10.1056/NEJMoa2007621. N Engl J
physiology of hyperinflammatory syndrome Medicine, The Hong Kong Med. 2020;382:2582.

LETTER TO THE EDITORS
“Second Wave” of and epidemiological characteristics of all Daniel Mata Zubillaga, MD, PhD
patients (Table 1). Department of Paediatrics. Hospital Vital
COVID-19 Pandemic During the “second wave,” coincid- Álvarez Buylla. Servicio de Salud de
Admittance on Pediatric ing with the onset of the state of alarm, Principado de Asturias, Mieres del Camino
Emergency Department of a we have observed a significant decrease Av. del Camino, 1B, 33619 Santullano
in the use of the pediatric emergency de- Asturias, Spain
Regional Hospital From North partment by the population, as in the first dmatzub@yahoo.es
of Spain During State of Alarm half of the year. This decrease has been
progressively accentuated during the pre- Lara Gloria González García, MD
vious weeks. The distribution of patients Cristina García Aparicio, MD
by sex and age has been similar. The Ana Elisa Laso Alonso, MD
greatest decrease in incidence was observed Silvia Rodríguez Manchón, MD
To the Editors: in infectious processes and their complica- Sara Corral Hospital, MD
D uring 2020, the COVID-19 pandemic

situation declared on March 11, 2020,
by the World Health Organization has been
tions. However, assistance to patients with
febrile syndrome has increased consider-
ably, which has led to an increase in the
Department of Paediatrics. Hospital Vital
Álvarez Buylla. Servicio de Salud de
Principado de Asturias
maintained. On October 25, 2020, a state of use of diagnostic tests. Unlike the “first Asturias, Spain
alarm was declared in Spain (Real Decreto wave,” the number of chest X-rays has been
926/2020) in the face of the so-called “second the usual. The number of admissions has
wave” of the pandemic. There have been been the same. Disclosure: The authors declare no
multiple measures taken to reduce the trans- As previously stated, we consider that conflict of interest.
mission of the virus. However, home con- fear of contagion has once again been a de-
finement has not been applied, and activity cisive factor.1 This same fear has caused the REFERENCES
has been maintained in schools. increase in consultations for fever in order 1. González García LG, Rodríguez Manchón S, Mata
In the “first wave,” we found a clear to rule out COVID-19. In primary care cen- Zubillaga D, et al. Impact of admittance of children
decrease in the attendance to pediatric emer- ters, the telephone assistance network has on emergency department of a regional hospital from
gency department in our setting,1 as has been been consolidated as well as the assistance North of Spain during de COVID-19 state of alarm.
widely documented in the literature.2,3 In this circuits.4 Although the circulation of vi- Pediatr Emerg Care. 2020; [ahead of publication].
project, we have analyzed the admittance dur- ruses in the population may have decreased 2. Clavenna A, Nardeli S, Sala D, et al. Impact of
ing the first 15 days of the state of alarm because of current measures (use of a COVID-19 on the pattern of access to a pediatric
(October 25, 2020 to November 8, 2020) to mask, social distancing ...), the fact that emergency department in the Lombardy Region,
check if the pattern is repeated or if it was children are not confined and go to school Italy. Pediatr Emerg Care. 2020;36:e597–e598.
conditioned by home confinement. makes us think that the decline has not been 3. Parri N, Lenge M, Cantoni B, et al. COVID-19 in
The Vital Álvarez-Buylla Hospital is a so marked as previously. 17 Italian pediatric emergency departments.
reference for Health Area VII of Asturias Therefore, we have observed a similar Pediatrics. 2020;e20201235. doi: 10.1542/
(population approximately 62,000). During phenomenon in the use of the pediatric peds.2020-1235. [Epub ahead of print].
the study period, 39 patients were admit- emergency department between both epi- 4. Mata Zubillaga D, Rodríguez Manchón S,
ted, compared with 84 in the same period demic waves. Families have had full access González García LG, et al. Assistance to children
of 2019. to assistance when necessary, requiring ad- in a primary care pediatric unit during the
The number of patients admitted in mission on the same occasions, and in all COVID-19 state of alarm. Effectiveness of
the same period in 2020 and 2019 is shown cases, patients have been treated efficiently telephone assistance and specific circuits.
in Figure 1. We have analyzed the clinical at the appropriate time. Semergen. 2020;S1138-3593:30347–30346.
FIGURE 1. Patients admitted on pediatric emergency department during state of alarm (October 25, 2020 to November 8, 2020).

Letter to the Editors Pediatric Emergency Care • Volume 37, Number 4, April 2021
TABLE 1. Clinical Characteristics of the Patients During the State of Alarm (October 25, 2020 to November 8, 2020)
Year 2020 (October 25, 2020 Year 2019 (October 25, 2020 Statistical
to November 8, 2020) to November 8, 2020) Significance, P
n 39 84
Median age in months (range) 52 (2–166) 47 (0–162)
Age group
<1 y, n (%) 12 (30.8%) 14 (16.7%)
1–2 y, n (%) 6 (15.4%) 15 (17.9%)
2–3 y, n (%) 6 (15.4%) 14 (16.7%)
3–6 y, n (%) 3 (7.7%) 24 (28.6%)
6–14 y, n (%) 12 (30.8%) 17 (20.2%)
Male sex, n (%) 24 (61.5%) 47 (56.0%)
Duration of symptoms: median, h 70 ± 146 45 ± 91
Diagnosis
Upper respiratory infections, n(%) 6 (15.4%) 21 (25.0%)
Skin lesions, n (%) 6 (15.4%) 3 (3.6%)
Abdominal pain, n (%) 7 (17.9%) 8 (9.5%)
Febrile syndrome, n(%) 10 (25.6%) 3 (3.6%)
Traumatic head injuries, n (%) 3 (7.7%) 3 (3.6%)
Pneumonia, n (%) 0 1 (1.2%)
Acute gastroenteritis, n (%) 0 15 (17.9%)
Asthma/bronchiolitis, n (%) 2 (5.1%) 4 (4.8%)
Urinary tract infections, n (%) 0 1 (1.2%)
Streptococcal tonsillitis/otitis media, n (%) 1 (2.6%) 9 (10.7%)
Others 4 (10.2%) 16 (19.0%)
COVID-19 in health records
Suspected COVID-19 infection, n (%) 21 (53.9%)
Confirmed cases COVID-19 (positive PCR), n (%) 1 (2.6%)
Treatment
Antibiotic prescription, n (%) 4 (10.3%) 7 (8.3%)
Oral corticosteroids, n (%) 3 (7.7%) 6 (7.1%)
Complementary tests, n (%)
Chest x-ray, n (%) 0 2 (2.4%)
Blood analysis, n (%) 9 (23.1%) 7 (8.4%)
Urine analysis, n (%) 7 (17.9%) 5 (6.0%)
Ultrasound, n (%) 3 (7.7%) 1 (1.2%)
Oropharyngeal or nasopharyngeal swabs for respiratory virus 4 (10.2%) 1 (1.2%)
testing
Discharge/follow-up
Hospital admission, n (%) 6 (15.4%) 6 (7.1%)
Return within 15 d, n(%) 3 (7.7%) 1 (1.2%)
Primary care follow-up, n (%) 18 (46.2%) 16 (19.0%) 0.002
Telephone follow-up, n (%) 13 (76.5%) 0 <0.0001
PCR indicates polymerase chain reaction.

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ORIGINAL ARTICLE

Evaluation of a Focused Cardiac Ultrasound Protocol

FoCUS can facilitate a targeted, more precise approach to

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FIGURE 1. Key driver diagram for implementation of a FoCUS protocol.

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N = 92 Cardiologist + Cardiologist − Test Characteristics % (CI)

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Missed Diagnosis of Anaphylaxis in Patients With Pediatric

disseminated,7 they are subjective and symptom dependent. A

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FIGURE 1. Study subjects belonging to different groups.

TABLE 1. General Characteristics of Patients With Urticaria or Missed Anaphylaxis

Urticaria (n = 1014) Missed Anaphylaxis (n = 37) P

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anaphylaxis group and the anaphylaxis group, univariate analysis

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organs of these patients. When they are exposed to milk, milk

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Initial Characteristics and Clinical Severity of Hemophagocytic

recognition of the disease and preparations for clinical deterioration

H emophagocytic lymphohistiocytosis (HLH) is more common

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TABLE 2. Comparison Between the Clinically Unstable and Stable Groups

Variables Unstable Group (n = 19) Stable Group (n = 12) P

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Pediatric Esophageal Foreign Body

includes an esophagram. An esophagram requires patient co-

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Radiologic Assessment of Skull Fracture Healing

in a study using a US database of hospitalized children, almost all

FIGURE 1. Flow chart of subject selection.

fractures (71%), followed by the occipital bone with 4 fractures

Recognition, Evaluation, and Management of Pediatric

primarily in the prehospital, office, urgent care, or emergency de-

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TABLE 1. HAE Pediatric Cohort Epidemiologic Factors and Clinical Characteristics17–20

Farkas et al Nanda et al Bennett and Craig Aabom et al

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and juvenile idiopathic arthritis. Care was established at age 3 years

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GENERAL MANAGEMENT Long-Term Prophylaxis

TABLE 3. FDA-Approved Pediatric Therapies for HAE1,15,19,34,35

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ANSWER SHEET FOR THE PEDIATRIC EMERGENCY CARE

If yes, please explain:

Mail by March 31, 2023 to

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Associate Editor: J. Kate Deanehan, MD, RDMS