January 2023 - Pediatric Emergency Care

ORIGINAL ARTICLE
Immunization Status and the Management of Febrile

Children in the Pediatric Emergency Department
What Are We Doing?
Molly Curtis, MD,* Jessica Kanis, MD,* Brian Wagers, MD,* R. Lane Coffee, Jr, PhD, MS,†
Elisa Sarmiento, MSPH,‡ Sarah Grout, MD,§ Olivia Johnson, MD,|| Sydney DiGregory,¶
and Randall Grout, MD, MS, FAAP*#**
Conclusions: Higher rates of laboratory testing and interventions were

Objectives: Widespread Haemophilus influenzae and Streptococcus observed in UnderI and UnI versus FI febrile patients at a PED, likely dem-
pneumoniae immunization has decreased occult bacteremia and bacterial onstrating increased clinical suspicion for invasive bacterial infection in
meningitis rates. Practice has evolved in pediatric emergency departments this group despite lacking national guidelines. Given continued vaccine
(PEDs) to favor fewer diagnostic tests for and empiric treatment of invasive hesitancy, further studies are needed for guiding management of febrile
bacterial infection. We lack evidence-based guidance on evaluation and UnI and UnderI children presenting for emergency care.
treatment of unimmunized (UnI) or underimmunized (UnderI) febrile chil-
dren. This study aims to determine how parental report of immunization Key Words: unimmunized, unvaccinated, febrile, immunization status,
status in febrile PED patients impacts rates of diagnostic testing, interven- management
tions, and hospital admissions. (Pediatr Emer Care 2023;39: 1–5)
Methods: This is a retrospective cohort study with chart review of encoun-
ters of children aged 3 to 36 months presenting to an academic, tertiary care
PED in 2019 using International Classification of Diseases-10 code for fever
(R50.9). Inclusion criteria were documented fever of 38°C and higher and
T he Centers for Disease Control and Prevention recommends
children receive a combined 7-vaccine series that includes DTaP
(diphtheria, tetanus, pertussis), IPV (poliovirus), MMR (measles,
well appearance. Encounters were excluded if there was a history of chronic mumps, and rubella), Hib (Haemophilus influenzae type B), hepatitis
illness or documentation of ill appearance or hemodynamic instability. B, varicella, and PCV-13 (13-valent Streptococcus pneumoniae) by
Encounters were grouped by provider-documented immunization status. age 24 months.1 Nationally, it is estimated that only 70.5% of children
Fischer exact test and logistic regression compared rates of diagnostic testing complete this series on time, with 1% of children receiving no
(serum, urine or cerebrospinal fluid laboratory studies, and chest radiographs), vaccines.2 In the state in which this study is based (Indiana),
interventions (intravenous fluid bolus, intravenous antibiotic or steroid admin- 70% of children are considered fully immunized (FI) with the
istration, respiratory support, or breathing treatment), and hospital admissions 7-vaccine series by 24 months, with approximately 1% of children
between UnderI, UnI, and fully immunized (FI) groups. claiming exemption on starting kindergarten, reflecting the na-
Results: Of the 1813 encounters reviewed, 1093 (60%) included tional rates of nonimmunization.3
provider-documented immunization status and 788 (43%) met final inclu- Widespread Hib and S. pneumoniae immunization has de-
sion criteria: 23 (2.1%) UnI, 44 (5.8%) UnderI, and 721 (92.1%) FI. The creased rates of occult bacteremia and bacterial meningitis.4,5 Hence,
UnderI and UnI children experienced significantly higher rates of labora- pediatric emergency medical (PEM) practice has evolved to favor
tory evaluation including complete blood count and blood culture, medical fewer diagnostic tests for and empiric treatment of invasive bacterial
intervention, and antibiotic prescriptions while in the PED. No significant infection (IBI) in children aged 3 to 36 months.6–8 Until recently,
differences were observed for rates of chest radiographs, hospital admis- there was a dearth of evidence-based guidance regarding evaluation
sions, or 72-hour PED return visits. and management of unimmunized (UnI) febrile young children. A
retrospective cohort study by Dunnick et al9 reported bacteremia
from S. pneumoniae or Hib were independent of immunization sta-
From the *Division of Pediatric Emergency Medicine, Department of Emer-
tus, and no vaccine-preventable pathogens were isolated in unvacci-
gency Medicine, Indiana University School of Medicine, Indianapolis, IN; †De- nated children. However, the county of the institution in which this
partment of Internal Medicine, University of Central Florida College of Medi- study took place had an immunization rate of 96.6%. Robust local
cine, Orlando, FL; ‡Department of Biostatistics & Health Data Science, herd immunity likely contributed to the low number of children with
Indiana University School of Medicine and The Richard M. Fairbanks School
of Public Health, Indianapolis, IN; §Department of Pediatrics, Indiana Univer-
blood cultures positive for vaccine-preventable organisms in their co-
sity School of Medicine, Indianapolis, IN; ||Department of Emergency Medi- hort, and their results therefore were not necessarily generalizable.
cine, Indiana University School of Medicine, Indianapolis, IN; ¶Indiana Univer- Haut and Wagers10 proposed considering prevaccination-era rates
sity School of Medicine, Indianapolis, IN; #Regenstrief Institute, Indianapolis, of IBI when encountering UnI patients in the pediatric emergency de-
IN; and **Eskenazi Health, Indianapolis, IN.
Disclosure: RG has received unrelated institutional grant support from Pfizer,
partment (PED). Likewise, a recent review article by Finkel et al11 of-
Inc. The other authors declare no conflict of interest. fers an algorithm for managing fever without a source in UnI children
Reprints: Molly Curtis, MD, Division of Pediatric Emergency Medicine, that suggests obtaining urinalysis and urine culture, complete blood
Department of Emergency Medicine, Indiana University School of count (CBC), and a viral detection panel as initial screening tests if
Medicine, 705 Riley Hospital Dr, Indianapolis, IN 46202 (e‐mail:
molly.gail.curtis@gmail.com).
unvaccinated 2- to 24-month-old children have a fever of 39°C or
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. higher and are clinically well appearing. Blood culture, chest radiog-
This is an open-access article distributed under the terms of the Creative raphy, and empiric antibiotics are only recommended at or higher
Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY- than specific thresholds for white blood cell count, absolute neu-
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
trophil count, absolute band count, and procalcitonin.11
used commercially without permission from the journal. In clinical practice, PEM providers often rely on adult care-
ISSN: 0749-5161 givers for confirmation of a patient's immunization status despite
Pediatric Emergency Care • Volume 39, Number 1, January 2023 www.pec-online.com 1

Curtis et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
existing literature that suggests this may not be an adequate method.12,13 aged 3 to 36 months presenting to a large PED during a 12-month
For this reason, the Centers for Disease Control and Prevention period (January 1–December 31, 2019). The PED is part of a free-
has supported initiatives to develop state immunization registries standing, urban, academic, tertiary care children's hospital with an
to improve population-based health.14 It has been demonstrated annual emergency department (ED) volume of approximately
that blood screens for occult bacteremia by emergency medicine 50,000 visits per year. The chart review time frame was chosen
physicians were reduced when using an immunization registry in an effort to control for seasonality. We screened for eligible en-
for children presenting with fever without a source.15 However, counters in an analytics database using the diagnosis International
we are not aware of reported rates of immunization registry use Classification of Disease (ICD)-10 code for fever (R50.9). During
by PEM providers, and it is unknown if PEM providers at our in- initial chart extraction, if the diagnosis did not match the clinical
stitution are querying the state registry for this information. In ad- documentation (eg, the patient presented for a clinically distinct
dition, immunization registry integration into an electronic health and different reason and the patient never had a fever or reported
record (EHR) is complex and can be limited by incomplete re- a fever), the encounter was deemed miscoded, and no information
cords (eg, patient recently immigrated to state), poor patient was extracted from the chart. The clinical inclusion criteria were
matching, or manual steps required for synchronization. Given temperature of 38°C and higher (as documented per parental report
the rapid pace required for patient care and inevitable shortcom- or as measured during the ED encounter) and well appearance. Fe-
ings of integration of the state registry with the EHR, we believe ver was defined as 38°C and higher, which is consistent with the
the immunization status documented by providers is overwhelm- American College of Emergency Physicians' pediatric fever policy.7
ingly obtained via caregiver report. Charts were excluded if there was history of complex chronic illness
It remains unclear what impact provider-documented vacci- noted in any section of the EHR (defined as sickle cell disease, con-
nation status has on the evaluation and management of young fe- genital heart disease, immunodeficiency, immunosuppressed status
brile children seeking emergency care. Mintegi et al16 reported from chemotherapy or other immunosuppressive therapy, or trache-
that children who were incompletely immunized or UnI specifi- ostomy ventilation-dependent) or the provider indicated ill appear-
cally against PCV-7 were significantly more likely to have CBC ance or hemodynamic instability during that encounter.
and blood culture obtained and ceftriaxone administered when Study-related patient information was accessed in the elec-
compared with completely immunized counterparts. However, tronic medical record by manual chart review. REDCap (Vander-
there has yet to be a study that has investigated the impact of im- bilt University, Nashville, TN),17 a data collection tool, was used
munization status as reported by a parent or caregiver on the emer- in the chart review process to characterize each encounter in re-
gency management of febrile children. This study aims to deter- gard to patient demographics, vaccination status, ED course, and
mine if febrile children who are perceived as underimmunized ED disposition. Vaccination status was recorded from the natural
(UnderI) or UnI experience higher rates of diagnostic testing, in- language of provider documentation (eg, “imm utd”, indicating
terventions, and hospital admissions compared with FI children. immunizations were up to date or “vaxed only to 2 months”, indi-
cating the child has had some but not all immunizations). From
METHODS this, each patient encounter was categorized by vaccination status
This institutional review board-approved retrospective cohort into 1 of 3 groups: FI, UnderI, or UnI. The ED course information
study consisted of a chart review of encounters of febrile children was collected as it related to the evaluation and management of the
FIGURE 1. Flow diagram of encounters included in chart review.
2 www.pec-online.com © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Management of Unimmunized Children in PED
and 95% confidence intervals (CIs) were calculated, and results were
TABLE 1. Demographic Information reported in terms of OR, where appropriate. Statistical tests were
2-sided, and P < 0.05 was considered statistically significant. All sta-
FI UnderI UnI P
tistical analyses were performed using SAS 9.4 (SAS Institute,
Sex Cary, NC).
Male 391 54% 20 46% 15 65% 0.2904
Female 330 46% 24 54% 8 35% RESULTS
Age During the study time frame, there were 1813 encounters that
3–5 mo 65 9% 1 2% 4 18% 0.3504 were appropriately coded by diagnosis with ICD-10 code for fe-
6–11 mo 214 30% 16 36% 6 26% ver. Of those, 1093 (60%) included provider-documented immu-
12–17 mo 152 21% 13 30% 3 13% nization status, and 788 (43%) met all inclusion criteria: 23
18–23 mo 134 18% 6 14% 3 13% (3%) UnI, 44 (5.5%) UnderI, and 721 (91.5%) FI. Of the 305 en-
24–36 mo 156 22% 8 18% 7 30% counters that were excluded, 222 did not have a fever of 38°C and
higher documented, 68 had chronic illness, and 15 were ill appear-
Race
ing (Fig. 1). Patient demographics are shown in Table 1; sex, age,
White 396 55% 18 41% 7 30% 0.2259 race, and insurance type distribution was similar between groups.
Hispanic 26 4% 3 7% 0 — Comparisons of testing and management strategies of febrile
Black 265 37% 20 46% 16 70% young children by immunization status are summarized in Table 2.
Asian 17 2% 2 4% 0 — Laboratory testing was obtained in 48% of UnI and 32% of UnderI
Native American 2 0.3% 0 — 0 — patients (vs 24% of FI, P < 0.05). The odds of obtaining laboratory
Pacific Islander 4 1% 0 — 0 — studies were approximately 0.86 times higher in non-FI than FI pa-
Other 11 2% 1 2% 0 — tients (OR, 1.86; 95% CI, 1.10–3.14). More specifically, a CBC
Insurance type was obtained in 35% of UnI patients (vs 13% UnderI and 7% FI,
Private 85 12% 4 9% 4 17% 0.0559 P < 0.01) and a blood culture was obtained in 30% of UnI patients
(vs 7% UnderI and 2% FI, P < 0.001). Both CBC and blood culture
Medicaid 616 85% 39 89% 16 70%
were obtained more frequently in non-FI patients (OR, 3.18; 95%
Self-pay 16 2% 1 2% 3 13% CI, 1.35–7.48; OR, 7.33; 95% CI, 3.35–17.82). Non-FI patients
Military 4 1% 0 — 0 — were also 83% more likely to experience a medical intervention
during their PED visit and 99% more likely to receive an antibiotic
prescription on discharge from the PED (OR, 1.86; 95% CI, 0.89–3.73;
patient during that encounter. Specifically, any laboratory evalua-
OR, 1.99; 95% CI, 1.13–3.53).
tion (urine, serum, or CSF), chest radiography, medical resuscita-
There were no significant differences in rates of chest radiog-
tion (intravenous [IV]/intramuscular antibiotic, steroid or IV fluid
raphy (16% FI vs 22% UnderI vs 30% UnI, P = 0.1669), hospital
administration, supplemental oxygen or breathing treatments), ad-
admissions (3% FI vs 2% UnderI vs 9% UnI, P = 0.2429), or
mission, systemic antibiotic prescription on discharge, or 72-hour
72-hour ED return visits (7% FI vs 2% in UnderI vs 0% UnI,
return visits were identified, and these characteristics were com-
P = 0.3116).
pared between FI, UnderI, and UnI groups.
The χ2 and Fisher exact tests were used to analyze the differ-
ences among immunization status groups. For purposes of logistic DISCUSSION
regression, UnderI and UnI groups were combined into a non-FI Our study showed that young children documented by providers
group that was compared against the FI group. The odds ratio (OR) as non-FI (UnderI or UnI) underwent higher rates of laboratory
TABLE 2. Differences in Management
FI (n = 721) UnderI (n = 44) UnI (n = 23) P OR (95% CI)*

†
Serum, urine, or CSF laboratory test 175 (24%) 14 (32%) 11 (48%) 0.0229 1.86 (1.10–3.14)
CBC 50 (7%) 6 (13%) 8 (35%) 0.0006 3.18 (1.35–7.48)
Blood culture 16 (2%) 3 (7%) 7 (30%) <0.0001 7.73 (3.35–17.82)
Any urine study 108 (15%) 13 (30%) 4 (17%) 0.0392
Any CSF study 1 (0.1%) 1 (2%) 0 (0.0) 0.1629
Chest radiograph 112 (15%) 11 (25%) 5 (22%) 0.1669 1.71 (0.94–3.10)
ED Intervention‡ 63 (9%) 4 (9%) 6 (26%) 0.0272 1.83 (0.89–3.76)
Hospital admission 22 (3%) 1 (2%) 2 (9%) 0.2429
Antibiotic prescription at ED discharge§ 122/698 (18%) 13/43 (30%) 6/21 (29%) 0.0532 1.99 (1.13–3.53)
Return to ED w/in 72 h 50 (7%) 1 (2%) 0 (0.0) 0.3116
*Odds ratio comparing differences in management between UnderI and UnI as a group versus FI.
†Basic metabolic panel, liver function test, CBC, urinalysis, urine culture, urine dip, C-reactive protein, erythrocyte sedimentation rate, procalcitonin, CSF
studies (culture, Gram stain, protein, glucose, viral studies), blood culture, or other. Subgroups listed only represent specific laboratory testing analyzed and will
not add up to the group totals shown; overlap also exists such that patients could have had only 1 or multiple tests obtained during the same encounter.
‡Intravenous fluid bolus, IV antibiotics, respiratory support, steroids, breathing treatment, or other.
§Twenty-five patients admitted to hospital and 1 incomplete record not included.
© 2022 The Author(s). Published by Wolters Kluwer Health, Inc. www.pec-online.com 3

Curtis et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
testing and interventions when presenting for fever in the PED. patients was not within the scope of this study. Further studies
Non-FI children were almost 3 times more likely to have a CBC are needed to determine if there are truly higher rates of IBI in
obtained, almost 8 times more likely to have had a blood culture non-FI children and whether this necessitates additional testing
drawn, and received both ED interventions and antibiotic pre- and treatment in this population.
scriptions on discharge at almost twice the rate as FI children. This
suggests providers' clinical decision making may be influenced by
the immunization status of their patients and could reflect a higher REFERENCES
index of suspicion for IBI, as was seen in the prevaccine era. Because 1. Wodi AP, Murthy N, Bernstein H, et al. Advisory committee on
urinary tract infections are not vaccine-preventable, we completed a immunization practices recommended immunization schedule for children
sensitivity analysis in which patients who only underwent urine test- and adolescents aged 18 years or younger. United States, 2022. MMWR
ing were removed. A significant pattern across groups remained Morb Mortal Wkly Rep. 2022;71:234–237.
(11% FI vs 17% UnderI vs 43% UnI, P = 0.0004). In fact, an even 2. Hill HA, Yankey D, Elam-Evans LD, et al. Vaccination coverage by age
stronger association was found for laboratory testing between the 24 months among children born in 2017 and 2018. National Immunization
non-FI and FI children (OR, 2.9; 95% CI, 1.5–5.4). Survey-Child, United States, 2018–2020. MMWR Morb Mortal Wkly Rep.
For purposes of logistic regression, UnderI and UnI groups 2021;70:1435–1440.
were collapsed for comparison against FI. This was done to reflect 3. Indiana State Department of Health. County immunization rate assessment,
our belief that providers' threshold at which they consider a child 2019. Available at: https://www.in.gov/health/immunization/files/
low risk for IBI is when they are reported as being FI. Therefore, Immunization-Rates-by-County-2019.pdf. Accessed January 22, 2020.
we feel providers likely view UnderI and UnI children at a simi-
4. Herz AM, Greenhow TL, Alcantara J, et al. Changing epidemiology of
larly increased risk of IBI when making clinical decisions about
outpatient bacteremia in 3- to 36-month-old children after the introduction
their evaluation and management. Our results support the idea
of the heptavalent-conjugated pneumococcal vaccine. Pediatr Infect Dis J.
of a substantial difference in provider behavior in diagnostic spec- 2006;25:293–300.
imen testing between FI and non-FI groups.
Of equal interest, we did not find higher rates of chest radiog- 5. Wilkinson M, Bulloch B, Smith M. Prevalence of occult bacteremia in
raphy for non-FI patients, which could indicate that providers did children aged 3 to 36 months presenting to the emergency department with
fever in the postpneumococcal conjugate vaccine era. Acad Emerg Med.
not have increased concern for bacterial pneumonia or that they
2009;16:220–225.
are more comfortable using clinical evidence alone in diagnosing
this condition. It is also possible that providers are using laboratory 6. Kuppermann N. The evaluation of young febrile children for occult
values to guide their decision to obtain chest radiography, as sug- bacteremia: time to reevaluate our approach? Arch Pediatr Adolesc Med.
gested by Finkel et al.11 Likewise, similar rates of hospital admis- 2002;156:855–857.
sions between groups suggest a lack of elevated concern for clin- 7. American College of Emergency Physicians Clinical Policies Committee;
ical decompensation in an otherwise healthy child, despite being American College of Emergency Physicians Clinical Policies
unvaccinated. Subcommittee on Pediatric Fever. Clinical policy for children younger than
A large portion of parents who choose not to vaccinate their three years presenting to the emergency department with fever. Ann Emerg
children perceive that this choice reduces risk of medical interven- Med. 2003;42:530–545.
tion.18 Our study suggests otherwise in that UnderI or UnI status 8. Cioffredi LA, Jhaveri R. Evaluation and management of febrile children: a
increases a child's odds for experiencing invasive testing and man- review. JAMA Pediatrics. 2016;170:794–800.
agement strategies if they were to present to a PED with fever. 9. Dunnick J, Taft M, Tisherman RT, et al. Association of bacteremia with
Taken with the findings of Dunnick et al,9 that blood culture isolates vaccination status in children aged 2 to 36 months. J Pediatr. 2021;232:
of unvaccinated children had higher rates of contaminants than true 207–213.e2.
pathogens, it is important for parents to be made aware of this in- 10. Haut L, Wagers B. Challenges encountered in the emergency department in
creased risk of medical intervention as they make vaccination deci- the unimmunized pediatric population. Curr Emerg Hosp Med Rep. 2018;
sions for their children. This is especially salient in the current con- 6:152–156.
text of the COVID-19 pandemic that has resulted in a dramatic de-
11. Finkel L, Ospina-Jimenez C, Byers M, et al. Fever without source in
cline in routine childhood immunization rates globally.19,20 unvaccinated children aged 3 to 24 months: what workup is recommended?
There were limitations to our study. This is a single-center Pediatr Emerg Care. 2021;37:e882–e885.
study involving a single PED, which may limit the generalizability
of our results. In addition, given the retrospective study design, 12. Stecher DS, Adelman R, Brinkman T, et al. Accuracy of a state
immunization registry in the pediatric emergency department. Pediatr
our data were limited to extractable information from charts, in-
Emerg Care. 2008;24:71–74.
cluding whether a provider documented immunization status. It
is also possible that there were encounters of febrile children that 13. Williams ER, Meza YE, Salazar S, et al. Immunization histories given by
were missed because they were given an ICD-10 code other than adult caregivers accompanying children 3–36 months to the emergency
fever. Although immunization status was extracted and coded department: are their histories valid for the Haemophilus influenzae B and
from the natural language of provider documentation in an effort pneumococcal vaccines? Pediatr Emerg Care. 2007;23:285–288.
to capture the motivation behind clinical decisions, it is possible 14. Centers for Disease Control and Prevention (CDC). Progress in
that the clinician's management was not related to the immuniza- immunization information systems. United States, 2011. MMWR Morb
tion status documented. We opted to rely on provider documenta- Mortal Wkly Rep. 2013;62:48–51.
tion of immunization instead of an immunization registry to cap- 15. Zeretzke CM, McIntosh MS, Kalynych CJ, et al. Reduced use of occult
ture the provider's perception of immunization status, which is bacteremia blood screens by emergency medicine physicians using
more likely to influence their decision making than documenta- immunization registry for children presenting with fever without a source.
tion elsewhere that they may not have reviewed. Pediatr Emerg Care. 2012;28:640–645.
Our observational study provides insight into the clinical de- 16. Mintegi S, Benito J, Gonzalez M, et al. Impact of the pneumococcal
cisions providers are making while taking care of febrile UnderI conjugate vaccine in the management of highly febrile children aged 6 to
and UnI children in the PED while lacking an evidence-based 24 months in an emergency department. Pediatr Emerg Care. 2006;22:
guideline. Analyzing the outcomes of the identified non-FI 566–569.

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Management of Unimmunized Children in PED
17. Harris PA, Taylor R, Thielke R, et al. Research electronic data capture 19. Nuzhath T, Ajayi KV, Fan Q, et al. Childhood immunization during
(REDCap) – a metadata-driven methodology and workflow process for the COVID-19 pandemic in Texas. Vaccine. 2021;39:
providing translational research informatics support. J Biomed Inform. 3333–3337.
2009;42:377–381. 20. Maltezou HC, Medic S, Cassimos DC, et al. Decreasing routine
18. Smith LE, Amlôt R, Weinman J, et al. A systematic review of factors vaccination rates in children in the COVID-19 era. Vaccine. 2022;40:
affecting vaccine uptake in young children. Vaccine. 2017;35:6059–6069. 2525–2527.

ORIGINAL ARTICLE
Pharmacogenomic Profiling of Pediatric Patients on

Psychotropic Medications in an Emergency Department
Pallavi Ghosh, MD,* Jesse Martinez, MD,† Nipam Shah, MBBS, MPH,* Will Kenan, MS,‡
Andrew Fowler, MD,§ Nita Limdi, PharmD, PhD, MSPH,|| Lindsey Burns, MBA,¶ Elizabeth S. Cogan, PhD,#
Anna Gardiner, PhD,# Daniel Hain, BS,¶ Holly Johnson, PhD,¶ David Lewis, MS,¶
Richard Shelton, MD,** and Erica Liebelt, MD*††
Key Words: combinatorial pharmacogenomic testing, psychiatric disorders,

Objective: The aim of the study was to evaluate the ability of a combina- psychotropic medications, pediatric population, blood levels
torial pharmacogenomic test to predict medication blood levels and relative
clinical improvements in a selected pediatric population. (Pediatr Emer Care 2023;39: 6–12)
Methods: This study enrolled patients between ages 3 to 18 years who
presented to a pediatric emergency department with acute psychiatric,
behavioral, or mental health crisis and/or concerns, and had previously
been prescribed psychotropic medications. Patients received combinato-
P harmacogenomic testing is becoming more common in psychi-
atric settings to guide medication selection in adults. The im-
pact of genetic variation on drug safety and efficacy has been well
rial pharmacogenomic testing with medications categorized according to established for a variety of psychotropic medications, and several
gene-drug interactions (GDIs); medications with a GDI were considered organizations, including the Clinical Pharmacogenetic Implemen-
“incongruent,” and medications without a GDI were considered “congru- tation Consortium (CPIC), provide dosing recommendations based
ent.” Blood levels for escitalopram, fluoxetine, aripiprazole, and clonidine on phenotypes for individual genes.1–3 In pediatric patients, recom-
were evaluated according to level of GDI. Relative clinical improvements mendations surrounding the use of pharmacogenomic testing to
in response to the prescribed psychotropic medications were measured guide psychotropic medication selection are mixed,4–6 and profes-
using a parent-rated Clinical Global Impression of Improvement (CGI-I) sional organizations have questioned whether pharmacogenomic
assessment, where lower scores corresponded with greater improvement. testing is appropriate in the pediatric population.7 Despite con-
Results: Of the 100 patients enrolled, 73% reported taking ≥1 incongruent cerns, the potential for individualized treatment to improve clinical
medication. There was no significant difference in CGI-I scores between pa- outcomes in the pediatric population warrants further exploration.
tients prescribed congruent versus incongruent medications (3.37 vs 3.68, Medication selection and dosing for psychiatric and behav-
P = 0.343). Among patients who presented for depression or suicidal idea- ioral conditions are challenging because adverse reactions can of-
tion, those prescribed congruent medications had significantly lower CGI-I ten result in patient noncompliance and treatment failure.4,8,9 As
scores compared with those taking incongruent medications ( P = 0.036 for such, medications in pediatric patients are typically initiated at a
depression, P = 0.018 for suicidal ideation). There was a significant associ- low dose, with a slow upward taper. This approach can lead to
ation between medication GDI and blood levels for aripiprazole (n = 15, underdosing10 and, consequently, a longer duration to achieve effi-
P = 0.01) and escitalopram (n = 10, P = 0.01). cacy, potentially resulting in increased emergency department visits
Conclusions: Our preliminary findings suggest that combinatorial and/or hospitalizations for psychiatric reasons (eg, suicide attempts,
pharmacogenomic testing can predict medication blood levels and relative aggressive behavior).11 Even with medication management, remis-
outcomes based on medication congruency in children presenting to an sion rates in pediatric mental health conditions (ie, depression, anx-
emergency department with acute psychiatric/behavioral crises. Additional iety, bipolar disorder, and attention-deficit/hyperactivity disorder
studies will be needed to confirm these findings. [ADHD]) range from 16% to 66%.12–14 Although a variety of
From the *Division of Pediatric Emergency Medicine, Department of Pediat- Alkermes, Inc, Allergan, Plc, Assurex, Inc, Avanir Pharmaceuticals, Inc,
rics, The University of Alabama at Birmingham Heersink School of Medicine; Cerecor, Inc, Intracellular Therapies, Janssen Pharmaceutica, LivaNova
†Division of Child and Adolescent Psychiatry, Department of Psychiatry and PLC, Navitor Pharmaceuticals, Neurorx, Novartis Pharmaceuticals, Otsuka
Behavioral Neurobiology, The University of Alabama at Birmingham Heersink America, and Takeda Pharmaceuticals; he has received consulting fees from
School of Medicine; ‡Department of Biomedical and Health Sciences, The Uni- Acadia Pharmaceuticals, Allergan plc, Alfasigma USA, Inc, Myriad
versity of Alabama at Birmingham, School of Health Processions, Birmingham, Neuroscience, Novartis International AG, Evecxia Therapeutics, Seelos
AL; §Pediatric Residency Program at Arkansas Children's Hospital, University Therapeutics, Sunovion Pharmaceuticals, Inc, and Neurorx, Inc. The other
of Arkansas for Medical Sciences, College of Medicine, Little Rock, AR; ||De- authors declare no conflict of interest.
partment of Neurology, The University of Alabama at Birmingham Heersink Financial support: This study was funded by Myriad Genetics, Inc
School of Medicine, Birmingham, AL; ¶Myriad Neuroscience, Mason, OH; (formerly Assurex Health, Inc, OSP Link 000513265, award dates:
#Myriad Genetics, Inc, Salt Lake City, UT; **Department of Psychiatry, The 2016–2017.
University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Data availability: The data sets generated during and/or analyzed during the
AL; and ††Department of Pediatrics, Section of Pediatric Emergency Medicine current study are not publicly available but are available from the
and Pharmacology and Medical Toxicology, University of Arkansas for Medical corresponding author on reasonable request.
Sciences, Little Rock, AR. Supplemental digital content is available for this article. Direct URL citations
Reprints: Pallavi Ghosh, MD, MPH, The University of Alabama at appear in the printed text and are provided in the HTML and PDF versions
Birmingham, Department of Pediatrics, Division of Pediatric Emergency of this article on the journal’s Web site (www.pec-online.com).
Medicine, 1600 7th Ave S, Children's Park Place, Ste #110, Birmingham, Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.
AL 35233 (e‐mail: pghuge@uabmc.edu). This is an open-access article distributed under the terms of the Creative
Disclosure: L.B., D.H., H.J., and D.L. were all employed by Myriad Commons Attribution-Non Commercial-No Derivatives License 4.0
Neuroscience at the time this study was conducted and received salary and (CCBY-NC-ND), where it is permissible to download and share the work
stock options. E.S.C. and A.G. were employed by Myriad Genetics, Inc, at provided it is properly cited. The work cannot be changed in any way or
the time this study was conducted and received salary and stock options. used commercially without permission from the journal.
R.S. has received research support from Acadia Pharmaceuticals, ISSN: 0749-5161
6 www.pec-online.com Pediatric Emergency Care • Volume 39, Number 1, January 2023

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Pediatric Pharmacogenomic Testing
factors may influence medication treatment success, this range Pharmacogenomic Testing
conservatively suggests that at minimum, one third of patients All patients were tested with the GeneSight Psychotropic and
do not achieve remission. Implementing pharmacogenomic test- GeneSight ADHD panels (Myriad Neuroscience, Mason, Ohio).27
ing in this population may improve clinical outcomes by identify- Tests were performed in a Clinical Laboratory Improvement
ing gene-drug interactions (GDIs), which can be used to guide Amendments– and College of American Pathologists–accredited
medication selection and dosing to increase the likelihood that laboratory. The test was developed, and its performance characteris-
patients will benefit from medication management. tics were determined by Assurex Health. The GeneSight Psychotro-
Studies in pediatric patients have found that variants in pic test included evaluation of genotypes for 58 alleles and variants
genes related to medication metabolism (ie, pharmacokinetics) across 8 genes, and the GeneSight ADHD test included evaluation
and mechanism of action (ie, pharmacodynamics) are associated of genotypes for 20 alleles and variants across 3 genes (see Supple-
with medication response, adverse effects, and tolerability.11,15 mental Materials, http://links.lww.com/PEC/B46).
Although phenotypes and recommendations based on individual For each medication, a combined phenotype was assigned
genes can be useful, a more comprehensive assessment of GDIs based on a weighted algorithmic assessment of multiple pharmaco-
based on multiple genes can be achieved through combinatorial kinetic and pharmacodynamic genes. On the test report, medica-
pharmacogenomic (CPGx) testing. The CPGx test provides rec- tions were categorized according to combined level of GDI with ac-
ommendations using a weighted algorithm based on multiple companying footnotes on recommendations for medication use (eg,
genes involved in the pharmacokinetic and pharmacodynamic dosage adjustment). For this study, medications were divided into
aspects of a particular medication. In adults with depression, the following 2 categories based on the combined phenotype: (1)
clinical validation studies have demonstrated that the CPGx test medications with a moderate or significant GDI and (2) medications
predicts medication blood levels,16–18 and clinical utility studies with no GDI. Medications with a GDI were considered “incongru-
have shown improved outcomes when treatment is guided by ent,” and medications without a GDI were considered “congruent.”
CPGx testing compared with treatment as usual.19–21 In pediatric
patients with depression, findings have been mixed, with no clear Blood Levels
evidence to support the utility of CPGx testing in this popula-
tion.22,23 To appropriately assess the clinical utility and validity Blood samples were collected for each medication but anal-
of CPGx testing in pediatric patients with depression, anxiety, ysis was only conducted if there were at least 10 patients with re-
and other psychiatric disorders, additional studies will be needed. corded blood levels per medication. Blood draws were performed
No previous studies have reported on the utility of CPGx testing during the PED visit after consent/assent was obtained. Venous
in pediatric patients presenting in crisis to a pediatric emergency blood samples (15–20 mL, 10 mL if the patient was <14 kg) were
department (PED), potentially highlighting a vulnerable cohort collected from each patient; 5 mL of the blood collected was re-
where GDIs may be impacting medication response. Indeed, served for future DNA genomic analyses at the UAB. The samples
PED visits for mental health and behavioral complaints, including were then labeled, centrifuged at UAB, stored at −80°C, and were
suicidality and self-harm, have increased over the last decade.24,25 then retrieved by Quest Diagnostics within 48 hours of collection
With the exacerbation of this trend by the onset of the COVID-19 for further analysis. Serum quantitation of psychiatric medication
pandemic,26 there may be an opportunity for PED health care to concentrations was performed using liquid chromatography with
include personalized medication treatment to improve mental tandem mass spectrometry at NMS Labs (Willowgrove, Pa) with
health outcomes in this population. a reporting threshold of 10 ng/mL.
Here, we present a cross-sectional pilot study on the ability of For the analyses involving blood levels, rather than being cat-
a CPGx test to predict medication blood levels and relative im- egorized based on a combined phenotype using pharmacokinetic
provements in pediatric patients presenting to a PED with acute and pharmacodynamic genes, medications were categorized based
psychiatric and behavioral emergencies; all included patients pre- on the level of GDI for pharmacokinetic genes only and the direc-
sented for treatment of a psychiatric disorder that was being man- tion of the predicted change in metabolism: (1) GDI with decreased
aged with medication. metabolism, (2) GDI with increased metabolism, and (3) no GDI/
unknown impact on metabolism.
METHODS Data Collection and Analysis

Demographic data included patient age at the time of admis-
Cohort sion to the PED, sex, race/ethnicity, and weight. Medical history
All patients enrolled in this study presented to the Children's included the following: medication history, indication for psycho-
of Alabama PED at the University of Alabama at Birmingham tropic medication use, and reason for PED visit (eg, anxiety, panic
(UAB) over an 18-month period. Patients were eligible for en- attack, intentional self-injury, suicidal/homicidal ideation, aggres-
rollment if they were 3 to 18 years of age, had been prescribed sion, severe depression). Study data were collected and managed
≥1 psychotropic medications (ie, antidepressants, antipsychotics, using REDCap electronic data capture tools hosted at the
and medications for ADHD), and presented with a mental health, UAB.28,29 Demographic characteristics were assessed using de-
behavioral, or psychiatric concern. Patients were excluded if scriptive statistics and compared between patients prescribed con-
they presented with acute drug or alcohol intoxication, were in gruent medications (ie, with no GDI) and patients prescribed at
Alabama Department of Human Resources custody, or were least one incongruent medication (ie, with moderate/significant
medically unstable. Blood and buccal samples were collected GDI) using χ2 tests, Fisher exact tests, and t tests.
for CPGx and blood levels testing during the PED visit. Patient outcomes were evaluated at a single-time point using
This study was approved by the UAB Institutional Review the Clinical Global Impression–Improvement (CGI-I) survey tool,
Board. Informed consent was obtained from all patients before which was completed by the parent/guardian of the patient during
participating in the study. Signed and dated written informed the PED visit. Clinical personnel were present to explain CGI-I
consent was obtained from each patient, parent, or legal guard- questions and scoring to parents/guardians and were available to
ian before enrollment. Assent was obtained for patients between answer any additional questions and/or assist with completing
7 and 13 years of age. the questionnaire. The CGI-I was used to determine the degree

Ghosh et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
of relative improvement of the underlying psychiatric disorder

from when the patient began taking the prescribed psychotropic TABLE 1. Demographic Characteristics of Patients Taking
Congruent and Incongruent Medications
medication(s). The CGI-I is a validated scale that can be used to
assess relative improvement for a variety of psychiatric conditions
Patient Congruent (No Incongruent Total
using a single-time point; this scale is designed to provide a mea-
Demographic GDI, n = 27) (GDI, n = 73) (N = 100)
sure of relative improvement and therefore does not require a
baseline measure. The assessment consisted of a 0- to 7-point Age
scale with the following values: 7 = “very much worse,” 6 = “much Median 13.00 14.00 14.00
worse,” 5 = “minimally worse,” 4 = “no change,” 3 = “minimally Min–max 5.0–18.0 4.0–18.0 4.0–18.0
improved,” 2 = “much improved,” 1 = “very much improved,” and IQR 4.0 5.0 5.0
0 = “not assessed.”30 In this study, no patients were classified as Sex, n (%)
“not assessed.” Mean CGI-I scores were calculated and compared
Female 8 (29.6) 36 (49.3) 44 (44.0)
among patients taking congruent and incongruent medications ac-
cording to reason for PED admission using a 2-sample t test. Male 19 (70.4) 37 (50.7) 56 (56.0)
Blood levels for medications with at least 10 blood-drug Race, n (%)
level samples were analyzed, including the antipsychotic aripipra- American Indian/ 1 (3.7) 0 1 (1.0)
zole, the selective serotonin reuptake inhibitors escitalopram and Alaska Native
fluoxetine, and the ADHD medication, clonidine. To account for Black or African 8 (29.6) 17 (23.3) 25 (25.0)
variability in medication dosing across patients, concentration/ American
dose ratios were log transformed using the following equation: White/Caucasian 17 (63.0) 54 (74.0) 71 (71.0)
More than one race 1 (3.7) 2 (2.7) 3 (3.0)
Concentration Ethnicity, n (%)
Log10
Dose Hispanic or Latino 1 (3.7) 0 1 (1.0)
Not Hispanic or 24 (88.9) 69 (94.5) 93 (93.0)
Effect coding was used to weight patients based on their clin- Latino
ical consideration so that the linear trend between predicted and Unknown/not 2 (7.4) 4 (5.5) 6 (6.0)
observed relative blood-drug levels could be assessed. Patients reported
with a significant GDI with decreased metabolism were assigned Weight
an effect code of 1, patients with a significant GDI with increased Median 56.00 62.00 61.00
metabolism were assigned an effect code of −1, and patients with
Min–max 20.0–137.0 18.0–170.0 18.0–170.0
no/moderate GDI were assigned an effect code of 0. Analysis of
variance was used to evaluate the relationship between the effect IQR 32.0 32.5 32.25
coded clinical consideration category and log-transformed blood- Reason for PED visit
drug levels for each medication. Analysis of variance was also used Behavioral problem 13 (48.1) 33 (45.2) 46 (46.0)
to evaluate the relationship between bodyweight, age, sex, or race Depression 15 (55.6) 28 (38.4) 43 (43.0)
and log-transformed blood-drug levels for each medication. Psychiatric 10 (37.0) 36 (49.3) 46 (46.0)
Statistical analyses were performed using SAS software (Ver- evaluation
sion 9.4), JMP 15 (SAS Institute), R 3.5.1, and R's “car” package. Suicidal ideation 17 (63.0) 40 (54.8) 57 (57.0)
Two-sided P values ≤0.05 were considered statistically significant. Violent behavior 9 (33.3) 27 (37.0) 36 (36.0)
RESULTS in the study. Twenty-five percent of the samples were African

American, and most patients (93%) identified as non-Hispanic/
Patient Population Latino (Table 1). The 5 most common reasons for PED visit are in-
A total of 303 patients taking at least one psychotropic med- cluded in Table 1. Overall, more patients were on incongruent med-
ication presented to the PED for a psychiatric related visit. A total ications (73%) than congruent medications (27%). No significant
of 100 patients met eligibility criteria (Fig. 1). demographic differences were observed between the 2 groups.
Patient demographics are provided in Table 1 according to
medication congruency (ie, no GDI vs moderate/significant GDI). Patient Outcomes
The median age of both groups was 14 years (interquartile range The average CGI-I score was lower (indicating improvement)
[IQR], 5). More males than females (56% vs 44%) were enrolled for those who were on congruent medications (3.37) compared
FIGURE 1. Patient enrollment diagram.

with those on incongruent medications (3.68); however, this was http://links.lww.com/PEC/B46). Only escitalopram was found to
not statistically significant ( P = 0.343; Fig. 2). Among patients have a significant difference according to weight ( P = 0.02; Sup-
who presented for depression, those taking an incongruent medica- plemental Fig. 1, http://links.lww.com/PEC/B46). Patients with a
tion had a significantly higher CGI-I score (indicating less improve- higher weight had lower blood levels of escitalopram. All other
ment) compared with those taking only congruent medications (4.1 demographic characteristics were not significantly associated with
vs 3.1, P = 0.036). Similarly, among patients who presented for sui- medication blood levels.
cidal ideation, those who were taking an incongruent medication Medication blood levels were analyzed according to GDIs
had a significantly higher CGI-I score than those taking a congruent that included pharmacokinetic, but not pharmacodynamic genes,
medication (3.9 vs 3.0, P = 0.018; Fig. 2). and predicted change in metabolism (Fig. 3). There was a signifi-
cant difference between medication blood levels across GDI cate-
gories for aripiprazole ( P = 0.01). Six patients with decreased me-
Medication Blood Levels tabolism had significantly higher levels compared with patients
Blood levels were analyzed for escitalopram (n = 10), fluox- with no GDI/unknown impact on metabolism, whereas 2 patients
etine (n = 10), aripiprazole (n = 15), and clonidine (n = 11). The with increased metabolism were not significantly different from
frequency of psychotropic and ADHD medications prescribed those with no/unknown impact on metabolism (Fig. 3A). Simi-
and the number of patients who had blood drug levels analyzed larly, there was a significant difference between medication blood
is provided in Supplemental Table 1, http://links.lww.com/PEC/ levels across GDI categories for escitalopram ( P = 0.01; Fig. 3B).
B46. Weight, age, race/ethnicity, and sex were all evaluated ac- Four patients with decreased metabolism had significantly higher
cording to concentration/dose for each of the 4 medications to de- levels compared with patients who had no GDI/unknown impact
termine impact on medication metabolism (Supplemental Fig. 1, on metabolism, whereas one patient with increased metabolism
FIGURE 2. Mean CGI-I score based on reason for admission to the pediatric emergency department in patients on incongruent versus
congruent medications. Error bars represent ± standard errors of the mean.

FIGURE 3. Gene-drug interaction and impact on metabolism for each medication type. IM, increased metabolism; DM, decreased metabolism.
was not different from those with no GDI/unknown impact on escitalopram, but not for fluoxetine and clonidine. It is possible
metabolism. In contrast, there was no significant difference in that the sample size in this preliminary study was too small to
blood levels between GDI categories for clonidine ( P = 0.31; consistently detect significant differences across all psychiatric
Fig. 3C) or fluoxetine ( P = 0.11; Fig. 3D). conditions and medications; nonetheless, these findings suggest
that CPGx testing has the potential to benefit pediatric patients
with depression and/or suicidal ideation.
DISCUSSION To our knowledge, studies evaluating the association be-
The ability of the CPGx test to predict clinical outcomes and tween CPGx testing and patient outcomes in pediatric patients
medication blood levels in psychiatric settings has been previ- across multiple psychiatric conditions have not yet been per-
ously reported in adults with depression.16–19 To date, reports in formed. However, our findings align with a recent retrospective
pediatric patients with depression and other psychiatric condi- study that demonstrated improved outcomes after CPGx testing
tions have been mixed. The preliminary findings presented here in children and adolescents with depression and anxiety.23 In con-
demonstrate that patients taking medications categorized as contrast, a randomized controlled trial in adolescents with major de-
gruent by the CPGx test had greater relative improvements (nu- pressive disorder found no improvement associated with CPGx
merically) compared with those taking incongruent medications, testing.22 Although it is possible that CPGx testing may not have
although differences were not statistically significant across all clinical utility in adolescents with major depressive disorder, the
psychiatric conditions assessed. In addition, significant differences authors point out that the impact of CPGx testing could have been
were observed in medication blood levels between GDI categories diluted by patients in the control arm who were incidentally pre-
for aripiprazole and escitalopram. These results are consistent with scribed congruent medications (ie, medications without a GDI).
reports in adults; however, larger, intervention-based studies in pe- Additional analyses that control for medication congruency will
diatric populations will be needed to confirm these findings. be important to appropriately assess the clinical utility of CPGx
Although numeric improvements in CGI-I score were ob- testing in this population.
served in patients taking congruent medications compared with The design and methodology of the present study provided
those taking incongruent medications, this difference was not sta- an opportunity to efficiently obtain a preliminary account of
tistically significant. In patients who presented to the PED with clinical improvement and blood levels associated with CPGx
depression and/or suicidal ideation, significantly lower CGI-I testing in the PED pediatric population. Although it is difficult
scores were observed in patients taking congruent medications to draw meaningful conclusions from a small sample size, these
compared with those who were taking incongruent medications. findings are consistent with larger cohorts in adult patients with
In addition, a significant difference between medication blood depression.16–21,31 Although larger, more methodologically
levels across GDI categories was observed for aripiprazole and complex studies in this area are needed, the findings presented

here demonstrate the validity of CPGx testing in pediatric pa- 2. PharmGKB. PharmGKB Publications. 2021. Available at: https://www.
tients for 2 medications, and a potential clinical benefit for deter- pharmgkb.org/pgkbPublications. Accessed July 30, 2021.
mining medication congruency through testing, particularly in 3. PharmVar. PharmVar Publications. 2021. Available at: https://www.
pediatric patients with depression and/or suicidal ideation. pharmvar.org/publications. Accessed July 30, 2021.
Prior literature has shown that finding the appropriate dose
4. Brown JT, Bishop JR, Sangkuhl K, et al. Clinical pharmacogenetics
for pediatric patients can be challenging. In some cases, children implementation consortium guideline for cytochrome P450 (CYP)2D6
may be underdosed, which can result in failure to respond to a pre- genotype and atomoxetine therapy. Clin Pharmacol Ther. 2019;106:
scribed medication, particularly in poor metabolizers.10 In the 94–102.
present study, it was not possible to determine whether patients
were overdosed or underdosed based on the blood level data be- 5. Hicks JK, Bishop JR, Sangkuhl K, et al. Clinical Pharmacogenetics
cause there are insufficient blood-drug reference ranges for pedi- implementation consortium (CPIC) guideline for CYP2D6 and CYP2C19
genotypes and dosing of selective serotonin reuptake inhibitors. Clin
atric populations. However, there were a substantial number of pa-
Pharmacol Ther. 2015;98:127–134.
tients taking incongruent medications, indicating that regardless
of the dosing, clinically actionable GDIs occur in this population. 6. Hicks JK, Sangkuhl K, Swen JJ, et al. Clinical pharmacogenetics
Genetic determinants of drug metabolism and receptor binding implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19
can be responsible for drug failure and adverse drug reactions. genotypes and dosing of tricyclic antidepressants: 2016 update. Clin
These variations represent the need to predict patient blood levels Pharmacol Ther. 2017;102:37–44.
to reduce potential medication failure resulting from GDIs. Be- 7. American Academy of Child & Adolescent Psychiatry. Clinical use of
cause the number of pediatric patients who are being treated for pharmacogenetic tests in prescribing psychotropic medications for children
psychiatric disorders has continued to rise, the use of CPGx test- and adolescents. 2020. Available at: https://www.aacap.org/AACAP/Policy_
ing to personalize treatment might be beneficial, especially for Statements/2020/Clinical-Use-Pharmacogenetic-Tests-Prescribing-Psychotropic-
those who are being treated for depression and for those present- Medications-for-Children-Adolescents.aspx. Accessed July 30, 2021.
ing in crisis to a PED. 8. Perroud N, Uher R, Ng MY, et al. Genome-wide association study of
There are several limitations in the current study. This was a increasing suicidal ideation during antidepressant treatment in the
cross-sectional pilot study in a single PED, and no further outcome GENDEP project. Pharmacogenomics J. 2012;12:68–77.
data were obtained. Therefore, the impacts of GDIs on long-term out-
9. Tulisiak AK, Klein JA, Harris E, et al. Antidepressant prescribing by
comes of the patients involved in the study are unknown. Future stud- pediatricians: a mixed-methods analysis. Curr Probl Pediatr Adolesc
ies including intervention-based methodology will be important to Health Care. 2017;47:15–24.
appropriately evaluate the impact of CPGx testing. This study was
also limited to pediatric patients presenting to a PED; whether GDIs 10. Poweleit EA, Aldrich SL, Martin LJ, et al. Pharmacogenetics of sertraline
have an effect on broader groups of pediatric patients is also not tolerability and response in pediatric anxiety and depressive disorders.
J Child Adolesc Psychopharmacol. 2019;29:348–361.
known. Because of the design and setting of this study, it was not pos-
sible to control for factors that could have impacted medication blood 11. Wehry AM, Ramsey L, Dulemba SE, et al. Pharmacogenomic testing in
levels, including time since last medication dose, adherence, concom- child and adolescent psychiatry: an evidence-based review. Curr Probl
itant medications, and duration of treatment. In addition, data on Pediatr Adolesc Health Care. 2018;48:40–49.
previous medication trials were not collected. Finally, because this 12. Hathaway EE, Walkup JT, Strawn JR. Antidepressant treatment duration in
was a preliminary study, the sample size was relatively small. pediatric depressive and anxiety disorders: how long is long enough? Curr
Research regarding CPGx testing in pediatrics has been lim- Probl Pediatr Adolesc Health Care. 2018;48:31–39.
ited thus far. Professional societies, such as the American Academy 13. Washburn JJ, West AE, Heil JA. Treatment of pediatric bipolar disorder: a
of Child and Adolescent Psychiatry, currently recommend limited review. Minerva Psichiatr. 2011;52:21–35.
use of pharmacogenomic testing and call for continued research to
assess the clinical significance of pharmacogenomic testing in the 14. Steele M, Jensen PS, Quinn DM. Remission versus response as the goal of
pediatric population.7 Although more research is needed and this therapy in ADHD: a new standard for the field? Clin Ther. 2006;28:
caution is warranted, there is an escalating pediatric mental health 1892–1908.
crisis in the United States that is overwhelming PEDs and draining 15. Maruf AA, Greenslade A, Arnold PD, et al. Antidepressant
limited mental health resources. Psychotropic medication use in pharmacogenetics in children and young adults: a systematic review.
the pediatric population can have a profound positive impact on pa- J Affect Disord. 2019;254:98–108.
tient outcomes; CPGx testing in pediatric patients who present to 16. Rothschild AJPS, Hain D, Law R, et al. Clinical validation of combinatorial
the PED during acute crisis may lead to more effective and efficient pharmacogenomic testing and single-gene guidelines in predicting
use of health care resources. The encouraging results presented psychotropic medication blood levels and clinical outcomes in patients with
here support the need for further study in this area. depression. Psychiatry Res. 2020;296:113649.
17. Shelton RC, Parikh SV, Law RA, et al. Combinatorial pharmacogenomic
ACKNOWLEDGMENTS algorithm is predictive of citalopram and escitalopram metabolism in
The authors thank Krystal Brown, PhD, and Bryan Dechairo, patients with major depressive disorder. Psychiatry Res. 2020;290:113017.
PhD, for their editorial assistance and Brenda Rubalcaba for her 18. Parikh SV, Law RA, Hain DT, et al. Combinatorial pharmacogenomic
assistance with figure development (Myriad Genetics, Inc, Salt algorithm is predictive of sertraline metabolism in patients with major
Lake City, UT). The authors also thank Oliver Vranjkovic, PhD, depressive disorder. Psychiatry Res. 2022;114354:114354.
and Naryan Katel, MS, for their assistance with the study as well
19. Greden JF, Parikh SV, Rothschild AJ, et al. Impact of pharmacogenomics
as Paige Davies, MS, and James Li, PhD, for their assistance with
on clinical outcomes in major depressive disorder in the GUIDED trial: a
statistical analyses (Myriad Neuroscience, Mason, OH). large, patient- and rater-blinded, randomized, controlled study. J Psychiatr
Res. 2019;111:59–67.
REFERENCES 20. Hall-Flavin DK, Winner JG, Allen JD, et al. Using a pharmacogenomic
1. CPIC. Guidelines. 2021. Available at: https://cpicpgx.org/guidelines/. algorithm to guide the treatment of depression. Transl Psychiatry. 2012;
Accessed July 30, 2021. 2:e172.

21. Hall-Flavin DK, Winner JG, Allen JD, et al. Utility of integrated before and during the COVID-19 pandemic—United States, January
pharmacogenomic testing to support the treatment of major depressive 2019–May 2021. Morb Mortal Wkly Rep. 2021;70:888–894.
disorder in a psychiatric outpatient setting. Pharmacogenet Genomics. 27. Jablonski M, King N, Wang Y, et al. Analytical validation of a psychiatric
2013;23:535–548. pharmacogenomic test. Pers Med. 2018;15:189–197.
22. Voort JLV, Orth SS, Shekunov J, et al. A randomized controlled trial of 28. Harris PA, Taylor R, Minor BL, et al. The REDCap consortium: building an
combinatorial pharmacogenetics testing in adolescent depression. J Am international community of software platform partners. J Biomed Inform.
Acad Child Adolesc Psychiatry. 2022;61:46–55. 2019;95:103208.
23. Dagar A, Cherlopalle S, Ahuja V, et al. Real-world experience of using 29. Harris PA, Taylor R, Thielke R, et al. Research electronic data capture
combinatorial pharmacogenomic test in children and adolescents with (REDCap)—a metadata-driven methodology and workflow process for
depression and anxiety. J Psychiatr Res. 2021;146:83–86. providing translational research informatics support. J Biomed Inform.
24. Cutler GJ, Rodean J, Zima BT, et al. Trends in pediatric emergency 2009;42:377–381.
department visits for mental health conditions and disposition by presence 30. Busner J, Targum SD. The clinical global impressions scale: applying
of a psychiatric unit. Acad Pediatr. 2019;19:948–955. a research tool in clinical practice. Psychiatry (Edgmont). 2007;4:
25. Gonzalez-Urdiales P, Kuppermann N, Dalziel SR, et al. Pediatric 28–37.
intentional self-poisoning evaluated in the emergency department: an 31. Winner JG, Carhart JM, Altar CA, et al. A prospective, randomized,
international study. Pediatr Emerg Care. 2021;37:e1631–e1636. double-blind study assessing the clinical impact of integrated
26. Yard E, Radhakrishnan L, Ballesteros MF, et al. Emergency department pharmacogenomic testing for major depressive disorder. Discov Med.
visits for suspected suicide attempts among persons aged 12–25 years 2013;16:219–227.

ORIGINAL ARTICLE
Utilizing Near-Infrared Spectroscopy to Identify Pediatric

Trauma Patients Needing Lifesaving Interventions
A Prospective Study
David W. Ashby, DO, MS,* Binod Balakrishnan, MD,† David M. Gourlay, MD,† Michael T. Meyer, MD, MS,†
Mark Nimmer, BS,† and Amy L. Drendel, DO, MS†
direct interventions to optimize patient outcomes. Currently, the

Objectives: The aim of this study was to prospectively investigate the detection of shock relies heavily on hemodynamic monitoring
role of near-infrared spectroscopy (NIRS) in identifying pediatric trauma (blood pressure, pulse oximetry, and electrocardiography), clinical
patients who required lifesaving interventions (LSIs). examination, and laboratory evidence (acid-base status or serum
Methods: Prospective cohort study of children age 0 to 18 years who ac- lactate levels). These have been shown to be relatively late indica-
tivated the trauma team response between August 15, 2017, and February tors of shock and are of limited use in the early identification and
12, 2019, at a large, urban pediatric emergency department (ED). optimal resuscitation of shock.6–17
The relationship between the lowest somatic NIRS saturation and the Regional oxygen extraction is an established early objective
need for LSIs (based on published consensus definition) was investigated. predictor of shock that has historically been measured by invasive
Categorical variables were analyzed by χ2 test, and continuous variables methods such as central line placement and/or blood extraction.18–21
were analyzed by Student t test. Near-infrared spectroscopy (NIRS) is a real-time, noninvasive, con-
Results: A total of 148 pediatric trauma patients had somatic NIRS mon- tinuous monitoring device that assesses oxyhemoglobin and deoxy-
itoring and met the inclusion criteria. Overall, 65.5% were male with a hemoglobin in tissue to provide a measure of regional oxygen extrac-
mean ± SD age of 10.9 ± 6.0 years. Injuries included 67.6% blunt trauma tion. Two of the most common sites where tissue perfusion is moni-
and 28.4% penetrating trauma with mortality of 3.4% (n = 5). Overall, the tored in pediatrics are over the forehead (cerebral NIRS) and over the
median lowest somatic NIRS value was 72% (interquartile range, 58%– flank (somatic NIRS). Near-infrared spectroscopy monitoring has
88%; range, 15%–95%), and 43.9% of patients had a somatic NIRS value been shown to identify developing shock states in critically ill patients
<70%. The median somatic NIRS duration recorded was 11 minutes (inter- by providing a regional oxygen saturation that reflects tissue per-
quartile range, 7–17 minutes; range, 1–105 minutes). Overall, 36.5% of pa- fusion to these areas.22,23 There is strong evidence for improved
tients required a LSI including 53 who required a lifesaving procedure, 17 outcomes in patients with evolving septic shock states if global
required blood products, and 17 required vasopressors. Among procedures, oxygen balance measures are measured.14,24
requiring a thoracostomy was significant. Near-infrared spectroscopy has been used in adult trauma stud-
Pediatric trauma patients with a somatic NIRS value <70% had a sig- ies. Beekley et al25 showed an association between the need for life-
nificantly increased odds of requiring a LSI (odds ratio, 2.11; 95% confi- saving interventions (LSIs) and low regional oxygen saturation in
dence interval, 1.07–4.20). Somatic NIRS values <70% had a sensitivity adult combat casualties. A minimum NIRS value <70% within 1 hour
and specificity of 56% and 63%, respectively. of emergency department (ED) arrival in adult trauma patients corre-
Conclusions: Pediatric trauma patients with somatic NIRS values <70% lated with the need for blood transfusion within 24 hours of arrival
within 30 minutes of ED arrival have an increased odds of requiring LSIs. that was not predicted by hypotension, tachycardia, arterial lactate,
Among LSIs, pediatric trauma patients requiring thoracostomy was signif- base deficit, or hemoglobin.26 Near-infrared spectroscopy measure-
icant. The role of NIRS in incrementally improving the identification of ments <75% were associated with an increased risk of multiple organ
critically injured children in the ED and prehospital setting should be eval- dysfunction syndrome and mortality for adult trauma patients.23,27–29
uated in larger prospective multicenter studies. The NIRS measurements <78% were also correlated with acute
Key Words: near-infrared spectroscopy, lifesaving interventions blood loss and need for massive transfusion in adults.25,30
Prior somatic NIRS research in the pediatric trauma popula-
(Pediatr Emer Care 2023;39: 13–19)
tion has shown that pediatric trauma patients with low somatic ox-
ygen saturation (<70%) during the first 30 minutes of ED arrival
T raumatic injury continues to be the leading cause of death for
children aged 1 to 19 years.1 Children with traumatic injuries
present in hypovolemic, obstructive, and distributive shock states.
have an increased odds of requiring LSIs (odds ratio [OR], 2.67;
95% confidence interval [CI], 1.10–6.47) with a sensitivity and
specificity of 67% and 57%, respectively, in 1 retrospective
These patients may display nearly normal vital signs even in the
study.31 To date, no prospective studies of pediatric trauma pa-
presence of severe shock.2–5 It is important to detect early shock states
tients have evaluated the association between somatic NIRS
in pediatric trauma patients to minimize morbidity and mortality and
values and the requirement for LSIs. This would reduce the risk
of bias associated with differential application of NIRS and the
From the *Texas Children's Hospital, Baylor College of Medicine, Houston, TX; opportunity for more rigorous data collection.
and †Children's Wisconsin, Medical College of Wisconsin, Milwaukee, WI. The goal of this study was to evaluate the hypothesis that pediatric
Disclosure: The authors declare no conflict of interest.
Reprints: David W. Ashby, DO, MS, Department of Pediatrics, Division of
trauma patients with a somatic NIRS oxygen saturation <70% within
Pediatric Emergency Medicine, Texas Children's Hospital, Baylor College 30 minutes of ED arrival was associated with the need for LSIs.
of Medicine, Suite A2210, 6621 Fannin, Houston, TX 77030 (e‐mail:
dwashby@texaschildrens.org).
This study was presented at the 2019 Pediatric Academic Societies Poster METHODS
Presentation.
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. This was a prospective cohort study of pediatric trauma pa-
ISSN: 0749-5161 tients aged 0 to 18 years who activated the Children's Hospital
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Ashby et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
of Wisconsin (CHW) trauma team response between August 15, of the potential confounding effect of bilirubin on NIRS values).
2017, and February 12, 2019 (Table 1). A consecutive sample of Children with skin breakdown in the area of probe placement were
patients was identified in the CHW trauma registry. Patients were also excluded because impaired adhesion of the NIRS sensors
excluded if they could have a predisposition to abnormal baseline could confound the NIRS regional oxygen saturation value. Exclu-
NIRS values, and this included patients with cyanotic heart dis- sion criteria similar to these have been used in prior pediatric NIRS
ease, cystic fibrosis, and chronic lung disease because of possible studies.31–33 The CHW is an American College of Surgeons–
chronic hypoxemia. Other patients excluded include those with verified level 1 pediatric trauma center. The institutional review
kidney disease (because of the somatic NIRS measuring the re- board (IRB) at CHW approved the study without need for informed
gional saturation of the kidneys) and hyperbilirubinemia (because consent (IRB number 1103259-1).
Near-infrared spectroscopy monitoring was recommended
TABLE 1. Children's Hospital of Wisconsin Trauma Criteria With by hospital practice guidelines for all pediatric patients that acti-
Corresponding Trauma Level vated the trauma team response as a part of the evaluation for this
patient population. A NIRS sensor (INVOS; Somanetics, Troy,
Trauma MI) was expected to be applied to either side of the paravertebral
Trauma Criteria Level space between T12 and L2 (somatic NIRS) of each patient by a
trauma nurse to monitor oxygen saturation in the underlying tis-
Airway sue, approximating the renal vascular bed. A NIRS sensor was
Intubation/assisted ventilation Level 1 also applied to the forehead (cerebral NIRS) approximating the
(excluding hanging or near drowning) cerebral vascular bed. The minimum NIRS value during the ED
Breathing visit was abstracted for each patient from the hospital data warehouse.
Respiratory arrest Level 1 Trauma patients with NIRS sensors applied within 30 minutes of
Respiratory distress (ineffective respiratory Level 1 arrival to the ED and who registered at least 60 seconds of NIRS
effort, stridor, or grunting) values to abstract were included. This methodology is consistent
Respiratory rate with prior literature.31,34,35 For those patients admitted to the hos-
0 to 5 mo of age: RR <20 Level 1 pital, the NIRS sensors either remained on the patient for contin-
6 mo to 12 y of age: RR <16 Level 1 ued monitoring or were removed at the discretion of the admitting
≥13 y of age: RR <12 Level 1 trauma or PICU physician.
Suspected airway injury from facial burns, Level 2
A somatic NIRS saturation of <70% was deemed to be the
chemical or smoke inhalation threshold in this study based on our team's prior work conducted
Circulation
in the pediatric trauma population,31 a study in the pediatric criti-
cal care population,32 and studies of the adult trauma population
0 to 5 mo of age: SBP <60; HR <90 Level 1
using the thenar eminence or an uninjured extremity.22,23,25,27 In
6 mo to 5 y of age: SBP <70; HR <70 Level 1 addition, this value is 2 standard deviations (SDs) below the mean
≥6 y of age: SBP <90; HR <60 Level 1 somatic NIRS range of 86.8% ± 8.1% established in healthy new-
Clinical signs of shock (pale, cold, clammy, Level 1 borns.36 Cerebral NIRS values were also collected and assessed in
tachycardia with weak pulses, capillary this study, and a cerebral NIRS saturation <60% was evaluated. A
refill >3 s [assuming a cerebral NIRS value of 60% is 2 SDs below a mean ± SD of
warm environment])
77% ± 8.5% established in term neonates.36
Patients receiving >40 mL/kg intravenous fluid Level 1 The association between NIRS measurement and the need
Patients who are receiving blood Level 1 for LSIs was investigated. Lifesaving interventions included any
Neurological lifesaving procedure within 4 hours of arrival, initiation of vaso-
Glasgow Coma Scale ≤12 Level 1 pressor within 4 hours of arrival, or blood product within 2 hours
Anatomic diagnosis of arrival (Table 2) as defined by the Consensus-Based Criterion
Penetrating injury to head, neck, torso, groin Level 1 Standard Definition for Pediatric Trauma Patients Who Needed
Flail chest Level 1 the Highest-Level Trauma Team Activation.37
Open chest wound Level 1
Open or depressed skull fracture — blunt trauma Level 2 Data Collection
Suspected spine or spinal cord injury Level 2
Once eligible patients were identified, prehospital, interfacility,
Bilateral femur fractures Level 2 and ED vital signs were collected by manual chart review by the
Pelvic fracture Level 2 trauma registry. Details related to the LSIs were also abstracted from
Complete/partial amputation or degloving above Level 2 the trauma registry, and manual chart review was performed by a
wrist and above ankle single abstractor (D.W.A.) collecting patient medical record num-
Deep penetrating injuries above elbow and above knee Level 2 ber, ED arrival time, ED departure time, LSIs (Table 2), LSI time,
Significant, blunt maxillofacial trauma Level 2 maximum oxygen flow rate, fraction of inspired oxygen, oxygen
Tourniquet placement Level 1 delivery device, hospital admission unit, age, sex, race, ethnicity,
Gunshot wounds or trauma to neck, chest, abdomen, Level 1 past medical history, injury diagnosis, mechanism of injury, prehos-
or extremities above the knee or elbow pital vitals, prehospital cardiopulmonary resuscitation, prehospital
Hanging or near drowning that needs intubation, Level 2 tourniquet, prehospital cardiac arrest, arrival signs of life, ED car-
with or without on-scene CPR with ROSC or diopulmonary resuscitation, trauma level designation, ED Glasgow
CPR in progress Coma Score, raw revised trauma score, body mass index, ED dis-
position, injury severity score, total ventilator days, total intensive
CPR indicates cardiopulmonary resuscitation; HR, heart rate; RR, re-
spiratory rate; ROSC, return of spontaneous circulation; SBP, systolic
care unit length of stay, hospital length of stay, mortality, minutes
blood pressure. to somatic and cerebral NIRS application, minimum somatic
NIRS value, and minimum cerebral NIRS value.
14 www.pec-online.com © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Pediatric Emergency Care • Volume 39, Number 1, January 2023 NIRS for Identifying Trauma Patients Needing LSIs
(Fig. 2). Of the 148 patients who met inclusion criteria having so-
TABLE 2. Lifesaving Interventions and Timeframe matic NIRS monitoring, 112 patients also had cerebral NIRS
monitoring applied. Overall, 65.5% were male with a mean ± SD
LSIs Timeframe, h
age of 10.9 ± 6.0 years. Injuries included 67.6% blunt trauma and
Procedures 28.4% penetrating trauma. The overall mortality in patients with
Advanced airway management (ie, 2 somatic NIRS monitoring was 3.4% (n = 5) (Table 3). Overall,
endotracheal intubation, supraglottic airway, etc) the median lowest somatic NIRS value recorded was 72% (IQR,
Thoracostomy 2 58%–88%; range, 15%–95%). Furthermore, 43.9% of patients
Pericardiocentesis 2 had a somatic NIRS value <70%. The median somatic NIRS du-
Thoracotomy 2 ration recorded was 11 minutes (IQR, 7–17 minutes; range, 1–
105 minutes). Overall, among the 112 patients who had cerebral
CPR 2
NIRS applied, the median lowest cerebral NIRS value recorded
Vascular, neurologic, abdominal, thoracic, 4 was 70% (IQR, 57%–77%; range, 15%–95%). Moreover, 28.6%
pelvic, spine, or limb-conserving surgery
of patients had a NIRS cerebral value <60%. The median cerebral
IR for interventional or diagnostic surgery 4 NIRS duration recorded was 11 minutes (IQR, 7–17 minutes;
Emergency cesarean delivery 4 range, 1−106 minutes). Overall, 36.5% of patients required a
Burr hole or intracranial pressure relieving 4 LSI including 53 who underwent a lifesaving procedure, 17 re-
procedure or intracranial pressure monitoring quired blood products, and 17 received vasoactive medications
Blood products (Table 4). Of the patients who received a LSI, 20 required 1, and
>1 unit of blood products or at least 10 mL/kg 2 34 required 2 or more.
packed red blood cells, fresh frozen plasma, Pediatric trauma patients with somatic NIRS <70% had a sig-
and/or platelets nificantly increased odds of requiring a LSI (OR, 2.11; 95% CI,
Vasoactive medications 1.07–4.20). Among procedures, requiring a thoracostomy was
Epinephrine, norepinephrine, vasopressin, 4 significant. Among vasopressors, requiring epinephrine was sig-
phenylephrine, milrinone, or dopamine nificant. Pediatric trauma patients with NIRS <70% were not
CPR indicates cardiopulmonary resuscitation; IR, interventional radiology.
more likely to receive a blood product. Patients with somatic
NIRS <70% had a sensitivity and specificity of 56% and 63%, re-
spectively, with an area under the receiver operating characteris-
Near-infrared spectroscopy regional oxygen saturation mon- tics curve of 0.592. When different cutoffs were investigated, a so-
itors obtain data through serial outputs every 5 to 6 seconds that matic NIRS <71% had the highest area under the receiver operat-
were saved into the hospital data warehouse. A hospital data inte- ing characteristic curve of 0.610 with an OR of 2.45 (95% CI,
gration analyst specialist abstracted the relevant NIRS data for the 1.24–4.92) (Fig. 1). There was no significant association between
eligible patients into a spreadsheet that was linked to each unique pediatric trauma patients with minimum cerebral NIRS <60% and
trauma patient. requiring a LSI procedure, blood product, or vasopressor.
Statistical Analysis Subgroup Analyses

Eligible patient baseline demographics and clinical charac- A subgroup of pediatric trauma patients had both cerebral
teristics were summarized using descriptive statistics. Dichoto- and somatic NIRS monitoring (n = 112). Pediatric trauma patients
mous variables were analyzed using χ2 test. Continuous variables
were analyzed using the Student t test. Parametric variables were
described as means and SDs, and nonparametric variables were
described as medians and interquartile ranges (IQRs). The lowest
somatic NIRS value abstracted during the ED visit was used to
classify the patients into 2 groups: minimum somatic NIRS values
<70% and 70% or greater. The proportion of patients receiving
LSIs was compared for those two groups. The lowest cerebral
NIRS value was also abstracted during the ED visit used to clas-
sify the patients in to two groups: minimum cerebral NIRS values
<60% and minimum cerebral NIRS values 60% or greater. The
proportion of patients receiving LSIs was evaluated for these
two groups. Demographics and clinical characteristics were com-
pared by LSIs using χ2 test or Fisher exact test. A receiver oper-
ating characteristic curve was generated to establish a cutoff for
the somatic NIRS value as a predictor of LSIs (Fig. 1). The OR
with the 95th percentile CI for pediatric trauma patients with so-
matic NIRS <70% who required a LSI was also investigated. A
significance level of 5% was used for all analyses. All statistical
analyses were done using SAS Software for Windows version 9.4.
RESULTS
Between August 15, 2017, and February 12, 2019, 223
trauma patients activated CHW's trauma activation team and pre- FIGURE 1. Receiver operating characteristic curve shows an area of
sented to the ED. A total of 148 patients (66.7%) had somatic 0.610 for pediatric trauma patients with somatic NIRS < 70% as a
NIRS monitoring and were included in the final analysis predictor of LSIs.
© 2022 Wolters Kluwer Health, Inc. All rights reserved. www.pec-online.com 15

FIGURE 2. Consort diagram.
whose somatic NIRS values were <70% had cerebral NIRS values Prior NIRS research in the pediatric trauma population has
significantly lower (58%; IQR, 50%–69%; range, 15%–95%) also shown that children with a low NIRS somatic oxygen satura-
than the cerebral NIRS values of patients whose somatic NIRS tion (<70%) during the first 30 minutes of ED arrival have an in-
values were ≥70% (75%; IQR, 69%–79%; range, 35%–94%) creased odds of requiring LSIs (OR, 2.67; 95% CI, 1.10–6.47)
( P < 0.05). with a sensitivity and specificity of 67% and 57%, respectively,
Another subgroup of patients had only somatic NIRS moni- in one retrospective study.31 This study includes more patients,
toring (n = 36). When this group was compared with the subgroup identifies the significant LSIs pediatric trauma patients are more
of patients who had both cerebral and somatic NIRS monitoring likely to require, and allows for subgroup analyses. The findings
(n = 112), there was no significant difference between the groups are remarkably comparable and consistent. These findings are
for requiring a LSI (OR, 1.42; 95% CI, 0.63–3.17). There was also also similar to a prior study of critical care patients that showed
no significant difference between the groups for having somatic a NIRS somatic oxygen saturation <70% during the first 4 hours
NIRS values <70% (OR, 0.97; 95% CI, 0.46–2.07). of pediatric intensive care unit admission was associated with
the need for LSIs in the initial 24 hours.32 Although this study
population included only a small number of pediatric trauma pa-
tients (17% [n = 32]), it highlighted the usefulness of NIRS mon-
DISCUSSION itoring for critically ill pediatric patients.
This study has several important implications for the pediat- This is the first prospective study to examine the association
ric trauma population evaluation and builds on prior evidence between pediatric NIRS somatic oxygen saturation and LSIs in
helping pediatric trauma providers consider the role of this moni- the ED setting and found that pediatric trauma patients with so-
toring device to identify high-risk pediatric trauma patients. Our matic NIRS <70% are likely to require LSI procedures. In this pa-
primary finding is that pediatric trauma patients with somatic tient cohort, requiring a thoracostomy was significant. The opti-
NIRS values <70% within 30 minutes of ED arrival are associated mal somatic NIRS cut point that identifies pediatric trauma pa-
with an increased odds for receiving a LSI. tients requiring LSIs was also found to be a somatic NIRS value
Prior NIRS research in the adult trauma population has also <71%. There is a devastating cost of missing a severely injured pe-
shown an association between the need for LSIs and low regional diatric trauma patient who requires a LSI, and this study defines a
oxygen saturation in combat casualties.25 Near-infrared spectros- NIRS threshold for early identification of patients who are more
copy has also been able to differentiate between patients who died likely to require LSIs. More studies are needed, and attention to
or developed multiple organ dysfunction syndrome from their in- the balances of sensitivity and specificity is critically important
juries.23 Another study also showed that a minimum NIRS value in this patient population. This also highlights the importance of
<70% within 1 hour of ED arrival correlated with the need for having a thorough evaluation by skilled trauma providers and that
blood transfusion within 24 hours of arrival that was not predicted they designate experienced physicians to be in charge of these
by hypotension, tachycardia, arterial lactate, base deficit, or hemo- bedside procedures. Trauma is a major mechanism of injury that
globin.26 Our study similarly highlights the need for LSIs in can create the need for these emergent procedures like placing
trauma patients who present with low somatic NIRS values, chest tubes and intubation, and the trauma team should be pre-
namely, LSI procedures like thoracostomy. pared to manage these situations in this patient population. The

our study did not find that patients with cerebral NIRS <60% re-
TABLE 3. Demographics of Pediatric Trauma Patients quired significantly more LSIs, this could be important data mov-
ing forward. However, this study did find that pediatric trauma pa-
Somatic NIRS Placed
tients with somatic NIRS values <70% had cerebral NIRS values
Minimum Minimum significantly lower (58%; IQR, 50%–69%; range, 15%–95%)
Somatic Somatic No Somatic than the cerebral NIRS values of patients whose somatic NIRS
NIRS <70 NIRS ≥70 NIRS Placed values were ≥70% (75%; IQR, 69%–79%; range, 35%–94%). It
has been previously hypothesized that intact cerebral autoregula-
No. patients 65 83 75
tion maintains adequate cerebral perfusion in compensated shock
Age, mean ± SD, y 10.7 ± 6.6 11.0 ± 5.5 10.0 ± 5.8 at the expense of renal and mesenteric perfusion. Thus, a near nor-
Sex, n (%) mal cerebral NIRS saturation can persist despite a decreased so-
Male 43 (66.2) 54 (65.1) 47 (62.7) matic NIRS value.32 These findings suggest a relationship be-
Female 22 (33.8) 29 (34.9) 28 (37.3) tween cerebral and somatic NIRS values and the possibility of a
Race, n (%) somatic NIRS threshold that, when somatic NIRS values drop be-
Black* 45 (69.2) 20 (24.1) 25 (33.3) low this threshold, identifies a change in cerebral perfusion. Thus,
White* 16 (24.6) 52 (62.7) 34 (45.3) when somatic NIRS values drop below this value, cerebral auto-
American Indian 1 (1.5) 0 (0.0) 0 (0.0) regulation may become compromised, and perfusion to the brain
may be altered demonstrated by a decreased cerebral NIRS value.
Multiracial 1 (1.5) 1 (1.2) 5 (6.7)
Further research should be performed to identify a potential range
Unknown 2 (3.1) 10 (12.0) 11 (14.7)
of somatic NIRS values that maintain normal cerebral perfusion
Ethnicity, n (%) until a possible critical threshold is reached and cerebral NIRS
Hispanic/Latino 6 (9.2) 10 (12.0) 13 (17.3) values start to decline.
Not Hispanic/Latino 55 (84.6) 67 (80.7) 56 (74.7) There are limitations to this study's design. This was a single-
Unknown 4 (6.2) 6 (7.2) 6 (8.0) center study and limited to patients who presented to the pediatric
BMI (kg/m2), mean ± SD 21.0 ± 14.9 20.4 ± 11.4 28.7 ± 57.2 ED. The findings may not be generalizable to other EDs. Because
Mechanism of injury, n (%) the NIRS monitoring is recommended for all pediatric trauma pa-
Anoxic 0 (0.0) 1 (1.2) 0 (0.0) tients at CHW, the providers who cared for the injured patients
Blunt 43 (66.2) 57 (68.7) 52 (69.3) knew the NIRS values and may have provided differential clinical
care. During this timeframe at this institution, these health care
Fire/burn 1 (1.5) 1 (1.2) 2 (2.7)
providers were not using NIRS regularly for any other patient care
Penetrating 19 (29.2) 23 (27.7) 20 (26.7)
Other 2 (3.0) 1 (1.2) 1 (1.3)
TABLE 4. Number and Type of LSIs in Pediatric Trauma Patients
Injury Severity Score, 13.7 ± 12.4 11.7 ± 10.3 16.1 ± 14.7 With Somatic NIRS Values
mean ± SD
Trauma level designation (50/15) (56/27) (48/27) Minimum Minimum
(Level 1/Level 2) Somatic NIRS Somatic NIRS
Mortality, n (%) <70 (n = 65) ≥70 (n = 83) P
Lived 62 (95.4) 81 (97.6) 72 (96.0)
Died 3 (4.6) 2 (2.4) 3 (4.0) No. LSIs per patient, 0.75 (0.99) 0.46 (0.80) 0.046
mean ± SD*
*Significant at P < 0.05. Any LSI, n (%)* 30 (46.2) 24 (28.9) 0.031
BMI indicates body mass index; NIRS, near-infrared spectroscopy. Procedures (within 4 h 29 (44.6) 24 (28.9) 0.048
after arrival), n (%)*
Surgery 9 (13.8) 15 (18.1) 0.489
utilization of NIRS monitoring may cue the trauma team and act Advanced airway 22 (33.8) 17 (20.5) 0.067
as an early warning system or severity marker to skilled providers management
ready to perform lifesaving procedures. The leading cause of CPR 3 (4.6) 0 (0.0) 0.083
death for children aged 1 to 19 years continues to be traumatic in- Intracranial pressure 4 (6.2) 4 (4.8) 0.731
jury.1 Trauma deaths have a trimodal distribution of immediate monitoring
(seconds to minutes after injury), early (minutes to hours after in- IR for interventional or 1 (1.5) 0 (0.0) 0.439
jury), and late (days to weeks after injury) death. It is imperative that diagnostic purposes
trauma researchers continue to identify and use diagnostic modali- Thoracostomy* 11 (16.9) 1 (1.2) 0.001
ties that can improve earlier detection of those trauma patients who Thoracotomy 1 (1.5) 0 (0.0) 0.439
require LSIs that reduce the risk of mortality in trauma patients who Blood products, n (%) 10 (15.4) 7 (8.4) 0.188
are at risk of early and late death. Near-infrared spectroscopy device Fresh frozen plasma 8 (12.5) 6 (7.2) 0.280
is a promising technology to identify this high-risk population. Platelets 6 (9.2) 3 (3.6) 0.182
This study is also the first study to examine the association Packed red blood cells 10 (15.4) 8 (9.6) 0.288
between pediatric NIRS cerebral oxygen saturation and LSIs in
Vasoactive medications, n (%) 10 (15.4) 7 (8.4) 0.188
the ED setting. A subgroup of our pediatric trauma patients
(n = 112) had both cerebral and somatic NIRS monitoring. A prior Epinephrine* 10 (15.4) 3 (3.6) 0.017
study evaluating 4 regions of the brain bilaterally with a NIRS de- Phenylephrine 2 (3.1) 4 (4.8) 0.695
vice (InfraScan, Philadelphia, PA) found that abnormal cerebral *Significant at P < 0.05.
NIRS measurements predicted the presence of intracranial hemor- CPR indicates cardiopulmonary resuscitation; IR, interventional radiol-
rhage in the majority of pediatric patients with computed tomog- ogy; NIRS, near-infrared spectroscopy.
raphy images identifying intracranial hemorrhage.38 Although

in the ED, making it is less likely that this design flaw impacted 2. Partrick DA, Bensard DD, Janik JS, et al. Is hypotension a reliable indicator
the results. The design of the study limits the information available of blood loss from traumatic injury in children? Am J Surg. 2002;184:
for analysis to what has been recorded in the medical record, 555–559. discussion 559–60.
trauma registry, and NIRS devices, as trauma providers were not 3. Sinniah D. Shock in children. JSME. 2012;6(suppl 1):S129–S136.
interviewed and trauma documentation rarely described providers' 4. American College of Surgeons on Trauma. Shock. In: ATLS Student
rationale or the indications for the individual LSIs. Further pro- Course Manual. 8th ed. Chicago, IL: American College of Surgeons on
spective interventional studies focusing on providers' rationale Trauma; 2008:56–61.
for LSIs and the timing of LSIs in relation to NIRS values should
5. Brysiewicz P, Clarke D, Sartorius B, et al. Defining predictors of mortality
be performed. The database used was limited to only the single in pediatric trauma patients. S Afr J Surg. 2017;55:36–40.
primary diagnosis, which did not allow for comparison of the ac-
tual diagnoses of the trauma patients. Near-infrared spectroscopy 6. Shoemaker WC. Relation of oxygen transport patterns to the
sensors may have been applied differentially. Reasons for missed pathophysiology and therapy of shock states. Intensive Care Med. 1987;
13:230–243.
eligible patients may include delay in application of NIRS sensors,
NIRS sensors not being applied to patient because of short time 7. Schlag G, Redl H, Hallstrom S. The cell in shock: the origin of multiple
spent in trauma room, trauma team member inexperience in ap- organ failure. Resuscitation. 1991;21:137–180.
plying sensor correctly, and nonadherence of NIRS sensor to 8. Proulx F, Gauthier M, Nadeau D, et al. Timing and predictors of death in
patient's skin (because of perspiration, dirt, etc). To evaluate for pediatric patients with multiple organ system failure. Crit Care Med. 1994;
any bias in the application of somatic NIRS monitoring among pa- 22:1025–1031.
tients or injury characteristics in the total trauma patient popula- 9. Hatherill M, Waggie Z, Purves L, et al. Mortality and the nature of
tion, patients with somatic NIRS monitoring placed were com- metabolic acidosis in children with shock. Intensive Care Med. 2003;
pared with those without somatic NIRS monitoring. There were 29:286–291.
no significant differences for sex, race, ethnicity, or injury charac- 10. Tantalean J, Leon R, Santos A, et al. Multiple organ dysfunction syndrome
teristics, but not all factors can be accounted for in this design. To in children. Pediatr Crit Care Med. 2003;4:181–185.
evaluate for any bias in the application of the cerebral NIRS sensor
11. Rhodes A, Bennett ED. Early goal-directed therapy: an evidence-based
among patients who had somatic NIRS monitoring, the patients
review. Crit Care Med. 2004;32:S448–S450.
who had cerebral and somatic NIRS monitoring were compared
with those who had only somatic NIRS monitoring. There was 12. Yu M, Burchell S, Hasaniya NW, et al. Relationship of mortality to
no significant difference between groups who required LSIs nor increasing oxygen delivery in patients > or = 50 years of age: a prospective,
between groups who had somatic NIRS <70%. The effect of skin randomized trial. Crit Care Med. 1998;26:1011–1019.
pigmentation on NIRS has not been well studied with a study sug- 13. Alia I, Esteban A, Gordo F, et al. A randomized and controlled trial of the
gesting that NIRS should be interpreted with caution in dark skin effect of treatment aimed at maximizing oxygen delivery in patients with
pigmentation because of melanin affecting the quality of returned severe sepsis or septic shock. Chest. 1999;115:453–461.
near-infrared light.39 Near-infrared spectroscopy device data analyzed 14. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in
were from 2 anatomic sites at a single tissue depth. We chose the fore- the treatment of severe sepsis and septic shock. N Engl J Med. 2001;
head (cerebral NIRS) and the flank (somatic NIRS) because these are 345:1368–1377.
the most common sites used in other pediatric NIRS studies.31–33 15. Rivers EP, Ander DS, Powell D. Central venous oxygen saturation
monitoring in the critically ill patient. Curr Opin Crit Care. 2001;
CONCLUSIONS 7:204–211.
For pediatric trauma patients, a somatic NIRS oxygen satura- 16. Han YY, Carcillo JA, Dragotta MA. Early reversal of pediatric-neonatal
tion value <70% within 30 minutes of ED arrival is associated septic shock by community physicians is associated with improved
with the need for LSIs. Among LSIs, pediatric trauma patients outcome. Pediatrics. 2003;112:793–799.
with somatic NIRS <70% are most likely to require LSI proce- 17. Tibby SM, Murdoch IA. Monitoring cardiac function in intensive care.
dures including thoracostomy. A cerebral NIRS oxygen saturation Arch Dis Child. 2003;88:46–52.
value <60% within 30 minutes of ED arrival is not associated with 18. Haljamae H. The pathophysiology of shock. Acta Anaesthesiol Scand
the need for LSIs. Near-infrared spectroscopy is a valuable tool in Suppl. 1993;98:3–6.
delineating the pediatric trauma patients that require the highest
19. Dyess DL, Powell RW, Swafford AN. Redistribution of organ blood flow
level of pediatric trauma care. Near-infrared spectroscopy appears
after hemorrhage and resuscitation in full-term piglets. J Pediatr Surg.
to be a promising tool in delineating trauma patients who require 1994;29:1097–1102.
the highest level of pediatric trauma care. The role of NIRS in in-
crementally improving the identification of critically injured chil- 20. Reilly PM, Wilkins KB, Fuh KC, et al. The mesenteric hemodynamic
response to circulatory shock: an overview. Shock. 2001;15:329–343.
dren in the ED and prehospital setting should be evaluated in
larger prospective multicenter studies. 21. Ceppa EP, Fuh KC, Bulkley GB. Mesenteric hemodynamic response to
circulatory shock. Curr Opin Crit Care. 2003;9:127–132.
ACKNOWLEDGMENTS 22. Crookes BA, Cohn SM, Bloch S, et al. Can near-infrared spectroscopy
The authors acknowledge Raphael Fraser, PhD, and Alexis identify the severity of shock in trauma patients? J Trauma. 2005;
Visoctcky, MS, for statistical analyses; Jill Jaeger, RN, for 58:806–816.
obtaining trauma registry data; and Duke Wagner, DC, for com- 23. Cohn SM, Nathens AB, Moore FA, et al. Tissue oxygen saturation predicts
pliance with IRB procedures. the development of organ dysfunction during traumatic shock resuscitation.
J Trauma. 2007;62:44–54.
REFERENCES 24. de Oliveira CF. Early goal-directed therapy in treatment of pediatric septic
1. National Vital Statistics System, National Center for Health Statistics, shock. Shock. 2010;34:44–47.
CDC. 10 Leading causes of death by age group, United States—2019. 25. Beekley AC, Martin MJ, Nelson T, et al. Continuous noninvasive tissue
2019. Available at: https://webappa.cdc.gov/sasweb/ncipc/leadcause.html. oximetry in the early evaluation of the combat casualty: a prospective study.
Accessed March 26, 2021. J Trauma. 2010;69(suppl 1):S14–S25.

26. Smith J, Bricker S, Putnam B. Tissue oxygen saturation predicts the need 33. Hanson SJ, Berens RJ, Havens PL, et al. Effect of volume resuscitation
for early blood transfusion in trauma patients. Am Surg. 2008;74: on regional perfusion in dehydrated pediatric patients as measured
1006–1011. by two-site near-infrared spectroscopy. Pediatr Emerg Care. 2009;
27. Moore FA, Nelson T, McKinley BA, et al. Massive transfusion in trauma 25:150–153.
patients: tissue hemoglobin oxygen saturation predicts poor outcome. 34. Johnson A, Roskosky M, Freedman B, et al. Depth penetration of near
J Trauma. 2008;64:1010–1023. infrared spectroscopy in the obese. J Trauma Treat. 2015;4:263.
28. Beilman GJ, Blondet JJ, Nelson TR, et al. Early hypothermia in severely 35. Hyttel-Sorensen S, Sorensen LC, Riera J, et al. Tissue oximetry: a
injured trauma patients is a significant risk factor for multiple organ comparison of mean values of regional tissue saturation, reproducibility
dysfunction syndrome but not mortality. Ann Surg. 2009;249:845–850. and dynamic range of four NIRS-instruments on the human forearm.
29. Sagraves SG, Newell MA, Bard MR, et al. Tissue oxygenation monitoring Biomed Opt Express. 2011;2:3047–3057.
in the field: a new EMS vital sign. J Trauma. 2009;67:441–443. 36. Bernal NP, Hoffman GM, Ghanayem NS, et al. Cerebral and somatic near-
30. Torella F, Cowley RD, Thorniley MS, et al. Regional tissue oxygenation infrared spectroscopy in normal newborns. J Pediatr Surg. 2010;45:
during hemorrhage: can near infrared spectroscopy be used to monitor 1306–1310.
blood loss? Shock. 2002;18:440–444. 37. Lerner EB, Drendel AL, Falcone RA, et al. A consensus-based criterion
31. Ashby DW, Gourlay DM, Balakrishnan B, et al. Utilizing near-infrared standard definition for pediatric patients who needed the highest-level
spectroscopy (NIRS) to identify pediatric trauma patients needing trauma team activation. J Trauma Acute Care Surg. 2015;78:634–638.
lifesaving interventions (LSIs): a retrospective study. Pediatr Emerg Care. 38. Salonia R, Bell MJ, Kochanek PM, et al. The utility of near infrared
2022;38:e193–e199. spectroscopy in detecting intracranial hemorrhage in children.
32. Balakrishnan B, Dasgupta M, Gajewski K, et al. Low near infrared J Neurotrauma. 2012;29:1047–1053.
spectroscopic somatic oxygen saturation at admission is associated with 39. Wassenaar EB, Van den Brand JGH. Reliability of near-infrared
need for lifesaving interventions among unplanned admissions to the spectroscopy in people with dark skin pigmentation. J Clin Monit Comput.
pediatric intensive care unit. J Clin Monit Comput. 2018;32:89–96. 2005;19:195–199.

ORIGINAL ARTICLE
Characteristics of Pediatric Patient Transfers From General

Emergency Departments in California From 2005 to 2018
Moon O. Lee, MD, MPH,* Jessica Wall, MD, MPH, MSCE,† Olga Saynina, MA,‡
Carlos A. Camargo, Jr, MD, DrPH,§ and N. Ewen Wang, MD*
Objective: Each year, approximately 300,000 pediatric patients are trans-

ferred out of emergency departments (EDs). Emergency department trans-
C hildren account for approximately 27 million visits to US emer-
gency departments (EDs) yearly.1 Most children are seen and
treated in EDs located in general hospitals rather than EDs located in
fers may not only provide a higher level of care but also incur increased re- children's hospitals.2 An important subset of pediatric patients requires
source use and cost. Our objective was to identify hospital characteristics resources not available at the initial ED and is transferred to another
and patient demographics and conditions associated with ED transfer as ED or hospital for a higher level of care.3,4 Although ED transfers
well as the trend of transfers over time. can be essential for patient outcomes, they also require many system re-
Methods: This was a retrospective cohort study of pediatric visits to EDs sources, are time intensive, and can be expensive to patient and family.5
in California using the California Office of Statewide Health Planning and Most research in pediatric transfers is primarily from the per-
Development ED data set (2005–2018). Hospitals were categorized based spective of the hospitals that received pediatric transfers.5–9 Sev-
on inpatient pediatric capabilities. Patients were characterized by demo- eral studies have shown that ED transfers to children's hospitals
graphics and Clinical Classifications Software diagnostic categories. Re- often result in discharge from the ED or a less than 24-hour hospi-
gression models were created to analyze likelihood of outcome of transfer tal stay.6,9–11 These studies examined patients who were trans-
compared with admission. ferred into tertiary care pediatric hospitals but did not look at the
Results: Over the 14-year period, there were 38,117,422 pediatric visits to overall number of patients who were initially seen in general EDs
364 EDs in California with a transfer rate of 1% to 2%. During this time, for those same conditions.9–11 We examined pediatric transfers from
the overall proportion of pediatric transfers increased, whereas pediatric ad- the perspective of the general EDs that transferred patients for a
missions decreased for all hospital types. Transfers were more likely in higher level of care. Our objective was to identify hospital character-
general hospitals without licensed pediatric beds (odds ratio [OR], 16.26; istics, patient demographics, and clinical conditions associated with
95% confidence interval [CI], 15.87–16.67) and in general hospitals with transfers from general EDs, as well as the trend of transfers over time.
licensed pediatric beds (OR, 3.54; 95% CI, 3.46–3.62) than in general hospi- We hypothesize that the transferring EDs' pediatric inpatient capabil-
tals with pediatric intensive care unit beds. Mental illness (OR, 61.00; 95% ity coupled with the patient's medical condition was strongly associ-
CI, 57.90–63.20), poisoning (OR, 11.78; 95% CI, 11.30–12.30), diseases ated with the likelihood of ED pediatric transfer.
of the circulatory system (OR, 6.13; 95% CI, 5.84–6.43), diseases of the ner-
vous system (OR, 4.61; 95% CI, 4.46–4.76), and diseases of the blood and
blood-forming organs (OR, 3.21; 95% CI, 3.62; 95% CI, 3.45–3.79) had METHODS
increased odds of transfer.
Conclusion: Emergency departments in general hospitals without pedi- Study Design and Setting
atric intensive care units and patients' Clinical Classifications Software cat-
egory were associated with increased likelihood of transfer. A higher pro-
This retrospective cohort study used the California Office of
portion of patients with complex conditions are transferred than those with
Statewide Health Planning and Development (OSHPD) ED data set
common conditions. General EDs may benefit from developing transfer
from 2005 to 2018. The OSHPD collects and manages data from ap-
processes and protocols for patients with complex medical conditions.
proximately 7000 California-licensed health care facilities. The
California OSHPD ED data set uses statewide counts for individ-
Key Words: general hospitals, emergency service hospital, patient transfer, ual patient visits submitted each time a patient is treated at a li-
patient admission censed acute care hospital with mandated statewide reporting of patient
(Pediatr Emer Care 2023;39: 20–27) demographic information, diagnostic information, treatment informa-
tion, disposition of patient, charges for treatment, and expected source
of payment The ED data sets contain emergency care data collected
from EDs from general acute care hospitals in California. Each record
From the *Department of Emergency Medicine, Stanford University School of within the data set consists of 1 ED encounter. An ED encounter is in-
Medicine, Stanford, CA; †Department of Pediatrics and Emergency Medicine, cluded only for patients who had encounter with a provider. If an ED
University of Washington School of Medicine, Seattle Children's Hospital, Emer- encounter results in an admission at the same hospital, the ED encoun-
gency Department, Seattle, WA; ‡Stanford Center for Policy, Outcomes and Pre-
vention, Stanford, CA; and §Department of Emergency Medicine, Massachusetts
ter is combined with the inpatient record.12 A list of all pediatric inten-
General Hospital, Harvard Medical School, Boston, MA. sive care units (PICUs) in California hospitals was obtained from the
Presented at the Pediatric Academic Societies Meeting, April 27, 2019, California Department of Health Care Services.13 Specialty children's
Baltimore, MD, and at the Society for Academic Emergency Medicine hospitals were identified from the California Children's Hospital Asso-
Conference, May 16, 2019, Las Vegas, NV.
ciation Web site.14 The California Health Board and Stanford Univer-
Reprints: Moon O. Lee, MD, MPH, Department of Emergency Medicine, sity Institutional Review Board approved this study.
Stanford University School of Medicine, 900 Welch Rd MC 5119, Suite
350, Stanford, CA 94304 (e‐mail: moonlee@stanford.edu). Study Population
Supplemental digital content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF versions Hospital Characteristics
of this article on the journal’s Web site (www.pec-online.com).
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. Hospitals were categorized into groups based on inpatient pe-
ISSN: 0749-5161 diatric capabilities: (1) general hospitals without licensed inpatient

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Patient Transfers From General EDs in California
pediatric beds, (2) general hospitals with licensed inpatient pediatric which leads to undertriage of severely injured children, which may
beds, (3) general hospitals with a PICU, and (4) children's hospitals. confound the likelihood of transfers.20 The primary outcome was
The mean annual ED volume, discharges, admissions, and transfers disposition of transfer to an acute care hospital.
were calculated for each type of hospital. Transfers were defined as
patients transferred to an acute care hospital or psychiatric facility. Data Analysis
Nonacute transfers were defined as transfers to skilled nursing facil- California hospitals were categorized by inpatient pediatric
ities and facilities that provide custodial care. Nonacute transfers capability, hospital ED discharge volume, teaching hospital status,
and deaths were excluded from tables and regression. Hospital char- for-profit hospital, and rural hospital. Patient characteristics and
acteristics included the following: ED discharge volume in terciles CCS categories were categorized by hospitals' inpatient pediatric
(high, medium, low), teaching hospital status, for profit hospital, capability and disposition. We developed regression models to ana-
and rural hospital. To calculate ED discharge terciles, we used the lyze likelihood of transfer compared with admission based on hospi-
2013 OSHPD hospital utilization data and separated hospitals into tal characteristics, patient demographics, CCS diagnostic categories,
approximately 3 equal groups (terciles) by ED discharge volume: and time trend. Children's hospitals were excluded from regression
low, medium, and high. We chose a year in the middle of our study analyses because they provide the highest level of medical care and
period to achieve a relative ranking between hospitals. If a hospital are often the receiving hospital for transfers from general EDs.
closed or opened after 2013, they were not included in the tercile Statistical analysis was performed using SAS 9.4 (SAS Institute
calculation. Rural hospitals were designated by the metropolitan Inc, Cary, NC) and STATA 14 for Windows (StataCorp LP, College
statistical area of the county.15 Station, Tex).
Patient Characteristics RESULTS

Patient demographic data were obtained from the OSHPD There were 38,117,422 pediatric patient visits to EDs to 364
ED data set. Pediatric patients 0 to 17 years of age were included California hospitals from 2005 to 2018. All patients included in
in the study. Patient age was stratified into the following age groups: the study had a disposition. The total number of pediatric visits
0 days to less than 1 year, 1 to 4 years, 5 to 9 years, 10 to 14 years, to EDs and mean number of ED visits and disposition by hospi-
and 15 to 17 years old. Sex was categorized as female and male. tals' inpatient pediatric capability are shown in Table 1. General
Race was categorized as White, Black, Asian/Pacific Islander, and hospitals without licensed pediatric beds (n = 225) comprised
other. Ethnicity was categorized as Hispanic and or non-Hispanic. the largest category of hospitals, with 36.4% of all pediatric visits
Insurance was categorized as public, private, self-pay, or other. to EDs, whereas general hospitals with licensed pediatric beds
The US Census Bureau median household income quartile catego- (n = 112) saw 41.8% of all pediatric visits to EDs. General hospi-
ries and whether this median income was 200% above or below the tals with PICUs (n = 18) and children's hospitals (n = 9) cared for
federal poverty limits for a family of four were derived from pa- a smaller percentage of the total ED visit population, 6.7% and
tients' zip code.16 Disposition was identified from OSHPD “patient 15.2% of pediatric visits to EDs, respectively. However, children's
disposition” category and classified as discharge, admission, and hospitals had the highest mean number of ED visits per hospital
transfer to acute care hospital or psychiatric facility. Nonacute trans- each year (n = 45,925). The vast majority of pediatric visits to EDs
fers were defined as transfers to skilled nursing facilities and facil- in all hospital types resulted in discharge. The mean percentage of
ities that provide custodial care. Nonacute transfers and deaths were transfers for all hospital types was 1% to 2%.
excluded from tables and regression. Primary International Classi- Over the 13-year study period, the overall proportion of pedi-
fication of Diseases, Ninth Revision and Tenth Revision diagnostic atric transfers increased, whereas pediatric admissions decreased
codes were grouped into diagnostic categories by Clinical Classifi- for all hospital types (Fig. 1). General hospitals without licensed
cations Software (CCS).17 Complex medical conditions were iden- pediatric beds increased ED transfers almost 80% from 1.9% to
tified as CCS categories that included complex chronic conditions, 2.7%, whereas admissions decreased from 1.9% to 0.6%. In general
which are defined as any medical conditions that can be reasonably hospitals with licensed pediatric beds, transfers increased from 1.3%
expected to last at least 3 to 12 months and to involve either several to 2.1%, whereas admissions decreased from 4.8% to 2.4%. In gen-
different organ systems or 1 organ system severely enough to require eral hospitals with PICUs, transfers increased from 1.1% to 1.4%,
specialty pediatric care and probably some period of hospitalization whereas admission decreased from 10% to 7.6%.
in a tertiary care center.18,19 We excluded patients with trauma-related Patient characteristics and ED discharges, admissions, and trans-
diagnoses. California does not have a fully coordinated trauma system, fers by hospitals' inpatient pediatric capability are shown in Table 2
TABLE 1. California Hospitals' Inpatient Pediatric Capability and ED Visit Volume and Disposition*
General Hospital General Hospital General Hospitals With

Without Licensed With Licensed Licensed Pediatric Beds Children's
Pediatric Beds Pediatric Beds and PICU Hospitals
(n = 225) (n = 112) (n = 18) (n = 9)
Total pediatric visits to ED over study period 13,872,338 15,921,428 2,537,097 5,786,559
Mean no. pediatric visits to EDs per year 4404 10,154 10,068 41,021
Mean no. ED discharges per year, no. (%) 4230 (94.0) 9593 (94.0) 8985 (88.0) 45,925 (89.0)
Mean no. ED admissions per year, no. (%) 51 (3.0) 342 (3.0) 865 (8.0) 4035 (9.0)
Mean no. ED transfers to acute care hospitals per year, no. (%) 99 (2.0) 175 (2.0) 146 (1.0) 752 (2.0)
*Disposition does not sum to total because of exclusion of nonacute transfers and deaths. For discharges, admissions, and transfers by hospital type, see
Supplementary Table 1, http://links.lww.com/PEC/B55.

Lee et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
FIGURE 1. Emergency department transfers and admission disposition over time by hospital type.
and Supplemental Table, http://links.lww.com/PEC/B55. Hospitals 71,029 (0.5%) nonacute transfers and 3509 (0.03%) deaths. General
without licensed pediatric beds admitted some pediatric patients; hospitals with licensed pediatric beds had 63,765 (0.4%) nonacute
15- to 17-year age group had the highest number of admission transfers and 4569 (0.03%) deaths. General hospitals with PICUs had
(n = 52,859). In hospitals without licensed pediatric beds, the 17,258 (0.7%) nonacute transfers and 748 (0.03%) deaths.
top 2 CCS categories with admissions were diseases of the respi- Emergency department visits for common conditions com-
ratory system (n = 39,995) and diseases of the digestive system prised large absolute numbers, but a small proportion were trans-
(39,680). The highest numbers of transfers for both general hospitals ferred within each CCS category (1%–3.8%) (Table 2). In abso-
without licensed pediatric beds and general hospitals with licensed lute numbers, the greatest number of transfers in general hospitals
pediatric beds were among children aged 0 to 1 years (3.5% and without and with inpatient pediatric beds was for poisoning, dis-
2%, respectively) and children aged 15 to 17 years (3% and 2.9%, re- eases of the respiratory system, mental illness, general symptoms
spectively). In contrast, general hospitals with PICUs had higher ad- signs and ill-defined symptoms, and diseases of the digestive sys-
missions of children aged 0 to 1 years, with only 0.6% transferred; tem. Overall, general hospitals with PICUs transferred a much
children 15 to 17 years were transferred the most (4%) compared with lower volume of patients for all CCS categories compared with
other age groups. General hospitals without licensed pediatric beds had general hospitals without and with licensed pediatric beds.

TABLE 2. Characteristics of Patients Transferred Based on Hospital Type*
General Hospital
Without Licensed General Hospital With General Hospital With
Pediatric Beds Licensed Pediatric Beds PICU
Total Transfer (%) Total Transfer (%) Total Transfer (%)
Age, y
0–1 1,585,431 55,306 (3.5) 2,245,379 45,710 (2) 337,191 2127 (0.6)
1–4 4,341,221 72,653 (1.7) 5,244,108 60,304 (1.1) 809,773 3548 (0.4)
5–9 2,965,222 50,992 (1.7) 3,287,515 40,706 (1.2) 518,560 3299 (0.6)
10–14 2,688,020 64,878 (2.4) 2,786,992 59,908 (2.1) 466,815 11,462 (2.5)
15–17 2,292,444 68,015 (3) 2,357,434 68,762 (2.9) 404,758 16,381 (4.0)
Sex
Female 6,518,307 144,964 (2.2) 7,425,848 131,365 (1.8) 1,158,161 19,615 (1.7)
Male 7,352,889 166,850 (2.3) 8,485,623 143,751 (1.7) 1,378,804 17,198 (1.2)
Unknown 1142 30 (2.6) 9957 274 (2.8) 132 4 (3.0)
Race
White 7,901,984 180,410 (2.3) 8,925,370 158,939 (1.8) 1,222,326 19,662 (1.6)
Black 1,276,187 27,494 (2.2) 1,373,701 23,819 (1.7) 299,457 5541 (1.9)
Asian, Pacific Islander 526,160 14,586 (2.8) 650,365 13,766 (2.1) 226,682 2125 (0.9)
Native American/Alaskan 202,438 4909 (2.4) 152,118 3184 (2.1) 24,776 387 (1.6)
Other 3,545,534 75,173 (2.1) 4,369,564 68,473 (1.6) 626,201 7700 (1.2)
Unknown 420,035 9272 (2.2) 450,310 7209 (1.6) 137,655 1402 (1.0)
Ethnicity
Hispanic 6,506,805 130,729 (2) 8,936,610 137,665 (1.8) 1,218,167 15,262 (1.3)
Non-Hispanic 6,860,357 169,414 (2.5) 6,470,777 129,442 (2.0) 1,175,363 19,507 (1.7)
Unknown 505,176 11,701 (2.3) 514,041 8283 (1.6) 143,567 2048 (1.4)
Insurance
Public 7,396,192 150,711 (2) 8,654,844 141,449 (1.6) 1,238,234 16,196 (1.3)
Private 5,260,252 138,122 (2.6) 5,853,348 113,186 (1.9) 931,734 14,643 (1.6)
Self-pay 1,155,926 22,009 (1.9) 1,320,003 19,109 (1.4) 353,636 5827 (1.6)
Other 59,931 1002 (1.7) 93,157 1646 (1.8) 13,475 151 (1.1)
Unknown 36 - 76 - 18 -
Poverty
FPL: <200% 3,674,673 71,487 (1.9) 4,599,177 67,925 (1.5) 755,252 11,081 (1.5)
FPL: 200%–300% 5,892,237 125,693 (2.1) 6,744,634 115,981 (1.7) 955,636 12,691 (1.3)
FPL: >300% 3,779,864 102,718 (2.7) 4,098,468 82,228 (2.0) 766,412 12,060 (1.6)
Unknown 525,564 11,947 (2.3) 479,149 9257 (1.9) 59,797 985 (1.6)
Clinical Classifications Software
Poisoning 3,892,149 67,293 (1.7) 4,010,074 58,612 (1.5) 653,377 5587 (0.9)
Diseases of the respiratory system 3,132,813 59,449 (1.9) 3,741,984 41,904 (1.1) 516,935 2089 (0.4)
Symptoms, signs, and ill-defined conditions and 2,198,711 35,354 (1.6) 2,733,668 27,160 (0.9) 416,663 2337 (0.6)
factors influencing health status
Diseases of the nervous system and sense organs 1,472,288 19,850 (1.3) 1,602,993 19,784 (1.2) 241,921 1182 (0.5)
Diseases of the digestive system 781,921 29,396 (3.8) 946,644 20,676 (2.2) 157,462 797 (0.5)
Infectious and parasitic diseases 535,365 4887 (0.9) 647,313 3628 (0.6) 108,048 234 (0.2)
Diseases of the skin and subcutaneous tissue 433,340 5578 (1.3) 507,408 5203 (1.0) 80,420 374 (0.5)
Diseases of the genitourinary system 428,937 7451 (1.7) 472,746 4036 (0.9) 77,034 468 (0.6)
Diseases of the musculoskeletal system and 279,192 2727 (0.9) 309,252 2587 (0.8) 75,972 272 (0.4)
connective tissue
Mental illness 224,445 45,850 (20.4) 272,369 60,769 (22.3) 65,247 21,332 (26.5)
Diseases of the circulatory system 117,417 3932 (3.3) 179,845 6044 (3.4) 42,989 848 (2.0)
Certain conditions originating in the perinatal period 108,821 8838 (8.1) 141,660 4222 (2.9) 26,192 283 (1.1)
Unclassified codes 102,174 4709 (4.6) 127,474 4653 (3.7) 26,079 224 (0.9)
Endocrine, nutritional, and metabolic diseases and 76,224 10,714 (14.1) 104,607 9484 (9.1) 22,120 424 (1.9)
immunity disorders
Complications of pregnancy, childbirth, and the puerperium 65,606 1124 (1.7) 85,315 579 (0.7) 9322 126 (1.4)
Continued next page

TABLE 2. (Continued)
General Hospital
Without Licensed General Hospital With General Hospital With
Pediatric Beds Licensed Pediatric Beds PICU
Total Transfer (%) Total Transfer (%) Total Transfer (%)
Diseases of the blood and blood-forming organs 13,313 3105 (23.3) 20,892 3599 (17.2) 8322 150 (1.8)
Congenital anomalies 5406 1041 (19.3) 10,564 1624 (15.4) 5092 47 (0.9)
Neoplasms 4216 546 (12.9) 6620 826 (12.5) 3902 43 (1.1)
*Disposition does not sum to total because of exclusion of nonacute transfers and deaths. For discharges, admissions, and transfers by hospital type see
Supplementary Table 1, http://links.lww.com/PEC/B55.
FPL indicates federal poverty level.
Although ED visits by children with complex medical condi- the characteristics most strongly associated with ED transfer of pe-
tions comprised small absolute numbers, they generally comprised diatric patients. Over the study period, transfers increased for EDs
the highest proportion of transfers within a CCS category (Table 2). in hospitals without and with licensed pediatric beds, whereas
This proportion varied by the hospitals' inpatient pediatric capability. admission decreased for all 3 types of hospitals. We identified a
In general hospitals without and with inpatient pediatric beds, the top large number of transfers for common conditions; however, we
5 CCS categories with the highest proportion of transfers were dis- note that the proportion of children transferred in these diagnostic
eases of the blood and blood-forming organs (23.3% and 17.2%, re- categories was low (1%–3.8%). In contrast, the absolute number
spectively), mental illness (20.4% and 22.3%), congenital anomalies of pediatric ED visits by children with complex medical condi-
(19.3% and 15.4%), endocrine and immunity (14.1% and 9.1%), and tions was low, but the proportion of these patients who were trans-
(13.0% and 12.5%). In hospitals with PICU beds, the proportion of ferred was high (13%–20%). More complex conditions such as
transfers for all CCS categories was less than 3% except for mental mental illness, poisoning, diseases of the circulatory system, dis-
illness (26.5%). eases of the nervous system and sense organs, and disease of the
In the regression models to analyze likelihood of transfer blood and blood-forming organs were associated with an increased
compared with admission, the strongest predictor of ED transfer odds of transfer. The premise of ED transfer is the need for a higher
was the hospital inpatient pediatric capability. In the unadjusted level of inpatient care that cannot be provided at the originating hos-
model, general hospitals without licensed pediatric beds and those pital. Thus, this analysis of characteristics associated with transfer
with licensed pediatric beds were more likely to transfer than provides new detailed information about the impact of inpatient pe-
general hospitals with PICUs (odds ratio [OR], 1.36; 95% confi- diatric services in general hospitals on transfers using a large data
dence interval [CI], 1.34–1.38; and OR, 1.03; 95% CI, 1.02–1.04) set to validate studies from single institutions or health systems.
(Table 3). In the adjusted model, we accounted for patient demo- Barata et al21 found that general EDs had 1.5% of ED visits that re-
graphics, hospital characteristics, and changes over time. In the sulted in transfers. We found a similar rate of transfer (1%–3.8%),
adjusted model, general hospitals without licensed pediatric beds depending on the type of hospital where the EDs were located. Pee-
were approximately 16 times more likely to transfer patients (OR, bles et al8 examined all transfers from general, community EDs to a
16.26; 95% CI, 15.87–16.67) than hospitals with PICUs, and gen- tertiary care pediatric ED and found that the presence of inpatient
eral hospitals with licensed pediatric beds were 3.5 times more pediatric services at general EDs was associated with decreased
likely to transfer patients (OR, 3.54; 95% CI, 3.46–3.62) than general likelihood of being discharged home after being transferred to a
hospitals with PICU beds. children's hospital. Our study found new differences in transfer pat-
Pediatric visits to EDs for all age categories had approximately terns by general EDs based on their pediatric inpatient capabilities.
twice the odds of transfer than those 15 to 17 years old (Table 3). By examining the number of patients seen in general EDs for
Black and Native American patients had higher odds of transfer a given condition and determining the proportion of those patients
compared with White patients (OR, 1.44; 95% CI, 1.41–1.47; and who were transferred out, we have a better understanding of the
OR, 2.41; 95% CI, 2.28–2.54), respectively. Patients with self-pay pediatric transfers from the perspective of general EDs who are
insurance had the highest odds of transfer when compared with transferring patients for a higher level of care. We found similar
public insurance (OR, 2.92; 95% CI, 2.85–2.99). Odds of transfer conditions had higher odds of transfer as Barata et al21 described
were lower for ED visits by patients living at <200% compared with using a different reference group for the clinical condition. We
>300% of the federal poverty level (OR, 0.84; 95% CI, 0.83–0.86). found patients with circulatory, mental illness, nervous system, and
The highest odds of transfers were for pediatric visits to EDs for diseases of the blood and blood-forming organs had higher odds of
CCS categories of mental illness (OR, 61; 95% CI, 58.87–63.20), being transferred than patients with infectious diseases. Our study dif-
poisoning (OR, 11.78; 95% CI, 11.33–12.26), diseases of the circu- fered from Barata et al21 in that we excluded trauma patients because
latory system (OR, 6.13; 95% CI, 5.84–6.43), diseases of the nervous trauma patients are initially often sent to trauma-designated hospitals,
system (OR, 4.61; 95% CI, 4.46–4.76), and diseases of the blood and and we previously found a high undertriage rate of seriously injured
blood-forming organs (OR, 3.62; 95% CI, 3.45–3.79), as compared children in California.20 Unlike Barata et al,21 we found poisoning
with patients with infectious diseases (Table 3). had higher odds of transfer when compared with infectious diseases.
We found in our study that children with complex medical conditions
had lower absolute number of ED visits, but the proportions of chil-
DISCUSSION dren with these disease processes who were transferred were much
This statewide study of more than 38 million pediatric ED higher than those with common conditions, and these complex con-
visits between 2005 and 2018 found that a hospital's pediatric in- ditions were associated with an increased odds of transfer. Our study
patient capability and a patient's CCS diagnostic categories were provides new detailed evidence where to focus efforts around pediatric

TABLE 3. Unadjusted and Adjusted Regression Model Testing the Association Between Transfers and Hospital and Patient
Characteristics*
Unadjusted OR (95% CI) Adjusted OR (95% CI)

Hospital characteristics
General hospitals without licensed pediatric beds 1.31 (1.29–1.33) 16.30 (15.90–16.70)
General hospitals with licensed pediatric beds 1.03 (1.02–1.04) 3.54 (3.46–3.62)
General hospitals with PICU Reference Reference
ED discharge tercile (high) 0.86 (0.85–0.88)
ED discharge tercile (medium) 0.94 (0.92–0.96)
ED discharge tercile (low) Reference
Nonteaching hospital 2.05 (2.01–2.09)
Teaching hospital Reference
For-profit 1.12 (1.11–1.14)
Nonprofit Reference
Rural hospital 0.54 (0.53–0.56)
Nonrural hospital Reference
Age
0–1 y 1.81 (1.78–1.85)
1–4 y 1.88 (1.85–1.91)
5–9 y 2.03 (2.00–2.07)
10–14 y 1.89 (1.85–1.92)
15–17 y Reference
Sex
Female Reference
Male 1.01 (1.00–1.02)
Race
White Reference
Black 1.44 (1.41–1.47)
Asian, Pacific Islander 0.91 (0.89–0.93)
Native American/Alaskan 2.41 (2.28–2.54)
Other 1.36 (1.35–1.38)
Ethnicity
Hispanic 0.98 (0.97–1.00)
Non-Hispanic Reference
Insurance
Public Reference
Private 1.16 (1.15–1.17)
Self-pay 2.92 (2.85–2.99)
Other 1.00 (0.92–1.09)
Income
FPL: <200% 0.84 (0.83–0.86)
FPL: 200%–300% 1.02 (1.00–1.03)
FPL: >300% Reference
Clinical Classifications Software
Mental illness 61.00 (57.90–63.20)
Poisoning 11.78 (11.30–12.30)
Diseases of the circulatory system 6.13 (5.84–6.43)
Diseases of the nervous system and sense organs 4.61 (4.46–4.76)
Diseases of the musculoskeletal system and connective tissue 3.21 (3.06–3.38)
Diseases of the blood and blood-forming organs 3.62 (3.45–3.79)
Endocrine, nutritional, and metabolic diseases and immunity disorders 1.90 (1.83–1.96)
Diseases of the skin and subcutaneous tissue 1.67 (1.61–1.74)
Diseases of the respiratory system 1.46 (1.42–1.50)
Congenital anomalies 2.40 (2.26–2.55)
Neoplasms 2.70 (2.50–2.93)
Certain conditions originating in the perinatal period 0.97 (0.94–1.01)
Continued next page

TABLE 3. (Continued)
Unadjusted OR (95% CI) Adjusted OR (95% CI)

Diseases of the genitourinary system 1.13 (1.09–1.17)
Disease of the digestive system 0.94 (0.92–0.97)
Complications of pregnancy, childbirth, and the puerperium 0.60 (0.56–0.64)
Infectious and parasitic diseases Reference
Trend over time 1.12 (1.12–1.12)
*Multivariable models were adjusted for hospital discharge tercile, teaching hospital, for profit status, rural hospital, patient age, patient sex, patient race/
ethnicity, insurance, income, Clinical Classifications Software, and time.
transfers, specifically for those patients with circulatory, mental illness, diverse patient population and California's pediatric patient popula-
nervous system, and hematology-oncology diseases. tion were similar in age distribution and diagnoses to the national
Based on our analysis over a 14-year period, we identified the population described in the Healthcare Cost and Utilization Project.1
contribution of pediatric inpatient capability and specific conditions California also has 364 hospitals that span the types of hospitals seen
that predict transfer for general EDs. Our unadjusted OR found that across the country, including trauma centers, rural hospitals, teaching
EDs located in hospitals without pediatric beds were 1.36 times more hospitals, small and large hospitals, and pediatric inpatient capabil-
likely to transfer than EDs located in hospital with PICUs. After ities. Our study used an administrative database, which has limited
adjusting for patient characteristics, CCS conditions, hospital charac- clinical information and is subject to transcription bias. However,
teristics, and changes over time, we found EDs located in hospitals administrative databases are often the only option for generating
without inpatient pediatric beds were actually 16 times more likely population-level analyses. The study database and other adminis-
to transfer than EDs located in hospitals with PICUs. Emergency de- trative databases have been used successfully in the past to offer
partments located in general hospitals with inpatient pediatric beds insight in transfer mechanisms.10,22,23 We excluded transfers re-
were 3.5 times more likely to transfers than EDs in hospitals with lated to trauma diagnoses, which may impact the likelihood of
PICUs. These data align with studies that examined patients who transfer for the hospitals and cannot analyze trauma as a potential
are transferred into pediatric EDs from general EDs.6,10 However, factor for transfer.
our study is the first to our knowledge to examine pediatric transfer
patterns in the context of different types of general EDs. An under-
standing of ED transfers by hospital pediatric capability and condi- CONCLUSIONS
tion allows for a more nuanced understanding of pediatric care trans- Hospitals' inpatient pediatric capabilities and patient clinical
fer patterns and thus allows for targeted process improvement. diagnoses were the highest predictors of pediatric transfers from
Over the study period, we found that the proportion of admis- general EDs. Children with complex conditions are being trans-
sions has decreased, whereas the proportion of transfers has increased ferred at a higher rate than those with common conditions. Gen-
in general hospitals both without and with pediatric inpatient beds. In eral EDs may benefit by developing transfer processes and proto-
contrast, general hospitals with PICUs had decreased admissions, cols for patients with complex medical conditions.
whereas transfers remained relatively stable over time. The scope of
pediatric conditions treated at hospitals has declined over time.22,23
This is mirrored in our data, which showed admissions decreased
REFERENCES
for general hospitals without and with pediatric inpatient beds. Defin-
itive care is becoming less common, and transfers are increasing.23,24 1. McDermott KW, Stocks C, Freeman WJ. Overview of Pediatric Emergency
Over time, the field of medicine has become more specialized.25 Department Visits, 2015. 2018 Aug 7. In: Healthcare Cost and Utilization
Transfers may be necessary because of increased specialized care Project (HCUP) Statistical Briefs [Internet]. Rockville, MD: Agency for
Healthcare Research and Quality (US); 2006. Statistical Brief #242.
to provide emergency care for children or because of increased rates
of hospitalization of children with medical complexity.24,26–29 2. Gausche-Hill M, Ely M, Schmuhl P, et al. A national assessment of
Dharmar et al26 found that the quality of care for pediatric patients pediatric readiness of emergency departments. JAMA Pediatr. 2015;
in EDs varied based on teaching status of the hospital and physi- 169:527.
cian level of training. Transfers may have increased as general 3. Horeczko T, Marcin JP, Kahn JM, et al, On behalf of the Consortium of
EDs form institutional partnerships with tertiary care children's Regionalization Efforts in Emergency Medical Services for Children
hospitals for increased access to subspecialty consults. (CORE-EMSC). Urban and rural patterns in emergent pediatric transfer: a
Given the costs associated with transfer,30 improved outpatient call for regionalization. J Rural Health. 2014;30:252–258.
follow-up with subspecialists may allow some children to stay in 4. Bourgeois FT, Shannon MW. Emergency care for children in pediatric and
the general ED instead of transferring.31 Another potential solution general emergency departments. Pediatr Emerg Care. 2007;23:94–102.
for reducing transfers is to use telemedicine consultations as the uti- 5. Gattu RK, Teshome G, Cai L, et al. Interhospital pediatric patient
lization, efficacy, and acceptance are increased.32–35 Further explo- transfers—factors influencing rapid disposition after transfer. Pediatr
ration of the role of hospital proximity, parent decision-making, and Emerg Care. 2014;30:5–30.
disease severity on presentation will likely improve our understand-
6. Li J, Pryor S, Choi B, et al. Reasons for interfacility emergency department
ing of the risks associated with interfacility transfer. transfer and care at the receiving facility. Pediatr Emerg Care. 2020;36:
95–100.
Limitations 7. Fenton SJ, Lee JH, Stevens AM, et al. Preventable transfers in pediatric
Our study is limited to one state in the United States and may trauma: a 10-year experience at a level I pediatric trauma center. J Pediatr
not be generalizable to other states. However, we described a large, Surg. 2016;51:645–648.

8. Peebles ER, Miller MR, Lynch TP, et al. Factors associated with discharge acute-care facilities: an analysis of the Healthcare Cost and Utilization
home after transfer to a pediatric emergency department. Pediatr Emerg Project nationwide emergency department sample. Pediatr Emerg Care.
Care. 2018;34:650–655. 2020;36:309–311.
9. Walls TA, Chamberlain JM, Klein BL. Factors associated with emergency 22. França UL, McManus ML. Trends in regionalization of hospital care for
department discharge after pediatric interhospital transport: a role for common pediatric conditions. Pediatrics. 2018;141:e20171940.
outreach education? Pediatr Emerg Care. 2015;31:10–14.
23. França UL, McManus ML. Availability of definitive hospital care for
10. Cushing AM, Bucholz E, Michelson KA. Trends in regionalization of children. JAMA Pediatr. 2017;171:e171096.
emergency care for common pediatric conditions. Pediatrics. 2020;
24. Michelson KA, Hudgins JD, Lyons TW, et al. Trends in capability of
145:e20192989.
hospitals to provide definitive acute care for children: 2008 to 2016.
11. Li J, Monuteaux MC, Bachur RG. Interfacility transfers of noncritically ill Pediatrics. 2020;145:e20192203.
children to academic pediatric emergency departments. Pediatrics. 2012;
25. Dalen JE, Ryan KJ, Alpert JS. Where have the generalists gone? They
130:83–92.
became specialists, then subspecialists. Am J Med. 2017;130:766–768.
12. Hospital emergency department—diagnosis, procedure, and external cause
26. Dharmar M, Marcin JP, Romano PS, et al. Quality of care of children in the
codes. California Health and Human Services Open Data Portal. Available at:
emergency department: association with hospital setting and physician
https://data.chhs.ca.gov/dataset/hospital-emergency-department-diagnosis-
training. J Pediatr. 2008;153:783–789.e2.
procedure-and-external-cause-codes. Accessed December 16, 2021
13. Department of Health Care Services. Pediatric intensive care unit. Available 27. Burns KH, Casey PH, Lyle RE, et al. Increasing prevalence of medically
at: https://www.dhcs.ca.gov/services/ccs/scc/Pages/PICU.aspx. Accessed complex children in US hospitals. Pediatrics. 2010;126:638–646.
April 29, 2020 28. Li J, Pryor S, Choi B, et al. Profile of interfacility emergency department
14. California Children's Hospital Association. CCHA members. Available at: transfers: transferring medical providers and reasons for transfer. Pediatr
https://www.ccha.org/node/787. Accessed January 25, 2021 Emerg Care. 2019;35:38–44.
15. Ingram DD, Franco SJ. NCHS urban-rural classification scheme for 29. White MJ, Sutton AG, Ritter V, et al. Interfacility transfers among patients
counties. Vital Health Stat 2. 2012;154:1–s. with complex chronic conditions. Hosp Pediatr. 2020;10:114–122.
16. Assistant Secretary for Planning and Evaluation, US DHHS. 2004 Poverty 30. Mohr NM, Harland KK, Shane DM, et al. Potentially avoidable pediatric
guidelines. Federal Register Notice. Published online November 22, 2015. Interfacility transfer is a costly burden for rural families: a cohort study.
Available at: https://aspe.hhs.gov/2004-poverty-guidelines-federal-register- Newgard CD, ed. Acad Emerg Med. 2016;23:885–894.
notice. Accessed January 26, 2021 31. Marcin JP, Ellis J, Mawis R, et al. Using telemedicine to provide pediatric
17. Healthcare Cost and Utilization Project. Clinical Classifications Software subspecialty care to children with special health care needs in an
(CCS) for ICD-9-CM. Published 2018. Available at: www.hcup-us.ahrq. underserved rural community. Pediatrics. 2004;113:1–6.
gov/toolssoftware/ccs/ccs.jsp. Accessed November 19, 2021 32. Itrat A, Taqui A, Cerejo R, et al. Telemedicine in prehospital stroke
18. Feudtner C, Christakis DA, Connell FA. Pediatric deaths attributable to evaluation and thrombolysis: taking stroke treatment to the doorstep. JAMA
complex chronic conditions: a population-based study of Washington state, Neurol. 2016;73:162–168.
1980–1997. Pediatrics. 2000;106(1 pt 2):205–209. 33. Gattu R, Teshome G, Lichenstein R. Telemedicine applications for the
19. Perrin EC, Newacheck P, Pless IB, et al. Issues involved in the definition and pediatric emergency medicine: a review of the current literature. Pediatr
classification of chronic health conditions. Pediatrics. 1993;91:787–793. Emerg Care. 2016;32:123–130.
20. Wang NE, Newton CR, Spain DA, et al. Patient, hospital and regional 34. Mollen CJ, Henien M, Jacobs LM, et al. Parent perceptions on transfers to
characteristics associated with undertriage of injured children in California pediatric emergency departments and the role of telemedicine. Pediatr
(2005–2015): a retrospective cohort study. Trauma Surg Acute Care Open. Emerg Care. 2019;35:180–184.
2019;4:e000317. 35. Foster CC, Macy ML, Simon NJ, et al. Emergency care connect: extending
21. Barata IA, Akerman M, Mahmooth Z, et al. Characteristics of pediatric pediatric emergency care expertise to general emergency departments
patient transferred from hospital-based general emergency departments to through telemedicine. Acad Pediatr. 2020;20:577–584.

ORIGINAL ARTICLE
Evaluation of the Validity and Reliability of ANKUTRIAGE, a

New Decision Support System in Pediatric Emergency Triage
Aytaç Göktuğ, MD,* Nisa Eda Çullas İlarslan, MD,† Göksel Vatansever, MD,† İhsan Özdemir, MD,‡
Onur Polat, MD,§ Ahmet Burak Oğuz, MD,§ Ayça Koca, MD,§ Sinan Genç, MD,§ Ömer Özgür Tanrıöver, PhD,||
Salih Demir, PhD,¶ Mesut Sevindik, PhD,¶ Atilla Halil Elhan, MD,# and Deniz Tekin, MD‡
Key Words: reliability, triage, validity

Background: The intensity of emergency services is an increasing
health problem all over the world, necessitating an effective triage system. (Pediatr Emer Care 2023;39: 28–32)
The aim of this study was to evaluate the validity and reliability of the
“ANKUTRIAGE” in children.
Methods: This prospective, longitudinal study was carried out at a pediat-
ric emergency department. ANKUTRIAGE, a 5-level computer-aided triage
T he intensity of emergency services is an increasing health
problem all over the world. This intensity causes prolonged
waiting times, delays in the treatment of patients who require urgent
decision support system, was developed. Patients younger than 18 years who care, an increase in the number of patients leaving the hospital with-
do not need emergency intervention, who had complete vital sign mea- out being examined, and increased morbidity and mortality. Patients
surements, who gave consent for the study, and who were admitted to should be ranked according to their urgency level as effective, safe,
the emergency service during working hours with trained personnel were and fast as possible. For this purpose, triage systems are used in most
included. For validity, agreement between the urgency levels determined by emergency services. An effective triage system should be easy to un-
ANKUTRIAGE and the reference triage systems: Pediatric Canadian Triage derstand, implemented quickly and have high interrater agreement.1
and Acuity Scale and Emergency Severity Index, was evaluated. In addition, Children’s limited communication skills, uncertain symptoms in
the association of urgency levels with clinical outcomes was studied. To as- young children, changes in normal vital signs depending on age,
sess reliability, patients were evaluated by 2 blinded healthcare professionals and psychological factors make triage difficult in pediatric pa-
using ANKUTRIAGE and a quadratic weighted κ was estimated. tients.2 For this reason, various triage scales and decision support
Results: A total of 1232 children with a median age of 4.00 years were systems have been developed to guide the clinicians or other
included. ANKUTRIAGE acuity levels significantly correlated with the health workers in charge of triage for a correct decision.3 Pediatric
number of resources used, the number of patients undergoing life-saving Canadian Triage and Acuity Scale (PaedCTAS), Manchester Triage
procedures, pediatric intensive care unit, and overall hospitalization rates, System, Emergency Severity Index (ESI), and Australian Triage
respectively ( P < 0.001, P < 0.001, P < 0.001, P < 0.001). The agreement Scale are triage systems with relatively high validity and reliability
of ANKUTRIAGE with Pediatric Canadian Triage and Acuity Scale was and are used more widely in pediatric emergency departments
found to be 0.94 (95% confidence interval [CI], 0.93–0.94), with an Emer- (PEDs).4,5 It is emphasized that it is ideal for each country to
gency Severity Index of 0.75 (95% CI, 0.70–0.80). The interrater agree- use triage systems with high validity and reliability, which are
ment between 2 evaluators who used ANKUTRIAGE reflected as excellent formed by considering their own sociodemographic and cultural
consistency 0.92 (95% CI, 0.89–0.95; κ > 0.8). characteristics, provided that they benefit from internationally
Conclusions: ANKUTRIAGE demonstrated high agreement with clini- accepted triage decision support systems.6
cal outcomes and with proven triage systems and reflected high reliability The intensity of the emergency services and inadequate ex-
between users. ANKUTRIAGE will enable a more standardized and prac- perience of the triage personnel may negatively affect the right
tical triage, especially in crowded pediatric emergency departments and in decision-making capacity.7,8 For this reason, computerized sys-
situations where triage is performed by health professionals with different tems should become widespread and standardized electronic tri-
experience and professions. age decision support systems should be more accessible.
Because there is no nationally accepted electronic triage sys-
tem for children whose validity and reliability has been tested in
From the *Department of Pediatrics, Division of Pediatric Emergency Medicine, Turkey, we developed “ANKUTRIAGE,” which offers an easy-
Sami Ulus Pediatrics Training and Research Hospital; †Department of Pediatrics, to-apply, computer-aided triage decision support system for chil-
‡Department of Pediatrics, Division of Pediatric Emergency Medicine, and §Depart-
ment of Emergency Medicine, Ankara University School of Medicine; ||Department dren. ANKUTRIAGE determines the urgency level of patients be-
of Computer Engineering, Ankara University Faculty of Engineering; ¶Faculty of tween levels 1 and 5. To decide the level of urgency, it evaluates
Open and Distance Education, Ankara University; and #Department of Biostatistics, the patient's main complaint and vital signs.
Ankara University School of Medicine, Ankara, Turkey. ANKUTRIAGE is an objective decision support system that
Reprints: Aytaç Göktuğ, MD, Department of Pediatric Emergency Medicine, enables triage personnel to access treatment according to their
Dr. Sami Ulus Maternity and Child Health and Diseases Training and Research urgency, regardless of their knowledge, experience, and environ-
Hospital, Babur Street, Ankara 06080, Turkey (e‐mail: aytacyaylaci@yahoo.com). mental conditions. The aim of this study was to evaluate the va-
A.G., N.E.C.İ., G.V., İ.Ö., A.B.O., A.K., S.G., Ö.Ö.T., S.D., M.S., D.T., and O.P. lidity and reliability of the ANKUTRIAGE system in children.
conceptualized and designed the study, drafted the initial manuscript, and
reviewed and revised the manuscript. A.G., G.V., N.E.C.İ., and İ.Ö.
designed the data collection instruments and collected data. A.H.E., A.G.,
and N.E.C.İ. carried out the initial analyses and reviewed and revised the METHODS
manuscript. All authors approved the final manuscript as submitted and
agree to be accountable for all aspects of the work.
Supplemental digital content is available for this article. Direct URL citations Study Design
appear in the printed text and are provided in the HTML and PDF versions
This prospective longitudinal study was carried out at PED of
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. Ankara University Children’s Hospital between July and October
ISSN: 0749-5161 2019. Our hospital is a tertiary pediatric hospital, which serves

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Validity and Reliability of ANKUTRIAGE
approximately 120.000 patients annually. The study protocol was phy for the patient with palpitations, check the blood sugar in
approved by the institutional ethics committee of Ankara Univer- the patient with altered consciousness). A suitable field was cre-
sity School of Medicine (ethical approval number: 12-682-17). In- ated for the records, which are not expected to affect the triage cat-
formed consent was obtained from each parent and patients older egory but are thought to provide useful information to the doctor
than 6 years who can cooperate. who will evaluate the patient first (eg, indication of isolation/
decontamination or a forensic case warning).
The ANKUTRIAGE System
ANKUTRIAGE system was developed by a project team Selection Criteria
(TUBITAK) of 12 people consisting of 6 emergency specialists, Patients younger than 18 years, who applied to the PED with
2 pediatric emergency specialists, 1 general pediatrician, 1 computer any complaint, whose vital signs were all measured, and who
engineer, and 2 software development specialists. The system was agreed to participate in the study were included. Because the study
planned as a 5-level triage decision support system. It was designed was conducted with a limited number of evaluators trained on this
as 2 interfaces, for patients younger than 18 years and older. subject, all patients who met the inclusion criteria and applied to
According to the level of urgency, triage levels were determined the PED during working hours (8:00 A.M.–5:00 P.M.) on weekdays
as follows; 1 (urgent), 2 (high urgency), 3 (urgency), 4 (low urgency), when these 3 evaluators were in the emergency department at the
and 5 (no urgency). same time were included. Patients who were thought to deteriorate
The triage level of the patients was calculated by considering rapidly or needed urgent intervention were excluded from the
the main complaint and vital signs at admission. The main com- study. Before the initiation of patient inclusion, health workers
plaints of the patients and the distinctive questions to determine who will use ANKUTRIAGE were given 30 minutes of didactic
the severity of these complaints were determined by analyzing training about the ANKUTRIAGE system. After the training,
the globally accepted triage systems and the International Classi- each healthcare professional was given approximately 20 practical
fication of Diseases, Tenth Revision.9 The complaints of the pa- applications with patient scenarios.
tients were grouped into 15 main headings (general complaints,
trauma, poisoning, environmental, dermatology, gastroenterology, Sample Size
ophthalmology, urology, gynecology/obstetrics, cardiology, respi- The sample size of the study was calculated assuming the
ratory, ear/nose/throat, neurology, orthopedics, psychiatry) and possible triage category distributions of the patients, level 1:1%,
154 subheadings (complaints; Supplemental Data 1, http://links. level 2:10%, level 3:30%, level 4: 40%, and level 5: 19%, so that
lww.com/PEC/A952). Differentiating questions were determined the difference between κ values of 65 and 70 could be found with
for each complaint. The lowest and highest triage levels that can 80% power at the 5% margin of error. A total of 1200 volunteers
be given for each complaint were defined to the ANKUTRIAGE were planned to be included in the study for validity calculation.
system by specialist clinicians. As a result of this evaluation, a tri- For reliability, randomly selected 300 pediatric patients from the
age level is determined according to the patient's “complaint” study group were planned to be included and evaluated by 2 dif-
(Supplemental Data 2, http://links.lww.com/PEC/A953). ferent practitioners using the ANKUTRIAGE system.
Afterward, a second triage level is determined according to
the “vital signs” of the patients. The vital signs to be used in triage
were composed of heart rate, respiratory rate, oxygen saturation, Evaluations
body temperature, and consciousness level. The AVPU scale One pediatric emergency specialist, 1 senior triage nurse, and
(Alert, responds to Voice, responds to Pain, Unresponsive) was 1 general pediatrician, who received ANKUTRIAGE training,
used to assess state of consciousness. Values corresponding to ur- participated in the study to standardize the measurements. Ini-
gency levels for vital parameters were determined based on tially, a triage nurse apart from the study team evaluated the pa-
PaedCTAS.10 Because blood pressure measurement in pediatric tients. She recorded the patients' complaints and measured their
patients is difficult in triage and hypotension usually develops late vital signs. She also directed the patients who needed urgent inter-
even in critically ill patients, blood pressure measurement was not vention to the resuscitation room. Same nurse also obtained in-
included in the essential vital signs.11 The highest urgency level formed consent. For those who did not accept to participate in
corresponding to these parameters was assigned as the patient's the study, the level of triage was determined by the traditional tri-
“vital sign” triage level. age methods applied in our hospital. The patients who accepted to
At the end, the more urgent triage level is assigned to the pa- participate in the study were evaluated in a separate room by the
tient among the levels obtained by the evaluation of “main com- pediatric emergency specialist, and their triage levels were deter-
plaint and vital sign.” mined. Then, the general pediatrician determined the triage levels
The determined triage level provides decision support to of the patients using the PaedCTAS and ESI reference brochures
the personnel performing the triage. The discordant triage levels in a different area. For the evaluation of interrater reliability, 302
determined by the system can be changed as a result of the randomly selected patients underwent ANKUTRIAGE for the
careful evaluation of the triage personnel, provided the reason second time in a separate area by the triage nurse blinded to the
is explained. other evaluators.
The calculated triage level of the patients is increased to a
higher level (up triage) in pre-defıned conditions such as neonatal
period (postnatal age <28 days), congenital or acquired disability, Determination of Validity
technological device dependence, immunosuppression, and the The validity of triage systems depends on their ability to dis-
possibility of self/environmental harm. tinguish patients with different level of urgency. It is difficult to
If an alarm symptom or vital sign is encountered at any stage determine; because there is no criterion standard method for
during triage, the system gives a warning to the user, allowing the assessing validity.12 In the literature, 2 methods have been pre-
user to end triage as “level 1.” ferred when evaluating the validity of triage systems: (1) evaluat-
Meanwhile, a system was designed to give warnings to the ing the relationship of urgency levels with clinical outcomes such
user in defined special conditions (eg, perform electrocardiogra- as hospitalization, resource use, and length of stay in the

Göktuğ et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
and ANKU2 = triage nurse) using the ANKUTRIAGE system

were compared.
Statistical Analysis
Statistical analysis of this study was performed using the
SPSS statistical package (version 21). For continuous variables,
mean ± SD was used for normal distribution, while median values
and ranges were reported for nonnormally distribution. Counts
and percentages were used for categorical variables.
In the validity phase; 2 methods were used: (1) for the com-
parison of the relationship between triage levels and clinical out-
comes, differences between 2 groups in terms of categorical vari-
FIGURE 1. The distribution of triage urgency levels of systems. ables were compared using χ2 test. P value less than 0.05 was
considered significant. (2) Quadratic weighted κ coefficient was
emergency department and (2) comparing the results of the triage used to compare the levels determined by ANKUTRIAGE and
system with a reference standard.13 reference standard systems.
We used both of these methods to calculate validity: In the reliability phase, concordance among triage users was
calculated using κ, too. κ coefficient was defined as follow: excellent
(κ > 0.80), good (0.60 < κ ≤ 0.80), moderate (0.40 < κ ≤ 0.60), fair
Comparison of the ANKUTRIAGE With Clinical (0.20 < κ ≤ 0.40), or poor (κ ≤ 0.20).
Outcomes
The relationship between the urgency levels determined by
ANKUTRIAGE and the clinical outcomes of the patients was RESULTS
evaluated. Resource utilization, overall hospitalization rates, and A total of 25,182 patients admitted to the PED during the
pediatric intensive care unit (PICU) admission were evaluated as study period. A total of 23,950 could not be included in the study
“clinical outcomes.” “Resource utilization” as described by Gilboy for various reasons. Selection algorithm of patients included in the
et al14 includes diagnostic tests (laboratory tests, electrocardiogram, study is given in (Supplemental Digital Content, Fig. 1, http://
and imaging methods), therapeutic procedures (drug therapy, fluid links.lww.com/PEC/A954) Finally, 1232 children with a median
administration, interventional procedures), life-saving procedures age of 4.0 years (0.1–18.0 years) were included. General charac-
(intubation, mechanical ventilation, cardioversion), and specialty teristics and outcomes of the patients are given in (Supplemental
consultations. This variable was dichotomized (<2 resources and Digital Content, Table 1, http://links.lww.com/PEC/A955).
≥2 resources), similar with other studies.15–17 The distribution of the urgency levels of the patients accord-
ing to the different triage systems is shown in Figure 1.
Comparison of ANKUTRIAGE and Reference
Triage Systems Validity of the ANKUTRIAGE
The urgency levels determined by ANKUTRIAGE, PaedCTAS, Comparison of the ANKUTRIAGE With
and ESI were compared separately. The agreement rates, overtriage, Clinical Outcomes
and undertriage percentages were assessed. According to the refer- Triage acuity level correlated well with the number of re-
ence triage system, assigning a patient to a high urgency level was sources used. This means that patients with lower-acuity level
considered “overtriage,” and assigning a lower urgency level was were significantly more likely to require fewer resources. In addi-
considered “undertriage.” tion, the frequency of life-saving procedures increased as the level
of urgency increased. Overall hospitalization and PICU admission
Determination of Reliability rates were significantly higher as the urgency level of the patients
Reliability is the most frequently reported statistical mea- increased (Table 1).
surement method for demonstrating the agreement of 2 or more
users in triage systems. Interrater reliability shows the stability Comparison of the ANKUTRIAGE With
of the measurement made by different people, under similar PaedCTAS and ESI
conditions. In our study, 302 patients were evaluated by 2 as- The agreement of ANKUTRIAGE with PaedCTAS was
sessors blinded to each other. The urgency levels given by these found to be 0.94, whereas κ values seemed to be lower regarding
2 triage practitioners (ANKU1 = pediatric emergency specialist comparisons with an ESI of 0.75. Urgency levels and overtriage/
TABLE 1. Comparison of Urgency Levels and Clinical Outcomes Determined by the ANKUTRIAGE: Validity Study
Level 1 (n = 40), Level 2 (n = 109), Level 3 (n = 580), Level 4 (n = 119), Level 5 (n = 384),
Parameters n (%) n(%) n (%) n (%) n(%) P
≥2 resource utilization 39 (97.5) 96 (88.1) 319 (55) 23 (19.3) 9 (2.3) <0.001
Life-saving procedure 11 (27.5) 4 (3.7) 1 (0.2) 0 0 <0.001
PICU admission 4 (10) 1 (0.9) 2 (0.3) 0 0 <0.001
Overall hospitalization rate 28 (70) 50 (45.9) 116 (20) 5 (4.2) 28 (7.3) <0.001
Text in bold indicates statistical significance, P < 0.05.

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Validity and Reliability of ANKUTRIAGE
TABLE 2. Urgency Levels Determined by the ANKUTRIAGE TABLE 4. Urgency Levels Determined by Different
Versus PaedCTAS: Validity Study ANKUTRIAGE Users: Reliability Study
PaedCTAS ANKU2
ANKUTRIAGE Level 1 Level 2 Level 3 Level 4 Level 5 Total ANKU1 Level 1 Level 2 Level 3 Level 4 Level 5 Total
Level 1 34 3 2 1 0 40 Level 1 2 0 0 0 0 2
Level 2 1 94 12 2 0 109 Level 2 0 8 3 0 0 11
Level 3 1 5 536 35 3 580 Level 3 0 0 51 10 1 62
Level 4 0 0 10 101 8 119 Level 4 0 0 5 61 16 82
Level 5 0 0 2 59 323 384 Level 5 0 0 0 3 142 145
Total 36 102 562 198 334 1232 Total 2 8 59 74 159 302
Absolute agreement: 88.3% (1088/1232; κ = 0.94; 95% CI, 0.93–0.94). Absolute agreement: 94% (284/300; κ = 0.92; 95% CI, 0.87–0.97).
Undertriage: 6.3% (78/1232). ANKU1: pediatric emergency specialist.
Overtriage: 5.4% (66/1232). ANKU2: triage nurse.
95% CI indicates 95% confidence interval; κ, quadratic weighted κ. 95% CI indicates 95% confidence interval; κ, quadratic weighted κ.
undertriage rates determined by the ANKUTRIAGE versus patients is closely related to patient safety, while correct classi-
PaedCTAS are shown in Table 2 and ESI in Table 3. fication of low-urgency patients increases the efficiency of the
emergency department flow and shortens waiting times.19 An ideal
Reliability of the ANKUTRIAGE triage system must balance between safety and accuracy.14
The interrater agreement between evaluators who used ANKUTRIAGE acuity levels were significantly correlated with
ANKUTRIAGE reflected excellent consistency of 0.92. Urgency the number of resources used, the number of patients undergoing
levels determined by different ANKUTRIAGE users are shown in life-saving procedures, PICU, and overall hospitalization rates, re-
Table 4. spectively. Expectedly, this data show that patients with a higher ur-
gency level were more frequently admitted to the hospital and PICU
and required more interventions and resources. This can have sig-
DISCUSSION nificant implications for arranging transfers or admissions effi-
The triage process should be easy to understand, performed ciently, allowing ANKUTRIAGE to accurately detect sicker pa-
quickly, can predict clinical outcomes including ED resource use tients, thereby maximizing patient safety.
requirements, disease severity, and mortality, and should have Although there are no recommendations for overtriage and
high interrater agreement.18 In our study, there was a strong rela- undertriage rates, an effective and safe triage tool should have
tionship between the triage levels determined by ANKUTRIAGE low undertriage rates.18 A pediatric triage tool named “SATS”
and clinical outcomes. At the same time, ANKUTRIAGE was was reported to have an overtriage rate of 45.5% and undertriage
found to have high consistency with PaedCTAS and ESI. Further- rate of 9%,20 “CLARIPED” reported an overtriage rate of 59.1%
more, this study reports excellent interrater agreement. Thus, the and an undertriage rate of 7.4%.6 An overtriage rate of 16% was
scale is a reliable and valid triage tool for children who admit to reported for the ESI.16 Although our overtriage and undertriage
a PED. It also presents as the first pediatric, computer-aided deci- rates were within reasonable and acceptable limits when com-
sion support system in our country whose validity and reliability pared with PaedCTAS, overtriage rates were higher when com-
have been evaluated. pared with ESI. There is an ongoing debate on the use of vital
The “validity” of triage systems depends on their ability to signs in pediatric triage.21 Measuring vital signs in children may
distinguish levels of urgency. Correct classification of high-urgency be problematic, especially in small or uncooperative infants, and
normal ranges for children are not well defined.22 Furthermore,
children's vital parameters are affected by many physiological
TABLE 3. Urgency Levels Determined by the ANKUTRIAGE and emotional conditions such as fever, pain, and fear. Because
Versus ESI: Validity Study ESI only uses vital parameters to distinguish between level 2
and 3 patients in triage, ANKUTRIAGE may be overtriaging
ESI more because it uses vital signs for all levels of triage. Exagger-
ANKUTRIAGE Level 1 Level 2 Level 3 Level 4 Level 5 Total ated vital values might have been measured in many nonurgent
patients because of these factors, and higher triage urgency levels
Level 1 17 19 3 1 0 40 might have been determined because of these factors. Moreover,
Level 2 3 44 49 13 0 109 we also believe that our overtriage levels are very similar to
Level 3 1 12 306 219 42 580 PaedCTAS because both systems use the same vital sign levels
Level 4 0 0 23 82 14 119 for specific age groups.
Level 5 0 1 8 77 298 384 Clinical scenarios do not reflect the difficulties of the actual
Total 21 76 389 392 354 1232
triage process. Therefore, in our study, we tried to estimate reli-
ability by including only patients treated in real time, rather than
Absolute agreement: 60.6% (747/1232; κ = 0.75; 95% CI, 0.70–0.80). the scenarios commonly used in some studies. Therewithal reli-
Undertriage: 10.1% (125/1232). ability between different professional groups is low because of
Overtriage: 29.2% (360/1232). differences in knowledge, experience, and approach.15,20,23–25
95% CI indicates 95% confidence interval; κ, quadratic weighted κ. Gravel et al26 performed 2 studies on the PaedCTAS with actual
patients in Canada. One single-center study (n = 499) exhibited

Göktuğ et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
a substantial κ (κ = 0.61; 95% CI, 0.42–0.80) between triage 7. Reblora JM, Lopez V, Goh YS. Experiences of nurses working in a triage
nurses, although with poor precision. The other study including area: an integrative review. Aust Crit Care. 2020.
9 centers and actual patients (n = 1464) also presented a sub- 8. Di Somma S, Paladino L, Vaughan L, et al. Overcrowding in emergency
stantial κ (κ = 0.74; 95% CI, 0.71–0.76) between triage nurses, department: an international issue. Intern Emerg Med. 2015;10:171–175.
although there was wide variability between centers (κ = 0.58– 9. International Classification of Diseases. 10th Revision ed. 2019: Available
0.96).27 Three studies on the ESI-4 with actual patients were at: https://icd.who.int/browse10/2019/en. Accessed September 14, 2020.
performed. First, Travers et al16 included 498 patients and presented
10. Warren DW, Jarvis A, LeBlanc L, et al. Revisions to the Canadian triage
a moderate κ (κ = 0.57; 95% CI, 0.52–0.62) between nurses, and and acuity scale paediatric guidelines (PaedCTAS). Can J Emerg Med.
then, Green et al17 included 100 patients and presented an excellent 2008;10:224–232.
κ (κ = 0.92; 95% CI, 0.86–0.98) between triage nurses and sub-
stantial κ (κ = 0.78; 95% CI, 0.68–0.88) between a nurse and a 11. Poor KM, Ducklow TB. Benefit of BP measurement in pediatric ED
patients. Int Scholarly Res Notices. 2012;2012:627354.
doctor. Later on, Jafari-Rouhi et al28 found an almost perfect κ
(κ = 0.82; 95% CI, 0.68–0.98) between a triage nurse and a pedi- 12. Twomey M, Wallis LA, Myers JE. Limitations in validating emergency
atrist with a larger sample (n = 1104). Our study demonstrated ex- department triage scales. Emerg Med J. 2007;24:477–479.
cellent consistency among a triage nurse and a pediatric emer- 13. van Veen M, Moll HA. Reliability and validity of triage systems in
gency physician (κ = 0.92; 95% CI, 0.89–0.95). This difference paediatric emergency care. Scand J Trauma Resusc Emerg Med. 2009;
may be due to the fact that ANKUTRIAGE is a computer-based 17:1–8.
triage tool that provides the least exposure to information, experi- 14. Gilboy N, Tanabe P, Travers DA, et al. Emergency Severity Index, Version
ence, and external environmental factors. This high compatibility 4: Implementation Handbook. Rockville, MD: Agency for Healthcare
between users and professional groups has made pediatric triage Research and Quality; 2005:1–72.
more standardized. 15. Baumann MR, Strout TD. Evaluation of the Emergency Severity Index
Our study had some limitations. First of all, it was carried out (version 3) triage algorithm in pediatric patients. Acad Emerg Med. 2005;
in a single center and at certain times of the day. Second, the num- 12:219–224.
ber of patients included in level 1 and therefore our intensive care
16. Travers DA, Waller AE, Katznelson J, et al. Reliability and validity of the
admission rates were low. Because 2 different triage evaluations in emergency severity index for pediatric triage. Acad Emerg Med. 2009;16:
different areas (3 different triages for patients included in the 843–849.
safety stage) may delay the patients' access to urgent treatment, pa-
tients with poor general condition, unstable vital signs, and requir- 17. Green NA, Durani Y, Brecher D, et al. Emergency Severity Index version 4:
a valid and reliable tool in pediatric emergency department triage. Pediatr
ing emergency intervention at the time of admission were not in-
Emerg Care. 2012;28:753–757.
cluded in the triage process for ethical reasons. Similar approach
was mentioned in some other studies.6,10 Third, waiting times of 18. de Magalhães-Barbosa MC, Robaina JR, Prata-Barbosa A, et al. Validity of
the patients in triage were not recorded. Because accurate mea- triage systems for paediatric emergency care: a systematic review. Emerg
surement of vital findings in children is certainly more difficult Med J. 2017;34:711–719.
and time consuming, our triage application times may have 19. Zachariasse JM, van der Hagen V, Seiger N, et al. Performance of triage
been longer than expected. Although these measurements take systems in emergency care: a systematic review and meta-analysis.
longer time and cause overtriage, a safer triage is provided for BMJ Open. 2019;9:e026471.
pediatric patients. 20. Twomey M, Cheema B, Cohen K, et al. Vital signs for children at triage: a
In conclusion, these findings may pave the way for multicentre validation of the revised South African Triage Scale (SATS) for
ANKUTRIAGE to find wider use in other PED. We think that children. S Afr Med J. 2013;103:304–308.
ANKUTRIAGE will enable a more standardized and practical 21. Keddington RK. A triage vital sign policy for a children's hospital
triage especially in crowded PED and in situations where triage emergency department. J Emerg Nurs. 1998;24:189–192.
is performed by health professionals with different experience 22. Day A, Oldroyd C. The use of early warning scores in the emergency
and professions. For this purpose, multicenter clinical studies department. J Emerg Nurs. 2010;36:154–155.
are needed.
23. Bergeron S, Gouin S, Bailey B, et al. Agreement among pediatric health
care professionals with the pediatric Canadian triage and acuity scale
guidelines. Pediatr Emerg Care. 2004;20:514–518.
REFERENCES
24. Considine J, LeVasseur SA, Villanueva E. The Australasian Triage Scale:
1. Fernandes CM, Tanabe P, Gilboy N, et al. Five-level triage: a report from examining emergency department nurses' performance using computer and
the ACEP/ENA five-level triage task force. J Emerg Nurs. 2005;31:39–50. paper scenarios. Ann Emerg Med. 2004;44:516–523.
2. Hohenhaus SM, Travers D, Mecham N. Pediatric triage: a review of 25. van Veen M, Steyerberg EW, Van't Klooster M, et al. The Manchester triage
emergency education literature. J Emerg Nurs. 2008;34:308–313. system: improvements for paediatric emergency care. Emerg Med J. 2012;
3. Blunt I, Edwards N, Merry L. What's Behind the A&E ‘Crisis’. London: 29:654–659.
Nuffield Trust; 2015. 26. Gravel J, Gouin S, Manzano S, et al. Interrater agreement between nurses
4. Christ M, Grossmann F, Winter D, et al. Modern triage in the emergency for the Pediatric Canadian Triage and Acuity Scale in a tertiary care center.
department. Dtsch Arztebl Int. 2010;107:892–898. Acad Emerg Med. 2008;15:1262–1267.
5. Farrohknia N, Castrén M, Ehrenberg A, et al. Emergency department triage 27. Gravel J, Gouin S, Goldman RD, et al. The Canadian Triage and Acuity
scales and their components: a systematic review of the scientific evidence. Scale for children: a prospective multicenter evaluation. Ann Emerg Med.
Scand J Trauma Resusc Emerg Med. 2011;19:42. 2012;60:71–7. e3.
6. de Magalhães-Barbosa MC, Prata-Barbosa A, Raymundo CE, et al. 28. Jafari-Rouhi AH, Sardashti S, Taghizadieh A, et al. The emergency severity
Validity and reliability of a new triage system for pediatric emergency care: index, version 4, for pediatric triage: a reliability study in Tabriz Children's
CLARIPED. Revista Paulista de Pediatria. 2018;36:398. hospital, Tabriz. Iran Int J Emerg Med. 2013;6:1–5.

ORIGINAL ARTICLE
Factors Associated With Point-of-Care Ultrasound Use by

Recent Pediatric Emergency Medicine Fellowship Graduates
Simone L. Lawson, MD, Kristen A. Breslin, MD, MPH, Rosemary Thomas-Mohtat, MD,
Alyssa M. Abo, MD, MBA, and Joanna S. Cohen, MD
time to learn POCUS, and a negative impact of POCUS on effi-

Objective: The aims of this study were to describe point-of-care ultra- ciency2; however, there is scant information describing how
sound (POCUS) use by recent pediatric emergency medicine (PEM) fel- POCUS is used by PEM physicians in their daily clinical practice
lowship graduates and identify associations between frequency and breadth and describing factors that impact that practice. Knowledge of how
of POCUS use with variations in POCUS training and current clinical PEM providers use POCUS clinically can help guide POCUS edu-
practice environment. cation offered in PEM fellowships and encourage hospital leader-
Methods: This was a cross-sectional online survey of recent PEM fellowship to fund academic PEM faculty positions for providers with
ship graduates. Chi-square and nonparametric tests were used to compare training in POCUS.
POCUS use among physicians with varying types of POCUS training The objectives of this study were to describe the frequency
and varying clinical practice environments. and breadth of POCUS use by recent PEM fellowship graduates
Results: Eighty-two percent of 143 respondents reported using POCUS and determine associations of POCUS use with 1) POCUS train-
in their past 10 shifts. There was no association between the methods of ing before and during PEM fellowship and 2) current clinical
POCUS education and frequency or breadth of POCUS use. Pediatric practice environment.
emergency medicine fellowship graduates with additional POCUS fellow-
ship training performed more scans and used more applications than those
who completed a pediatrics or medicine-pediatrics residency before PEM METHODS
fellowship only [median 15 (9, 20) vs 2 (1, 5) ( P < 0.01) and median 11
(6.5, 13) vs 2 (1, 3) ( P < 0.01), respectively]. Participants who worked in ac- Study Design
ademic emergency departments performed more ultrasounds than those who
This was a prospective cross-sectional study. We distributed
did not [3.5 (1, 8) vs 1 (0, 2), P < 0.01] and used a greater breadth of appli-
electronic surveys to recent PEM fellowship graduates to deter-
cations [3 (1, 5) vs 1 (0, 3), P < 0.01]. Physicians who billed for POCUS
mine self-reported patterns of POCUS training, current practice
studies were more likely to use POCUS (odds ratio, 2.8; 95% confidence in-
environment, and POCUS use. The study was certified exempt
terval, 1.1–7.3) with greater frequency [5 (2.3, 10) vs 2 (0.8, 5), P < 0.01] and
by the Institutional Review Board.
use a broader range of applications [3 (2,6) vs 2 (0.8, 3.3), P < 0.01].
Conclusion: Most respondents report recent POCUS use in practice.
Point-of-care ultrasound fellowship training, working in an academic emer-
Study Population
gency department, and having the ability to bill were associated with Physicians who completed PEM fellowship in the United
increased POCUS use. States or Canada between 2014 and 2018 were eligible to partici-
pate. Physicians who had not provided care to pediatric patients in
Key Words: point-of-care ultrasound, POCUS, fellowship the 6 months before completing the survey were excluded.
Survey Design
P oint-of-care ultrasound (POCUS) use by pediatric emergency

medicine (PEM) physicians has increased dramatically over
the past decade.1–6 The American Board of Pediatrics includes
The study authors developed the survey instrument (see Sur-
vey instrument, Supplemental Digital Content, http://links.lww.
com/PEC/A839), which was reviewed by 3 PEM attendings with
POCUS content as required material for PEM board certification,7 survey design experience and subsequently modified for brevity
and the American Academy of Pediatrics has issued guidelines and clarity. The survey was then pilot tested on a sample of 5 PEM
for the use of POCUS in PEM.8 Regional and national studies fellowship graduates for content, length, and ease of comprehen-
suggest varying rates of POCUS use by emergency medicine sion. To answer the survey, we asked each respondent to recall the
(EM) physicians,9–12 but little is known about POCUS use by PEM last 10 shifts they worked as a representative sample of their prac-
physicians nationally. Barriers to POCUS use by PEM physicians tice pattern. We chose 10 shifts, rather than a larger amount, with
include discomfort with POCUS skills, insufficient educational the intention of limiting recall bias.
From the Children's National Hospital, Division of Emergency Medicine and Study Protocol
Trauma Services, The George Washington University School of Medicine and
Health Sciences, Washington, DC. We created a list of all 78 US and 10 Canadian PEM fellowships
Reprints: Simone L. Lawson, MD, 111 Michigan Avenue NW, Washington, DC using the Electronic Residency Application Service and the Interna-
20010 (e‐mail: sllawson@childrensnational.org). tional Federation for Emergency Medicine Web sites. An e-mail
Presentations: This abstract has been accepted for presentation as an e-poster at
was sent to each program director and/or program coordinator re-
the AIUM 2021 Annual Meeting (April 11–14, 2021) and the SAEM21 questing that a recruitment e-mail, including the survey link, be
Virtual Meeting (May 11–14, 2021). forwarded to all graduates of their program from 2014 to 2018.
Supplemental digital content is available for this article. Direct URL citations Over the following 2 weeks, we sent 2 reminder e-mails. If the
program director or program coordinator replied to the reminder
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. e-mail, they were asked how many graduates received the forwarded
ISSN: 0749-5161 e-mail. Surveys were completed individually by participants using

Lawson et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
REDCap, and responses were stored in a database on a secure studies and was assigned a maximum value of 20 when calculat-
server.13 No participation incentive was given. ing frequency of use as to not skew the results by a single outlier.
Absolute use was treated as a categorical outcome, and dif-
ferences between groups were calculated using Pearson χ2 or Fi-
Data Analysis scher exact test. Frequency and breadth of use were compared
Descriptive statistics for participant demographics were cal- using the Mann-Whitney U test for comparisons with 2 groups,
culated within REDCap. Further analyses were performed using and the Kruskal-Wallis test with post hoc pairwise comparisons
Microsoft Excel 2019 (Microsoft Corp, Redmond, Wash) and for variables with 3 groups.
SPSS version 26 (IBM, Armonk, NY). Absolute POCUS use
was defined as using POCUS at least once in the last 10 clinical
shifts. Frequency of use was defined as the number of patient en- RESULTS
counters in which the responding physician used POCUS during There were 772 PEM fellowship graduates from US PEM
the last 10 shifts, and breadth of use was defined as the number fellowships14–18 and an estimated additional 100 Canadian gradu-
of distinct POCUS applications used in the last 10 shifts. A single ates between 2014 and 2018. Although we could not confirm de-
respondent indicated he or she performed more than 20 POCUS livery of the survey link to all graduates, a total of 159 people
FIGURE 1. Flow diagram of participant recruitment and survey respondents.

Pediatric Emergency Care • Volume 39, Number 1, January 2023 POCUS Use By Recent PEM Graduates
TABLE 1. Participant Demographics, POCUS Education, and TABLE 1. (Continued)

Absolute POCUS Use
US fellow
No POCUS Yes 43 (30.1) 37 (86.0) 6 (14.0) 0.47
Pocus Use Use in Past No 100 (69.9) 81 (81.0) 19 (19.0)
Total in Past 10 10 Shifts EM physician without US fellowship
(Column %) Shifts (Row %) (Row %) P* Yes 33 (23.1) 27 (81.8) 6 (18.2) 0.90
Total 143 (100) 118 (82.5) 25 (17.5) No 110 (76.9) 91 (82.7) 19 (17.3)
Location of PEM Sonographer
fellowship Yes 12 (8.4) 12 (100.0) 0 (0) 0.12
United States 125 (87.4) 102 (81.6) 23 (18.4) 0.74 No 131 (91.6) 106 (80.9) 25 (19.1)
Canada 18 (12.6) 16 (88.9) 2 (11.1)
*Pearson χ2 or Fisher exact test.
PEM fellowship graduation year
2014 24 (16.8) 21 (87.5) 3 (12.5) 0.36
2015 27 (18.9) 19 (70.4) 8 (29.6) responded, of which 146 met inclusion and not exclusion criteria.
2016 21 (14.7) 19 (90.5) 2 (9.5) Three participants were excluded from data analysis as they did
2017 37 (25.9) 30 (81.1) 7 (18.9) not indicate whether they used POCUS in their last 10 shifts. As-
2018 34 (23.8) 29 (85.3) 5 (14.7) suming all graduates received a survey, this represents a complete
Practice location response rate of 16.4% (Fig. 1).
United States 122 (85.3) 99 (81.1) 23 (18.9) 0.58
The program directors/coordinators from 33 programs (30
US and 3 Canadian) indicated they distributed the survey to their
Canada 12 (8.4) 11 (91.7) 1 (8.3)
eligible graduates and confirmed delivery to at least 261 partici-
Other (Europe, 9 (6.3) 8 (88.9) 1 (11.1) pants. Twenty-six of these programs confirmed the number of
Asia, Africa)
graduates who were sent the recruitment e-mail. Four programs
Introduction to POCUS responded that they had no graduates from 2014 to 2018. One pro-
Medical school 12 (8.4) 12 (100) 0 (0) 0.20 gram declined to participate. Two programs confirmed send-
Residency 21 (14.7) 18 (85.7) 3 (14.3) ing the survey to alumni but did not provide the number of recip-
Fellowship 110 (76.9) 88 (80.0) 22 (20.0) ients. The program directors/coordinators from the remaining 55
Method of POCUS education in PEM fellowship PEM fellowship programs did not reply to our e-mails, so we
Lectures in PEM didactics could not determine whether the graduates of these programs re-
Yes 93 (65.0) 76 (81.7) 17 (18.3) 0.73 ceived the survey. Respondent demographics are described in
No 50 (35.0) 42 (84.0) 8 (16.0) Table 1.
Mandatory US
Of the 143 participants who provided complete survey re-
rotation sponses, 118 (82.5%) reported using POCUS at least once dur-
Yes 87 (60.8) 73 (83.9) 14 (16.1) 0.59
ing their last 10 shifts. Of the remaining 25 respondents, 2 (1.4%)
indicated they “sometimes” used POCUS, 18 (12.6%) indi-
No 56 (39.2) 45 (80.4) 11 (19.6)
cated they “rarely” used POCUS, and 5 (3.5%) reported “never”
Lectures in US using POCUS.
rotation
There was no significant association between POCUS edu-
Yes 69 (48.3) 60 (87.0) 9 (13.0) 0.18 cation and absolute POCUS use (Table 1). Whether the respon-
No 74 (51.7) 58 (78.4) 16 (21.6) dent was first introduced to POCUS as a medical student, resident,
US elective or fellow, the methods of POCUS education and the credentials of
Yes 35 (24.5) 29 (82.9) 6 (17.1) 0.95 POCUS instructors during PEM fellowship were not associated
No 108 (75.5) 89 (82.4) 19 (17.6) with absolute POCUS use by physicians (Table 1).
Mandatory Absolute POCUS use was associated with working in an ac-
scanning ademic emergency department (ED) and with the ability to bill for
shifts POCUS studies ( P < 0.01). There was no association between ab-
Yes 28 (19.6) 26 (92.9) 2 (7.1) 0.11 solute POCUS use and working in a community ED, regardless of
No 115 (80.4) 92 (80.0) 23 (20.0) supervisory responsibilities. Those who reported working at least
POCUS instructor education some shifts in an academic/teaching ED had increased frequency
EM physician with US fellowship and breadth of use as compared with those who did not. Partici-
Yes 78 (54.5) 67 (85.9) 11 (14.1) 0.24
pants who worked with a director of ultrasound did not have in-
creased odds of absolute POCUS use, but they used POCUS more
No 65 (45.5) 51 (78.5) 14 (21.5)
frequently and for more applications. The potential to bill for
PEM physician with US fellowship POCUS studies was associated with higher odds of having used
Yes 58 (40.6) 47 (81.0) 11 (19.0) 0.70 POCUS in the past 10 shifts (odds ratio, 2.8; 95% confidence in-
No 85 (59.4) 71 (83.5) 14 (16.5) terval, 1.1–7.3; Table 2). However, when this relationship was ad-
PEM physician without US fellowship justed for employment in an academic setting, the relationship was
Yes 53 (37.1) 46 (86.8) 7 (13.2) 0.30 no longer statistically significant (adjusted odds ratio, 2.4; 95%
No 90 (62.9) 72 (80.0) 18 (20.0) confidence interval, 0.92–6.4).
There was no association between methods of POCUS train-
ing during PEM fellowship and absolute POCUS use in the last 10
Continued next page shifts worked. There was a statistically significant difference in the

TABLE 2. Independent Factors and Their Association With POCUS Use
No POCUS Median Scans in Past Median Applications

Total, n (%) POCUS Use, n (%) Use, n (%) P* 10 Shifts (IQR) P† Used (IQR) P†
Practice description‡
Academic/teaching ED
Yes 124 (86.7) 106 (85.5) 18 (14.5) 0.02 3.5 (1, 8) <0.01 3 (1, 5) <0.01
No 19 (13.3) 12 (63.2) 7 (36.8) 1 (0, 2) 1 (0, 3)
Community ED with supervisory responsibilities
Yes 28 (19.6) 21 (75.0) 7 (25.0) 0.24 3 (0.25, 5.75) 0.24 1.5 (0.25, 5) 0.19
No 115 (80.4) 97 (84.3) 18 (15.7) 3 (1, 8) 3 (1, 5)
Community ED without supervisory responsibilities
Yes 19 (13.3) 14 (73.7) 5 (26.3) 0.28 1 (0, 3) 0.01 2 (0, 3) 0.13
No 124 (86.7) 104 (83.9) 20 (16.1) 3 (1, 8) 3 (1, 5)
Ability to bill for POCUS studies
Yes 69 (51.7) 62 (89.9) 7 (10.1) 0.03 5 (2, 10) <0.01 3 (2, 6) <0.01
No/unsure 74 (48.3) 56 (75.7) 18 (24.3) 2 (0.75, 5) 2 (0.75, 3.25)
Director of ultrasound at practice location
Yes 95 (66.4) 81 (85.3) 14 (14.7) 0.22 3 (1, 10) 0.02 3 (1, 5) 0.02
No/unsure 48 (33.6) 37 (77.1) 11 (22.9) 2 (1, 5) 2 (1, 3)
†
Mann-Whitney U.
‡
Location where respondent provided care to pediatric patients.
IQR indicates inter quartile range.
frequency of scans and breadth of applications used related to DISCUSSION

training before and after PEM fellowship (Table 3). In post hoc
pairwise testing, PEM fellowship graduates who completed an Pediatric emergency medicine fellowship graduates have had
additional POCUS fellowship performed more scans ( P < 0.01) the opportunity to incorporate POCUS into their clinical practice
and used more applications ( P < 0.01) than those who completed since curricular recommendations for POCUS education during
a pediatric or medicine-pediatrics (pediatrics-based) residency PEM fellowship were issued.7 Before this study, there was limited
before PEM fellowship. However, we did not show a difference knowledge of how extensively POCUS was incorporated into
in the number of scans ( P = 0.17) or breadth of applications clinical practice after PEM fellowship or factors associated with
( P = 0.35) between those who completed POCUS fellowship POCUS use. In this study, we surveyed PEM fellowship graduates
and those who completed EM residency before PEM fellowship. from the past 5 years regarding their use of POCUS in their cur-
We also found that those completing EM residency used a broader rent provision of care to their patients. To our knowledge, this is
range of applications than those who completed a pediatrics-based the first study to investigate POCUS use by recent PEM fellow-
residency ( P = 0.02), but we did not demonstrate a difference in ship graduates.
the median number of studies performed ( P = 0.15) (Figs. 2 The majority of respondents self-reported POCUS use in
and 3). There were no participants who completed an EM resi- their clinical practice. Aspects of respondents' current work envi-
dency, PEM fellowship, and POCUS fellowship. Furthermore, ronment, including working in an academic institution and the
we did not find greater absolute POCUS use or greater breadth ability to bill for POCUS studies, were significantly associated
of POCUS use among PEM fellow graduates with a specific inter- with POCUS use in practice, whereas methods of POCUS train-
est in global health. ing during fellowship were less likely to impact current practice.
TABLE 3. Training and POCUS Use
POCUS No POCUS Median Scans in Past Median Applications

Training Total, n (%) Use, n (%) Use, n (%) P* 10 Shifts (IQR) P† Used (IQR) P†
Pediatrics or Med/Peds and PEM 114 (79.7) 91 (79.8) 23 (20.2) 0.24 2 (1, 5) <0.01 2 (1, 3) <0.01
fellowship
EM and PEM fellowship 12 (8.4) 11 (91.7) 1 (8.3) 5 (3.25, 10) 5 (3.25, 6)
Pediatrics, PEM fellowship, US 17 (11.9) 16 (94.1) 1 (5.9) 15 (9, 20) 11 (6.5, 13)
fellowship
†
Kruskal-Wallis.
IQR indicates inter quartile range.

FIGURE 2. Frequency of POCUS use by training type. Outliers (cases with values between 1.5 and 3 times the IQ range) are represented by an
open circle. Extremes (cases with values more than 3 times the IQ range) are represented by an asterisk. The grand median (median across all
groups) is indicated by a horizontal bar.
Training programs in academic institutions may have require- the strength of POCUS education in EM residency programs.
ments for POCUS training for their residents and fellows, which Alternatively, this similarity could indicate that both groups ap-
is likely to be associated with greater POCUS use in academic en- proach a ceiling in the current utility of POCUS in PEM given
vironments. Ultrasound fellowship–trained faculty performed POCUS the available clinical evidence base.
more frequently and used a greater breadth of POCUS applica- In this survey, the method and timing of POCUS education
tions, but we did not show that they were more likely to incorpo- did not significantly impact incorporation of POCUS into prac-
rate POCUS into their practice than those who did not train in US tice. This is reassuring as the method of POCUS training varies
fellowship. It is possible that PEM fellow graduates who under- widely among PEM fellowships.5,23,24 It is important to note that
take more training may have less exposure or confidence in their training in either an EM residency or a US fellowship is associated
POCUS training in PEM fellowship, and therefore seek it out with a wider breadth of applications practiced. This may be a re-
even if they subsequently do not use it in their clinical practice. sult of clear guidelines for core application requirements within
This finding may also reflect our low response rate, and it may those programs. With the recent publication of Consensus Core
be that with more respondents, this finding would be different. Point-of-Care Ultrasound Applications for Pediatric Emergency
It may seem counterintuitive that physicians who sought ad- Medicine Training,6 we anticipate a similar structure of well-
ditional POCUS training were not more likely to include POCUS defined core applications for POCUS training during PEM fel-
in their clinical practice than those who did not pursue additional lowship. Although there was an even distribution of respondents
training. However, PEM fellowship graduates had a considerably for each year of fellowship graduation, we did not have a large
high rate of POCUS use overall (>80%), which would make it dif- enough sample size to see if there was more POCUS use through
ficult to show a statistically significant difference. Although PEM the years, as POCUS training in PEM fellowship has likely be-
physicians who completed a pediatrics-based residency were less come more robust with time.
likely to incorporate POCUS into practice, EM residency gradu- The association of POCUS use with the potential for billing
ates and US fellowship graduates used a similar breadth of US ex- is a novel finding that may have implications for POCUS training.
aminations and at a similar frequency. This could indicate that the Physicians who bill for POCUS studies were more likely to use
POCUS education offered in EM residency and US fellowship POCUS. In this case, it may be beneficial to both patients and
programs includes more applications than are covered in PEM PEM practices to educate PEM fellows during their training about
fellowship POCUS education. Longstanding POCUS training POCUS billing and financial sustainability. Although a recent
requirements and recommendations for EM residents from the consensus statement identified 21 core applications6 to be in-
Accreditation Council for Graduate Medical Education,19 the cluded in POCUS training during PEM fellowship, there has been
American Board of Emergency Medicine,20 and the American little discussion around incorporation of billing knowledge in
College of Emergency Physicians21,22 may also contribute to POCUS training.

FIGURE 3. Breadth of POCUS use by training type. Outliers (cases with values between 1.5 and 3 times the IQ range) are represented by an
open circle. Extremes (cases with values more than 3 times the IQ range) are represented by an asterisk. The grand median (median across all
groups) is indicated by a horizontal bar.
Limitations CONCLUSIONS
Most respondents continued to use POCUS in clinical prac-
The primary limitation of this study was the low response tice after PEM fellowship graduation. Incorporation of POCUS
rate. Although the respondents' demographics seem to accurately into clinical practice after fellowship was associated with factors
represent the targeted provider group, less than a quarter of the related to work environment but not to methods of ultrasound ed-
intended participants responded, leading to missing data and po- ucation during fellowship. A more robust survey response in the
tential nonresponse bias.25,26 We intended to contact all recent future may reveal further nuances into the relationships between
PEM fellowship graduates; however, because there is no publicly training, work environment, and POCUS use.
available list of PEM fellowship graduates, we had to rely on the
program directors/coordinators to distribute the survey on our be-
half. The program directors/coordinators from 55 PEM fellowship ACKNOWLEDGMENT
programs did not reply to our e-mails to confirm that they sent the The authors would like to thank Dr Jim Chamberlain for his
survey to their graduates, so we could not determine whether the assistance with the development of the survey instrument used for
graduates of these programs received the survey. We did not ask data collection.
the respondents to identify which programs they graduated from.
Therefore, we do not know how many eligible participants received
the survey, and as a result, we cannot determine the actual response REFERENCES
rate. There are known limitations of survey studies including survey
fatigue and missing data.27 We attempted to limit survey fatigue by 1. Cohen JS, Teach SJ, Chapman JI. Bedside ultrasound education in pediatric
emergency medicine fellowship programs in the United States. Pediatr
keeping the survey relatively brief. Recall bias may have limited
Emerg Care. 2012;28:845–849.
self-report of POCUS use and education.26 There was potential se-
lection bias as those more interested in POCUS may have been 2. Gold DL, Marin JR, Haritos D, et al. Pediatric emergency medicine
more likely to complete the survey, skewing our results to a higher physicians' use of point-of-care ultrasound and barriers to implementation:
level of use. In addition, our survey has not been tested for validity. a regional pilot study. AEM Educ Train. 2017;1:325–333.
Our anonymous survey had no way to prohibit multiple responses 3. Ramirez-Schrempp D, Dorfman DH, Tien I, et al. Bedside ultrasound in
from the same participant. The first question of the survey served pediatric emergency medicine fellowship programs in the United States:
as a screening question, asking participants if they had taken a sur- little formal training. Pediatr Emerg Care. 2008;24:664–667.
vey about POCUS training in PEM fellowship and POCUS use in 4. Gonzalez LK, Yellin S, Arroyo AC. Point-of-care ultrasound in the
clinical practice, so although it is unlikely, some responses could pediatric emergency department where we're at, where we're going.
theoretically be duplicate responses. Adv Pediatr. 2018;65:121–142.

5. Marin JR, Zuckerbraun NS, Kahn JM. Use of emergency ultrasound in of Applications and Data Analysis ACGME; 2017. Available at: https://
United States pediatric emergency medicine fellowship programs in 2011. www.acgme.org/globalassets/pfassets/publicationsbooks/2016-2017_
J Ultrasound Med. 2012;31:1357–1363. acgme_databook_document.pdf. Accessed December 8, 2021.
6. Shefrin AE, Warkentine F, Constantine E, et al. Consensus core point-of- 17. Accreditation Council for Graduate Medical Education. ACGME Data
care ultrasound applications for pediatric emergency medicine training. Resource Book Academic Year 2017–2018. [online] Chicago: Department
AEM Educ Train. 2019;3:251–258. of Applications and Data Analysis ACGME; 2018. Available at: https://
7. Vieira R, Hsu D, Nagler J, et al. Pediatric emergency medicine fellow www.acgme.org/globalassets/pfassets/publicationsbooks/2017-2018_
training in ultrasound: consensus educational guidelines. Acad Emerg Med. acgme_databook_document.pdf. Accessed December 8, 2021.
2013;20:300–306. 18. Accreditation Council for Graduate Medical Education. ACGME Data
8. Marin JR, Lewiss RE. Point-of-care ultrasonography by pediatric Resource Book Academic Year 2018–2019. [online] Chicago: Department
emergency medicine physicians. Pediatrics. 2015;135:e1097–e1104. of Applications and Data Analysis ACGME; 2019. Available at: https://
www.acgme.org/globalassets/pfassets/publicationsbooks/2018-2019_
9. Herbst MK, Camargo CA Jr., Perez A, et al. Use of point-of-care ultrasound acgme_databook_document.pdf. Accessed December 8, 2021.
in Connecticut emergency departments. J Emerg Med. 2015;48:191–196.e2.
19. Accreditation Council for Graduate Medical Education, 2021. ACGME
10. Amini R, Wyman MT, Hernandez NC, et al. Use of emergency ultrasound Program Requirements for Graduate Medical Education in Emergency
in Arizona community emergency departments. J Ultrasound Med. 2017; Medicine. [online]. Available at: https://www.acgme.org/Portals/0/
36:913–921. PFAssets/ProgramRequirements/110_EmergencyMedicine_2021.pdf?
11. Das D, Kapoor M, Brown C, et al. Current status of emergency department ver=2021-06-22-142223-527. Accessed December 8, 2021.
attending physician ultrasound credentialing and quality assurance in the 20. Beeson M, Ankel F, Bhat R, et al. The 2019 model of the clinical practice of
United States. Crit Ultrasound J. 2016;8:6. emergency medicine. J Emerg Med. 2020;59:96–120.
12. Moore CL, Molina AA, Lin H. Ultrasonography in community emergency 21. American College of Emergency Physicians. Emergency ultrasound
departments in the United States: access to ultrasonography performed by guidelines. Ann Emerg Med. 2009;53:550–570.
consultants and status of emergency physician-performed ultrasonography.
Ann Emerg Med. 2006;47:147–153. 22. American College of Emergency Physicians. Ultrasound guidelines:
emergency, point-of-care and clinical ultrasound guidelines in medicine.
13. Harris PA, Taylor R, Thielke R, et al. Research electronic data capture Ann Emerg Med. 2017;69:e27–e54.
(REDCap)—a metadata-driven methodology and workflow process for
providing translational research informatics support. J Biomed Inform. 23. Thomas-Mohtat R, Breslin K, Cohen JS. Quality assurance for
2009;42:377–381. point-of-care ultrasound in north American pediatric emergency
medicine fellowships [published online ahead of print July 5, 2019].
14. Accreditation Council for Graduate Medical Education. ACGME Data Pediatr Emerg Care. doi:10.1097/PEC.0000000000001871.
Resource Book Academic Year 2014–2015. [online] Chicago: Department
of Applications and Data Analysis ACGME; 2015. Available at: https:// 24. Hoeffe J, Desjardins MP, Fischer J, et al. Emergency point-of-care
www.acgme.org/globalassets/pfassets/publicationsbooks/2014-2015_ ultrasound in Canadian pediatric emergency fellowship programs: current
acgme_databook_document.pdf. Accessed December 8, 2021. integration and future directions. CJEM. 2016;18:469–474.
15. Accreditation Council for Graduate Medical Education. ACGME Data 25. Brick J, Kalton G. Handling missing data in survey research. Stat Methods
Resource Book Academic Year 2015–2016. [online] Chicago: Department Med Res. 1996;5:215–238.
of Applications and Data Analysis ACGME; 2016. Available at: https:// 26. Alderman AK, Salem B. Survey research. Plast Reconstr Surg. 2010;126:
www.acgme.org/globalassets/pfassets/publicationsbooks/2015-2016_ 1381–1389. doi:10.1097/prs.0b013e3181ea44f9.
acgme_databook_document_locked.pdf. Accessed December 8, 2021. 27. Debois S. 10 advantages and disadvantages of questionnaires (updated
16. Accreditation Council for Graduate Medical Education. ACGME Data 2019). 2019. Survey Anyplace Blog. Available at: https://surveyanyplace.
Resource Book Academic Year 2016–2017. [online] Chicago: Department com/questionnaire-pros-and-cons/. Accessed January 15, 2020.

ORIGINAL ARTICLE
How Much Do Parents Know About Pain in Their Children?

María Escobar-Castellanos, MD,* María Concepción Míguez-Navarro, PhD, MD,†
Julia García-Mancebo, MD,* Belén Fernández-Monteagudo, MD,* Patricia Pascual-García, RN,*
Gloria Guerrero-Márquez, RN,† and Arístides Rivas-García, MD†
The aim of this study is to evaluate parent's knowledge

Objectives: Adequate pain control is essential to the comprehensive about pain in the pediatric population patient and secondarily
management of pediatric patients within the emergency department. describe erroneous concepts that can affect a correct children's
The aim of this study is to evaluate parents' knowledge about pain in pain management.
the pediatric population patient and secondarily describe erroneous con-
cepts that can affect a correct children's pain management.
Methods: A single-center descriptive study of cross-sectional surveys METHODS
was performed between October and December 2018, with a previously
validated ad hoc and anonymous questionnaire consisting of 9 items. All Study Design
parents/guardians participating in the study had a child aged 0 to 18 years
A descriptive cross-sectional single-center study of surveys
who had been admitted to the emergency department.
was conducted with an anonymous ad hoc questionnaire handed
Results: Sixty-nine percent (n = 315) were women, 49.9% (n = 226) had
over to parents or guardians. The study was approved by the Local
university degrees and only 11% (n = 50) had professions related to the
Committee of Ethics and Investigation and complies with the re-
healthcare system. A linear association was observed between the number
quirements of the Declaration of Helsinki. The principles of good
of correct answers and the level of education (β = 1.04; 95% confidence
clinical practice were followed during the study. Informed consent
interval, 0.76–1.32; P < 0.001), as well as between parents with professions
was obtained from all of those included in the study.
related to the healthcare system compared with other professions (61.4%
vs 51.2% with P = 0.005). The responses of Spanish parents offered better
results than answers obtained from parents from the American continent
Study Setting
(56.4% vs 41.4% with P < 0.001). No differences were observed between The study was performed in the pediatric emergency depart-
parents of children with chronic diseases. ment (PED) of a tertiary referral hospital in Madrid, Spain, with
Conclusions: In our study, we observed that a considerable percentage of approximately 56,000 annual emergency department admissions.
parents hold misconceptions about how children express pain, and there-
fore, it would be necessary to encourage formation programs for parents Sampling
to help identify, evaluate, and correctly treat pain in their children. Our study included parents or guardians who attended the
Key Words: pain knowledge, parents, pain expressions PED from October 1 to November 30, 2018. To reduce selection
bias and guarantee generalization, the participants were selected
(Pediatr Emer Care 2023;39: 40–44) from all 3 work shifts (morning 0800–1500 hours, afternoon
1500–2200 hours and night 2200–0800 hours) systematically,
A ccording to the International Association for the Study of

Pain, pain is an unpleasant sensory and emotional experience
associated with actual or potential tissue damage or described in
and the questionnaires were offered to the parents of the first
5 patients seen in each shift. All participants signed an informed
consent form.
terms of such damage. Despite the increasing knowledge about the Parents who did not speak Spanish or with cognitive impair-
long-term adverse effects of pain in children's developing brains,1–4 ment were excluded, as well as those questionnaires with less than
many children's pain is underdiagnosed and undertreated.5 90% of the form filled out.
An adequate treatment of pain requires a proper assessment, A sample size of 450 questionnaires was predetermined
the choice of the appropriate analgesic, route of administration with a confidence level of 95% and a margin of error of ±5%,
and dose, and the possible addition of other physical and psycho- according to the worst hypothesis of a maximum degree of un-
logical strategies.6 certainty ( P = q = 50% correct questions), counting with 15%
In previous studies, up to 50% to 60% of parents adminis- of nonresponse.
tered lower doses than prescribed to their children.7–9 The reasons
for this undertreatment are not clear, but it has been associated Questionnaire
with incorrect information and erroneous ideas about the manage-
The questionnaire was prepared according to the following
ment of pain in children.10
steps: review of the previous literature, selection of demographic
Currently, advances are being made by professionals for the pro-
variables, and translation and adaptation, adding further questions
motion of early management of pain and anxiety in children, high-
to the previously validated questionnaire. The questionnaire was
lighting the importance of parent's education on this subject.11,12
divided into 2 parts, one for demographic variables and another
with the 14 questions/affirmations for the evaluation of parents' at-
From the *HGU Gregorio Marañón; and †Foundation for Biomedical Research
titudes toward pain expression and pain management in children.
of Hospital Gregorio Marañón. A pilot study was performed on 15 parents with professions
Disclosure: The authors declare no conflict of interest. not related to health care. According to their feedback, the final
Reprints: María Escobar-Castellanos, MD, Emergency Department, C/ Doctor questionnaire was completed. The final questionnaire required ap-
Esquerdo, 46, 28007 Madrid, Spain (e‐mail:
mariaescobarcastellanos121091@gmail.com).
proximately 10 minutes for its completion.
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. Every participant who met the inclusion criteria was invited to
ISSN: 0749-5161 participate in the study. Parents were asked to read and sign the

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Parents’ Knowledge About Pain in Their Children
informed consent form. After this, the questionnaire was handed Gathering Data
over to the parents in an envelope. When both parents were present This was carried out with a closed and personally filled-out
with the patient, they only received one envelope. The form was questionnaire, <ad hoc> for the investigation, which comprises 2
then filled out personally and deposit anonymously in a box for parts, one destined for demographic variables and another with
this purpose. the 14 questions/affirmations for the evaluation of the knowledge
that parents have of pain in children.
Study Variables The questionnaire was elaborated following these steps: revi-
Demographic variables included sex, age, nationality, level sion of bibliography, selection of demographic variables and scale
of education (primary, secondary, career training, university), of pain to be used, linguistic translation of the scale, and elabora-
and whether or not their profession was related to health care, tion of other questions that were not included in the scale used.
number of children, and if they had any children with chronic Then, the order and the design of the format of the questionnaire
diseases. were chosen.
To optimize the analysis, the country of birth was categorized After the period of elaboration, a pilot test was carried out
using the World Health Organization's grouping regions, which with 15 parents with professions other than the health profes-
differentiates 6 regions: Europe, America, West Pacific, Africa, sionals. According to their feedback, the final questionnaire was
South East Asia, and the Eastern Mediterranean.13 Because our written, clarifying those questions that might have elicited doubt-
study was performed in Spain, to establish comparisons, Spanish ful answers. The final “ad hoc” questionnaire required approxi-
were analyzed in its own group separated from the rest of the mately 10 minutes for its completion.
European countries included in the “Europe” region. Every participant that met the inclusion criteria was invited to
The result variable was the percentage of correct answers participate in the study. To this end, its reading and acceptance, via
among the 14 statements to assess parents' knowledge about pain informed consent, was requested. Once accepted and the consent
in children (Table 1). form signed, the questionnaire was handed over in an envelope.
When both parents accompanied the patient, only one enve-
Outcome Evaluation lope was given.
To study parents' knowledge toward pain expression and
pain management, a previously validated survey, Parental Pain
Data Analysis
Expression Perceptions (PPEP) developed by Zisk et al,10 was The statistical analysis was performed using IBM SPSS Sta-
used as reference. The prior study consists of 9 statements and tistics, version 21.0 (IBM Corp, Armonk, NY).
was modified by adding 5 more items for its use in this study Qualitative variables were described as absolute frequency
about different aspects of pain in children. This scale has proven and percentage.
to have an internal validity by Cronbach α of 0.79 and has been Quantitative variables with normal distribution were expressed
used in previous studies.14,15 After the addition of 5 more items, as mean values and SD, and those without were expressed as
the internal validity of Cronbach α of 0.79 was persistent. median values and interquartile ranges.
The responses use a Likert-type scale from 1 to 7, with 1 in- Differences between qualitative variables were assessed by
dicating in total disagreement and 7 indicating in total agreement. the χ2 test, whereas comparison between qualitative and quantita-
All the statements are misconceptions about children's pain ex- tive variables was carried out by Student t test. The correlation be-
pression, and therefore, the higher the scores, the less knowledge tween the number of correct answers and the level of education
about pain in children (Table 1). In our study, to analyze the corre- was assessed by linear correlation coefficient.
lation with the demographic variables, the responses were divided A P value <0.05 was considered statistically significant.
into 3 groups: 1 to 3 as disagree, 4 as nonspecific, and 5 to 7 as
agree (Table 1). For the purpose of the statistical analysis, the “dis-
agree” answers were considered correct and the “agree” answers RESULTS
were considered incorrect, and our results are presented as correct During the study period, a total of 502 questionnaires were
answers out of the 14 questions. handed over, finally including 453 valid questionnaires (Fig. 1).
TABLE 1. PPEP Modified Questionnaire
1. Children always express pain by crying or whining 1 2 3 4 5 6 7

2. Children always tell their parents when they are in pain 1 2 3 4 5 6 7
3. Children who are quiet are not in pain 1 2 3 4 5 6 7
4. Children who are playing are not in pain 1 2 3 4 5 6 7
5. Children experiencing pain report it immediately 1 2 3 4 5 6 7
6. Children exaggerate pain 1 2 3 4 5 6 7
7. Children complain about pain to get attention 1 2 3 4 5 6 7
8. Children in pain have trouble sleeping 1 2 3 4 5 6 7
9. Children feel pain less than adults 1 2 3 4 5 6 7
10. Children complain less about pain than adults 1 2 3 4 5 6 7
11. Pain is useful for children's education and they must learn to deal with it 1 2 3 4 5 6 7
12. It's not possible to know how much pain children who don't speak are suffering 1 2 3 4 5 6 7
13. The treatment or medicine to be used for pain is independent of its intensity 1 2 3 4 5 6 7
14. Babies have less pain than older children 1 2 3 4 5 6 7

Escobar-Castellanos et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
time that this scale is used in the pediatric population with non-
postsurgical pain; as previously, it had just been used to evaluate
the knowledge of parents whose children had undergone surgery
and therefore suffered from postoperative pain.
More than half of the questions were answered correctly, and
it was found that many parents have misconceptions regarding
how children express pain, as previously published by Zisk Rony
et al14 and Twycross et al.15
The most common misconceptions are that “children in pain
have trouble sleeping” and “children always tell their parents when
they are in pain.” The latter can be considered prevalent and has
been documented in other studies, although it has been proven that
children do not always express pain if they are not questioned.16,17
As previously described, up to 11% of parents agreed with
the statement “children feel less pain than adults,”10,14,15 a surpris-
ing fact as this myth was refuted more than 20 years ago.18 On one
hand, the nociceptive descendant inhibitory pathways are not
functionally mature until several weeks or months after birth,
FIGURE 1. Flowchart. which means that the inhibition of pain is diminished at a very
early age. On the other hand, neonates and young infants have a
Table 2 summarizes the demographic variables of our higher density of nociceptive nervous terminations in their skin
population. than the adult, as well as a lower threshold of excitement and sen-
sitization. All of this suggests that children can feel pain from the
Pain Expression Perceptions by Parents first postconception weeks and that the final perception of pain
Around half of the answers (53.2%; n = 241) of parents were could be even higher in children than in adults, especially in very
correct (95% confidence interval, 51.2%–53.3%). Parent's re- young children.19,20
sponses are described in Table 3. Fifty-seven percent of parents agreed to the misconception
There were no differences between mean (SD) scores obtained “children always express pain by crying or whining.” It has been
by fathers and mothers (7.3 of 14 [52.2% corrected answers; SD proven that very often, behavior is the first indicator of pain taken
3.0] vs 7.5 of 14 [53.5% corrected answers; SD, 3.1]; P = 0.562).
Although when analyzing statement by statement, fathers specifi- TABLE 2. Demographic Characteristics
cally responded wrong in item 2 (83 of 135 [61.5%] vs 163 of
318 [51.2%]; P = 0.046) and in item 11 (29 of 135 [21.5%] vs 44 n (%)
of 318 [13.8%]; P = 0.043) as compared with female partners.
Nevertheless, they had more correct answers in item 10 (82 of Kinship
135 [60.7%] vs 154 of 318 [48.5%]; P = 0.016). Mothers 315 (69.5)
Analyzing the differences between the OMS's geographic Fathers 135 (29.8)
zones, Spanish parents obtained an average higher score than Legal tutors 3 (0.7)
those from the American continent (8.0 of 14 [56.4% correct Parental age, y* 38.9 (6.8)
answers; SD, 2.9] vs 5.8 of 14 [41.4% correct answers; DE, 2.7]; No. children† 2 (1–2)
P < 0.001), finding statistical significant differences in all the items
Education
except in 6, 10, and 11. No differences were found between Spanish
compared with other regions. Primary 32 (7.2)
Parents with a higher level of education obtained higher cor- Secondary 82 (18.1)
rect scores (Fig. 2), obtaining 1.04 more correct answers for each Professional education 108 (23.7)
level of education (β =1.04; 95% confidence interval, 0.76–1.32; College (university) education 231 (51)
P < 0.001). Healthcare providers 50 (11)
Parents with professions related to health care obtained more Doctors 7 (1.5)
correct answers as compared with those with non-healthcare pro- Nurses 9 (2)
fessions (8.6 of 14 [61.4% corrected questions; SD, 2.8] vs 7.3 of Not specified 34 (7.5)
14 [51.2% corrected questions; DE, 3.1]; P = 0.005), with greater Chronic illness 125 (27.6)
differences in items 2 (24 of 50 [48%] vs 110 of 391 [28.1%];
In one of the parents 77 (17.1)
P = 0.003) and in 13 (40 of 50 [80%] vs 220 of 391 [56.2%];
P = 0.003). In one of the children 48 (10.6)
No significant differences were found in the percentage of WHO geographic zones/areas
correct answers between parents with children with chronic dis- Spain 341 (75.3)
eases (404 of 452 [89%] vs 48 of 452 [10%]; P = 0.063). Europe (except Spain) 19 (4.2)
American continent 87 (19.2)
DISCUSSION Others 6 (1.3)
We studied parental knowledge about pain in their children Data are expressed in absolute numbers (n) and percentage (%).
using a previously validated scale, modified with 5 additional *Data are expressed in mean and SD.
items. This is the first study to validate the PPEP tool in Spain. †
Data are expressed in mean and interquartile interval.
Our aim was to study parental basal knowledge about pain, serv- WHO indicates World Health Organization.
ing as a reference for future research. In addition, this is the first

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Parents’ Knowledge About Pain in Their Children
TABLE 3. Answers to PPEP Modified (1)
Disagree Nonspecific Agree

(1–2–3) (4) (5–6–7)
1. Children always express pain by crying or whining 118 (26%) 77 (17%) 258 (57%)
2. Children always tell their parents when they are in pain 139 (30.7%) 68 (15%) 246 (54.3%)
3. Children who are quiet are not in pain 260 (57.4%) 65 (14.3%) 128 (28.3%)
4. Children who are playing are not in pain 233 (51.4%) 83 (18.3%) 137 (30.3%)
5. Children experiencing pain report it immediately 190 (42%) 74 (16.3%) 189 41.7%)
6. Children exaggerate pain 222 (49%) 104 (23%) 127 (28%)
7. Children complain about pain to get attention 260 (57.4%) 84 (18.5%) 109 (24.1%)
8. Children in pain have trouble sleeping 102 (22.5%) 62 (13.7%) 289 (63.8%)
9. Children feel pain less than adults 370 (81.7%) 32 (7%) 51 (11.3%)
10. Children complain less about pain than adults 236 (52.1%) 86 (19%) 131 (28.9%)
11. Pain is useful for children's education and they must learn to deal with it 332 73.3%) 48 (10.6%) 73 (16.1%)
12. It's not possible to know how much pain children who don't speak are suffering 268 (59.2%) 54 (11.9%) 131 (28.9%)
13. The treatment or medicine to be used for pain is independent of its intensity 268 (59.2%) 78 (17.2%) 107 (23.6%)
14. Babies have less pain than older children 379 (83.7%) 30 (6.6%) 44 (9.7%)
Data are expressed as absolute numbers and percentages. The “Disagree” column corresponds to those answers considered correct (scores 1–3) and the
“Agree” column with those incorrect (scores 5–7). Affirmations 1 to 9 correspond to the PPEP original scale; affirmations 10 to 14 are items that were added
to the study.
into consideration by medical professionals and parents21; never- on the assessment of children pain and concluded that ethnic
theless, behavior in children is influenced by many factors, such minorities in the United States were at higher risk of oliganalgesic
as temperament22 and previous painful experiences,23 so children and that minority groups have similar perception of pain than
express pain differently. Crying is not necessarily the most rele- others, but differences in provider assessment of their pain nega-
vant manifestation. tively affect their pain management. A recent review also con-
Differences were observed between the answers of fathers cluded that the way children perceive, express, and respond to
and mothers, especially in the statement “pain is useful for the ed- pain is shaped by sociocultural factors, previous pain experiences,
ucation of children and they must learn to deal with it,” item with and their expectations of pain.30
which fathers agreed more than mothers. This shows that pain is Along with previous studies,10,24 parents with a higher level
still considered a form of education and that this misconception of education have more correct answers than parents with a lower
seems to be more prevalent in males. level of education. Zisk et al10 observed that, although parents
As analyzed in previous studies,10,24 sociodemographic dif- with a higher educational level had a higher percentage of correct
ferences affect the perceptions of pain and analgesia, with those answers globally, they scored lower in the questions “children al-
parents from the American continent offering worse results than ways express pain by crying” and “children always tell their par-
those of Spanish origin. Cultural differences may contribute to ents when they are in pain.” There were no differences in these
pain expression and also affect the interpretation of pain and statements in our study. However, in our study, they had more in-
anxiety25–27; a previous study that analyzed ethnic differences in correct answers in the statements “children who are quiet are not in
pain expression found that African Americans were more likely pain” and “children who are playing are not in pain.” In a population
to rely on passive coping strategies that may be maladaptative (like study in the United States, it has been shown that limited education is
seeking social support, praying, hopping, and diverting attention associated with a decreased likelihood of pain consultation.31
away from pain).28 Finley et al29 studied the cultural influence Parents with professions related to health care demonstrated a
better knowledge, being more aware that the analgesia to be admin-
istered depends on the intensity of the pain suffered by the child.
Contrary to what was expected, parents with chronic diseases
or parents of children with chronic diseases did not demonstrate a
higher knowledge about pain. A higher percentage of correct an-
swers could be expected because of the fact that they visit medical
centers more frequently, but this was not observed in this study.
This study has several limitations. First, because the ques-
tionnaire was handed solely to parents who visited the PED and
therefore presented an acute intercurrent illness. As such, the results
cannot be generalized to other populations. Second, questionnaires
were not collected from parents with an important idiomatic barrier,
and therefore, the knowledge of parents who do not speak Spanish
cannot be evaluated, so the generalization of this study to popula-
tions is limited. Therefore, more studies to corroborate these data
FIGURE 2. Flowchart of scores (number of questions correctly are necessary. Third, the origin and the level of studies of the parents
answered: 0, none, and 14 every question correct) obtained were gathered, but other sociocultural or religious aspects that could
according to level of education. affect the culture of pain were not evaluated. Lastly, a systematic

Escobar-Castellanos et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
sample was chosen, when a randomized selection would have been Academy of Pediatrics. Relief of pain and anxiety in pediatric patients in
more appropriate for greater validity. emergency medical systems. Pediatrics. 2012;130:e1391–e1405.
Although there is growing concern about the adequate man- 13. Who member states. Available at: https://www.who.int/about/who-we-are/
agement of pain in the pediatric population, pain continues to be regional-offices. Accessed November 24, 2021.
undertreated and underdiagnosed and very often the reason for 14. Zisk Rony RY, Fortier MA, Chorney JM, et al. Parental postoperative pain
this are parent's misconceptions. Therefore, more studies are neces- management: attitudes, assessment, and management. Pediatrics. 2010;
sary to evaluate the knowledge and beliefs of parents about analge- 125:e1372–e1378.
sia in general populations, not only in surgical or trauma patients, to 15. Twycross AM, Williams AM, Bolland RE, et al. Parental attitudes to
optimize educational programs. children's pain and analgesic drugs in the United Kingdom. J Child Health
The assessment of the knowledge and beliefs of parents con- Care. 2015;19:402–411.
cerning pain is the first step to the understanding of parent's atti-
16. Zisk RY, Grey M, Medoff-Cooper B, et al. Accuracy of parental-global-
tudes toward analgesia for their children. According to our study,
impression of children's acute pain. Pain Manag Nurs. 2007;8:72–76.
for an active educational intervention, target populations are those
parents with a lower level of education and those Spanish speakers 17. Zisk RY, Grey M, Medoff-Cooper B, et al. The squeaky wheel gets the
from the American OMS geographic zone. grease: parental pain management of children treated for bone fractures.
Pediatr Emerg Care. 2008;24:89–96.
REFERENCES 18. Anand KJ, Hickey PR. Pain and its effects in the human neonate and fetus.
N Engl J Med. 1987;317:1321–1329.
1. Mitchell A, Boss BJ. Adverse effects of pain on the nervous systems of
newborns and young children: a review of the literature. J Neurosci Nurs. 19. Fitzgerald M, Beggs S. The neurobiology of pain: developmental aspects.
2002;34:228–236. Neuroscientist. 2001;7:246–257.
2. Grunau RE, Holsti L, Peters JW. Long-term consequences of pain in human 20. Fitzgerald M. Developmental biology of inflammatory pain. Br J Anaesth.
neonates. Semin Fetal Neonatal Med. 2006;11:268–275. 1995;75:177–185.
3. von Baeyer CL, Spagrud LJ. Systematic review of observational 21. Vincent C. Pediatric nurses' cognitive representations of children's pain.
(behavioral) measures of pain for children and adolescents aged 3 to J Pain. 2007;11:S49. doi:10.1016/j.jpain.2007.02.198.
18 years. Pain. 2007;127:140–150. 22. Kleiber C, Suwanraj M, Dolan LA, et al. Pain-sensitive temperament and
4. Lee GY, Yamada J, Kyololo O, et al. Pediatric clinical practice guidelines postoperative pain. J Spec Pediatr Nurs. 2007;12:149–158.
for acute procedural pain: a systematic review. Pediatrics. 2014;133: 23. Noel M, Chambers CT, McGrath PJ, et al. The influence of children's pain
500–515. memories on subsequent pain experience. Pain. 2012;153:1563–1572.
5. Ferrante P, Cuttini M, Zangardi T, et al. Pain management policies and 24. Fortier MA, Martin SR, Kain DI, et al. Parental attitudes regarding
practices in pediatric emergency care: a nationwide survey of Italian analgesic use for children: differences in ethnicity and language. J Pediatr
hospitals. BMC Pediatr. 2013;13:139. Surg. 2011;46:2140–2145.
6. Howard RF, Carter B, Curry J, et al. Association of Pediatric Anaesthetists: 25. Lipton JA, Marbach JJ. Ethnicity and the pain experience. Soc Sci Med.
good practice in postoperative and procedural pain. Pediatr Anaesth. 2008; 1984;19:1279–1298.
18(suppl 1):1–81. 26. Wolf BB. Ethnocultural factors influencing pain and illness behavior. Clin J
7. Finley AG, McGrath PJ, Forward PS, et al. Parents' management of Pain. 1985;1:23–30.
children's pain following ‘minor’ surgery. Pain. 1996;64:83–87. 27. Martinelli AM. Pain and ethnicity. How people of different cultures
8. Hamers JP, Abu-Saad HH. Children's pain at home following (adeno) experience pain. AORN J. 1987;46:273–281.
tonsillectomy. Eur J Pain. 2002;6:213–219. 28. Campbell CM, Edwards RR. Ethnic differences in pain and pain
9. Warnock FF, Lander J. Pain progression, intensity and outcomes following management. Pain Manag. 2012;2:219–230.
tonsillectomy. Pain. 1998;75:37–45. 29. Finley GA, Kristjánsdóttir Ó, Forgeron PA. Cultural influences on the
10. Zisk RY, Grey M, MacLaren JE, et al. Exploring sociodemographic and assessment of children's pain. Pain Res Manag. 2009;14:33–37.
personality characteristic predictors of parental pain perceptions. Anesth 30. Pope N, Tallon M, McConigley R, et al. Experiences of acute pain in
Analg. 2007;104:790–798. children who present to a healthcare facility for treatment: a systematic
11. Petrack EM, Christopher NC, Kriwinsky J. Pain management in the review of qualitative evidence. JBI Database System Rev Implement Rep.
emergency department: patterns of analgesic utilization. Pediatrics. 1997; 2017;15:1612–1644.
99:711–714. 31. Portenoy RK, Ugarte C, Fuller I, et al. Population-based survey of pain in
12. Fein JA, Zempsky WT, Cravero JP, Committee on Pediatric Emergency the United States: differences among White, African American, and
Medicine and Section on Anesthesiology and Pain Medicine; American Hispanic subjects. J Pain. 2004;5:317–328.

CME REVIEW ARTICLE
Behavioral Management of Children With Autism in the

Emergency Department
Katherine H. Wolpert, MD* Ian Kodish, MD, PhD,† Soo-Jeong Kim, MD,†‡ and Neil G. Uspal, MD*
ing the challenges of effective behavioral management at baseline

Abstract: Autism spectrum disorder (ASD) is characterized by impaired and the complexities of emergency stabilization.4,6
social communication in conjunction with patterned behaviors. Often asso- Behavioral concerns, mood symptoms, agitation, and self-
ciated with emotional dysregulation, irritability, aggression, depression, injurious behaviors are common reasons for ED referral.2 Success-
and suicidality, ASD youth frequently present to the emergency department fully navigating behavioral health ED visits in ASD youth requires
for behavioral and mental health evaluation. Psychiatric comorbidities, ag- knowledge of common psychiatric comorbidities, staying attuned
itation, and depression are commonly encountered. During these visits, to potential organic etiologies of agitation, working closely with
practitioners must thoughtfully consider organic etiologies for presenting caregivers to identify goals of care and disposition, and under-
symptoms, formulate plans to address risk of agitation, and understand standing interventions to safely address behavioral escalations.
how to effectively formulate disposition options in this patient population.
Key Words: autism spectrum disorder, agitation, depression, mental health,
PSYCHIATRIC COMORBIDITIES
suicidality
Psychiatric comorbidities are more common in youth with
(Pediatr Emer Care 2023;39: 45–52) ASD than in neurotypical peers or other children with develop-
mental disability.3,7 A lack of standardized assessments, the pres-
TARGET AUDIENCE ence of communication barriers, and a wide range of intellectual
This review is intended for healthcare providers who care for capabilities within the population makes evaluation challenging.7,8
patients with autism spectrum disorder (ASD) in the ED, acute Identification of underlying psychiatric comorbidities can allow
care, hospital, and outpatient settings. providers to better care for ASD patients in the acute care setting.
Attention-deficit/hyperactivity disorder, depression, anxiety, oppo-
sitional defiant disorder, and obsessive-compulsive disorder are
LEARNING OBJECTIVES
common.3,4,6,8,9 Comorbid diagnoses of schizophrenia or bipolar
After completion of this article, the reader should be able to: disorder are much less frequent.5,8
1. Identify factors which may suggest an organic etiology of
symptoms in agitated ASD youth APPROACH TO THE BEHAVIORAL ED VISIT
2. Describe indications for inpatient psychiatric admissions for ASD
youth presenting with depression and externalizing behaviors Routine Behavioral Management in the
3. Explain indications and pharmacologic options for managing Emergency Department
agitation in ASD youth in acute care settings As discussed in our previous work on the ED medical man-
agement of patients with ASD, EDs can use strategies to minimize
stress during an emergent care visit. Emergency departments
BACKGROUND should attempt to minimize wait times and provide families with
Autism spectrum disorder is a developmental disorder de- quiet, low stimulus spaces in which to receive care.10 Families
fined by impairment of social communication in combination with should be encouraged to provide information on their children's
restrictive, repetitive and stereotyped behaviors.1 Children with preferred accommodations, potential stressors, and preferred
ASD are 4 times more likely than neurotypical peers to present communication style.11
to the emergency department (ED), and the number of ED visits Providers should create a calm atmosphere within the care
in ASD youth has increased over the past 2 decades.2 Up to 20% space while offering preferred somatosensory items, which can
of ED visits in adolescent ASD patients are related to emotional decrease anxiety and likelihood for agitation.11 Augmentative
and behavioral health concerns.2 It is estimated that nearly 70% and Alternative Communication systems and visual schedules
of patients with ASD carry at least one comorbid psychiatric diag- can guide patients during the ED visit and enhance comfort and
nosis and 40% carry 2 or more.3–5 Approximately two thirds of familiarity with the care plan.12 Parents should be considered ex-
ASD patients are prescribed psychotropic medications, highlight- perts in their child's care, and ED staff should respond to their
guidance on what communication styles and accommodations
work best. Child life specialists should be used when available.13
From the *Assistant Professor (Wolpert) and Associate Professor (Uspal), Division
of Emergency Medicine, Department of Pediatrics, University of Washington;
†Associate Professor (Kim and Kodish), Department of Psychiatry and Behav- Medical Workup Considerations
ioral Sciences, University of Washington; and ‡Seattle Children's Autism Center,
Seattle, WA.
In ASD patients with behavioral concerns, clinicians should
Dr. Uspal discloses that the U.S. Food and Drug Administration has not approved conduct a thorough evaluation for organic etiologies. Symptoms
the use of olanzapine for the treatment of agitation in children, as discussed in must be considered in the context of both the patient's medical
this article. Please consult the product’s labeling for approved information. and social history.1 In agitated ASD youth, attention to changes in
Reprints: Katherine Wolpert, MD, 4800 Sand Point Way NE, Mail-Stop MB.7.
520 Seattle WA, 98105 (e‐mail: katherine.wolpert@seattlechildrens.org).
behavioral patterns may be particularly helpful in identifying poten-
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. tial organic causes,1 and caregiver history plays a critical role.1 A
ISSN: 0749-5161 broad differential should be considered, including ingestion,

Wolpert et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
intoxication, causes of pain, medication side effects, sequelae of vi- If no medical cause of symptoms is identified, environmental
tamin and nutritional deficiencies from a selective diet (eg, bone and social stressors at home or school should be explored. Changes
pain from scurvy), infection, and traumatic brain injury.1,14–16 Con- in routine, family stressors, and patient maltreatment are issues that
stipation, gastrointestinal complaints, seizures, and metabolic ab- can lead to externalizing behaviors in patients with ASD.28 Psychi-
normalities are frequently associated with ASD and should also atric comorbidities including attention-deficit/hyperactivity disor-
be considered. An organic cause is more likely in patients present- der, anxiety, and mood disorders can exacerbate behavioral issues.
ing at a very young age, with symptoms without clear psychosocial Communication impairments can escalate frustration, contributing
associations, and in patients with delirium, abnormal vital signs, or to risk of externalizing behaviors. Sleep disturbances and maladap-
abnormal physical findings.1,14 tive reinforcement patterns can also be causative.29
The decision to admit a patient for behavior should balance
COMMON BEHAVIORAL HEALTH CONCERNS immediate safety concerns with likelihood of benefit, potential
harms from disruption of routine and schooling, separation from
family and support systems, and cost. Careful consideration should
Suicidality be made as to whether the patient's behaviors have exceeded the
Patients with ASD are often subject to significant stressors. family's coping mechanisms.30 Predictors for need of inpatient ad-
Communication and behavioral challenges can result in bullying mission in ASD patients include low adaptive functioning, ASD
and social isolation. Patients with ASD are highly routine depen- symptom severity, primary caregiver's marital status, mood disor-
dent and often struggle greatly with disruptions in routine caused ders, and sleep problems.21 While there may be benefit in hospital-
by social stressors. These and other factors can lead to the develop- ization for acute stabilization, longstanding behavioral issues are
ment of significant behavioral reactivity, including suicidiality.17 better treated in longitudinal programs that allow for consistent ap-
Children with ASD in one study were twice as likely to have proaches to nurture more adaptive coping styles.
suicidal thoughts as children with other neurodevelopmental is- Alternatives to inpatient psychiatric admission should be
sues18 and, in a second study, were 28 times more likely to have considered, because optimizing naturalistic environments is pre-
a history of suicidal ideation or attempt versus neurotypical chil- ferred. Respite care use is associated with a short-term decrease in
dren.19 Children with ASD present to EDs for suicidality nearly admission risk,31 although this service is often difficult to access.32
as frequently because they present for externalizing behavioral The type of psychiatric program a patient may be admitted to is also
disturbances.20 Children with ASD and mood disorders are 7 an important consideration. Strategies used in general pediatric psy-
times as likely to require inpatient psychiatric hospitalization ver- chiatric units, such as nuanced verbal interventions and high levels
sus children with ASD alone.21 Adults with ASD are more likely of social interaction, may be counterproductive in children with
to die by suicide than neurotypical peers; this effect is greatest in ASD. Patients may receive greater benefit from specialized ASD
individuals without intellectual disability.22,23 units,33 although general psychiatric units may effectively treat chil-
However, identification of suicidality in children with ASD dren with ASD with appropriate accommodation.34
is challenging. Suicide screening tools, such as the Ask Suicide For patients appropriate for discharge, continuity with outpa-
Screening Questions toolkit, are not validated in this population. tient providers is critical. Crisis planning should be completed, with
Using adult suicide screening tools may underestimate suicidality attention to potential triggers for distress and feasible mitigation
in adults with ASD.24 At present, a combination of screening tools strategies. Autism Speaks hosts multiple online resources designed
and direct clinical evaluation is considered the most effective way to improve maladaptive behaviors and alleviate caregiver strain.35,36
to identify risk for suicide in children with ASD. Outpatient crisis services to rapidly follow-up with families should
Once suicidality is identified, assessment should evaluate be used where available.37 Medication management is generally
risk with consideration of the specific needs of patients with performed in the outpatient setting, but families and outpatient pro-
ASD. Particular attention should be paid to acute stressors, includ- viders can be directed to psychiatric support resources, including
ing increased bullying or loss of supportive relationships. Impul- specialty consultation.38,39 Clear return to care guidelines should
sivity and externalizing behaviors are associated with increased be offered to families so they feel comfortable seeking further care
risk of suicide attempt.19 Clinicians should evaluate for risk fac- if symptoms escalate.
tors, such as statements of intent, access to dangerous means, re-
cent attempt or plans, and profound impulsivity or dysphoria.25
The presence of social supports is protective against suicide.25 AGITATION MANAGEMENT IN THE ED
If a patient is felt appropriate for discharge, safety planning Up to 20% of the ASD population has moderate to severe irri-
should include clear directives to address sources of distress and tability and aggression.40 Agitation and aggression can be unpre-
environmental risks, using reasoning patterns that match patient dictable and dangerous, creating stress for families and medical
communication styles. Coping strategies should be tailored to teams. Interventions are often needed for de-escalation in the acute
the interests of the child, such as engagement in circumscribed ac- care setting (Fig. 1). Consulting with caregivers often gives insight
tivities, as more social demands may be anxiety provoking.26 into which techniques and therapeutic options may offer the most
Caregivers should also receive lethal means restriction counseling, benefit. If agitation escalates, specialized care teams trained in
a critical aspect of postdischarge safety. de-escalation and patient safety should be used to support frontline
clinicians.41
Externalizing Behaviors/Aggression
In children presenting with externalizing behaviors, the first Nonpharmacologic Interventions
objective is to try to identify the cause of the patient's reactivity. When assessing agitation, providers should first evaluate ex-
If behaviors are new or different, do they have any historical ante- acerbating factors specific to the ED visit. Creating a calming en-
cedents, and what were their causes? A medical cause of behav- vironment and providing somatosensory items may help reduce
ioral change should be assumed until proved otherwise.1 In many concerning behaviors.
cases, the identification and addressing of a source of pain or dis- If behaviors continue to escalate, clinicians can attempt to
comfort improve patients' behaviors, even in patients admitted to verbally redirect patients. Directives should be simple and clear,
inpatient psychiatric units.27 avoiding metaphors and abstract analogies. Patients should be

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Behavioral Management of Children With Autism
FIGURE 1. Approach to youth with ASD presenting with agitation.
given time to process directives, and directives should be repeated If restraint is required, vests, safety boards and other specialized
(or clearly displayed for those with language impairment) to in- equipment designed to reduce injury should be used by a trained
crease understanding. Clinicians can offer toys and food to induce safety team. The period of restraint should not exceed the length
patient compliance.1 required to de-escalate the situation to a safe state.1 Clinicians
Patients exhibiting behaviors posing an imminent risk to must adhere to federal and local guidelines regarding patient as-
themselves or others may require physical or mechanical restraint. sessment, reassessment, and documentation (Table 1).44
Alternatives to restraint should be considered before its use with
the goal of supporting the preferences of the child and family.
The patient's room can be made safe by removing bed frames, Pharmacologic Interventions
workstations, and other sources of potential harm. Blocking Agitated youth with ASD may require pharmacologic inter-
the room door may reduce risk while allowing some freedom vention in situations where patient, staff, or caregiver safety is at
of movement and utilization of distracting activities. Staff should risk or there is significant property damage risk.14 Administration
be present just outside the room to avoid a sense of isolation and of medications should prompt providers to reconsider potential
to coach de-escalation. medical contributors to agitation.
Physical restraint should be considered a last resort. Its use is There is a paucity of evidence supporting the use of specific
associated with significant physical and mental harms,42 with nu- medications for treatment of agitation in pediatric patients. Rec-
merous reports of restraint associated deaths in children in dispa- ommendations are based on clinical expertise, expert consensus,
rate care settings.42 Patterns of restrain use have also revealed in- and adult data (Table 2).42 Patient age, history, and the perceived
equities suggestive of racial and ethnic bias in implementation.43 cause of agitation should be considered in medication selection.
TABLE 1. Selected Center for Medicaid and Medicare Services Requirements for the Use of Restraints
• Restraint may only be imposed to ensure immediate physical safety

• Restraint may only be used when less restrictive interventions are ineffective.
• The use of restraint or seclusion must be in accordance with the order of a physician or other licensed independent practitioner who is
responsible for the care of the patient
• Unless superseded by State law that is more restrictive each order for restraint may only be renewed in accordance with the following limits for
up to a total of 24 h:
○ 4 h for adults 18 y or older
○ 2 h for children and adolescents aged 9–17 y or
○ 1 h for children younger than 9 y and
• Restraint or seclusion must be discontinued at the earliest possible time
• The condition of the patient who is restrained must be monitored
• The patient must be seen face-to-face within 1 h after the initiation of the intervention to evaluate
○ The patient's immediate situation
○ The patient's reaction to the intervention
○ The patient's medical and behavioral condition
○ The need to continue or terminate the restraint or seclusion
• When restraint or seclusion is used, there must be documentation in the patient's medical record of the following:
○ The 1-h face-to-face medical and behavioral evaluation
○ A description of the patient's behavior and the intervention used
○ Alternatives or other less restrictive interventions attempted (as applicable)
○ The patient's condition or symptom(s) that warranted the use of the restraint or seclusion
○ The patient's response to the intervention(s) used, including the rationale for continued use of the intervention

TABLE 2. Pharmacologic Management for Acute Agitation
Medication Dose Route tmax t1/2 Clinical Pearls and Application

Diphenhydramine • 1 mg/kg/dose q4–6 h PO 2h 5–9 h • Can consider for: anxiety
(Benadryl) • Max dose = 50 mg IM • May give if muscle stiffness or
IV movement problems develop
after use of an antipsychotic
• Risk for EPS, seizure
• May cause disinhibition,
especially with very young
children and those with
developmental delay
• Risk for euphoric rush if
pushed too fast via IV route
Hydroxyzine • 0.5 mg/kg/dose q6–8 h PO 2h 7–29 h • Can consider for: anxiety
(Atarax) • Max dose = 50 mg • Risk for EPS, seizure
developmental delay
Lorazepam • 0.05 mg/kg/dose q30 min PO 2h 12 h • Can consider for: anxiety;
(Ativan) • Max dose = 2 mg IM 1–3 h 12 h EtOH withdrawal
IV 14 h • Risk for respiratory depression,
sedation
developmental delay
Risperidone 5–17 y/o AND < 20 kg PO (ODT) Extensive Extensive • Can consider for: psychosis
(Risperdal) • 0.25 mg/dose q2 h metabolizers: metabolizers: or mania; impulsive,
• Max daily dose = 1 mg 3 h; poor 21 h; poor maladaptive aggression
5–17 y/o AND ≥ 20 kg metabolizers: metabolizers: • Risk for EPS, QTc prolongation
• 0.5 mg/dose q2 h 17 h 30 h (less than haloperidol)
• Max daily dose = 2 mg
≥18 y/o
• 2 mg/dose q2 h
• Max daily dose = 6 mg
Haloperidol 3–12 y/o IM 0.33 h 21 h • Can consider for: psychosis
(Haldol) • 0.025 mg/kg/dose q30 min or mania
• Max daily dose = 2 mg • Risk for QTc prolongation, EPS
≥13 y/o (and NMS), seizure
• 0.05 mg/kg/dose q30 min • IV administration is associated
• Max daily dose = 5 mg with high cardiac risk
• IM injection very rapidly absorbed
Olanzapine 3–12 y/o PO (ODT) 6–8 h 7h • Can consider for: psychosis or
(Zyprexa) • 2.5 mg/dose q30 min children children mania; impulsive, maladaptive
• Max daily dose = 10 mg (10–18 y/o) (10–18 y/o) aggression
13–17 y/o 4.7 ± 3.7 h; 37.2 ± 5.1 h; • Risk for cardiorespiratory
• 5 mg/dose q30 min adults ~6 h adults ~30 h depression—bradycardia,
• Max daily dose = IM 0.25–0.75 h hypotension, EPS, QTc
20 mg ≥ 18 y/o prolongation (less than
• 10 mg/dose q30 min haloperidol)
• Max daily dose = 30 mg • ODT well absorbed (not
• 2–4 mg/kg/dose IM 5–30 min 3–4 h affected by food); IM
• Max dose = 200 mg injection rapidly absorbed
• Avoid coadministering IM
formulation with
benzodiazepines within
60 min of administration—risk
of respiratory depression
Adapted from Hilt and Woodward (2008).45 Additional data from Lexicomp.46
IM indicates intramuscular; IV, intravenously; ODT, orally disintegrating tablet; PO, per mouth.
Caregivers should be involved in decision making, because they Medications may be administered to improve behaviors and
may provide guidance based on prior experience and commonly allow increased interaction with staff and the environment. Chem-
maintain decision-making capacity for their child in the context ical restraint, on the other hand, is defined as a pharmacologic in-
of emergent care. tervention that is nonroutine and specifically administered to

restrict a patient's movement or interaction with their environ- verse effect profile of benzodiazepines is advantageous, because
ment.14,44 It is only indicated to prevent harm to self or others movement disorders are not present and a reversal agent is avail-
and should only be considered if all other de-escalation options have able.14 Children receiving benzodiazepines should be monitored
been pursued. Chemical restraint should not be used as a form of dis- for sedation and respiratory depression.
cipline or as a convenient solution to staffing limitations.14
Oral formulations of medications should be offered as a first
option for agitation management.14,15 They are considered as ef- CONCLUSIONS
fective as injectable preparations and may give patients a sense Children with ASD frequently present to EDs with psychiat-
of control, while avoiding exposure to the trauma of a compelled ric and behavioral acuity. Care must be taken to identify potential
intramuscular injection.14 When the underlying cause of agitation organic etiologies contributing to dysregulation. Hospitals and cli-
is consistent with a known psychiatric disorder, treatment should nicians should provide a calm care environment and use appropriate
use medication that is that disorder's standard of care. For any communication strategies and caregiver perspectives to facilitate
medication, low doses should be used with titration to effect, pref- engagement. Acute treatment for externalizing behaviors should
erably using agents with known benefit for the patient or carrying be as least restrictive as possible. Disposition decisions should bal-
the lowest risk of adverse effects.1 ance patient and family safety with recognition of the limitations of
hospitalization and the priority of optimizing naturalistic settings to
Antipsychotics foster behavioral stabilization.
Atypical antipsychotics are the medications most frequently
used to treat acute agitation in youth with ASD.14,47 There is
strong evidence for scheduled use of these medications in reducing REFERENCES
aggression and irritability in this population. Risperidone and 1. McGonigle JJ, Venkat A, Beresford C, et al. Management of agitation in
aripiprazole are the only medications currently approved by the individuals with autism spectrum disorders in the emergency department.
Food and Drug Administration for the treatment of agitation in pa- Child Adolesc Psychiatr Clin N Am. 2014;23:83–95.
tients with ASD.40 However, aripiprazole is not recommended for 2. Liu G, Pearl AM, Kong L, et al. A profile on emergency department
acute agitation secondary to concerns for akathisia.14 Subsequently, utilization in adolescents and young adults with autism spectrum disorders.
olanzapine and risperidone are the most commonly used in clinical J Autism Dev Disord. 2017;47:347–358.
settings for management of agitation in ASD youth.1,14 Olanzapine
3. Ivanović I. Psychiatric comorbidities in children with ASD: autism centre
is more sedating than risperidone15 and is available in an intramus- experience. Front Psych. 2021;12:673169.
cular formulation,1 although use of intramuscular olanzapine and
benzodiazepines within 60 minutes of each other should be avoided 4. Houghton R, Ong RC, Bolognani F. Psychiatric comorbidities and use of
psychotropic medications in people with autism spectrum disorder in the
secondary to potential respiratory depression.
United States: psychotropic medications in autism in the US. Autism Res.
Haloperidol is a typical antipsychotic frequently used to treat
2017;10:2037–2047.
agitation in emergent settings14,48 with demonstrated efficacy in
the ASD population.48 Atypical antipsychotics are generally pre- 5. Lai MC, Kassee C, Besney R, et al. Prevalence of co-occurring mental
ferred over typical antipsychotics, however, secondary to a stron- health diagnoses in the autism population: a systematic review and meta-
ger safety profile and greater efficacy in pediatric patients.48,49 analysis. Lancet Psychiatry. 2019;6:819–829.
Adverse reactions of antipsychotics include extrapyramidal 6. Popow C, Ohmann S, Plener P. Practitioner's review: medication for
symptoms (EPS), dystonia, and akathisia.14 Children and adoles- children and adolescents with autism spectrum disorder (ASD) and
cents are at particular risk of EPS.14 Patients treated with antipsy- comorbid conditions. Neuropsychiatr. 2021;35:113–134.
chotics should be monitored for neuroleptic malignant syndrome 7. Simonoff E, Pickles A, Charman T, et al. Psychiatric disorders in children
(NMS), characterized by hyperthermia, altered mental status, au- with autism spectrum disorders: prevalence, comorbidity, and associated
tonomic instability, rigidity, and elevated creatine kinase.14 Typi- factors in a population-derived sample. J Am Acad Child Adolesc
cal antipsychotics like haloperidol are more likely to cause NMS Psychiatry. 2008;47:921–929.
and dyskinesias and should be used cautiously in ASD youth.14 8. Leyfer OT, Folstein SE, Bacalman S, et al. Comorbid psychiatric
disorders in children with autism: interview development and rates of
Antihistamines disorders. J Autism Dev Disord. 2006;36:849–861.
Antihistamines, such as diphenhydramine and hydroxyzine, 9. Bougeard C, Picarel-Blanchot F, Schmid R, et al. Prevalence of autism
although frequently used for behavioral management, have not spectrum disorder and co-morbidities in children and adolescents: a
been formally approved for treatment of anxiety, agitation, or in- systematic literature review. Front Psych. 2021;12:744709.
somnia in pediatric patients and limited evidence supports their 10. Nicholas DB, Zwaigenbaum L, Muskat B, et al. Toward practice
use in ASD youth.14 Paradoxical reactions to diphenhydramine advancement in emergency care for children with autism spectrum
are more common than in neurotypical children, and caregivers disorder. Pediatrics. 2016;137(suppl 2):S205–S211.
should be consulted about past experiences before administra- 11. Straus J, Coburn S, Maskell S, et al. Medical encounters for youth with
tion.14,15 In addition to unintended agitation, adverse reactions in- autism spectrum disorder: a comprehensive review of environmental
clude anticholinergic effects, dizziness, and tachycardia.14,45 considerations and interventions. Clin Med Insights Pediatr. 2019;13:
117955651984281.
Benzodiazepines 12. Chun TH, Mace SE, Katz ER, et al. Evaluation and management of
Benzodiazepines should also be used cautiously in the ASD children with acute mental health or behavioral problems. Part II:
population because of potential disinhibitory effects and paradox- recognition of clinically challenging mental health related conditions
ical reactions.14,15,47 They may be particularly beneficial in pa- presenting with medical or uncertain symptoms. Pediatrics. 2016;138:
tients with acute anxiety or toxic ingestion. If given, lorazepam e20161573.
is often preferable because of rapid absorption and quick onset. 13. Jensen EJ, Geisthardt C, Sarigiani PA. Working with children with autism
In rare cases of youth with ASD and catatonia, this medication spectrum disorder in a medical setting: insights from certified child life
also plays a central role in both testing and treatment.50 The ad- specialists. J Autism Dev Disord. 2020;50:189–198.

14. Sonnier L, Barzman D. Pharmacologic management of acutely agitated 32. Cooke E, Smith V, Brenner M. Parents' experiences of accessing respite
pediatric patients. Paediatr Drugs. 2011;13:1–10. care for children with autism spectrum disorder (ASD) at the acute and
primary care interface: a systematic review. BMC Pediatr. 2020;20:244.
15. Gerson R, Malas N, Feuer V, et al. Best practices for evaluation and
treatment of agitated children and adolescents (BETA) in the emergency 33. Taylor BJ, Sanders KB, Kyle M, et al. Inpatient psychiatric treatment of
department: consensus statement of the American Association for serious behavioral problems in children with autism spectrum disorder
Emergency Psychiatry. West J Emerg Med. 2019;20:409–418. (ASD): specialized versus general inpatient units. J Autism Dev Disord.
2019;49:1242–1249.
16. Swed-Tobia R, Haj A, Militianu D, et al. Highly selective eating in autism
spectrum disorder leading to scurvy: a series of three patients. Pediatr 34. McGuire K, Erickson C, Gabriels RL, et al. Psychiatric hospitalization of
Neurol. 2019;94:61–63. children with autism or intellectual disability: consensus statements on best
practices. J Am Acad Child Adolesc Psychiatry. 2015;54:969–971.
17. Siegel M, Gabriels RL. Psychiatric hospital treatment of children with
autism and serious behavioral disturbance. Child Adolesc Psychiatr 35. Autism Speaks. ATN/AIR-P Strategies to Improve Sleep in Children with
Clin N Am. 2014;23:125–142. Autism. Available at: https://www.autismspeaks.org/tool-kit/atnair-p-
strategies-improve-sleep-children-autism. Accessed January 21, 2022.
18. Rybczynski S, Ryan TC, Wilcox HC, et al. Suicide risk screening in
36. Autism Speaks. ATN/AIR-P Parent's Guide to Applied Behavior Analysis.
pediatric outpatient neurodevelopmental disabilities clinics. J Dev Behav
. Available at: https://www.autismspeaks.org/tool-kit/atnair-p-parents-
Pediatr. 2022;43:181–187.
guide-applied-behavior-analysis. Accessed January 21, 2022.
19. Mayes SD, Gorman AA, Hillwig-Garcia J, et al. Suicide ideation and
37. Sowar K, Thurber D, Vanderploeg JJ, et al. Psychiatric community crisis
attempts in children with autism. Res Autism Spectr Disord. 2013;7:109–119.
services for youth. Child Adolesc Psychiatr Clin N Am. 2018;27:479–490.
20. Bourke EM, Say DF, Carison A, et al. Emergency mental health 38. Sarvet B, Gold J, Bostic JQ, et al. Improving access to mental health care
presentations in children with autism spectrum disorder and attention for children: the Massachusetts Child Psychiatry Access Project.
deficit hyperactivity disorder. J Paediatr Child Health. 2021;57: Pediatrics. 2010;126:1191–1200.
1572–1579.
39. Hilt RJ, Romaire MA, McDonell MG, et al. The partnership access line:
21. Righi G, Benevides J, Mazefsky C, et al. Predictors of inpatient evaluating a child psychiatry consult program in Washington state. JAMA
psychiatric hospitalization for children and adolescents with autism Pediatr. 2013;167:162–168.
spectrum disorder. J Autism Dev Disord. 2018;48:3647–3657.
40. Fung LK, Mahajan R, Nozzolillo A, et al. Pharmacologic treatment of
22. Hirvikoski T, Mittendorfer-Rutz E, Boman M, et al. Premature mortality severe irritability and problem behaviors in autism: a systematic review and
in autism spectrum disorder. Br J Psychiatry. 2016;208:232–238. meta-analysis. Pediatrics. 2016;137(suppl 2):S124–S135.
23. Kõlves K, Fitzgerald C, Nordentoft M, et al. Assessment of suicidal 41. Hopper SM, Babl FE, Stewart CE, et al. Aggression management in a
behaviors among individuals with autism spectrum disorder in Denmark. children's hospital setting. Med J Aust. 2012;196:198–201.
JAMA Netw Open. 2021;4:e2033565. 42. Chun TH, Mace SE, Katz ER, et al. Evaluation and management of
24. Cassidy SA, Bradley L, Cogger-Ward H, et al. Measurement properties of children and adolescents with acute mental health or behavioral problems.
the suicidal behaviour questionnaire-revised in autistic adults. J Autism Dev Part I: common clinical challenges of patients with mental health and/or
Disord. 2020;50:3477–3488. behavioral emergencies. Pediatrics. 2016;138:e20161570.
25. Shain B, Committee on Adolescence, Braverman PK, et al. Suicide and 43. Nash KA, Tolliver DG, Taylor RA, et al. Racial and ethnic disparities in
suicide attempts in adolescents. Pediatrics. 2016;138:e20161420. physical restraint use for pediatric atients in the emergency department.
JAMA Pediatr. 2021;175:1283–1285.
26. Schwartzman JM, Smith JR, Bettis AH. Safety planning for suicidality in
autism: obstacles, potential solutions, and future directions. Pediatrics. 44. State operations manual appendix A - survey protocol, regulations and
2021;148:e2021052958. interpretive guidelines for hospitals. Center for Medicare and Medicaid
Services. Available at: https://www.cms.gov/Regulations-and-Guidance/
27. Guinchat V, Cravero C, Diaz L, et al. Acute behavioral crises in Guidance/Manuals/downloads/som107ap_a_hospitals.pdf. Accessed
psychiatric inpatients with autism spectrum disorder (ASD): recognition of January 31, 2022.
concomitant medical or non-ASD psychiatric conditions predicts enhanced
improvement. Res Dev Disabil. 2015;38:242–255. 45. Hilt RJ, Woodward TA. Agitation treatment for pediatric emergency
patients. J Am Acad Child Adolesc Psychiatry. 2008;47:132–138.
28. Périsse D, Amiet C, Consoli A, et al. Risk factors of acute behavioral
46. Lexicomp Online, Pediatric and neonatal Lexi-drugs Online. Waltham,
regression in psychiatrically hospitalized adolescents with autism. J Can
MA: UpToDate, Inc; Available at: https://online.lexi.com. Accessed March
Acad Child Adolesc Psychiatry. 2010;19:100–108.
1, 2022.
29. McGuire K, Fung LK, Hagopian L, et al. Irritability and problem behavior
47. Kendrick JG, Goldman RD, Carr RR. Pharmacologic management of
in autism spectrum disorder: a practice pathway for pediatric primary care.
agitation and aggression in a pediatric emergency department—a
Pediatrics. 2016;137(suppl 2):S136–S148.
retrospective cohort study. J Pediatr Pharmacol Ther. 2018;23:455–459.
30. Weiss JA, Wingsiong A, Lunsky Y. Defining crisis in families of 48. LeClerc S, Easley D. Pharmacological therapies for autism spectrum
individuals with autism spectrum disorders. Autism. 2014;18:985–995. disorder: a review. P T. 2015;40:389–397.
31. Mandell DS, Xie M, Morales KH, et al. The interplay of outpatient 49. McCracken JT, McGough J, Shah B, et al. Risperidone in children with
services and psychiatric hospitalization among Medicaid-enrolled children autism and serious behavioral problems. N Engl J Med. 2002;347:314–321.
with autism spectrum disorders. Arch Pediatr Adolesc Med. 2012;166:
50. Ghaziuddin N, Andersen L, Ghaziuddin M. Catatonia in patients with
68–73.
autism spectrum disorder. Psychiatr Clin North Am. 2021;44:11–22.

CME EXAM
INSTRUCTIONS FOR OBTAINING AMA PRA CATEGORY 1 CREDITS™
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 CREDITS™ is available through the twelve 2023 issues of Pediatric Emergency Care. This activity is
available for credit through December 31, 2024. 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
January 2023
Please mark your answers on the ANSWER SHEET.
Behavioral Management of Children with Autism in the Emergency Department, Wolpert et al
1) Which of the following has been associated with increased 4) Which of the following is true when considering medication
suicide risk in patients with ASD? for treatment of agitated ASD youth?
a) Greater intellectual disability a) Consulting caregivers can help in medication selection
b) An absence of externalizing behaviors b) Intramuscular medication should be given preferentially
c) Life events resulting in alteration of routines for rapid onset of action
d) Absence of concomitant psychiatric diagnosis c) Chemical restraint may be used if there is limited staff
d) Neuroleptic malignant syndrome manifests only with
2) Which of the following is true regarding inpatient hospitali- chronic antipsychotic medication use
zation in children with ASD?
a) Children with ASD should only be admitted to specialized 5) Which of these presentations is most concerning for an or-
autism units ganic etiology of agitation in ASD youth?
b) Children with ASD do not need special accommodation in a) An 8-year-old boy with a heart rate of 100 beats per minute
general pediatric psychiatric units with escalating agitation after beginning a new school year.
c) Inpatient psychiatric treatment should focus on verbal in- b) An 15-year-old adolescent girl with normal vital signs,
teraction and socialization pacing around the room after a recent medication taper
d) Inpatient admission is not appropriate to treat the patient's c) A 5-year-old nonverbal boy with escalating aggression
underlying ASD diagnosis and recent weight loss
d) A 13-year-old adolescent boy with auditory hallucinations,
3) Which of the following is true regarding use of restraint in a normal neurologic exam, and normal mental status
patients with ASD?
a) The threat of restraint can be used to redirect behaviors
b) Restraint is not associated with significant harms if
applied appropriately
c) Per CMS, a restrained patient must be evaluated face-to-
face within 2 hours of restraint application
d) Per CMS, the time interval between restraint order re-
newal is age dependent

ANSWER SHEET FOR THE PEDIATRIC EMERGENCY CARE

CME PROGRAM EXAM
January 2023
Please answer the questions on page 51 by filling in the appropriate circles on the answer sheet below. Please mark the one best an-
swer and fill in the circle until the letter is no longer visible. To process your exam, you must also provide the following information:
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3. 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. Identify factors which may suggest an organic etiology of symptoms in agitated ASD youth
2. Describe indications for inpatient psychiatric admissions for ASD youth presenting with depression and
externalizing behaviors
3. Explain indications and pharmacologic options for managing agitation in ASD youth in acute care
settings
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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REVIEW ARTICLE
Lipid Emulsion Treatment for Drug Toxicity Caused by

Nonlocal Anesthetic Drugs in Pediatric Patients
A Narrative Review
Soo Hee Lee, MD,*† Sunmin Kim, MD,‡ and Ju-Tae Sohn, MD§||
ported the first case of successful LE resuscitation of a 17-year-

Objective: Lipid emulsion (LE) has been used to treat children with car- old adolescent girl with toxicity of bupropion and lamotrigine,
diovascular collapse induced by toxic doses of nonlocal anesthetics with who was unresponsive to epinephrine, defibrillation, calcium,
high lipid solubility. We aimed to analyze case reports on LE administration magnesium, and amiodarone. Furthermore, the use of LE as an
for resuscitation of toxicity induced by these drugs in pediatric patients. adjuvant therapy with supportive treatments was reported to alle-
Methods: Case reports involving pediatric patients undergoing LE treat- viate the cardiovascular collapse induced by toxic doses of nonlo-
ment for toxicity caused by nonlocal anesthetic drugs until December 31, cal anesthetics, including amitriptyline, bupropion, flecainide,
2021, were searched through PubMed and Scopus using the following terms: propranolol, lamotrigine, verapamil, quetiapine, diphenhydramine,
“toxicity, or intoxication, or poisoning, or overdose” and “LE or intralipid.” olanzapine, and amlodipine.1,3 Drug toxicity is common because
Results: Twenty-eight cases on LE treatment for toxicity induced by non- of accidental ingestion and intentional suicide attempts in pediatric
local anesthetic drugs in pediatric patients (younger than 19 years) were re- patients; however, many drugs do not have specific antidotes. To
trieved. The total number of patients was 31. Lipid emulsion treatment was the best of our knowledge, the analysis of LE treatment as an adju-
carried out during toxicity caused by amitriptyline, flecainide, bupropion, vant during the systemic drug toxicity caused by only nonlocal an-
propranolol, and lamotrigine, which was unresponsive to supportive treat- esthetic drugs in pediatric patients is not available. Furthermore,
ment. These drugs are highly lipid-soluble and inhibit cardiac sodium chan- clinical studies on such cases are impossible because of ethical rea-
nels, which is similar to pharmacological properties of the local anesthetic sons. Here, we analyzed human case reports on LE treatment during
bupivacaine. The most frequent method of delivery involved bolus adminis- drug toxicity caused by toxic doses of nonlocal anesthetics via en-
tration followed by continuous infusion; 1.5 mL/kg LE administration teral administration in pediatric patients (younger than 19 years)
followed by 0.25 mL/kg/min LE was most frequently used. Lipid emulsion available from PubMed and Scopus databases. The focus of this re-
improved various symptoms of drug toxicity in 29 patients (29/31, 93.54%), view was to analyze LE effectiveness, the dosage and nature of LE
and symptoms were improved in 14 patients (14/31, 45.16%) within an h used, and the kind of drugs responsive to LE treatment, as well as to
after LE administration. The trend in frequency of improved symptoms af- summarize the mechanisms of LE resuscitation and suggest poten-
ter LE treatment was as follows: the cardiovascular symptom alone > symp- tial research directions.
toms of the central nervous system alone > symptoms of the cardiovascular
and central nervous systems. The adverse effects of LE treatment in the re-
ported cases were hypertriglyceridemia, mild pancreatitis, and elevated METHODS
levels of aspartate and alanine aminotransaminases.
Conclusions: Lipid emulsion treatment may be effective in ameliorating intrac- Data Sources and Selection
table cardiovascular depression when systemic toxicity caused by drugs, including The case reports involving pediatric patients undergoing LE
cardiac sodium channel blockers, is unresponsive to supportive treatments. treatment for toxicity caused by nonlocal anesthetic drugs until
Key Words: lipid emulsion treatment, nonlocal anesthetic, toxicity, case December 31, 2021, were retrieved from PubMed and Scopus.
report, cardiovascular system, central nervous system “Toxicity, or intoxication, or poisoning, or overdose” and “LE
or intralipid” were used in PubMed using the filter “case reports”
(Fig. 1). “Toxicity, or intoxication, or poisoning, or overdose,” and
“LE or intralipid,” and “case report” were used in Scopus (Fig. 1). We
L ipid emulsion (LE) was originally developed for parenteral nu-
trition. Currently, LE is widely used to treat local anesthetic
systemic toxicity in adult and pediatric patients.1 Sirianni et al2 re-
found a total of 1438 articles from PubMed (n = 431) and Scopus
(n = 1007) and removed 268 duplicated articles (Fig. 1). We excluded
1142 articles from the remaining 1170 articles because of the follow-
From the *Department of Anesthesiology and Pain Medicine, Gyeongsang Na-
ing reasons: not a case report regarding LE treatment, inappropriate
tional University Changwon Hospital, Changwon-si; †Department of Anesthe- age (older than 19 years), article not in English, local anesthetic tox-
siology and Pain Medicine, Gyeongsang National University College of Medi- icity, nonhuman, and letter to the editor (not a case report). Finally,
cine; ‡Department of Anesthesiology and Pain Medicine, Gyeongsang National the remaining 28 case reports were analyzed. A total of 31 pa-
University Hospital; §Department of Anesthesiology and Pain Medicine, tients, included in 28 case reports, were used to analyze the effi-
Gyeongsang National University College of Medicine, Gyeongsang National
University Hospital; and ||Institute of Health Sciences, Gyeongsang National cacy of LE treatment during drug toxicity caused by nonlocal an-
University, Jinju-si, Republic of Korea. esthetic drugs in pediatric patients younger than 19 years (Fig. 1).
Reprints: Ju-Tae Sohn, MD, Department of Anesthesiology and Pain Medicine,
Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju-si, 52727, RESULTS
Korea (e‐mail: jtsohn@gnu.ac.kr).
This research was supported by Basic Science Research Program through the
National Research Foundation of Korea (NRF) funded by the Ministry of Age Distribution, Underlying Diseases, and Cause
Education (NRF-2021R1I1A3040332). of Drug Toxicity
S.H.L. and S.K. contributed equally to this work as first authors.
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. Twenty-eight cases on LE treatment for toxicity induced by
ISSN: 0749-5161 nonlocal anesthetic drugs in pediatric patients (younger than 19 years)

FIGURE 1. Flow chart to search through PubMed and Scopus, clinical case reports involving LE treatment for toxicity caused by nonlocal
anesthetic drugs in pediatric patients.
were retrieved. As one case report involved 3 and another in- (1/31, 3.22%). However, LE did not improve symptoms in one pa-
volved 2 patients, the total number of patients was 31 (Table 1). tient. Information regarding improved symptoms was not avail-
The numbers of male and female patients were 9 (9/31, 29.03%) able for one patient. Twenty-eight patients (28/31, 90.32%) recov-
and 22 (22/31, 70.97%), respectively (Table 1). Twenty-four patients ered fully from drug toxicity, but 3 patients died (3/31, 9.68%).
(77.42%) were adolescents (older than 13 years) and 7 patients The adverse effects of LE treatment in the reported cases were
(22.58%) were preadolescents (younger than 13 years). More than hypertriglyceridemia, mild pancreatitis, and elevated levels of as-
half of the pediatric patients was without underlying diseases (18/31, partate and alanine aminotransaminases (Case no. 13 and 18).
58.06%), and the underlying diseases of the remaining patients Cytochrome P450 2D6 polymorphism was found during flecainide
(13/31) were as follows: depression, epilepsy, intrauterine growth treatment (Case no. 11) for supraventricular tachycardia. Extra-
retardation, permanent junctional reciprocating tachycardia, atten- corporeal membrane oxygenation was used because of persistent
tion deficient hyperactive disorder, systemic lupus erythematosus, hypotension and decreased pH after LE administration for bupropion
ectopic atrial tachycardia, supraventricular tachycardia, and cyto- toxicity (Case no. 24). Lipid emulsion treatment decreased serum
chrome P450 2D6 polymorphism (Table 1). The frequencies of bupropion from 880 to 62 ng/mL and serum lamotrigine from 24 to
underlying causes of drug toxicity were as follows: suicide (14/31, 18 μg/mL during bupropion and lamotrigine toxicity (Case no. 25).
45.16%), not available (9/31, 29.03%), accident (7/31, 22.85%),
and treatment (1/31, 3.22%). The accidental cases were ingestion
of drugs by children without the supervision of parents (6/7) or Specific Drug Toxicity and the Requirement of
confusion regarding drug administration (1/7). LE Treatment
The patients taking only 1 drug and more than 2 drugs in-
volved in drug toxicity were 21 (21/31, 67.74%) and 10 (10/31,
Kind and Dosage of LE, Methods of LE 32.26%), respectively (Table 1). A total of 50 drugs showed toxic-
Administration, Improved Symptoms After LE ity in the pediatric patients; 10 patients experienced multiple drug
Treatment, Outcome, and Adverse Effects of LE toxicity involving more than 2 drugs. The frequencies of drugs to
The kinds of LE were as follows (Table 1): not available (just cause toxicity were as follows (Table 1): antidepressant (13/50),
description “20% LE or fat emulsion,” 19/31, 61.29%), Intralipid antiarrhythmic drugs (5/50), β-blocker (5/50), anticonvulsant (4/50),
(10/31, 32.26%), SMOFlipid (1/31, 3.22%), and ClinOleic (1/31, calcium channel blocker (5/50), other (3/50), antihistamine (2/50),
3.22%). The methods of LE administration were as follows (Table 1): antipsychotic drug (2/50), attention-deficit/hyperactive disorder
bolus administration followed by continuous infusion (21/31, 67.74%), drug (1/50), α-adrenergic blocker (1/50), analgesic and antipyretics
continuous infusion alone (4/31, 12.90%), bolus administration (1/50), antibiotics (1/50), antioxidant (1/50), central nervous system
alone (2/31, 6.45%), and not available (4/31, 12.90%). Among stimulant (1/50), diuretics (1/50), gout drug (1/50), muscle relaxant
the methods of administration involving bolus administration (1/50), organophosphate insecticide (1/50), and antimalarial drug
followed by continuous infusion, 1.5 mL/kg LE administration (1/50). The range of available log P (log [octanol/water partition
followed by 0.25 mL·kg−1·min−1 LE was most frequently used coefficient]) of 49 drugs was −1.1 to 5.77 (Table 1). The offending
(12/21, 57.14%; Table 1). The infusion time of LE was available drugs that required LE treatment in more than 2 of the 31 patients
for 21 patients, which was common within an h (13/21, 61.90%). included antidepressant (amitriptyline: 5 patients, bupropion: 4
Lipid emulsion improved various symptoms of drug toxicity in 29 patients), antiarrhythmic (flecainide: 5 patients), β-blocker (pro-
patients (29/31, 93.54%), and symptoms were improved in 14 pa- pranolol: 3 patients), calcium channel blocker (amlodipine: 2 pa-
tients (14/31, 45.16%) within an h after LE administration. The fre- tients), and anticonvulsant (lamotrigine: 2 patients). Drugs with
quencies of improved symptoms after LE administration was as fol- log P > 2, which is considered as highly lipid-soluble, were 44
lows (Table 1): the cardiovascular symptom alone (17/31, 54.83%), (44/49, 89.80%; Table 1). The correlation coefficient between fre-
symptoms of the central nervous system alone (6/31, 19.35%), quency of LE treatment (amitriptyline: 5/31 [16.1%], flecainide:
symptoms of the cardiovascular and central nervous systems (5/31, 5/31 [16.1%], flecainide: 4/31 [12.9%], propranolol: 3/31 [9.7%],
16.12%), and attenuation of muscarinic and nicotinic effects amlodipine: 2/31 [6.5%], and lamotrigine: 2/31 [6.5%]) and lipid

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Lipid Emulsion Treatment for Drug Toxicity
TABLE 1. Lipid Emulsion Treatment for Drug Toxicity Caused by Nonlocal Anesthetic Drugs in Pediatric Patients
Cause of Drug
Case No. Sex Age, y BW, kg UD Toxicity Drug Log P Kind of LE
14 F 15 N/A N Suicide Carbamazepine 2.45 20% fat emulsion
25 F 16 86.2 N N/A Felodipine 3.86 20% LE
Doxazosin 2.1
Cinnarizine 5.77
Bendroflumethiazide 1.89
Flucloxacillin 2.58
Alcohol −0.31
36 F 15 67.2 N N/A Bupropion 3.6 20% Intralipid
47 F 14 86.5 Depression Suicide Bupropion 3.6 Lipid

Hydroxyzine 2.36
Citalopram 3.76
58 F 15 N/A N Suicide Carisoprodol 2.1 20% LE
69 F 18 N/A Epilepsy Suicide Lamotrigine 2.57 20% LE
Sertraline 5.51
79 M 17 N/A N N/A Bonsai Unknown 20% LE
89 F 18 N/A N N/A Amitriptyline 4.92 20% LE
α-Lipoic acid 3.4
910 F 14 55 ADHD Suicide Atomoxetine 3.9 N/A
1011 F 18 N/A N Suicide colchicine 1.3 Intralipid
1112 F 18 N/A cytochrome P450 2D6 Treatment Flecainide 3.78 LE
polymorphism
1213 F 20 mo 10 N Accident Dothiepin 4.49 20% Intralipid
1314 F 13 N/A Depression Suicide Amitriptyline 4.92 20% Intralipid
1415 F 13 N/A N N/A Amitriptyline 4.92 LE
1516 M 17 N/A Bipolar disorder Suicide Amlodipine 3 LE
Caffeine −0.07
Metoprolol 1.88
1617 M 4 N/A Epilepsy Accident Olanzapine 3 20% Intralipid
1718 F 18 50 N Suicide Sustained-release dilitazem 2.7 20% Intralipid
1819 F 13 45 N N/A Bisoprolol 1.87 20% Intralipid
Flecainide 3.78
Aspirin 1.18
1920 F 17 N/A SLE Suicide Hydrochloroquine 2.89 LE
2021 M 18 N/A Depression, ADHD Suicide Amitriptyline 4.92 20% LE
Venlafaxine 3.20
2122 M 7 mo N/A Ectopic atrial tachycardia Accident Flecainide 3.78 LE
2222 M 2 N/A Fetal SVT (resolved) Accident Flecainide 3.78 20% LE
2323 M 4 N/A PJRT Accident Flecainide 3.78 20% LE

2424 M 11 Mo 12 N Accident Bupropion 3.6 Intralipid
252 F 17 55 N Suicide Bupropion 3.6 20% LE
Lamotrigine 2.57
2625 F 7 mo 6.1 IUGR Accident Propranolol 3.48 20% LE
2726 F 17 N/A N N/A Amlodipine 3 20% LE

Propranolol 3.48
2827 M 18 N/A N Suicide Monocrotophos (organic −0.2 Clinoleic 20%
phosphor compounds)
2928 F 17 N/A N N/A Propranolol 3.48 Intralipid
Amytriptiline 4.92
Fluphenazine 4.36
Gabapentin −1.1
3029 F 14 N/A N Suicide Yew (Taxus baccata) 0.6 SMOF lipid 20%
3130 F 14 N/A N N/A Verapamil hydrochloride 3.8 20% Intralipid
ADHD indicates attention-deficit/hyperactivity disorder; BW, body weight; CNS, central nervous system; D, death; CV, cardiovascular; ECMO, extracorporeal
membrane oxygenation; F, female; ILE, intravenous lipid emulsion; IUGR, intrauterine growth restriction; LE, lipid emulsion; M, male; N, none; N/A, not available;
PJRT, permanent junctional reciprocating tachycardia; R, recovery; SLE, systemic lupus erythematosus; SVT, supraventricular tachycardia; UD, underlying disease.

TABLE 1. Lipid Emulsion Treatment for Drug Toxicity Caused by Nonlocal Anesthetic Drugs in Pediatric Patients
Bolus Time From Drug Time From LE

Administration Continuous Infusion Time Overdose to ILE Administration to Improved
of LE Infusion of LE (h) of LE Total Dose of LE Administration Improved Symptom Symptoms Outcome
1.5 mL/kg 0.25 mL/kg/min 1 16.5 mL/kg N/A 6d CNS R
1.5 mL/kg 15 mL/kg/h 1 11.6 mL/kg (1000 mL) N/A 10 min CV R
N 1st: 3 mL/kg/h 1st: 0.5 3 mL/kg (201.6 mL) N/A 30 min CNS R
2nd: 3 mL/kg/h 2nd: 0.5
1.16 mL/kg × 2 0.25 mL/kg/min 1 46 mL/kg (4000 mL) N/A Immediate response CV R
N 1 mL/kg/h 1 1 mL/kg 10 h Within an hour CNS R

(100 mL) 0.5 mL/kg/min 2 (3100 mL) N/A Within an hour CNS R
(100 mL) 0.5 mL/kg/min 2 (4000 mL) N/A 2h CV, CNS R

(100 mL) 0.5 mL/kg/min N/A (500 mL) N/A 20 min CV D
1.5 mL/kg 0.25 mL/kg/min 1.5 15.54 mL/kg (855 mL) N/A Within an hour CNS R
N 100 mL/d 48 (200 mL) N/A No response none D
1st: 1.5 mL/kg 1st: 0.25 mL/kg/min 1st: 0.5 3.25 mL/kg N/A N/A CV R
2nd: 1.5 mL/kg 2nd: 0.25 mL/kg/min 2nd: 0.5
1 mL/kg 0.25 mL/kg/min 1 16 mL/kg (160 mL) 2h Within minutes CV R
1.5 mg/kg × 2 0.25 mg/kg/min 0.5 N/A 20 h Immediate response CV, CNS R
N/A N/A N/A N/A 19 h N/A CNS, CV R
1.5 mL/kg 0.5 mL/kg/min N/A N/A N/A N/A CV R
1.5 mL/kg 0.25 mL/kg/min N/A N/A 4h 15 min CNS R

1.5 mL/kg 0.25 mL/kg/min 1 16.5 mL/kg (825 mL) 34 h Within an hour CV R
1.5 mL/kg 0.25 mL/kg/min 0.33 6.5 mL/kg (295 mL) 3h 12 h CV R
1.5 mL/kg N N 1.5 mL/kg 7h 4h CV R

N/A N/A N/A N/A N/A N/A CNS, CV R
1.5 mL/kg N N 1.5 mL/kg N/A N/A CV R

1st: 1.5 mL/kg 1st: 0.25 mL/kg/min N/A N/A N/A N/A CV R
2nd: 1.5 mL/kg 2nd: 0.5 mL/kg/min
1.5 mL/kg 0.25 mL/kg/min N/A N/A N/A N/A CV R
N/A N/A N/A 20 mL/kg (240 mL) 21 h N/A CV, CNS R
N/A N/A N/A 1.81 mL/kg (100 mL) 11.5 h 1 min CV R
1st: 0.25 mL/kg 0.0125 mL/kg/min 2 1.2 mL/kg (7.32 mL) N/A Within an hour CV R
2nd: 0.2 mL/kg
(100 mL) × 2 10 mL/min 0.5 N/A N/A N/A N/A D
(75 mL) 80 mL/h N/A N/A 2h N/A Sympathetic R
(90 mL) 450 mL/h 2 (990 mL) 36 h 12 h CV R
1.5 mL/kg 1.5 mL/kg/h 6 10.5 mL/kg 6h 90 min CV R

N 1.5 mL/kg/h 2 N/A 12 h 30 min CV R

solubility of drugs (log P: amitriptyline = 4.92, flecainide = 3.78, life support and extracorporeal membrane oxygenation and (2)
bupropion = 3.6, propranolol = 3.48, amlodipine = 3, and lamotrigine = recommended administration of LE by toxicologist, even after the
2.57) associated with the drug toxicity involving at least more restoration of spontaneous circulation from drug toxicity, consid-
than 2 patients among the 31 patients was R2 = 0.7438 (Fig. 2; fre- ering high lipid solubility of calcium channel and β-blockers.
quency of LE treatment [%] = 4.79 log P – 5.77). Intralipid improved altered mental status caused by bupropion
toxicity in a 15-year-old patient (Case no. 3); however, the mental
DISCUSSION status was again altered after cessation of LE administration, prob-
Bolus administration of LE followed by continuous infusion ably because of the long half-life of bupropion (29 ± 8 hours) com-
was most commonly used (21/31, 67.74%) in this analysis. Lipid pared with that of triglycerides of Intralipid (13.7 ± 5.2 minutes).33,34
emulsion dosage used during the systemic toxicity induced by lo- In general, the half-life of triglycerides contained in LE is less than
cal anesthetics was as follows: 20% LE 1.5 mL/kg over 2 to that of offending drugs.34 Therefore, re-elevation of plasma concen-
3 minutes followed by 20% LE 0.25 mL·kg−1·min−1.1 Then, the tration of the offending drugs or recurrence of subsided symptoms
infusion of 20% LE was increased to 0.5 mL·kg−1·min−1 for he- may occur after the cessation of LE administration. This difference
modynamically unstable patients.1 Among children receiving reg- of half-life should be considered in LE treatment for drug toxicity.
imens involving bolus administration followed by continuous in- The adverse effects of LE treatment include hypertriglyceridemia,
fusion, 1.5 mL/kg 20% LE followed by 0.25 mL·kg−1·min−1 LE hypercoagulability, irritation, allergic reaction, transient elevation
was used (11/21 = 52.3%) in more than half of the case reports of aspartate and alanine aminotransferase, infection, and interfer-
commenting on LE dosage. This dosing regimen was in agree- ence with laboratory examination that is self-limited.1 Hypertri-
ment with that during systemic toxicity induced by local anes- glyceridemia, mild pancreatitis, and elevated levels of aspartate
thetics.1 However, local anesthetic systemic toxicity was mostly and alanine aminotransferases were reported in 3 patients (Case
caused by intravenous administration of local anesthetics, whereas no. 4, 13, and 18). Intralipid with 100% long-chain fatty acids from
drug toxicity in pediatric patients included in this analysis was soybean oil was originally developed for parenteral nutrition in
caused by oral administration. Thus, the clinical situations were 1961. Intralipid contains large amount of linoleic acid (18:2n-6,
different in pharmacokinetics of drug toxicity. As 1% plasma tri- polyunsaturated essential fatty acid) derived from soybean, which
glyceride provides positive inotropic and scavenging effects, the increases the production of potent proinflammatory mediators.35,36
suggested dosing regimen for this is as follows: an initial bolus ad- Therefore, 20% Lipofundin MCT/LCT with 50% long-chain (from
ministration of 20% LE 1.5 mL/kg followed by 0.25 mL·kg−1·min−1 soybean) and 50% medium-chain fatty acids, 20% SMOFlipid with
for 3 minutes and subsequently 0.025 mL·kg−1·min−1 continuous 30% long-chain fatty acid (from soybean oil), and ClinOleic acid
infusion.31 This suggested that dosing regimen can be used for with 20% soybean oil, which have soybean oil contents less than
maximum 8.5 hours because the maximum recommended dose that of 20% Intralipid, were developed to decrease proinflammatory
of 20% Intralipid in pediatric patients by the Food and Drug Ad- responses and lipid peroxidation.35,36 Intralipid was commonly
ministration is 3 g/kg per 24 hours.31,32 The main reasons to ad- used (10/12, 83.3%) in the remaining 12 cases commenting on
minister LE as an adjuvant therapy in this analysis were as fol- the kind of LE.
lows: (1) persistent cardiovascular and neurological deterioration The magnitude of reduction of drug concentration by LE is
even after supportive and charcoal treatments or advanced cardiac mainly dependent on lipid solubility (log P, 75%) and partially
FIGURE 2. Correlation coefficient between the frequency of LE treatment and lipid solubility (log P: log [octanol/water partition coefficient]) of
offending drugs (amitriptyline, flecainide, bupropion, propranolol, amlodipine, and lamotrigine) involving more than 2 of a total of 31
pediatric patients undergoing LE treatment as an adjuvant therapy for drug toxicity, analyzed using linear regression. Frequency of LE
treatment (%) = 4.79 log P – 5.77. R2 = 0.7438.

dependent on the distribution volume (13%) of drugs.37 The fre- Thus, studies regarding optimal dosing regimen and timing of LE
quency of offending drugs involving more than 2 patients undergo- administration as adjuvant therapy for drug toxicity induced via
ing LE treatment as adjuvant therapy was as follows: amitriptyline enteral administration in pediatric patients are needed. As the va-
(log P = 4.92, 5/31), flecainide (log P = 3.78, 5/31), bupropion (log sopressors and inotropic agents, which include phenylephrine,
P = 3.6; 4/31), propranolol (log P = 3.48, 3/31), amlodipine (log norepinephrine, epinephrine, vasopressin, and dopamine, and ex-
P = 3, 2/31), and lamotrigine (log P = 2.57, 2/31). The lipid solubil- tracorporeal membrane oxygenation are commonly used for he-
ity (log P) of these offending drugs is high (>2). The correlation co- modynamic support in drug toxicity, the effects of LE on the he-
efficient between the frequency of LE treatment and log P of these modynamic responses induced by these drugs as well as their
offending drugs was 0.743 (R2), suggesting that the frequency of plasma concentrations remain to be determined.42
LE treatment during drug toxicity was strongly correlated with lipid In conclusion, LE administration as an adjuvant therapy may
solubility (log P) of drugs. In a total of 21 patients with toxicity in- be effective in pediatric patients with drug toxicity caused by am-
duced by these highly lipid-soluble drugs, 19 recovered from drug itriptyline, flecainide, bupropion, propranolol, lamotrigine, and
toxicity, but 2 died because of multiple drug toxicity involving ei- amlodipine, in which cardiovascular depression and neurologic
ther amitriptyline and α-lipoic acid (Case no. 8) or amlodipine deterioration are unresponsive to supportive treatment and cardiac
and propranolol (Case no. 27). In addition, flecainide, which is used support.
to treat supraventricular tachycardia, is metabolized by cytochrome
P450 2D6.38 The cytochrome P450 2D6 polymorphism (intermedi-
ate metabolizer), which was found during flecainide treatment for REFERENCES
supraventricular tachycardia, caused flecainide toxicity because of
a decreased metabolism (Case no. 11). 1. Ok SH, Hong JM, Lee SH, et al. Lipid emulsion for treating local anesthetic
systemic toxicity. Int J Med Sci. 2018;15:713–722.
Lipid emulsion was reported to alleviate the cardiovascular
collapse induced by toxic doses of local anesthetics (bupivacaine, 2. Sirianni AJ, Osterhoudt KC, Calello DP, et al. Use of lipid emulsion in the
lidocaine, and ropivacaine) and nonlocal anesthetic drugs with resuscitation of a patient with prolonged cardiovascular collapse after
high lipid solubility.1,3 The following underlying mechanisms of overdose of bupropion and lamotrigine. Ann Emerg Med. 2008;51:
LE treatment have been suggested. First, static lipid sink, in which 412–415.
the lipid phase of LE absorbs lipid-soluble drugs (eg, log P of bu- 3. Ok SH, Park M, Sohn JT. Lipid emulsion treatment of nonlocal anesthetic
pivacaine = 3.41) from the heart and brain, was a widely accepted drug toxicity. Am J Ther. 2020;28:e742–e746.
mechanism at the early history of LE treatment as nonspecific an- 4. Agulnik A, Kelly DP, Bruccoleri R, et al. Combination clearance therapy
tidotes.1 This is still considered by some investigators as the only and barbiturate coma for severe carbamazepine overdose. Pediatrics. 2017;
underlying mechanism of LE treatment. However, several clinical 139:pii: e20161560.
and laboratory studies do not consider this as the sole mecha- 5. Barnicott LR, Tarmey NT, Craig GR, et al. Intravenous lipid emulsion (ILE)
nism.1 Currently, “lipid shuttle (subway)” is a widely accepted therapy for severe felodipine toxicity. J Intensive Care Soc. 2013;14:346–348.
mechanism underlying LE treatment.39 The dynamic lipid shuttle
6. Bornstein K, Montrief T, Anwar Parris M. Successful management of
(subway) theory states that LE produces numerous lipid compart- adolescent bupropion overdose with intravenous lipid emulsion therapy.
ments in the blood and subsequently absorbs lipid-soluble drugs J Pediatr Intensive Care. 2019;8:242–246.
(eg, bupivacaine) from the organs with high blood flow (the heart
and brain), which seems to be dependent on the lipid solubility of 7. Bucklin MH, Gorodetsky RM, Wiegand TJ. Prolonged lipemia and
pancreatitis due to extended infusion of lipid emulsion in bupropion
drugs.39 Then, LE containing highly lipid-soluble drugs (log P > 2)
overdose. Clin Toxicol (Phila). 2013;51:896–898.
is transported to the muscle, liver, and adipose tissue for storage and
detoxification.39 Drugs such as amitriptyline, flecainide, bupropion, 8. Chegondi M, Badheka A, Chacham S, et al. Intravenous lipid emulsion
lamotrigine, and propranolol, the toxicity of which frequently un- rescue therapy in a child with carisoprodol overdose. Cureus. 2019;
derwent LE treatment in this analysis, have high lipid solubility 11:e6250.
(log P > 2) and inhibit cardiac sodium channels, leading to QRS 9. Eren Cevik S, Tasyurek T, Guneysel O. Intralipid emulsion treatment as an
widening, myocardia depression, and arrhythmia.40 Because these antidote in lipophilic drug intoxications. Am J Emerg Med. 2014;32:
pharmacological characteristics of the previously mentioned drugs 1103–1108.
are similar to those of bupivacaine, when cardiac toxicity by these 10. Gün E, Kocabay K. Use of intravenous lipid emulsion therapy in a case of
drugs is unresponsive to supportive treatments, including sodium atomoxetine (Strattera®) toxicity. J Emerg Med. 2020;59:e49–e51.
bicarbonate, LE is administered to treat intractable cardiotoxicity 11. Gunasekaran K, Mathew DE, Sudarsan TI, et al. Fatal colchicine
arising from toxic doses of these drugs.1,40 In the present analysis, intoxication by ingestion of Gloriosa superba tubers. BMJ Case Rep. 2019;
LE treatment reduced serum bupropion concentration from 880 to 12:pii: e228718.
62 ng/mL and serum lamotrigine concentration from 24 to 18 μg/mL
12. Hantson P, Wuidart C, Haufroid V. Severe and prolonged flecainide
(Case no. 25), which may be associated with the lipid solubility of intoxication treated by extracorporeal life support: possible role of cytochrome
these drugs (log P: bupropion = 3.6 vs lamotrigine = 2.57). The high P450 2D6 polymorphism? Clin Toxicol (Phila). 2019;57:672–673.
lipid solubility of these drugs may contribute to successful LE resus-
13. Hendron D, Menagh G, Sandilands EA, et al. Tricyclic antidepressant
citation through lipid shuttle. Other potential mechanisms of LE re-
overdose in a toddler treated with intravenous lipid emulsion. Pediatrics.
suscitation include inotropic effect, fatty acid supply, reversal of mito-
2011;128:e1628–e1632.
chondrial dysfunction, and inhibition of nitric oxide synthesis.1
Taking into consideration that negative case reports regard- 14. Levine M, Brooks DE, Franken A, et al. Delayed-onset seizure and cardiac
ing LE treatment for toxicity induced by nonlocal anesthetics are arrest after amitriptyline overdose, treated with intravenous lipid emulsion
relatively difficult to publish compared with that for positive case therapy. Pediatrics. 2012;130:e432–e438.
reports, and a small sample size used in the analysis (N = 31), sim- 15. Levine M, Skolnik AB, Ruha AM, et al. Complications following antidotal
ilar studies on large cohorts are necessary for a better understand- use of intravenous lipid emulsion therapy. J Med Toxicol. 2014;10:10–14.
ing of the effects of LE resuscitation. Pharmacokinetically, plasma 16. Maskell KF, Ferguson NM, Bain J, et al. Survival after cardiac arrest:
protein binding, absorption, metabolism, and excretion decrease ECMO rescue therapy after amlodipine and metoprolol overdose.
in pediatric patients, whereas volume of distribution is augmented.41 Cardiovasc Toxicol. 2017;17:223–225.

17. McAllister RK, Tutt CD, Colvin CS. Lipid 20% emulsion ameliorates the 30. Havan M, Kendirli T, Özcan S, et al. A successful treatment with
symptoms of olanzapine toxicity in a 4-year-old. Am J Emerg Med. 2012; intravenous lipid emulsion therapy in a child with verapamil poisoning.
30:1012.e1–1012.e2. Turk J Emerg Med. 2021;21:217–220.
18. Montiel V, Gougnard T, Hantson P. Diltiazem poisoning treated with 31. Fettiplace MR, Akpa BS, Rubinstein I, et al. Confusion about infusion:
hyperinsulinemic euglycemia therapy and intravenous lipid emulsion. Eur J rational volume limits for intravenous lipid emulsion during treatment of
Emerg Med. 2011;18:121–123. oral overdoses. Ann Emerg Med. 2015;66:185–188.
19. Mukhtar O, Archer JR, Dargan PI, et al. Lesson of the month 1: acute 32. Intralipid: FDA. Available at: https://www.accessdata.fda.gov/drugsatfda_
flecainide overdose and the potential utility of lipid emulsion therapy. Clin docs/label/2007/017643s072,018449s039lbl.pdf. Accessed June 21, 2022.
Med (Lond). 2015;15:301–303.
33. BUPROPION [package insert]. GlaxoSmithKline. Available at: https://
20. Noda K, Akioka S, Kubo H. Detoxification with intravenous lipid emulsion gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_
for fatal hydroxychloroquine poisoning. Mod Rheumatol. 2021;31:772–774. Information/Wellbutrin_SR/pdf/WELLBUTRIN-SR-PI-MG.PDF.
21. Odigwe CC, Tariq M, Kotecha T, et al. Tricyclic antidepressant overdose Accessed June 21, 2022.
treated with adjunctive lipid rescue and plasmapheresis. Proc (Bayl Univ 34. Cohen JC. Chylomicron triglyceride clearance: comparison of three
Med Cent). 2016;29:284–287. assessment methods. Am J Clin Nutr. 1989;49:306–313.
22. Kwan D, Vohra R, Dyer JE, et al. An infant with a heartbreaking medication
35. Wanten GJA, Calder PC. Immune modulation by parenteral lipid
error. Pediatr Emerg Care. 2014;30:e1–e5.
emulsions. Am J Clin Nutr. 2007;85:1171–1184.
23. Gardner Yelton SE, Leonard JB, de la Uz CM, et al. Flecainide toxicity
36. Hippalgaonkar K, Majumdar S, Kansara V. Injectable lipid emulsions—
secondary to accidental overdose: a pediatric case report of two brothers.
advancements, opportunities and challenges. AAPS PharmSciTech. 2010;
Case Rep Crit Care. 2021;2021:6633859–6633856.
11:526–540.
24. Shenoi AN, Gertz SJ, Mikkilineni S, et al. Refractory hypotension from
37. French D, Smollin C, Ruan W, et al. Partition constant and volume of
massive bupropion overdose successfully treated with extracorporeal
distribution as predictors of clinical efficacy of lipid rescue for toxicological
membrane oxygenation. Pediatr Emerg Care. 2011;27:43–45.
emergencies. Clin Toxicol (Phila). 2011;49:801–809.
25. Thompson AM, Franco Palacios CR, Henriksen MN. Intravenous lipid
emulsion and high-dose insulin as adjunctive therapy for propranolol 38. Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6
toxicity in a pediatric patient. Am J Health Syst Pharm. 2016;73:880–885. (CYP2D6): clinical consequences, evolutionary aspects and functional
diversity. Pharmacogenomics J. 2005;5:6–13.
26. Tse CW, Chan YC, Lau FL. Intravenous lipid emulsion as antidote:
experience in Hong Kong. Hong Kong J Emerg Med. 2015;22:100–107. 39. Fettiplace MR, Weinberg G. The mechanisms underlying lipid resuscitation
therapy. Reg Anesth Pain Med. 2018;43:138–149.
27. Turkdogan KA, Duman A, Avcil M, et al. Treatment methods following
suicidal self-administration of IV organophosphate: what can additional 40. Bruccoleri RE, Burns MM. A literature review of the use of sodium
lipid administration change? Am J Emerg Med. 2017;35:1388.e3–1388.e5. bicarbonate for the treatment of QRS widening. J Med Toxicol. 2016;12:
121–129.
28. Vignesh C, Kumar M, Venkataraman R, et al. Extracorporeal membrane
oxygenation in drug overdose: a clinical case series. Indian J Crit Care 41. Fernandez E, Perez R, Hernandez A, et al. Factors and mechanisms for
Med. 2018;22:111–115. pharmacokinetic differences between pediatric population and adults.
Pharmaceutics. 2011;3:53–72.
29. Zutter A, Hauri K, Evers KS, et al. “Chaotic arrhythmia” during successful
resuscitation after ingestion of yew (Taxus baccata) needles. Pediatr Emerg 42. Kim W, Kwon HW, Min J, et al. Percutaneous bicaval dual lumen cannula
Care. 2019;35:e223–e225. for extracorporeal life support. Acute Crit Care. 2020;35:207–212.

ULTRASOUND CASE REVIEW
Associate Editor: J. Kate Deanehan, MD, RDMS
Point-of-Care Ultrasound for Pulse Checks in Pediatric

Cardiac Arrest
Two Illustrative Cases
Julie I. Leviter, MD, Susan Walsh, MD, and Antonio Riera, MD
was admitted to the pediatric intensive care unit where the patient
Abstract: Cardiac arrest is an infrequent but high-stakes scenario in pedi- ultimately died, and her organs were donated.
atrics. Manual central pulse checks are unreliable. Point-of-care ultrasound is a
noninvasive technique to visualize the heart and central vessels during resusci-
tation. We describe 2 cases in which point-of-care ultrasound helped aid CASE 2
management decisions in pediatric cardiac arrest. A 12-year-old male patient with a history of asthma presents
to emergency department after a self-inflicted asphyxiation epi-
Key Words: point-of-care ultrasound, cardiac arrest, resuscitation,
sode. He was found apneic and in asystole by emergency medical
critical care
services who intubated the child and initiated chest compressions
(Pediatr Emer Care 2023;39: 60–61) with a mechanical Lund University Cardiac Assist System (LUCAS)
2 device. An IO line was placed in the proximal right tibia, and 4
rounds of epinephrine were administered en route to the pediatric
CASE 1 emergency department.
On initial examination in the trauma bay, the child was intubated,
A 4-month-old female patient with no medical history pre-
apneic, and pulseless with diffuse facial petechiae and a ligature
sented in asystolic cardiac arrest. She had been placed supine on a
line around the neck. Pupils were dilated and nonreactive. End-
bed for a nap and later found by caregivers to be in the prone position
tidal carbon dioxide measurements ranged from 15 to 20 mm Hg.
and unresponsive. Emergency medical services initiated cardiopul-
There was no palpable pulse. Point-of-care ultrasound was per-
monary resuscitation, placed an oropharyngeal airway, and ventilated
formed continuously by a pediatric emergency medicine attending
her with a bag-valve mask. They administered one dose of epineph-
and director of ultrasound throughout the resuscitation. Cardiac
rine through a tibial intraosseous (IO) device. On arrival to the pedi-
windows were difficult to obtain because of the LUCAS 2 system
atric emergency department, she was found to have a temperature of
positioning over the chest. Continuous pulse checks were obtained
33.4°C, a dusky appearance, fixed pupils, absent pulses, and cool ex-
over the right femoral vessels using a linear (L12-4) transducer of a
tremities. She was intubated and received 1 round of epinephrine.
Philips Sparq Ultrasound system. During chest compressions, dis-
A pulse and rhythm check was performed, at which time pulses
tension of the right femoral vein is visible with internal venous flow
were evaluated through manual palpation and through a cardiac
also seen from the saline infusion through the distal IO (Video 2,
point-of-care ultrasound (POCUS) evaluation by a pediatric emergency
http://links.lww.com/PEC/A926). In addition, IO function was fur-
medicine POCUS fellow. The patient was found to be in sinus rhythm
ther confirmed by color Doppler application with flow signals pres-
at a rate of 130 beats per minute. Manual pulses could not be palpated.
ent deep to the cortex and within the marrow (Video 3, http://links.
However, cardiac POCUS revealed the presence of organized cardiac
lww.com/PEC/A927). This can be easily performed by placing the
activity (Video 1, http://links.lww.com/PEC/A925). Clips were obtained
transducer just proximal to the IO site in short axis and placing a color
using a phased array (S4-2) transducer of a Philips Sparq Ultra-
Doppler or power Doppler box to check for flow signals below the
sound system in the apical 4-chamber view. This view was optimal
echogenic cortex. Intraosseous flow will be seen just below the bony
because defibrillator pads precluded parasternal views and partially
cortex, whereas extraosseous flow and malposition of the IO needle
obscured subxiphoid views. The discovery of cardiac activity by
will exhibit flow signals superficial to bone. When using color
POCUS led to a shift in management.
Doppler, a mixture of red (flow toward transducer) and blue (flow
At this point, compressions were halted, and post-return of
away from transducer) may be seen depending on probe placement.
spontaneous circulation (ROSC) care was initiated. The patient
In this case, we were able to confirm adequate IO flow with the ve-
was placed under a warmer given her hypothermia, an epinephrine
locity scale set at 7 cm/s. Resuscitative efforts were eventually dis-
drip was initiated for hypotension, calcium gluconate was initiated
continued because of persistent asystole after 6 rounds of epineph-
for hyperkalemia, and 2 normal saline boluses were pushed. The
rine in the pediatric trauma bay despite a secure airway and defin-
patient was also administered hydrocortisone, naloxone, and cef-
itive access for medications. A final femoral pulse check revealed
triaxone given the unknown cause of arrest, and a chest x-ray and
no spontaneous pulsations of the femoral artery (Video 4, http://
computed tomography scan of the brain were obtained. The patient
links.lww.com/PEC/A928).
From the Yale University School of Medicine, New Haven, CT. DISCUSSION AND REVIEW OF THE LITERATURE
Reprints: Julie I. Leviter, MD, 100 York St, Suite 1F, New Haven, CT 06511 Cardiac arrest is an infrequent but high-stakes scenario in pe-
(e‐mail: Julie.leviter@yale.edu). diatrics.1 Manual central pulse checks are unreliable and may erro-
Supplemental digital content is available for this article. Direct URL citations neously miss the presence of a pulse or fail to recognize the absence
of one.2–5 Point-of-care ultrasound is a noninvasive technique to
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. visualize the heart and central vessels during resuscitation.4,6 It
ISSN: 0749-5161 can help determine the presence or absence of cardiac activity in

Pediatric Emergency Care • Volume 39, Number 1, January 2023 POCUS for Pulse Checks in Pediatric Cardiac Arrest
conjunction with, or instead of, manual pulse checks, as is demon- CONCLUSIONS

strated in case 1.7,8 By demonstrating clear, organized cardiac ac- Point-of-care ultrasound is a valuable tool during resuscitation,
tivity, POCUS enabled the medical team to halt compressions and providing valuable information to the medical team and potentially
initiate post-ROSC care. While the use of POCUS during cardio- changing management in a timely way. We describe 2 cases in
pulmonary resuscitation is well described and studied in the adult which POCUS helped enhance management precision. The first
population, there are but several case series, which describe its use did so through visualization of cardiac activity in the absence of
in the pediatric population. One of these by Tsung and Blaivas7 a palpable pulse, leading to a pivot to post-ROSC care. In the sec-
describes 14 pediatric patients in whom POCUS was rapidly cor- ond, the visualization of femoral vessels confirmed effective com-
related with the presence or absence of a pulse, without prolonged pressions and IO fluid infusion, as well as prolonged absence of
interruption of chest compressions. Our case series adds to this cardiac activity during the pulse and rhythm check. Further re-
literature.7,9 search is needed to determine how POCUS is best incorporated
Point-of-care ultrasound can also be used to assess for quality to improve the quality of pediatric cardiac resuscitation.
of compressions and for central pulses during pulse and rhythm
checks in the femoral or carotid locations.4,5 In pulseless patients,
neither arterial nor venous vasculature will have blood flow; thus,
it will compress easily as the transducer is used to apply pressure REFERENCES
to the skin. Conversely, in the presence of central perfusion, the 1. Atkins DL, Everson-Stewart S, Sears GK, et al. Epidemiology and
artery will be noncompressible with pulsations visualized on ul- outcomes from out-of-hospital cardiac arrest in children: the Resuscitation
trasound.5 Badra et al4 demonstrated that POCUS carotid pulse Outcomes Consortium Epistry-Cardiac Arrest. Circulation. 2009;119:
checks are not slower than those using palpation and demon- 1484–1491.
strated a higher first-attempt success rate. A femoral pulse may 2. American Heart Association. 2005 American Heart Association (AHA)
be easily accessible by POCUS during both compressions and guidelines for cardiopulmonary resuscitation (CPR) and emergency
during the pulse and rhythm check in a pediatric patient, as was cardiovascular care (ECC) of pediatric and neonatal patients: pediatric basic
demonstrated in case 2. During compressions, POCUS can be life support. Pediatrics. 2006;117:e989–e1004.
used to evaluate the quality of compressions. During the pulse 3. Inagawa G, Morimura N, Miwa T, et al. A comparison of five techniques
and rhythm check, POCUS can be used to evaluate central pulses. for detecting cardiac activity in infants. Paediatr Anaesth. 2003;13:
Importantly, if a central artery is located sonographically during 141–146.
compressions, it can remain in place during the pulse and rhythm 4. Badra K, Coutin A, Simard R, et al. The POCUS pulse check:
check to instantly determine whether flow is present, thus reduc- a randomized controlled crossover study comparing pulse detection by
ing time to resumption of compressions when required. This can palpation versus by point-of-care ultrasound. Resuscitation. 2019;139:
help reliably and efficiently guide management in real time. 17–23.
Point-of-care ultrasound can also be used to confirm IO place- 5. Simard RD, Unger AG, Betz M, et al. The POCUS pulse check: a case
ment during resuscitation, as was described in case 2. It can detect series on a novel method for determining the presence of a pulse using
extraosseous flow in misplaced IO needles and confirmed IO flow point-of-care ultrasound. J Emerg Med. 2019;56:674–679.
in correctly positioned ones.10 Tsung and Blaivas7 described suc-
6. American College of Emergency Physicians. American College of
cessful use of POCUS with color Doppler to confirm IO place- Emergency Physicians. ACEP emergency ultrasound guidelines-2001.
ment during adult resuscitation. Ann Emerg Med. 2001;38:470–481.
Point-of-care ultrasound use during resuscitation can also pro-
vide additional information to the medical team, including second- 7. Tsung JW, Blaivas M. Feasibility of correlating the pulse check with
focused point-of-care echocardiography during pediatric cardiac arrest:
ary causes of arrest such as a pericardial effusion or tamponade as
a case series. Resuscitation. 2008;77:264–269.
a reversible cause of cardiac arrest, right heart strain, and response
to fluid, ionotrope, or vasopressor administration.7,8 It may thus 8. Hayhurst C, Lebus C, Atkinson PR, et al. An evaluation of echo in life
prompt the team to perform a life-saving procedure, such as a peri- support (ELS): is it feasible? What does it add? Emerg Med J. 2011;28:
cardiocentesis for cardiac tamponade, or thrombolysis for a pul- 119–121.
monary embolism. It may also provide key information about pa- 9. Rodriguez-Fanjul J, Perez-Baena L, Perez A. Cardiopulmonary
tient anatomy that was unknown at the start of resuscitation, such resuscitation in newborn infants with ultrasound in the delivery room.
as congenital cardiac disease. Lastly, it may also help to commu- J Matern Fetal Neonatal Med. 2021;34:2399–2402.
nicate a patient's diagnosis of critical illness or death to a family 10. Tsung JW, Blaivas M, Stone MB. Feasibility of point-of-care colour
member, by visual demonstration of poor cardiac activity or car- Doppler ultrasound confirmation of intraosseous needle placement during
diac standstill. resuscitation. Resuscitation. 2009;80:665–668.

LETTER TO THE EDITORS
Appropriate Statistical system, and the overall accuracy of the es- discriminator between weight estimation
timation system (Fig. 1). A percentage er- methods than MAPE. Mean absolute per-
Analysis and Data Reporting ror (Equation 1) should be used as the ba- centage error and RMSPE are not equiva-
for Weight Estimation Studies sis for all the analyses: an estimation error lent and cannot be directly compared with
of 1 kg may be inconsequential in a 50-kg each other.
child but may be highly significant in a An example of the difference between
3-kg infant. Although the absolute error MAPE and RMSPE can be seen in data
To the Editors: values (in kilograms) can be uninformative, from weight estimation in 29,580 adults
W eight estimation studies are impor-
tant because they inform clinicians
and decision makers about the relative
an error of 2% versus an error of 33% con-
veys a great deal more information.
(Table 1). Method A had a low bias, high
precision, and high accuracy; Method B
Equation 1 had a high bias, low precision, and very
merits of different weight estimation sys- ðestimated weight−actual weight Þ low accuracy. The differences between the
tems. From a methodological perspective, Percentage error ¼ 100
actual weight MAPE and RMSPE for each method reflect
these studies are method comparison stud- the number of large errors of estimation.
ies. This mandates that there is a specific Equation 2
method in which data should be reported Bias should be reported as the mean per-
95%lower limit of agreement
and analyzed to establish the performance centage error (MPE), which reflects the
¼ MPE 1:96 ðstandard deviation of MPEÞ
of the weight estimation systems. We refer- overall overestimation or underestimation
ence the recent article by Waltuch et al1 in of the weight estimation system in the study
this journal, in which weight estimations population. It is one of the least useful mea- 95%upper limit of agreement
from 2 devices were compared. This is an sures of the performance of a weight esti- ¼ MPE þ 1:96 ðstandard deviation of MPEÞ
innovative article, but the data reporting mation system. Bias should not be con-
and statistical methodology in this article fused with accuracy because the metrics Equation 3
pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
are incomplete and, in some parts, incor- represent very different concepts. A low ∑ percentage error2
rect. This leaves the reader without the es- bias may be present in an inaccurate weight Mean absolute percentage error ¼
N
sential information that is required to make estimation method; for example, if a weight
his or her own informed assessment of the estimation system has errors of +40%, Equation 4
performance of the weight estimation de- +50%, −40%, and −50% in 4 children, the
Root mean square percentage error
vices studied and without the data to com- bias will be 0% (average of 40, 50, −40, sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
P
pare this study with other similar studies. −50) but the accuracy and precision are ðpercentage error2 Þ
¼
Unfortunately, this deficiency is very com- clearly low. However, an accurate system N
mon in weight estimation studies and will usually also have a low bias. Comparing
method comparison studies.2,3 bias between methods is generally of limited The overall accuracy should be reported as
It is important to evaluate and then de- value, for the reasons explained previously. the percentage of estimations falling within
scribe the performance of a weight estima- Precision should be reported using at 10% and 20% of measured weight (P10
tion system correctly and comprehensively. least 2 metrics: the 95% Bland & Altman and P20, respectively). Both P10 and P20
In any weight estimation article, there are limits of agreement (LOA) of the MPE have been widely used in weight estimation
critical elements in the methodology and (Equation 2) and either the mean absolute studies from the earliest studies in the
statistical analysis that must be completed percentage error (MAPE) (Equation 3) or 1980s. They are useful cut points that cor-
and then the details of the data reported. the root mean square percentage error respond with what many authors consider
Firstly, the weight estimation system (RMSPE) (Equation 4). Mean absolute per- to be limits that are appropriate to classify
should be compared against actual mea- centage error differs from RMSPE in where drug dosing errors.2
sured weight (in kilograms). The analysis the square root appears in the equation. The Analyses that are inappropriate for
should describe the bias of the estimation RMSPE weights or amplifies large errors weight estimation studies include the
system, the precision of the estimation of weight estimation and is a more sensitive comparison of mean actual versus mean
FIGURE 1. A graphical representation of bias, precision, and accuracy as it applies to weight estimation studies. The darts on the target
represent weight estimations from a weight estimation system. Target A illustrates a high negative bias, low precision, and low accuracy.
Target B illustrates a low bias, low precision, and low accuracy. Target C illustrates a high positive bias, high precision, and low accuracy. Target
D illustrates a low bias, high precision, and high accuracy. High bias would be indicated by a large positive or large negative MPE, whereas a
low bias would be indicated by an MPE close to 0. High precision would be indicated by narrow 95% LOA and low MAPE or RMSPE. High
accuracy would be indicated by a high percentage of estimations falling within 10% and 20% of actual weight (P10 and P20).

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Letter to the Editor
Lara Goldstein, MBBCh, PhD

TABLE 1. Appropriate Performance Metrics for Weight Estimation Studies Division of Emergency Medicine
Faculty of Health Sciences
MPE (%) 95% LOA (%) MAPE (%) RMSPE (%) P10 (%) P20 (%)
University of the Witwatersrand
Method A −0.5 −18.8, 17.8 7.3 9.4 73.9 96.9 Johannesburg, South Africa
Method B −13.9 −54.2, 26.4 20.7 24.8 27.1 52.4
Mike Wells ORCID ID:
0000-0002-4520-2007.
estimated weights and all forms of correla- to ensure adequate representation of partici-
Lara Goldstein ORCID ID:
tion analysis, including intraclass correla- pants in relevant subgroups. The sampling
0000-0002-9427-8710.
tion (ICC). The use of ICC has been sug- strategy should include appropriate inclusion
Disclosure: The authors declare no conflict
gested to assess agreement in method com- and exclusion criteria to ensure an unbiased
of interest.
parison studies to overcome some of the study. For example, when studying the accu-
obvious problems in Pearson correlation racy of the Broselow tape, excluding children
analysis, in which any form of linear rela- who exceed the length of the tape introduces
tionship is misconstrued as agreement. substantial bias.6 The study would not reflect REFERENCES
However, the use of ICC in assessing how the tape would function in clinical prac- 1. Waltuch T, Munjal K, Loo G, et al. AiRDose:
agreement has been criticized by Bland tice for taller children, which would limit the developing and validating an augmented reality
and Altman3,4 as well as other experts. value of the study significantly. The study smartphone application for weight estimation
The premise of the ICC method, its depen- sample should represent the types of pa- and dosing in children. Pediatr Emerg Care.
dence on the range of data and the variance be- tients seen in clinical practice in the popu- 2022;38:e1257–e1261.
tween subjects, and the inability to compare lation in which the weight estimation system 2. Wells M, Goldstein LN, Bentley A. The accuracy
this metric between studies makes its appropri- is to be used. of emergency weight estimation systems in
ateness doubtful. These methods should not be Fourthly, the outcome measures used children - a systematic review and meta-analysis.
used in weight estimation studies. in the study need to be stipulated in ad- Int J Emerg Med. 2017;10:1–43.
Secondly, it is essential to include vance and reported in the article. If a study 3. Zaki R, Bulgiba A, Ismail R, et al. Statistical
analyses and data reporting for appropri- compares 2 or more weight estimation sys- methods used to test for agreement of medical
ate subgroups. The calculation of bias, pre- tems, the article should specify what differ- instruments measuring continuous variables in
cision, and accuracy should be performed ence between weight estimation systems method comparison studies: a systematic review.
for the entire sample as well as for the body would be considered clinically relevant. In PLoS One. 2012;7:e37908.
habitus and age subgroups. It has been well addition, an acceptable accuracy bench- 4. Bland J, Altman D. A note on the use of the
established that the performance of weight mark for the weight estimation systems intraclass correlation coefficient in the evaluation
estimation systems is very different in chil- should be specified; for example, 95% of of agreement between two methods of
dren of different age groups and, more im- estimations should fall within 20% of ac- measurement. Comput Biol Med. 1990;20:
portantly, in children in different weight tual weight.7 This standard must include a 337–340.
status groups (ie, underweight, normal measure of overall accuracy and not only 5. Wells M, Goldstein LN, Bentley A. A systematic
weight, overweight, and obese children).5 measures of bias or precision. review and meta-analysis of the accuracy of
It is essential that the reader can see how a The use of the correct methodology, weight estimation systems used in paediatric
weight estimation system performs in these statistical analysis, and data reporting will emergency care in developing countries. Afr J
subgroups because the overall outcome ensure that a weight estimation study accu- Emerg Med. 2017;7:S36–S54.
data might be unrealistically flattering if rately represents its findings and provides 6. Wells M, Goldstein LN, Bentley A, et al. The
the study sample had few older participants the information that is most relevant for accuracy of the Broselow tape as a weight
and/or few obese and underweight partici- the reader. estimation tool and a drug-dosing guide - a
pants. It is also imperative to report on the systematic review and meta-analysis.
details of the sample composition with re- Resuscitation. 2017;121:9–17.
spect to the important subgroups (eg, age 7. Stewart D. Accuracy of the Broselow tape for
and BMI-for-age centiles or z-scores, or Mike Wells, MBBCh, PhD estimating paediatric weight in two
weight status groups). Department of Emergency Medicine Australian emergency departments. 2009.
Thirdly, there are study design factors Florida Atlantic University Schmidt Available at: https://ses.library.usyd.edu.au//
that are essential to ensure a high-quality College of Medicine bitstream/2123/6265/1/Declan%
weight estimation study. These would include Boca Raton, FL 20Stewart%20WPP%20final.pdf. Accessed
an appropriate participant selection process profmikewells@gmail.com July 18, 2022.

Challenges in Demonstrating be higher than stated, and thus, different re- between culture-positive and culture-negative
sults might be shown in comparison with patients. However, as the authors stated, di-
an Association Between the UTI group. arrhea can also be associated with infec-
Non-infectious Diarrhea and Second, no specific information regard- tions other than UTIs; therefore, even if
Urinary Tract Infections ing the antimicrobial administration history concomitant pneumonia, septicemia, and
was provided in the report. Antimicrobials otitis media can be ruled out in addition to
can cause diarrhea by disrupting the balance enteritis, it is still challenging to exclude
of the intestinal microbiome,3 and a history all possible infectious diseases. If noninfec-
of antimicrobial administration, for both the tious patients are included in the compari-
groups, should therefore have been con- son group, the observation period for the
To the Editors: firmed. To exclude diarrhea related to antimi- presence or absence of diarrhea should
ellick et al1 recently examined the as-
M sociation between culture-positive uri-
nary tract infection (UTI) and noninfectious
crobials, the patient's history of antimicrobial
use within 2 months of the visit should have
been obtained.3 Because culture-negative
be defined. In addition, the evaluation of
diarrhea should be limited to the period
before antimicrobial therapy initiation, after
diarrhea in a tertiary pediatric medical center cases were excluded from the UTI group, excluding previous antimicrobial therapy
in the United States. They reported signifi- there may be few cases of previous antimi- cases from both groups.
cantly more diarrhea in UTI cases than in crobial administration in the UTI group;
the comparison group.1 Urinary tract infec- however, any cases of previous antimicro-
tions are commonly encountered diseases bial administration should have been ex- Akihiro Iguchi, MD
in pediatric bacterial infection practice; how- cluded to rule out antibiotic-associated diar- Department of Critical Care Medicine
ever, their diagnosis is challenging despite rhea. Furthermore, in the study, there was Saitama Prefectural
the risk of severe illness.2 Therefore, clarify- no mention of the period during which the Children's Medical Center
ing the association between diarrhea symp- presence or absence of diarrhea was investi- Saitama, Japan
toms and UTIs is crucial. However, several gated; therefore, we wonder whether the igupi.0306@icloud.com
points that require a more detailed discus- symptoms before the visit as well as those
sion are included in this report. after the hospitalization were assessed. Be- Yoshihiro Aoki, MD
The first is the assertion that there cause the basic treatment for febrile UTI School of Tropical Medicine
were fewer cases of diarrhea in the compar- is intravenous antimicrobial administration, and Global Health
ison group with head trauma and extremity the number of cases of diarrhea associated Nagasaki University
fractures. Although the authors mentioned with UTIs might have been overestimated Nagasaki, Japan
the limitation regarding the possibility of in the UTI group owing to diarrhea associ-
underestimation of diarrhea in the compar- ated with antibiotics. If posthospitalization Disclosure: The authors declare no
ison group, we believe this is a crucial point symptoms were also examined to ensure conflict of interest.
of the report and requires further careful that symptoms associated with UTIs were
consideration. To our knowledge, no evi- not omitted, the possibility that antibiotic
dence indicating a frequent association of use was a confounding factor in the compar-
diarrhea with trauma cases exists in the lit- ing of the 2 groups cannot be ruled out. REFERENCES
erature. Although they stated that a review This article was a novel report on the 1. MellickLB, MurrayC, KalraS. “Parenteral”
of the system was consistently documented association between UTI and diarrhea, which diarrhea associated with pediatric urinary tract
in the medical records, it is presumed that has not been studied in detail. However, it infections. A retrospective chart review. Pediatr
not all patients were queried about the pres- also has limitations because of the retrospec- Emerg Care. 2022;38:e1489–e1492.
ence or absence of diarrhea, as the authors tive study of trauma patients as a comparison 2. BecknellB, SchoberM, KorbelL, , et al. The
are concerned. Because trauma cases are group. Based on the aforementioned points, diagnosis, evaluation and treatment of acute and
very likely to be diarrhea-free at the outset, while designing a prospective study, it may recurrent pediatric urinary tract infections. Expert
usually, trauma patients are not questioned be advisable to include patients clinically di- Rev Anti Infect Ther. 2015;13:81–90.
on their diarrhea status during trauma case agnosed with UTIs and started on antimicro- 3. FeldmanM. Antibiotic-Associated Diarrhea.
management. Therefore, it is possible that bials, and finally compare the presence of Comprehensive Biotechnology. 2nd ed. Oxford,
the actual number of cases of diarrhea might diarrhea before and after hospitalization United Kingdom: Pergamon; 2021.

Concluding Which Martin et al1 concluded that, for minor Eduardo Mekitarian Filho, MD, PhD,
outcomes such as missed school days or MSc
Glucocorticoid Is More vomiting, no differences were found in the Pediatric Intensive Care Unit
Reliable for Children With 2 groups that received 0.6 or 1.2 mg/kg of Cancer's Institute, Faculty of Medicine
dexamethasone for mild to moderate asthma University of São Paulo
Asthma's Exacerbation crisis. Those conclusions raise a lot of ques- University Nove de Julho
tions. First, why did the authors use those São Paulo, Brazil
huge doses of dexamethasone in the study? emf2002@uol.com.br
And why more important outcomes, such as
To the Editors: hospitalization, length of stay in the emer-
I t was with great interest that we have read

the article, “Single-Dose Dexamethasone
Is Not Inferior to 2 Doses in Mild to Mod-
gency department, needing for ICU referral,
or time spent in the emergency department,
were not evaluated? Banoth et al4 compared
Disclosure: The author declares no con-
flict of interest.
erate Pediatric Asthma Exacerbations in the dexamethasone (total 0.3 mg/kg in 2 doses)
Emergency Department,” published by with prednisolone (total 1 mg/kg in 2 doses)
REFERENCES
Martin et al1 in the June issue of Pediatric and found that 6-hour emergency stay and
Emergency Care journal. rate of admission were significantly lower in 1. Martin M, Penque M, Wrotniak BH, et al.
The majority of the studies about gluco- the dexamethasone group. The use of acces- Single-dose dexamethasone is not inferior to 2
corticoids such as dexamethasone in children sory muscles and respiratory rate were also doses in mild to moderate pediatric asthma
with respiratory diseases included acute lar- better in the dexamethasone group at the fourth exacerbations in the emergency department.
Pediatr Emerg Care. 2022;38:e1285–e1290.
yngitis, but in the past years, it has been also hour and fifth day. In addition, oral dexameth-
reviewed for asthma exacerbation treatment.2 asone was shown to have less incidence of 2. Paniagua N, Lopez R, Muñoz N, et al.
Steroids are an essential component for asthma vomiting than prednisolone. However, the Randomized trial of dexamethasone versus
exacerbation treatment. The standard of care in difference between those mentioned doses prednisone for children with acute asthma
children has been a 5-day course of prednis- of glucocorticoids is huge and certainly im- exacerbations. J Pediatr. 2017;191:190–196.
olone, with daily dosing because of its rela- pacted on the outcomes. 3. Randolph C. Dexamethasone for acute asthma
tively short half-life. However, the length of Although there is a reported increase in exacerbations in children: a meta-analysis.
the course, taste, and associated nausea and dexamethasone use, prednisone was still pre- Pediatr. 2014;133:493–499.
vomiting adverse effects of prednisone can ferred for patients with more severe asthma, 4. Banoth B, Verma A, Bhalla K, et al. Comparative
lead to noncompliance. Dexamethasone, on suggesting that providers are less likely to effectiveness of oral dexamethasone vs. oral
the other hand, is relatively long-acting and deviate from the standard treatment for those prednisolone for acute exacerbation of asthma: a
can be administered as a 2-dose course, with with a higher severity of illness.5 Recom- randomized control trial. J Family Med Prim Care.
the second dose administered 36 to 48 hours mended standard doses of glucocorticoids 2022;11:1395–1400.
after the first. Dexamethasone is also consid- must be compared in asthma crisis, but out 5. Nelipovich S, Porada K, Vepraskas S, et al.
ered more tolerable than prednisone but may of selection bias due to low or high doses, Current practice and rationale of prescribing
be less commonly available than prednisone and main outcomes must be studied to find dexamethasone for pediatric patients hospitalized
at community pharmacies.3 the best drug choice in those patients. for asthma. WMJ. 2022;121:30–35.

ORIGINAL ARTICLE
Hyperkalemia in a Hemolyzed Sample in Pediatric Patients

Repeat or Do Not Repeat?
Rahul Kaila, MD,* Marissa Hendrickson, MD,* Pablo Avendano, MD,* Cynthia Davey, PhD,†
Ryan Cullen, MD,† Gretchen Colbenson, MD,† and Jeffery Louie, MD*
BACKGROUND
Objective: The aim of the study is to analyze whether repeat testing is
necessary in healthy children presenting to a pediatric emergency de- Hyperkalemia can be a life-threatening emergency requiring
partment (ED) who are found to have hyperkalemia on a hemolyzed specimen. immediate medical attention. At times, it can be mimicked by
Methods: A 5-year retrospective analysis of pediatric ED patients found pseudohyperkalemia, defined as a falsely elevated in vitro serum
to have elevated potassium values on laboratory testing of a sample reported potassium level due to release of potassium from blood cells that
to be hemolyzed. All patients aged 0 to 17 years who had an elevated po- are hemolyzed during the drawing or processing of the blood.1
tassium level after an intravenous draw resulted from a serum sample that Ninety-eight percent of potassium is intracellular under normal
was reported as hemolyzed during an ED visit were included in the study. circumstances, and any significant cell rupture can substantially
Results: One hundred eighty-seven patients with some degree of both he- elevate measured potassium.1 Risk factors for hemolysis leading
molysis and hyperkalemia were included in the final analysis. The median to pseudohyperkalemia include the use of small-bore intravenous
age was 1.9 years of age. The most common race among all patients was catheters, excessive tourniquet time, fist clenching during phle-
White, followed by African American, and Asian. One hundred forty-five botomy, and mechanical stress during venipuncture and specimen
children had repeat sampling for hemolyzed hyperkalemia, 142 children, transportation.2 A number of these issues are likely to be more
97.9% (95% confidence interval, 95.6%–100%) had a normal potassium common in younger infants and toddlers due to small veins, increased
on repeat and 3 children, 2.1% (95% confidence interval, 0.0%–4.4%) had adipose tissue, and potentially poor cooperation with phlebotomy
true hyperkalemia. The frequency of true hyperkalemia in our study popula- or intravenous catheter placement.
tion was 2% (3/145). All 3 of these patients had underlying conditions that In the adult literature, approaches to correcting presumed
would appropriately have raised clinician suspicion for hyperkalemia. pseudohyperkalemia based on plasma-free hemoglobin have been
Conclusions: It may be unnecessary to obtain repeat samples to confirm suggested, while others have concluded that repeat sampling is un-
normal potassium in a hemolyzed sample with normal blood urea nitrogen necessary in low-risk patients.3,4 However, there is no definitive
and creatinine. literature to support a specific approach to pediatric patients, and
practice patterns likely vary. We hypothesized that repeat testing
Key Words: pseudohyperkalemia, hyperkalemia, DKA, renal failure is unnecessary in otherwise healthy children presenting to a pediatric
(Pediatr Emer Care 2023;39: e1–e5) emergency department (ED) who are found to have hyperkalemia
on a hemolyzed specimen. Our secondary objective was to deter-
mine whether patients known to have renal disease or other preex-
isting medical conditions are more likely to have true hyperkalemia.
From the *University of Minnesota Masonic Children's Hospital, and †Univer- METHODS
sity of Minnesota Medical School, Minneapolis, MN.
Reprints: Rahul Kaila, MD, Division of Pediatric Emergency Medicine, Study Design and Setting
Department of Pediatrics, University of Minnesota Masonic Children's
Hospital, 2450 Riverside Ave, Minneapolis, MN, 55454 (e‐mail: rkaila@ This study was a 5-year retrospective analysis of pediatric ED
umn.edu). patients found to have elevated potassium level on laboratory testing
This research was supported by the National Institutes of Health's National of a sample reported to be hemolyzed. The hospital is an urban aca-
Center for Advancing Translational Sciences, grant UL1TR002494. demic pediatric teaching hospital that provides a quaternary level of
The NIH has no role in the design and conduct of the study. The content is solely
the responsibility of the authors and does not necessarily represent the care; the ED has a current annual census of approximately 16,000
official views of the National Institutes of Health's National Center for visits. In general, serum samples in this ED are drawn by ED nurses
Advancing Translational Sciences. and transported to the laboratory through a pneumatic tube system.
What's known on this subject: To our knowledge, this is first pediatric study to The study was approved by the university's institutional review
analyze whether we need to repeat hemolyzed hyperkalemia if renal
function is normal. There is wide variation in practice among emergency board, and the need for informed consent was waived (Fig. 1).
department physicians whether to repeat potassium in a hemolyzed blood
sample with hyperkalemia. There are no data until date about this. Patient Selection and Data Collection
What this study adds: This study suggests not to repeat potassium in a
hemolyzed blood sample with hyperkalemia and normal serum urea We queried the hospital's electronic health record to identify
nitrogen/creatinine. This will help reduce pain and anxiety related with all patients aged 0 to 17 years who had an elevated potassium level
another intravenous draw which is unnecessary. after an intravenous draw resulted from a serum sample that was
R.K. and J.L. conceptualized and designed the study, drafted the initial
manuscript, and reviewed and revised the manuscript. R.C. and G.C.
reported as hemolyzed during an ED visit between March 1, 2011,
collected data, coordinated, and supervised data collection. C.D. designed and December 31, 2016. Serum potassium was defined as elevated
the data collection instruments and carried out the data analyses. M.H. and if the level was greater than 6.0 mEq/dL among children younger
P.A. reviewed and edited the manuscript for important intellectual content. than 12 months and greater than 5.3 mEq/dL for children 12 months
All authors approved the final manuscript as submitted and agree to be
accountable for all aspects of the work.
and older. If a patient had more than one visit during the study period,
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. only the first encounter was included and patients with central
ISSN: 0749-5161 lines were also excluded.
Pediatric Emergency Care • Volume 39, Number 1, January 2023 www.pec-online.com e1

Kaila et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
FIGURE 1. Flow diagram.
Specimen analysis was carried out in the laboratory using a (interquartile range) and compared using the nonparametric Wilcoxon
Vista 500 Chemistry Analyzer (Siemens, Munich, Germany). rank-sum test. Discrete variables were summarized with frequency
Medical charts were reviewed by physician investigators, and (percent) and were compared with either the χ2 test or Fisher exact
the following variables were extracted: date of visit, date of birth, test. Adjusted odds of true hyperkalemia were estimated using pe-
sex, race, underlying medical or surgical history, discharge diag- nalized likelihood models address quasi-complete separation in
nosis, disposition from ED, degree of hemolysis reported by the the multiple logistic regression models due to sparse data resulting
laboratory, recorded potassium value, whether the sample was re- from the small number with true hyperkalemia. An α significance
peated, and electrocardiogram (ECG) results during the visit. We level of 0.05 was used to identify statistical significance. SAS ver-
identified reference ranges of serum urea nitrogen (BUN) as: 0 to sion 9.4 was used for all statistical analyses.
1 year, 3 to 17 mmol/L; 1 to 9 years, 9 to 22 mmol/L; and 10 to
18 years, 7 to 19 mmol/L. The following normal creatinine (Cr)
values were defined as: 0 to 21 days (0.06 years), 0.33 to 1.01;
22 days (0.06 years) to 8 years, 0.15 to 0.53; 9 to 14 years, 0.39 RESULTS
to 0.73; and greater than 14 years, 0.5–1.0. Any values outside of One hundred eighty-seven patients had some degree of both
age-appropriate ranges were identified as abnormal. The degree of hemolysis and hyperkalemia reported and were included in the fi-
hemolysis is determined by the Vista 500 machine and is reported nal analysis. Of 145 children who had repeat sampling for hemo-
as mild, moderate, and severe. The ECGs are read by the pediatric lyzed hyperkalemia, 142, 97.9% (95% confidence interval [CI],
emergency physician and later confirmed by a pediatric cardiologist. 95.6%–100%) had a normal potassium on repeat and 3, 2.1%
We assessed included children for the following medical or (95% CI, 0.0%–4.4%) had true hyperkalemia. Table 1 and Figure 1
surgical conditions: (1) history of neonatal intensive care unit hos- summarizes patient characteristics and compares children who had
pitalization; (2) history of tracheostomy; (3) history of congenital repeat samples with those who did not.
heart disease with or without surgery; (4) renal failure of any degree One hundred forty-five subjects (77.5%) had a single repeat
or etiology; (5) rheumatologic condition; (6) oncologic condition or sample. Of these patients, 135 (93.1%) had a normal repeat potas-
history of bone marrow transplant; (7) current presence of a ventric- sium level. Ten (7.4%) underwent a second repeat sample; 3 of
uloperitoneal shunt; (8) presence of a feeding tube or Mitrofanoff; these children had elevated potassium level with no hemolysis,
(9) documented genetic, metabolic, or endocrine condition; (10) and 7 again had sample hemolysis. All 7 of these patients had a
cystic fibrosis or known restrictive lung disease; (11) current or third repeat blood draw with normal potassium levels. The fre-
past requirement of a central line, children with a renal, liver, or quency of subsequent true hyperkalemia in the sample of 145 pa-
heart transplant were considered separately and not grouped with tients with repeated potassium was 3, 2.1% (95% CI, 0.0%–4.4%).
children with medical conditions; and (12) home medication es- The average measured potassium level regardless of reported
pecially potassium chloride supplements, angiotensin- converting degree of hemolysis was 6.7 mEq/L. Half of samples (50%) had
enzyme inhibitors, and spironolactone. moderate hemolysis, followed by 33% with slight hemolysis (Table 2).
There was no significant difference in Cr values between children
who had repeated and nonrepeated samples. There was, however,
Data Analysis a significant difference in BUN values between these two groups
Continuous variables were summarized with mean (SD) and ( P < 0.001; Table 2). Seventeen children who had repeat speci-
compared using 2-sample t tests for more normally distributed var- mens obtained and 4 who did not undergo ECG testing; none were
iables. Skewed continuous variables were summarized with median found to have peaked T waves or any arrhythmia.
e2 www.pec-online.com © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Do We Need to Repeat Hemolyzed Hyperkalemia?
TABLE 1. Patient Characteristics
All Patients Potassium Repeated Potassium Not Repeated

Patient Characteristic (N = 187) (n = 145) (n = 42)
Age, median, y 1.9 (0.8–6.4) 2.4 (0.9–7.6) 1.4 (0.7–2.3)
Sex, n (%)
Male 94 (50.3) 72 (49.7) 22 (52.4)
Female 93 (49.7) 73 (50.3) 20 (47.6)
Medical condition
Healthy 107 (57.2) 73 (50.3) 34 (81.0)
Cardiac disease (nontransplant) 16 (8.6) 13 (9.0) 3 (7.1)
Kidney disease (nontransplant) 15 (8.0) 14 (9.7) 1 (2.4)
Other medical conditions 49 (26.2) 45 (31.0) 4 (9.5)
Home medication, potassium chloride supplements, 13 (6.9) 13 (8.9)
angiotensin- converting enzyme inhibitors, spironolactone
Data are reported as number (%) or median (interquartile range).
Three patients (2.1%) were found to have true hyperkalemia and BUN/Cr ratio abnormality (abnormal vs normal) were not
(Table 3). One patient had known chronic renal failure and had significantly associated with odds of true hyperkalemia in this pa-
been referred to the ED because of concern for electrolyte abnor- tient sample. A sensitivity model was run without BUN/Cr ratio
malities, including abnormal potassium, BUN, and Cr. The other abnormality (missing for 15 patients); results of the model that in-
2 patients presented with diabetic ketoacidosis (DKA), one with cluded all 145 patients were similar to model results in Table 4,
normal BUN and Cr values and the other with abnormal values with only patient age significantly associated with odds of true
for both. hyperkalemia, odds ratio, 1.28 (95% CI, 1.06–1.54), P = 0.010.
Results from the penalized likelihood model indicate that,
adjusted for other factors in the model, only patient age was signif-
icantly associated with an odds ratio of true hyperkalemia 1.24 DISCUSSION
(95% CI, 1.05–1.48), P = 0.014, indicating that odds of true Pseudohyperkalemia due to specimen hemolysis may occur
hyperkalemia were 1.24 times higher for each additional year of with any blood draw. Repeat blood sampling to verify serum po-
age (Table 4). Medical condition (any vs healthy), initial hemoly- tassium may be unpleasant for the patient, parent, and ED staff.5
sis level (slightly vs moderately or more), initial potassium level, Clear guidelines to determine which patients require repeat blood
TABLE 2. Laboratory Findings by Group
All Patients Potassium Repeated Potassium Not Repeated P for Comparison Between
Initial Sample Laboratory Measures (N = 187) (n = 145) (n = 42) Repeated and Not Repeated
Initial Potassium (mEq/L) Mean ± SD 6.7 (1.3) 6.7 (1.4) 6.4 (1.1) 0.160*
Degree of hemolysis 0.505†
Slightly
N (%) 61 (32.6) 45 (31.0) 16 (38.1)
Potassium (mEq/L): Mean (SD) 6.0 (0.55) 6.0 (0.49) 6.1 (0.71)
Moderately
N (%) 93 (49.7) 72 (49.7) 21 (50.0)
Markedly or Very
N (%) 33 (15.6) 28 (19.3) 5 (11.9)
Initial BUN, Mean (SD) 15.4 (13.7) 16.9 (15.2) 10.9 (4.8) <0.001*
Abnormal for age N (%) 32 (18.1) 27 (19.8) 5 (12.2) 0.309‡
Initial Cr Mean (SD) 0.58 (1.15) 0.63 (1.24) 0.45 (0.77) 0.275*
Abnormal for age N (%) 29 (17.2) 25 (19.2) 4 (10.3) 0.224‡
Critical Cr >2.0 6 (3.6) 5 (3.9) 1 (2.6) 1.00†
*Two-sample t test.
†Fisher exact test.
‡χ2 test.
© 2022 Wolters Kluwer Health, Inc. All rights reserved. www.pec-online.com e3

Kaila et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
TABLE 3. Patients With Hyperkalemia Without Finding of Hemolysis on Repeat Specimen (True Hyperkalemia)
Initial Sample Repeat Sample

Age, Medical
y Sex Condition K BUN Cr BUN/Cr Ratio Hemolysis K Hemolysis BUN Cr
13.6 M Chronic renal failure 7.3 89 Abnormal 2.35 Abnormal 37.9 Abnormal Moderately 5.4 None 84 Abnormal 2.3 Abnormal
reported
15.7 M Diabetic ketoacidosis 5.9 20 Normal 0.68 Normal Normal Slightly 5.8 None — — — —
reported
16.3 M Diabetic ketoacidosis 6.9 46 Abnormal 1.89 Abnormal 24.3 Abnormal Slightly 7.3 None — — — —
and Hashimoto's reported
disease
sampling in this setting have not been established in the literature. Lastly, the goal of minimizing unnecessary blood draws in
To the authors' knowledge, this is the first pediatric study to assess children is supported by the literature. A study by Cummings et al8
the prevalence of true hyperkalemia in children with elevated po- ranked pain due to intravenous catheter insertion as the most com-
tassium levels obtained from specimens reported to be hemo- mon cause of pain in the pediatric inpatient population. Children's
lyzed. In the group of such children who had a repeat sample ob- memories of painful intravenous insertion experiences can lead to
tained, we observed that those with normal BUN and Cr levels and fear of future medical care and painful procedures.9 In addition,
without DKA were unlikely to have an abnormal potassium value studies have shown that needle phobias caused by repeat needle
on repeat sampling. Because almost 98% of the patients who had insertions lead to future failure rate of intravenous insertion use
repeat samples obtained being found to have normal potassium, to previous trauma.10
we propose that it would be safe not to repeat blood sampling to
confirm potassium level if the laboratory reports the specimen Limitations
was hemolyzed and potassium elevation was not expected in pa- In this retrospective study, it is possible that the construction
tients who has normal BUN and Cr values. This not only helps re- of our electronic health record filter led to unknown selection
duce the trauma of repeat blood draw on the child but also de- biases or missed cases. In addition, the method of blood collection
creases the visit costs and length of stay. and number of times patients had repeat sampling may have been
The frequency of true hyperkalemia in our study population underestimated or not documented given the busy ED environ-
was 2% (3/145). All 3 of these patients had underlying condi- ment. The classification of comorbid medical and surgical condi-
tions that would appropriately have raised clinician suspicion for tions is subjective and may lead to inaccuracies or biases. There
hyperkalemia. Two patients presented to the ED in DKA, which were 13 patients (9%) on potassium chloride supplements, angio-
is well known to be associated with initial hyperkalemia.6 The tensin- converting enzyme inhibitors, or spironolactone that could
third patient had known chronic renal failure and was sent to the contribute to hyperkalemia and so caution must be used in apply-
ED because of worsening electrolyte abnormalities; chronic renal ing this approach to patients taking these medications.
failure is known to cause hyperkalemia.7 Finally, we did not gather information on the future outcomes
For patients with underlying medical conditions, the rate of of patients who did not have their abnormal potassium levels re-
repeat laboratories being obtained was higher (90%) than for peated, so it is possible that a case or cases of true hyperkalemia
healthy patients (68%). It is possible that providers believe that may have been missed. Future prospective studies would be help-
patients with underlying medical condition had higher chances ful to further characterize the circumstances under which it is ap-
of having true hyperkalemia. However, this was not borne out propriate to forgo repeat sampling.
by our findings other than for renal failure and DKA as noted
previously. Approximately 22% of patients did not have repeat
potassium sampling obtained; the majority of these patients were CONCLUSIONS
healthy.
We observed that children who have hyperkalemia noted on
a blood sample that is reported to be hemolyzed are unlikely to
have true hyperkalemia if the BUN and Cr are normal and the
child is not experiencing DKA. It may be unnecessary to obtain
TABLE 4. Logistic Regression Model Results for Odds of True repeat samples for confirmation of normal potassium in patients
Hyperkalemia Among Those With a Repeat Potassium, n = 130
in Model with normal BUN and Cr, but further large studies are needed to
support the findings.
Adjusted Odds Ratio
Effect Estimate (95% CI) P
REFERENCES
Medical condition* vs healthy 0.54 (0.05–5.61) 0.605 1. Sevastos N, Theodossiades G, Efstathiou S, et al. Pseudohyperkalemia in
Age, each additional year 1.24 (1.05–1.48) 0.014 serum: the phenomenon and its clinical magnitude. J Lab Clin Med. 2006;
Initial hemolysis: slightly vs 4.64 (0.39–55.11) 0.224 147:139–144.
moderately or more 2. Don BR, Sebastian A, Cheitlin M, et al. Pseudohyperkalemia caused by fist
Initial potassium, 1 mEq/L increase 1.17 (0.62–2.20) 0.636 clenching during phlebotomy. N Engl J Med. 1990;322:1290–1292.
BUN/Cr ratio: abnormal vs normal 1.82 (0.19–17.09) 0.601 3. Owens H, Siparsky G, Bajaj L, et al. Correction of factitious
*Includes cardiac, kidney, or other condition. hyperkalemia in hemolyzed specimens. Am J Emerg Med. 2005;23:
872–875.

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Do We Need to Repeat Hemolyzed Hyperkalemia?
4. Khodorkovsk B, Cambria B, Lesser M, et al. Do hemolysed potassium 7. Einhorn LM, Zhan M, Hsu VD, et al. The frequency of hyperkalemia and
specimen need to be repeated? Clinical laboratory in emergency medicine. its significance in chronic kidney disease. Arch Intern Med. 2009;169:
J Emerg Med. 2014;47:313–317. 1156–1162.
5. Carr P, Rippey CRJ, Cooke LM, et al. Development of a clinical prediction 8. Cummings EA, Reid GJ, Finley GA, et al. Prevalence and source of pain in
rule to improve peripheral intravenous cannulae first attempt success in the pediatric inpatients. Pain. 1996;68:25–31.
emergency department and reduce post insertion failure rates: the Vascular 9. Von Baeyer CL, Marche TA, Rocha EM, et al. Children's memory
Access Decisions in the Emergency Room (VADER) study protocol. for pain: overview and implications for practice. J Pain. 2004;5:
BMJ Open. 2016;6:e009196. 241–249.
6. Gandhi M, Suvarna TT. Cardiovascular complications in diabetic 10. Jenkins K II. Needle phobia: a psychological perspective. Br J Anaesth.
ketoacidosis. Int J Diab Dev Countries. 1995;15:132–133. 2014;113:4–6.

ORIGINAL ARTICLE
Impact of a Faster Computed Tomography Scanner on

Sedation for Pediatric Head Computed Tomography Scans in
2 Large Emergency Departments—A Retrospective Study
Rebecca Kriss Burger, MD,* Janet Figueroa, MPH,† Ashishkumar K. Parikh, MD,‡ and Erica L. Riedesel, MD‡
helical CT.1,2 Recent technological advances have reduced CT im-

Objectives: Children in the emergency department (ED) often require se- age acquisition times and radiation doses without affecting image
dation for head computed tomography (CT) to ensure adequate image quality. quality.1,3,4 Specifically, newer dual-source dual-energy CT scan-
Image acquisition time for a head CT using a conventional single-source CT ners can perform a head CTwith an image acquisition time of 1 to
scanner is approximately 12 seconds; however, after installation in November 3 seconds. A growing body of literature has shown that this new
2017 of 2 new dual-source dual-energy CT scanners, that time decreased CT technology may significantly decrease or obviate the need
to 1 to 3 seconds. We hypothesized that fewer patients would require seda- for sedation in infants and young children.1,4,5
tion using the faster CT scanners. In November 2017, 2 new dual-source dual-energy helical
Methods: We conducted a retrospective chart review of patients aged 0 to CT scanners (Siemens SOMATOM Force) were installed within
18 years undergoing head CT at 2 pediatric EDs within 1 hospital system, our hospital system, 1 each at 2 separate campuses. After installa-
2 years before and 2 years after installation of the faster CT scanner. Patients tion of these new scanners with shorter image acquisition time, we
undergoing multiple CTs or other procedures were excluded. Demographic in- hypothesized that fewer patients in the pediatric ED undergoing
formation, diagnosis, disposition, sedatives (chloral hydrate, dexmedetomidine, head CT would require sedation compared with patients who un-
etomidate, fentanyl, ketamine, midazolam, methohexital, pentobarbital, and derwent head CT using the conventional single-source helical
propofol) administered before imaging, and ED length of stay were analyzed. CT scanner before November 2017. We also suspected that fewer
Results: A total of 15,175 patient encounters met inclusion criteria, 7412 patients would require deep sedation using the dual-source dual-
before and 7763 after installation of the new CT. The median age was energy CT scanners compared with the conventional single-source
7 years and 44% were female. Before the new CT scanner was installed helical CT scanners.
8% required sedation, compared with 7% after (effect size, 0.0341).
Midazolam was the most commonly administered sedative. Fewer patients
required deep sedation using the faster CT scanner. METHODS
Conclusions: After installation of a dual-source dual-energy CT scanner, We performed a retrospective chart review of patients aged 0
fewer patients required sedation to complete head CT in the pediatric ED. to 18 years seen in 2 EDs within our hospital system. These 2 free-
Faster image acquisition time decreased the need for deep sedation. standing children's hospitals, one of which is a level 1 trauma center
Key Words: head CT scan, sedation, CT technology with approximately 90,000 annual ED visits and the other a level 2
trauma center with approximately 100,000 annual ED visits, are
(Pediatr Emer Care 2023;39: e6–e10) both in a large metropolitan area. Both hospitals installed a new
dual-source dual-energy CT scanner (Siemens SOMATOM Force)
BACKGROUND in November 2017.
Neuroimaging with computed tomography (CT) is frequently Children who had a head CT ordered 2 years before and after
performed in the pediatric emergency department (ED) in the setting installation of the new dual-source dual-energy CT scanner (single-
of trauma or suspected neurologic disorder. A head CT using a con- source helical CT scanner—November 1, 2015–October 31, 2017,
ventional single-source CT scanner has an image acquisition time of and dual-source dual-energy helical scanner—January 1, 2017–
12 seconds. With this scan time, images are highly susceptible to mo- November 30, 2019) were included. Patients undergoing multiple
tion artifact. Patients who are unable to cooperate or hold still for that CT studies or patients requiring sedation for another procedure
length of time, particularly toddlers and young children, often require (ie, lumbar puncture) were excluded. Head CT scans were performed
sedation to produce higher-quality diagnostic images to detect subtle using standard departmental protocols on dual-source dual-energy
findings that might explain the patient's clinical symptoms. CT scanners (Siemens SOMATOM Force; Siemens Healthineers,
Multiple studies comparing helical CT to conventional CT in Forchheim, Germany) using the following parameters:
young children have demonstrated less need for sedation using
Patients aged 0 to 6 years: tube A (80 kV, ref mAs 311), tube B
(Sn150kV, ref mAs 207), rotation time 0.5 seconds, pitch 0.7
From the *Division of Emergency Medicine, Department of Pediatrics, Emory Patients 7 years and older: tube A (80 kV, ref mAs 350), tube B
University + Pediatric Institute; †Department of Pediatrics, Emory University
School of Medicine; and ‡Division of Pediatric Radiology, Department of Pedi-
(Sn150kV, ref mAs 233), rotation time 1.0 seconds, pitch 0.7
atrics, Emory University + Pediatric Institute, Atlanta, GA.
Disclosure: The authors declare no conflict of interest. At both hospitals, the treating ED physician determines whether
Reprints: Rebecca K. Burger, MD, Emory University and Children's Healthcare
of Atlanta, Department of Pediatrics, Division of Emergency Medicine,
a patient receives sedation and both the level of sedation and sedating
1547 Clifton Rd, 2nd Flr, Atlanta, GA 30322 (e‐mail: beckyburger@ medications administered. Patients are sedated by the treating physi-
emory.edu). cian or a separate sedation physician. At both campuses, some physi-
Supplemental digital content is available for this article. Direct URL citations cians can only perform anxiolysis or moderate sedation (pediatricians
who are not fellowship trained). If a patient being treated by a
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. nonfellowship-trained pediatrician requires deep sedation, a sepa-
ISSN: 0749-5161 rate ED physician would perform the deep sedation.
e6 www.pec-online.com Pediatric Emergency Care • Volume 39, Number 1, January 2023

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Impact of a Faster CT Scanner on Sedation
We collected demographic data, diagnosis, disposition, seda- There were no differences in patients requiring sedation in terms
tives (chloral hydrate, dexmedetomidine, etomidate, fentanyl, ke- of percentage female, ethnicity, race, or imaging study performed
tamine, methohexital, midazolam, pentobarbital, and propofol) (Table 2). More patients at hospital 1 received sedation compared
administered before head CT, and ED length of stay (LOS). There with patients treated at hospital 2 (Table 2). Of patients discharged
were no ED process changes implemented during the 4-year study home, the majority did not receive sedation (Table 2). Patients re-
period that affected the decision to sedate a patient for head CT ceiving sedation had longer lengths of stays (Table 2).
nor which sedative medications could be administered. The most common sedative administered was midazolam in
For the purposes of our study, administration of a medication both populations (51% of sedated patient before vs 62% of se-
with sedating properties (chloral hydrate, dexmedetomidine, etomidate, dated patients after, P = 0.0007; Supplemental Table http://links.
fentanyl, ketamine, methohexital, midazolam, pentobarbital, or lww.com/PEC/B11). Fewer patients underwent deep sedation with
propofol) was considered a sedation regardless of the level of propofol alone (5% of sedated patients before vs 0% of sedated pa-
sedation achieved. tients after, P < 0.0001) or with propofol plus midazolam (4% of se-
We obtained institutional review board approval from our insti- dated patients before vs 0% of sedated patients after, P < 0.0001) after
tution before study initiation and there was no funding for the study. the faster CT scanner was installed (Supplemental Table, http://links.
lww.com/PEC/B11). There were no other statistically significant
STATISTICAL ANALYSIS differences in the use of other individual sedating medications
(chloral hydrate, dexmedetomidine, etomidate, fentanyl, ketamine,
Descriptive statistics were calculated for all variables of in-
methohexital, or pentobarbital) or combination of sedating medica-
terest and included means and standard deviations, medians and
tions administered before and after installation of the faster CT
ranges, or counts and percentages, as appropriate. Continuous
scanner (Supplemental Table, http://links.lww.com/PEC/B11).
data were compared using Wilcoxon rank sum tests and categori-
cal data were compared using χ2 tests. Fisher exact tests were used
for comparisons of categorical data with expected cell counts less DISCUSSION
than 5. Rates of sedation for head CTs were calculated as a monthly
Increased awareness of radiation risks from CT has signifi-
rate per 100 head CTs during both eras (before/after installation).
cantly decreased the overall use of head CT in the pediatric ED
Interrupted time series analysis was used to compare trends in se-
since the early 2000s.6 However, head CT remains an important
dation before and after the new head CT scanner was installed.
diagnostic tool in the setting of pediatric trauma or suspected neu-
Specifically, segmented regression was used to examine changes
rologic disorder.6,7
in utilization trends by examining changes in the slope after the
Artifact related to patient motion can significantly hinder in-
new CT scanners were installed. Analysis was conducted using
terpretation of head CT. Depending on the indication for head CT,
SAS v. 9.4 (Cary, NC), and statistical significance was assessed
absolute motion control versus minimal motion control is toler-
at the 0.05 level, unless otherwise noted.
ated for diagnostic quality imaging in pediatric radiology, which
in turn affects sedation practice. Motion artifacts are particularly
RESULTS relevant for infants and young children (younger than 5 years)
A total of 15,175 patient encounters were analyzed during and in older patients with developmental delay or high levels of
the study period November 1, 2015 to November 30, 2019, with anxiety.1 Thus, certain patients can complete head CTwith an anxi-
7412 patients (48%, 7412/15,175) undergoing head CT using the olytic alone, while other patients require deep sedation to achieve
single-source helical CT scanner (before installation) and 7763 quality images.8,9
(51%, 7763/15,175) using the new dual-source dual-energy helical Recent technological advances in CT imaging including
CT scanner (after installation). dual-source ultrahigh pitch CT scan technique and dual-source
The median age, percentage female, hospital location where the dual-energy CT scan technique have significantly reduced CT
patient underwent CT, percent discharged home, percentage His- image acquisition times and radiation dose while maintaining
panic, and type of imaging study performed were similar in the pre high-quality diagnostic imaging.1,10 To date, only a few studies
and post groups (Table 1). There were no differences in racial or eth- have examined the effect of this new CT technology on the need
nic background of patients in the pre and post groups (Table 1). for sedation in the pediatric population. However, there is the po-
During the 4-year study period, the number of head CT scans tential for a significant sedation practice change with use of new
performed overall was similar with no observable trend. Type of CT scanners. For example, Kino et al4 have demonstrated that di-
imaging study performed—CT head without IV contrast, CT head agnostic chest CT imaging without or with IV contrast agent can
with IV contrast, and CT head with and without IV contrast—was be accomplished in patients younger than 3 years without general
further evaluated (Table 1). Computed tomography scan of the anesthesia using dual-source CT with total scan time of approxi-
head without IV contrast was the most commonly performed im- mately 0.5 seconds. Similar results have been reported by Lell
aging study with similar rates both before and after installation. et al11 and Bodelle et al.12
The top diagnoses for patients undergoing head CT were: (1) In this study, we hypothesized that fewer patients would
headache, (2) facial and head trauma, (3) epilepsy, and (4) concus- require sedation for head CT in the ED after installation of a
sion, whereas the top diagnoses for patients requiring sedation dual-source dual-energy CT scanner with faster image acquisi-
were: (1) facial and head trauma, (2) epilepsy, (3) concussion, tion time (average, 0.5–3 seconds).
and (4) headache. The ED LOS was longer after installation of Our findings suggest that most pediatric patients undergoing
the new CT scanner ( P < 0.0001; Table 1). head CT in the pediatric ED, regardless of CT scan type, do not
There was no significant change in the sedation rate over require sedation. Expectedly, those patients who received sedation
time (Fig. 1). However, fewer patients underwent sedation for tend to be younger with a median age of 2 years.
head CT performed with the dual-source dual-energy CT scanner We found a statistically significant difference in the number
(581, 7%) compared with those imaged with the single-source CT of patients receiving sedation after installation of the new CT scan-
scanner (623, 8%; Table 1). ners; however, the effect size13 is not significant, and given only a
The median age of patients requiring sedation was 2 years 1% reduction in need for sedation, this finding is likely not clinically
compared with 7 years for no sedation ( P < 0.0001; Table 2). relevant.

Burger et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
TABLE 1. Demographics of the Patients Before Versus After Installation of the New CT Scanner
Category, n (%) or Median (25th–75th) Pre (n = 7412) Post (n = 7763) Total (N = 15,175) P Effect Size
Age, y 7.0 (2–12) 7.0 (1–12) 7.0 (1–12) 0.0457 0.0333
Sex, female 43% 44% 44% 0.0609 —
Location 0.5978 —
Hospital 1 31% 32% 31%
Hospital 2 69% 69% 69%
Discharged home 66% 64% 65% 0.0100 0.0418
LOS in ED, min 205 (148–277) 211 (157–286) 208 (153–282) <0.0001 0.0565
Ethnicity (Hispanic) 16% 16% 16% 0.8962 —
Race 0.4640 —
Black 37% 36% 36%
White 50% 51% 51%
Other 6% 6% 6%
Unknown 7% 7% 7%
Imaging study 0.4920 —
CT head without contrast 7400 (99.8%) 7744 (99.8%) 15,144 (99.8%)
CT head with contrast 10 (0%) 15 (0%) 25 (0%)
CT head with and without contrast 2 (0%) 4 (0%) 6 (0%)
Sedated 623 (8%) 581 (7%) 1204 (8%) 0.0359 0.0341
P value: χ tests or Wilcoxon rank sum tests.
2
Value in bold font indicates statistically significant, P < 0.05.

Effect size: standardized differences calculated if P < 0.05; Cohen indices of 0.2, 0.5, and 0.80 for small, medium, or large effect.1
We also found a statistically significant difference in the num- to complete head CT imaging with an anxiolytic alone while fewer
ber of patients receiving deep sedation after installation of the new patients required deep sedation. Thus, for those pediatric patients in
CT scanners, which we believe is clinically relevant. After installa- whom sedation for head CT is necessary, patients are less likely to
tion of a dual-source dual-energy CT scanner with a faster image need deep sedation compared with patients undergoing head CT
acquisition time, a statistically greater number of patients were able using a single-source CT scanner.
FIGURE 1. Monthly rate of sedations per 100 head CT encounters (percent sedations of total head CT encounters/month). An interrupted
time series model shows that immediately after the CT installation, there was no significant change in the sedation rate (β = −1.6963, SE = 0.
90, P = 0.065). The trend in the rate of sedations per 100 monthly encounters (percent sedations) before CT installation was not significant
(preperiod trend β = 0.006, SE = 0.046, P = 0.895). The post-CT installation month-to-month trend did not change significantly from the
initial trend (Δβ =0.0487, SE = 0.06, P = 0.447).

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Impact of a Faster CT Scanner on Sedation
TABLE 2. Demographics of the Patients Sedated Versus Not Sedated
Category, n (%) or Median (25th–75th) Not Sedated (n = 13,971) Sedated (n = 1204) P

Age, y 7.0 (2–12) 2 (1–8) <0.0001
Sex 0.1391
Female (6597) 92% 8%
Male (8578) 92% 8%
Location <0.0001
Hospital 1 (4750) 4154 (87%) 596 (13%)
Hospital 2 (10,425) 9817 (94%) 608 (6%)
Discharged home (9869) 9186 (93%) 683 (7%) <0.0001
LOS in minutes 206 (151–278) 243 (179–322) <0.0001
Ethnicity 0.1346
Hispanic (2488) 2269 (91%) 219 (9%)
Non-Hispanic (12,621) 11,639 (92%) 982 (8%)
Unknown (66) 63 (95%) 3 (4.6%)
Race 0.4748
Black (5536) 5091 (92%) 445 (8%)
White (7713) 7122 (92%) 591 (8%)
Unknown (1064) 971 (91%) 93 (9%)
Other (862) 787 (91%) 75 (9%)
Imaging study 0.1165
CT head without contrast (15,144) 13,945 (92%) 1199 (8%)
CT head with contrast (25) 20 (80%) 5 (20%)
CT head with and without contrast (6) 6 (100%) 0 (0%)
P value: χ2 tests or Wilcoxon rank sum tests.
Value in bold font indicates statistically significant, P < 0.05.
Row percentages are displayed previously.
Benefits of decreased need for deep sedation for head CT in reason for this observed difference is not clear, but given that se-
the pediatric ED are multiple. While sedation is generally well tol- dated patients had longer lengths of stay and fewer patients re-
erated in children, there are potential long-term consequences of ceived sedation after installation of the new CT scanner, it does
sedation, including neurodegeneration and cognitive sequelae.14 not seem that the use of the new CT scanner was the reason for
Although deep sedation is routinely used in practice throughout the prolonged ED stay.
the United States, the risk for adverse events is not negligible.15 We also found that 20% of patients undergoing CT head with
Fewer clinical resources are required for patient care as typically IV contrast received sedation compared with only 8% of patients
a physician and nurse are required at bedside to perform deep seda- undergoing CT head without IV contrast. Head CT with IV con-
tion. In addition, decreased LOS in the ED to perform deep sedation trast generally requires more motion control and rapid infusion
for a head CT is a potential considerable benefit of implementation of IV contrast can often be physically painful, irritating and anxi-
of a new CT technology with faster scan times. ety provoking in children; thus, these imaging studies are more
However, our study findings must be interpreted in the con- likely to require sedation.
text of their limitations. Given the retrospective design, we cannot There was a statistically significant difference in patients se-
state conclusively if every sedated child received sedation specifi- dated for head CT when comparing our 2 campuses. Hospital one
cally for the CT scan or for another purpose. It is possible that many is a level 1 trauma center and therefore may have more acutely ill
of the older children and some of the younger children who re- and injured patients who often require sedation. Given the retro-
ceived sedation for head CT may have been successful without se- spective nature, we are unable to comment on other possible rea-
dation with the dual-source dual-energy CT scanner if given an sons for this observed difference.
initial “try without”; however, this was not routinely documented
in the clinical chart, and thus, we cannot factor it into our discus-
sion. Regardless of CT scanner technology, consideration of any CONCLUSIONS
history of developmental delay or autism, and preprocedure anxi- Similar to historical studies comparing helical to conven-
ety level must be considered when making the decision to sedate tional CT scanners, we found that advances in technology, in this
and at which level of sedation. Justification of sedation and pres- case utilization of new dual-source dual-energy CT scanners with
ence of child life were also not routinely documented, and there- image acquisition time of 0.5 to 3 seconds, led to fewer pediatric
fore, these variables cannot retrospectively be analyzed. Future patients undergoing head CT receiving sedation in the pediatric
prospective studies are needed to elucidate the effects of child life, ED.2,16,17 For patients who received sedation, fewer received deep
preprocedure anxiety, and developmental delay on need for seda- sedation using the dual-source dual-energy CT scanner compared
tion in this patient population. with the previously used single-source CT scanner. Multiple stud-
Interestingly, in our data set, we found that the median ED LOS ies have been published on pediatric sedation trends for CT18 and
after installation of the new CT scanner was 6 minutes longer. The magnetic resonance imaging19 as well as considerations about

Burger et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
sedation for pediatric imaging20,21; however, little literature exists 9. Goldwasser T, Bressan S, Oakley E, et al. Use of sedation in children
exploring the role of advancing technology on these trends. Mul- receiving computed tomography after head injuries. Eur J Emerg Med.
tidisciplinary collaboration is needed between pediatric sedation, 2015;22:413–418.
emergency medicine, and radiology to generate clinical decision 10. Siegel MJ, Ramirez-Giraldo JC. Dual-energy CT in children: imaging
rules and clinical practice guidelines to optimize the use of seda- algorithms and clinical applications. Radiology. 2019;291:286–297.
tion in radiology procedures. Future studies are needed to describe 11. Lell MM, May M, Deak P, et al. High-pitch spiral computed tomography:
which patients would benefit from anxiolysis, moderate or deep effect on image quality and radiation dose in pediatric chest computed
sedation before attempting a nonsedated or anxiolysis only head tomography. Invest Radiol. 2011;46:116–123.
CT to reduce time to image completion and ED LOS.
12. Bodelle B, Fischbach C, Booz C, et al. Free-breathing high-pitch 80kVp
dual-source computed tomography of the pediatric chest: image quality,
REFERENCES presence of motion artifacts and radiation dose. Eur J Radiol. 2017;89:
1. Gottumukkala RV, Kalra MK, Tabari A, et al. Advanced CT techniques for 208–214.
decreasing radiation dose, reducing sedation requirements, and optimizing
13. Yang D, Dalton J. A unified approach to measuring the effect size
image quality in children. Radiographics. 2019;39:709–726.
between two groups using SAS. SAS Global Forum 2012. Published online
2. Pappas JN, Donnelly LF, Frush DP. Reduced frequency of sedation of 2012. Available at: http://support.sas.com/resources/papers/proceedings12/
young children with multisection helical CT. Radiology. 2000;215:897–899. 335-2012.pdf. Accessed April 30, 2021.
3. Agostini A, Mari A, Lanza C, et al. Trends in radiation dose and image 14. Mellon RD, Simone AF, Rappaport BA. Use of anesthetic agents in
quality for pediatric patients with a multidetector CT and a third-generation neonates and young children. Anesth Analg. 2007;104:509–520.
dual-source dual-energy CT. Radiol Med. 2019;124:745–752.
15. Bhatt M, Johnson DW, Chan J, et al. Risk factors for adverse events in
4. Kino A, Zucker EJ, Honkanen A, et al. Ultrafast pediatric chest computed emergency department procedural sedation for children. JAMA Pediatr.
tomography: comparison of free-breathing vs. breath-hold imaging with 2017;171:957–964.
and without anesthesia in young children. Pediatr Radiol. 2019;49:
16. Kaste SC, Young CW, Holmes TP, et al. Effect of helical CT on the
301–307.
frequency of sedation in pediatric patients. AJR Am J Roentgenol. 1997;
5. Westra SJ. High-pitch CT, decreasing need for sedation and its potential 168:1001–1003.
side effects: some practical considerations and future directions. Pediatr
17. Sacchetti A, Carraccio C, Giardino A, et al. Sedation for pediatric CT
Radiol. 2019;49:297–300.
scanning: is radiology becoming a drug-free zone? Pediatr Emerg Care.
6. Marin JR, Rodean J, Hall M, et al. Trends in use of advanced imaging in 2005;21:295–297.
pediatric emergency departments, 2009–2018. JAMA Pediatr. 2020;
18. Burger RK, Figueroa J, McCracken C, et al. Sedatives used in children to
174:e202209.
obtain head CT in the emergency department. Am J Emerg Med. 2021;19:
7. Gerber N, Sookraj K, Munnangi S, et al. Impact of the Pediatric Emergency 198–202.
Care Applied Research Network (PECARN) guidelines on emergency
department use of head computed tomography at a level I safety-net trauma 19. Kamat PP, McCracken CE, Simon HK, et al. Trends in outpatient
center. Emerg Radiol. 2019;26:45–52. procedural sedation: 2007–2018. Pediatrics. 2020;145:e20193559.
8. Hoyle JD Jr., Callahan JM, Badawy M, et al, Traumatic Brain Injury Study 20. Berkenbosch JW. Options and considerations for procedural sedation in
Group for the Pediatric Emergency Care Applied Research Network pediatric imaging. Paediatr Drugs. 2015;17:385–399.
(PECARN). Pharmacological sedation for cranial computed tomography in 21. Dong SZ, Zhu M, Bulas D. Techniques for minimizing sedation in pediatric
children after minor blunt head trauma. Pediatr Emerg Care. 2014;30:1–7. MRI. J Magn Reson Imaging. 2019;50:1047–1054.

ORIGINAL ARTICLE
Increased Fellow Scholarly Publication Rate After

Implementation of a Comprehensive Research Curriculum
and Milestone-Based Research Timeline for Pediatric
Emergency Medicine Fellows
Kyle A. Schmucker, MD,* Noel S. Zuckerbraun, MD,* Melissa A. Vitale, MD,* Robert W. Hickey, MD,*
Clifton W. Callaway, MD,† Raymond D. Pitetti, MD,* Richard A. Saladino, MD,* and Mionora D. Manole, MD*
Objective: Pediatric subspecialty fellows are required to complete a schol-

arly product during training; however, many do not bring the work to publi-
P ediatric emergency medicine and other subspecialty pediatric
fellows are required by the American Board of Pediatrics
(ABP) to participate in a research core curriculum, complete a
cation. To amplify our fellows’ publication success, our pediatric emergency scholarly project during fellowship, and submit a written work
medicine fellowship program implemented a comprehensive research curric- product by the end of fellowship training.1 Each fellow is also re-
ulum and established a milestone-based research timeline for each compo- quired to have a Scholarship Oversight Committee (SOC) to eval-
nent of a project. Our objective was to assess whether these interventions in- uate the fellow's progress and determine whether the research pro-
creased the publication rate and enhanced the graduated fellows' perceived ject matches the ABP requirements for scholarly activity. How-
ability to perform independent research. ever, SOC structure, core curriculum format, and ultimate
Methods: Our study was conducted at a tertiary children's hospital affili- publication of the work product remain at the discretion of the fel-
ated with an academic university, enrolling 3 fellows each year in its pediatric low, mentor, and SOC committee.
emergency medicine program. A comprehensive research curriculum and a Our observations related to the scholarship process during
milestone-based research timeline were implemented in 2011. We analyzed fellowship include that many fellows complete their research pro-
the publication rate of our graduating fellows before (2004–2011) and after ject during the final 6 months before graduation without sufficient
(2012–2016) our intervention. In addition, in 2017 we surveyed our previous time for writing a publishable manuscript. Therefore, although all
fellows who graduated from 2004 to 2016 and analyzed factors favoring fellows complete a research project to fulfill the SOC require-
manuscript publication and confidence with various research skills. ments, our sense is that many fellows do not publish their work.
Results: During the study period, 38 trainees completed the fellowship Failure to publish may contribute to trainees' dissatisfaction with
program. Publication rate increased from 26% ± 17% to 87% ± 30 % ( P research and unfulfilled expectations of mentors.
< 0.05). When scoring the importance of various factors, fellows most val- A survey of program directors of pediatric fellowship pro-
ued mentorship (5 ± 0 vs 4.3 ± 1.0, P < 0.05, postintervention vs grams found that only one-third of programs had more than 75%
preintervention) for the completion of the fellowship study and manuscript. of graduates publish their scholarly work product.2 This same study
Fellows after the intervention reported greater confidence in performing an found that adherence to a research curricula and provision of the ex-
analysis of variance (89% vs 36%, odds ratio, 6.3; 95% confidence inter- pertise of a SOC increased the likelihood of scholarly publication
val, 1.4–150.1). by fellows. Potential barriers to the completion of publication may
Conclusions: Implementation of a comprehensive research curriculum include a lack of protected research time and difficulty balancing
and a milestone-based research timeline was associated with an increase clinical obligations with longitudinal research blocks.3,4 In addition,
in the publication rate within 3 years of graduation of our pediatric emer- unfamiliarity with the research process and inadequate time man-
gency medicine fellows. After implementation, fellows reported an in- agement may be obstacles. At least one previous study has demon-
creased importance of mentorship and greater confidence in performing strated that implementation of a structured research program within
an analysis of variance. We provide a comprehensive curriculum and a re- fellowship can increase trainee's publication rates.5
search timeline that may serve as a model for other fellowship programs. To amplify our fellows' success and enhance their experience
Key Words: medical education, pediatric emergency medicine, fellowship with scholarly work, our pediatric emergency medicine fellowship
program implemented a comprehensive research curriculum and
(Pediatr Emer Care 2023;39: e11–e14)
established a research timeline based on milestones representing
each research element of a project. To assess our intervention,
we analyzed the publication rates within 3 years of graduation be-
From the *Division of Pediatric Emergency Medicine, Department of Pediat- fore the implementation of our intervention (2004–2011) and after
rics, University of Pittsburgh School of Medicine, UPMC Children's Hospital the intervention (2012–2016). In addition, we surveyed our fel-
of Pittsburgh; and †Department of Emergency Medicine, University of
Pittsburgh School of Medicine, Pittsburgh, PA.
lows regarding their experiences in research among those who
Disclosure: The authors declare no conflict of Interest. graduated before versus those who graduated after implementa-
Reprints: Kyle A. Schmucker, MD, Section of Emergency Medicine, tion of our intervention, to analyze factors favoring publication
Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, 4401 and confidence with various research skills.
Penn Ave, AOB Suite 2400, Pittsburgh, PA 15226 (e‐mail: schmuckerka@
upmc.edu).
Presentations: Schmucker KA, Zucherbraun NS, Vitale M, Hickey RW,
Callaway CW, Pitetti RD, Saladino RA, Manole MD. Improved publication METHODS
rate by fellows after implementation of a comprehensive research This study was conducted at a tertiary children's hospital af-
curriculum for pediatric emergency medicine. Poster presentation. Pediatric
Academic Society. April 30, 2021; Virtual.
filiated with an academic university. The pediatric emergency
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. medicine program enrolls 3 fellows each year into the fellowship
ISSN: 0749-5161 training program.

Schmucker et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
included the 5 required elements of research training including

TABLE 1. Research Didactic Curriculum biostatistics, research methodology, study design, abstract writing,
and presenting a research study. Fellows were encouraged to select
Session
a scholarly project during the first year of the fellowship. In addi-
Session Title Duration, h
tion, to assist fellows in selecting a project, a “research brain-
Getting Started With Research and Study Design storming” session was held early during each year and included
Study Design—Getting Started and Literature Searches 1 brief presentations by faculty of their ongoing research projects
Selecting Subjects, Measures, and Sample Size 1 and nascent research ideas.
Introduction to Study Designs, Data Collection & 1 In 2011, we implemented a formal comprehensive research
Management curriculum (Table 1) and a recommended milestone-based research
Navigating the Institutional Review Board 1 timeline (Fig. 1). The research curriculum was tailored to equip fel-
lows with the skills for conducting and publishing research, prepa-
Statistics Part 1
ration of applications for approval of clinical or basic research pro-
Introduction to Statistics 1 tocols, principles of evidence-based medicine, ethical principles in-
Hands-on Statistical Analysis (Homework) 3 volving clinical research, and the achievement of proficiency in
Statistics Part 2 presenting and teaching. It included topics of research design, insti-
Hands-on Statistical Analysis (Group Workshop) 4 tutional review board submission, data management and analysis,
Presenting and Publishing Your Research poster design, and manuscript writing. The curriculum leveraged
Writing an Abstract 1 intentional adult-learning formats with hands-on workshops on data
Creating a Poster and the 10-min Scientific Talk 1 management, statistics, and literature review. Of note, the sessions
Writing and Publishing a Manuscript, Responding 1 dedicated to statistical analysis were structured as follows: one in-
to Editors troductory session followed by a hands-on independent statistical
Bias and Confounding 1 analysis by the trainees. These sessions were followed by a group
workshop consisting of a hands-on review of an assigned mock pro-
This comprehensive research curriculum was implemented in 2011 for ject, during which fellows navigated sample problems using statis-
pediatric emergency medicine fellows. The curriculum was repeated yearly. tical software under the guidance of experienced researchers.
Structure of the SOC Committee Milestone-Based Research Timeline

Our SOC structure and schedule remained constant during the In addition, to provide the trainees with guidelines for stepwise
period of the study. The SOC included a standardized membership progress to enable timely publication of their research work at the
of 3 investigators with expertise in the domains of clinical, basic, completion of the fellowship, in 2011 we instituted a milestone-
and translational research. In addition, 1 to 2 members were included based research timeline for the fellows to reference throughout the
who provided diversity of research interests and expertise as well as 3-year fellowship (Fig. 1). At the start of fellowship, the fellowship
experience and success in extramural funding (eg, National Institutes leadership reviewed the timeline with the fellows. At the end of the
of Health, World Health Organization, and Department of Defense). first year of fellowship, the fellows were expected to have identified
All members were expected to have successful publication records. a project and have approval by our institutional review board for
The SOC membership was also longitudinally consistent; that is, their project. During the second year of fellowship, the fellows were
the core 3 experienced investigators remained on the SOC, whereas expected to collect data, draft the introductory and methodology el-
other members rotated through the committee. To ensure all fellows ements of the manuscript, and begin to organize the results in mock
had consistently recurring SOC meetings, the SOC was scheduled to tables and figures. During the third year, the fellows were expected
meet quarterly and included all fellows in the program. Meetings to finalize and submit their draft manuscript. The SOC assessed
consisted of 20- to 30-minute sessions with each fellow, during each trainee's progress quarterly based on the timeline and provided
which time each fellow presented his/her work to the committee. support and guidance if progress was delayed.
Research Curriculum Postgraduate Survey

From 2007 to 2011, our ABP-compliant scholarly research In 2017, our graduated fellows completed a survey scoring
curriculum consisted of a series of didactic sessions. The sessions the value of their fellowship research experiences and comfort
FIGURE 1. Milestone-based research timeline. The research timeline was implemented to aid fellows in planning their research activities and
assess progress at scholarly oversite committee meetings. The milestone for the first year (July through June) of fellowship is the identification
of a research project. During the second year, fellows are expected to conduct the research. During the final year of fellowship, fellows finalize,
submit, and revise the manuscript.

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Increased Fellow Scholarly Publication Rate
with conducting research. Graduated fellows were asked to rate

the helpfulness of the research curriculum and SOC, mentorship TABLE 2. Survey Results From Graduated Fellows Scoring the
Importance of Available Resources for Completing Their
and statistical support in completing their project. They were also Research Study, Scored on a 5-Point Likert Scale, With a Score of
asked to rate their confidence in completing tasks associated with 5 Denoting the Most Important (n = 23)
conducting and publishing scholarly work. Survey responses
consisted of 15 questions answered as either a 5-point or 7-point Before Curriculum After Curriculum
Likert scale or yes/no format. Implementation Implementation P
The primary outcome measure of our intervention was the
percentage of graduated fellows who published their scholarly Mentorship 4.3 ± 1.0 5.0 ± 0.0 <0.05
project within 3 years of graduation between 2004 and 2011 (be- SOC 3.3 ± 0.9 3.6 ± 0.9 0.5
fore implementation of the formal curriculum and research time- Research 3.4 ± 0.7 3.8 ± 0.8 0.1
line) compared with the percentage published between 2012 and curriculum
2016 (after the implementation). Our secondary outcome was Statistical support 3.9 ± 1.4 4.3 ± 1.0 0.6
the trainees' reported confidence in conducting and publishing re-
search before and after the intervention.
showed a trend toward improvement, without reaching statistical
Statistical Analysis significance (5.8 ± 1.9 vs 5.4 ± 0.6 [P = 0.05] and 5.7 ± 1.8 vs
Data were analyzed using the IBM SPSS statistical package 5.1 ± 0.9 [P = 0.07], manuscript submission and manuscript re-
(Chicago, Ill). Data before the intervention were compared with view, postintervention vs preintervention, respectively; Table 3).
those after the intervention. Publication rates and Likert scores With regard to confidence with performing statistical analysis,
were analyzed by comparison of means. The Shapiro-Wilk test our survey indicated an increase in preparedness to independently
was used to assess if continuous data were normally distributed, perform an analysis of variance (89% vs 35.7%; odds ratio, 6.3;
and Mann-Whitney U test was used for nonnormally distributed 95% confidence interval, 1.4–150.1) after implementation of our in-
data. Categorical survey data were analyzed using χ2 analysis. tervention. Performance of t test and χ2 analyses was rated similarly
before and after the intervention (P = 0.2 and P = 0.5, respectively).
RESULTS DISCUSSION
During the study period, 38 trainees completed the fellowship In our study, implementation of a comprehensive research
program. Figure 2 illustrates the publication rate for each year, rep- curriculum and establishing a milestone-based research timeline
resented as percentage of a fellow class publishing within 3 years of to assess research progress were associated with a significant in-
graduation. Overall, the publication rate increased from 26% ± 17% crease in the publication rate of our fellows within 3 years of grad-
before implementation of the formal research curriculum and re- uation. Our comprehensive research curriculum, milestone-based
search timeline to 87% ± 30% after implementation (P < 0.05). research timeline, and SOC structure may serve as a model for op-
Of the 38 graduates, 23 (60.5%) responded to the online sur- timizing a supportive scholarly environment in fellowship training
vey regarding their fellowship research experiences. Of those, 14 programs. Leveraging an adult learning model and practical and
fellows graduated before the implementation of our intervention hands-on sessions while maintaining a focus on the milestones
and 9 graduated afterward. of a research project seems to provide a foundation for timely
When asked which resource was perceived as helpful for the completion of a scholarly project during a 3-year fellowship.
completion of the study and manuscript, mentorship scored higher After implementation of the structured curriculum and time-
for the postintervention group versus preintervention (5 ± 0 vs line, trainees perceived mentorship as a resource that enabled
4.3 ± 1.0, P < 0.05, postintervention vs preintervention). The other them to complete the study and draft a manuscript. This is consis-
resources, including SOC, research curriculum, and statistical sup- tent with previous literature that supports that building positive re-
port, were rated similarly after and before the intervention (Table 2). lationships with mentors is associated with research productivity
When asked which of 8 research tasks the graduated fellows of trainees.6 In addition, we feel that provision of a milestone-
were confident to perform independently, submitting a manuscript based research timeline reinforced timely progression of the re-
to a journal and responding to a journal's manuscript reviewers search projects and provided adequate time for manuscript
FIGURE 2. Publication rate within 3 years of graduation represented the percentage of graduating class. Percentage of fellows in each
graduation class who published their scholarly work within 3 years of graduation. In 2005 and 2011, no graduating fellow published his/her
scholarly work within 3 years of graduation. Arrow denotes the year of our implementation of the comprehensive research curriculum and
milestone-based research timeline.

Schmucker et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
implementation, was small, which might have contributed to

TABLE 3. Survey Results From Graduated Fellows Scoring Their the lack of statistical difference.
Confidence in Competing Various Research Tasks, Scored on a
7-Point Likert Scale, With a Score of 7 Denoting the Greatest We describe a model of a successful research curriculum,
Confidence (n = 23) milestone-based research timeline, and SOC structure that may
be replicated for other fellowships. This curriculum was created
Before Curriculum After Curriculum for a 3-year program. Shorter training programs may need to con-
Implementation Implementation P dense some of the content. In addition, we were not able to assess
how annual matriculation of fellows or addition of faculty mentors
Design a study 5.2 ± 1.5 5.8 ± 1.9 0.2 may have affected increased publication success. Nonetheless, the
Analyze study data 5.5 ± 1.3 5.7 ± 1.9 0.3 increase in publication rates after implementation of our enhanced
Write a manuscript 5.3 ± 1.0 5.6 ± 1.9 0.2 research program was remarkable. Future work might focus on the
Conduct a study 5.2 ± 1.0 5.7 ± 1.9 0.1 relationship between enhanced research curricula and long-term
Write and submit a 6.1 ± 0.8 5.7 ± 1.9 1.0 career research success.
study abstract for a
conference CONCLUSIONS
Submit a manuscript 5.4 ± 0.7 5.8 ± 1.9 0.06 Implementation of a comprehensive research curriculum and
to a journal milestone-based research timeline was associated with a signifi-
Respond to a 5.2 ± 0.9 5.7 ± 1.9 0.07 cant increase in the publication rate within 3 years of graduation
journal’s of our pediatric emergency medicine fellows. Importantly, our fel-
manuscript lows indicated that mentorship was the most important resource in
reviewers
completing their research project and drafting a manuscript and
Mentor others 4.1 ± 2.0 5.3 ± 0.9 0.2 expressed a high degree of confidence in independently complet-
in research
ing the steps of research study design, analysis, and publication.
We submit that our curricular and milestone-based approaches
to fellowship scholarly work and publication may serve as a model
preparation before graduation. Our experience has been that for other fellowship programs.
this sustained productivity fostered a positive mentor-mentee
relationship. REFERENCES
Our research curriculum included an emphasis on hands-on 1. General Criteria for Subspecialty Certification | The American Board of
statistical analysis. We believe that establishing familiarity with Pediatrics. Available at: https://www.abp.org/content/general-criteria-
the analytical elements of the research process benefitted fellows subspecialty-certification. Accessed July 6, 2021.
by providing a foundation of understanding before they began
2. Abramson E, Weiss P, Naifeh M, et al. Scholarly activity during pediatric
data collection for their own project. Although statistic support fellowship. Pediatrics. 2021;147.
is available to all fellows by an institutional statistical group,
speaking a common language and bringing informed questions 3. Titus M, Losek J, Givens T. Pediatric emergency medicine fellowship
to the statisticians may have fostered for more productive meet- research curriculum: a survey of fellowship directors. Pediatr Emerg Care.
2009;25:550–554.
ings. In our survey, 8 of 9 fellows graduating after implementation
of the comprehensive curriculum thought fellowship prepared 4. Carter AE, Anderson TS, Rodriguez KL, et al. A program to support
them to complete a t test, χ2 test, and analysis of variance. Future scholarship during internal medicine residency training: impact on academic
work should continue to focus on optimal content of research cur- productivity and resident experiences. Teach Learn Med. 2019;31:552–565.
ricula and statistical analysis. 5. Cruz AT, Doughty CB, Hsu DC, et al. Focused research infrastructure for
Fellows scored their confidence for completing 8 discrete re- postgraduate pediatric emergency medicine fellows increases dissemination
search tasks. Responses related to submitting a manuscript to a of scholarly work. AEM Educ Train. 2019;4:231–238.
journal and responding to reviewer comments showed a trend to- 6. Smith MA, Barry HC, Williamson J, et al. Faculty development factors
ward increased confidence for conducting research after interven- related to publication success among faculty development fellowship
tion. The small sample size of participants, particularly after graduates. Fam Med. 41:120–125.

ORIGINAL ARTICLE
In-Hospital Cardiac Arrest in Adult Patients Admitted to a

Quaternary Children's Center
Amanda J. O'Halloran, MD,* Charles G. Callif, BA,† Jane C. Romano, MSN,†
Catherine E. Ross, MD,‡§ and Monica E. Kleinman, MD†‡
Although the vast majority of adults are cared for in adult in-
Objective: This study aimed to describe baseline and event characteris- stitutions, pediatric inpatient wards and pediatric ICUs often admit
tics and outcomes for adult patients who experience in-hospital cardiac ar- patients 18 years or older.8–10 Data collected across multiple insti-
rest (IHCA) in a quaternary children's hospital and compare IHCA out- tutions have shown that adults admitted to pediatric services are a
comes in younger (18–24 years) versus older (≥25 years) adults. We hy- growing population, are more likely to have chronic conditions
pothesized that the rate of survival to hospital discharge would be lower originating in childhood, and have higher resource utilization for
in the older adult group. their hospital admissions than their pediatric counterparts.11 In ad-
Methods: We performed a retrospective single-center cohort study of in- dition, increasing age has been shown to correlate with an in-
patient areas of a quaternary children's center. Adult patients (≥18 years of creased risk of mortality for adults admitted to pediatric ICUs.9
age) with an index pulseless IHCA requiring at least 1 minute of cardiopul- Reports describing IHCA among adults admitted to pediatric
monary resuscitation or defibrillation were included. services are limited. The objective of this study was to describe
Results: Thirty-three events met the inclusion criteria with a median pa- this patient population, including demographics, prearrest and ar-
tient age of 23.9 years (interquartile range, 20.2–33.3 years). Twenty-one rest characteristics, and survival outcomes. We also compared
(64%) patients had congenital heart disease, and 25 (76%) patients had co- IHCA outcomes in younger (18–24 years) versus older (≥25 years)
morbidities involving ≥2 organ systems. The most common prearrest inter- adults. We hypothesized that the rate of survival to hospital dis-
ventions were invasive mechanical ventilation (76%) and vasoactive infu- charge would be lower in the older adult group.
sions (55%). Seventeen patients (52%) survived to hospital discharge.
Survival to discharge was lower in patients 25 years or older com-
pared with patients aged 18 to 24 years old (3 of 15 [20%] vs 14 of 18 METHODS
[78%], respectively; P = 0.002).
Conclusions: The majority of adult patients with IHCA in our pediatric
hospital had preexisting multisystem comorbidities, the most common of
Setting
which was congenital heart disease. Overall survival to discharge after Our children's hospital is a 415-bed quaternary academic
IHCA was 52%, similar to that reported for the general pediatric popula- center in the northeastern United States with a full complement of
tion. Survival to discharge was significantly lower in the subgroup of pa- medical and surgical subspecialities. Patients 18 years or older ac-
tients 25 years or older when compared with those between the ages of count for about 10% of inpatient hospital days annually. Many adult
18 and 24 years. patients admitted to our center have chronic conditions originating
in childhood and also receive outpatient care at our institution.
Key Words: cardiac arrest, resuscitation, adult
(Pediatr Emer Care 2023;39: e15–e19) Data Source and Study Cohort
Our center's Resuscitation Quality and Systems Committee
P revious studies have established that in-hospital cardiac arrest

(IHCA) incidence, characteristics, and outcomes differ be-
tween children and adults.1–5 In the United States, there are ap-
maintains an institutional resuscitation database that contains
Utstein-style cardiopulmonary resuscitation (CPR) data for all pa-
tients experiencing IHCA. This retrospective cohort study used
proximately 7100 instances of pulseless pediatric IHCA annually the database to identify all instances of IHCA in adult patients
as compared with an estimated 292,000 IHCAs involving adults.1 (≥18 years of age) between January 1, 2014, and December 31,
Children also differ from adults in the physiology and etiologies of 2018. Cases were included in the cohort if they received at least
IHCA, with children having a lower likelihood of a shockable 1 minute of CPR and/or defibrillation for an index pulseless event.
rhythm2 and a higher likelihood of arrest within intensive care Patients receiving CPR on arrival to the hospital were excluded.
units (ICUs) compared with the wards.3,6 Finally, reported sur- Patients who experienced IHCA in perioperative areas (operating
vival to hospital discharge differs between the patient populations: rooms and other procedural locations) were included in the cohort
after IHCA, approximately 40% of children survive to hospital if they were inpatients before the procedure or if they were subse-
discharge compared with only 20% of adults.4,5,7 quently admitted to an inpatient area. Additional data not included
in the database were abstracted from the electronic medical record.
The study was approved by the institutional review board.
From the *Department of Anesthesia and Critical Care, Children's Hospital of
Philadelphia, Philadelphia, PA; †Division of Critical Care Medicine, Depart-
ment of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Variables and Outcomes and Statistical Analysis
Hospital; ‡Harvard Medical School; and §Division of Medical Critical Care,
Department of Pediatrics, Boston Children's Hospital, Boston, MA.
For each case, collected variables included demographics,
Disclosure: The authors declare no conflict of interest. prearrest characteristics, resuscitation events, and outcomes. The
Reprints: Amanda J. O'Halloran, MD, Department of Anesthesiology and primary outcome was survival to hospital discharge. Secondary
Critical Care Medicine, Children's Hospital of Philadelphia, 3401 Civic outcomes included any return of circulation (which includes the
Centre Blvd, 6 Wood, Room 6107, Philadelphia, PA 19104 (e‐mail:
ohallorana@chop.edu).
use of extracorporeal cardiopulmonary resuscitation), return of
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. spontaneous circulation, and 24-hour survival. Descriptive statis-
ISSN: 0749-5161 tics are reported as counts with relative frequencies or medians

O'Halloran et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
with interquartile ranges (IQRs). We a priori divided the patients receiving invasive mechanical ventilation (25 of 33 [76%]); 18
in the cohort into 2 age groups (18–24 and ≥25 years of age) to of 33 patients (55%) had hemodynamic compromise and were re-
assess the association between age and outcome within the popu- ceiving vasoactive infusions.
lation. The primary and secondary outcomes were compared be- In-hospital cardiac arrest characteristics are presented in
tween the patient subgroups using Fisher's exact tests. P values Table 2. The median duration of CPR was 10 minutes (IQR, 3–
less than 0.05 were considered significant. Statistical analysis 25 minutes). Twenty of the events occurred in the ICU (61%),
was performed using the STATA IC statistical package (StataCorp 10 occurred in perioperative areas (30%), and 3 occurred on inpa-
16.0; College Station, TX). tient wards (9%). The initial rhythm was shockable in 11 of the
events (33%) and nonshockable in 19 of the events (58%). The
most common initial rhythm was pulseless electrical activity, oc-
RESULTS curring as the initial rhythm in 14 of the events (42%). Of the 8 pa-
tients (25%) who did not have an invasive airway in place at the
Baseline and Event Characteristics time of the event, 5 were intubated and 3 received bag-valve-
Between 2014 and 2018, 48 of 591 resuscitation events mask ventilation throughout the event; no patients had a
(8.1%) occurred in patients 18 years or older. After excluding 15 supraglottic airway placed.
cases that did not meet the inclusion criteria, there were 33 cases
in the final cohort (Fig. 1). During the same time period, adults ac-
counted for 10.8% of inpatient hospital days. Patient and prearrest Outcomes
characteristics are presented in Table 1. The adult cohort ranged Survival outcomes overall and by year of event are presented
from 18 to 64 years of age, with a median age of 23.9 years in Tables 3 and 4, respectively. Twenty-four patients (73%) had re-
(IQR, 20.2–33.3 years). Four of the 33 patients (12%) had no turn of circulation, including the 4 patients who received extracor-
prearrest comorbidities, and 25 (76%) had preexisting comorbid- poreal cardiopulmonary resuscitation. Seventeen (52%) survived
ities involving at least 2 organ systems. In the majority of cases to hospital discharge. Of those patients with an initial shockable
(21 of 33 [64%]), patients had at least 1 congenital cardiac condi- rhythm, 55% (6 of 11) survived to hospital discharge. Fifty per-
tion, including 6 of 33 (18%) with single ventricle lesions. Preex- cent (7 of 14) of patients with an initial rhythm of pulseless elec-
isting neuromuscular disease, which included muscular dystro- trical activity survived to discharge, and 20% (1 of 5) of patients
phies and cerebral palsy, was present in 7 of 33 patients (21%). Al- with an initial rhythm of asystole survived to discharge.
though 14 of 33 patients (42%) had preexisting respiratory When examining the cohort by age group, there were 18
insufficiency, none had cystic fibrosis. At the time of the event, younger adults (18–24 years) and 15 older adults (≥25 years).
the majority of patients had acute respiratory failure and were The median ages in each group were 20.7 (IQR, 19.1–23.3) and
FIGURE 1. Identification of adult IHCA cohort.

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Adult IHCA in a Quaternary Children's Center
TABLE 1. Patient and Cardiac Arrest Characteristics
Characteristic All Cases (n = 33) 18–24 y (n = 18) 25+ y (n = 15)

Age, median (IQR), y 23.9 (20.2–33.3) 20.7 (19.1–23.3) 33.3 (32.1–45)
Male sex, n (%) 21 (64) 11 (61) 10 (67)
Comorbidities, n (%)
Congenital heart disease 21 (64) 9 (50) 12 (80)
Neuromuscular disease 7 (21) 4 (22) 3 (20)
Seizure disorder 6 (18) 4 (22) 2 (13)
Oncologic disease 4 (12) 3 (17) 1 (7)
Chronic respiratory insufficiency 14 (42) 8 (44) 6 (40)
Preevent conditions, n (%)
Hemodynamic compromise 18 (55) 12 (67) 6 (40)
Acute respiratory failure 25 (76) 16 (89) 9 (60)
Sepsis or active infection 7 (21) 5 (28) 2 (13)
Prearrest interventions, n (%)
None 4 (12) 2 (11) 2 (13)
Invasive mechanical ventilation 25 (76) 16 (89) 9 (60)
Noninvasive mechanical ventilation 4 (12) 0 (0) 4 (27)
Vasoactive infusions 18 (55) 12 (67) 6 (40)
Renal replacement therapy 4 (12) 2 (11) 2 (13)
33.3 (IQR, 32.1–45) years, respectively. Baseline and event age group when compared with the 18- to 24-year-old age group
characteristics seemed similar between the 2 groups (Table 1). Al- (7 of 15 patients [47%] vs 15 of 18 patients [83%], P = 0.06). Sur-
though similar numbers of patients had return of circulation, there vival to hospital discharge was lower in the ≥25-year-old age
was a trend toward lower 24-hour survival in the ≥25-year-old group when compared with the 18- to 24-year-old age group
TABLE 2. Cardiac Arrest Characteristics
Characteristic All Cases (n = 33) 18–24 y (n = 18) 25+ y (n = 15)

Duration of CPR, median (IQR), min 10 (3–25) 7.5 (3–19) 16 (3–30)
Event location, n (%)
ICU 20 (61) 10 (56) 10 (67)
Perioperative 10 (30) 7 (39) 3 (20)
Floor 3 (9) 1 (6) 2 (13)
Initial rhythm, n (%)
Asystole 5 (15) 2 (11) 3 (20)
Pulseless electrical activity 14 (42) 8 (44) 6 (40)
Ventricular tachycardia 3 (9) 1 (6) 2 (13)
Ventricular fibrillation 8 (24) 5 (28) 3 (20)
Unknown 3 (9) 2 (11) 1 (7)
Shockable rhythm at any time during event, n (%) 13 (39) 7 (39) 6 (40)
Medication administration, n (%)
No medications administered 3 (9) 2 (11) 1 (7)
Epinephrine administration 28 (85) 16 (89) 12 (80)
Calcium administration 16 (48) 7 (39) 9 (60)
Sodium bicarbonate administration 16 (48) 8 (44) 8 (53)
Antiarrhythmic administration (amiodarone or lidocaine) 10 (30) 6 (33) 4 (27)
Airway management, n (%)
Invasive airway in place before event 25 (76) 16 (89) 9 (60)
Endotracheal intubation during event 5 (16) 1 (6) 4 (27)
Bag-valve-mask ventilation 3 (9) 1 (6) 2 (13)
Other interventions, n (%)
Defibrillation 13 (39) 6 (33) 7 (47)
Extracorporeal circulatory support 4 (12) 3 (17) 1 (7)

O'Halloran et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
TABLE 3. Survival Outcomes
Outcome All Cases (n = 33) 18–24 y (n = 18) 25+ y (n = 15) P

Return of spontaneous circulation, n (%) 20 (61) 12 (67) 8 (53) 0.49
Any return of circulation, including extracorporeal 24 (73) 15 (83) 9 (60) 0.24
circulatory support, n (%)
24-h survival, n (%) 22 (67) 15 (83) 7 (47) 0.06
Survival to hospital discharge, n (%) 17 (52) 14 (78) 3 (20) 0.002
(3 of 15 patients [20%] vs 14 of 18 patients [78%], P = 0.002; Survival to discharge in our cohort (52%) more closely ap-
Table 3). proximated previously published pediatric survival rates (38%)
relative to adult rates (22.3%).4,5,7 Notably, the 18- to 24-year-
old group had a survival to discharge of 78% compared with the
DISCUSSION patients 25 years or older, who had only 20% survival to dis-
To our knowledge, this is the first report of the characteristics charge. Potential reasons that our overall adult cohort had a higher
and outcomes of IHCA among adults admitted to a quaternary survival to discharge than the general adult IHCA population in-
children's medical center. During the 5-year period of review, 33 clude both patient and institutional factors. Adult studies have pre-
adult patients had an IHCA with an overall 52% survival to hospital viously shown an association between younger age and improved
discharge. Baseline and event characteristics seemed similar be- outcomes after IHCA.16,17 Because our cohort is younger than the
tween the younger and older adults in the cohort. However, survival general adult IHCA population,18 we suspect that this may have
to hospital discharge was lower in adults 25 years or older compared been an important factor for survival in this group despite the high
with those between the ages of 18 and 24 years. The majority of pa- frequency of chronic conditions. We also speculate that our
tients in the overall cohort had a preexisting condition, with the most cohort's high proportion of events occurring in highly monitored
common category being congenital heart disease (CHD). The large settings (ICU and perioperative areas) contributed to a high rate
proportion of patients with CHD in this cohort is likely due both to of survival to discharge due to the presence of critical care re-
our institution's designation as an adult CHD center as well as the sources, including invasive monitoring. The favorable outcomes
higher rate of IHCA reported in pediatric patients with cardiac disease found in our study suggest that adults with IHCA on a pediatric
compared with other underlying categories of illness.12–14 service are not at a disadvantage because of differences in the care
Several published analyses of pediatric IHCA using the provided between pediatric and adult facilities.
American Heart Association's Get With The Guidelines— The rate of survival to discharge in our patients 25 years or
Resuscitation (GWTG-R) database between 2000 and 2009 have older is similar to the reported overall adult IHCA survival rate
reported higher frequencies of critical care therapies in place be- of 22.3% in the GWTG-R registry5 despite the difference in mean
fore IHCA than have adult studies: 67.4% to 81.6% versus 27% age (37.6 years in our group compared with 66 years in the regis-
to 34.2% for mechanical ventilation, and 48.4% to 59.4% versus try).18 The reason for this finding is likely multifactorial, including
28.1% to 31.9% for vasopressors.4,5 The characteristics of our the high prevalence of complex diagnoses in our adult patients.
adult cohort seem to be more similar to the published pediatric Chronic conditions such as muscular dystrophies and complex con-
data, with 76% of IHCA patients receiving invasive mechanical genital heart disease are associated with increased cardiorespiratory
ventilation, 55% receiving vasoactive agents, and 12% receiving complications and/or reduced life expectancy. In addition, those
renal replacement therapy at the time of arrest. In contrast to adult young adult patients who continue to receive care at a pediatric cen-
IHCA, in which up to 41% of nonprocedural IHCAs occur in gen- ter rather than transitioning to adult care providers may be a select
eral inpatient wards,6 up to 95% of pediatric nonprocedural group with a high severity of illness and/or chronic organ dysfunc-
IHCAs occur in the ICU.3 Similarly, in our cohort, 87% of IHCA tion who are more susceptible to poor outcomes after IHCA.
occurred in the ICU, excluding events occurring in perioperative It should be noted that, in our cohort, 30% of all IHCA events
areas. However, certain characteristics of our cohort differed from occurred in a perioperative location. This differs from a 2000–
reports of both adult and pediatric IHCAs. For example, 33% of 2008 analysis of GWTG-R that demonstrated that approximately
patients in our study had an initial shockable rhythm, compared 1.7% of index pulseless adult cardiac arrests occurred intraopera-
with published rates of 9% and 15.3% in children and adults, re- tively or in the postanesthesia care unit.19 We speculate that the
spectively.15 This may reflect the high incidence of congenital reason for this is related to patient factors, similar to the previous
heart disease in our cohort, which is associated with a higher rate discussion of the impact of patient factors on survival to discharge.
of initial shockable rhythm during IHCA.12 The high prevalence of complex diagnoses in young adults
TABLE 4. Survival Outcomes by Year of Event Occurrence
Outcome 2014 (n = 7) 2015 (n = 10) 2016 (n = 3) 2017 (n = 9) 2018 (n = 4)

Any return of spontaneous circulation, n (%) 5 (71) 7 (70) 1 (33) 5 (56) 2 (50)
Return of circulation, including extracorporeal circulatory 6 (86) 8 (80) 1 (33) 6 (67) 3 (75)
support, n (%)
24-h survival, n (%) 6 (86) 7 (70) 1 (33) 6 (67) 2 (50)
Survival to hospital discharge, n (%) 3 (43) 6 (60) 1 (33) 5 (56) 2 (50)

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Adult IHCA in a Quaternary Children's Center
continuing to receive care at pediatric centers may result in a high 6. Perman SM, Stanton E, Soar J, et al. Location of in-hospital cardiac arrest
severity of illness predisposing them to (1) require high-risk sur- in the United States—variability in event rate and outcomes. J Am Heart
geries and (2) increase their risk of morbidity and/or mortality Assoc. 2016;5:e003638.
when undergoing anesthesia. In addition, 64% of the patients in 7. Holmberg MJ, Wiberg S, Ross CE, et al. Trends in survival after pediatric
our cohort had congenital heart disease, an illness category that in-hospital cardiac arrest in the United States. Circulation. 2019;
has previously been associated with an increased rate of 140:1398–1408.
anesthesia-related cardiac arrest in children.20 8. Goodman DM, Mendez E, Throop C, et al. Adult survivors of pediatric
Our study has several limitations. First, our small cohort and illness: the impact on pediatric hospitals. Pediatrics. 2002;110:583–589.
retrospective study design limit our ability to draw definitive con- 9. Edwards JD, Houtrow AJ, Vasilevskis EE, et al. Multi-institutional profile
clusions about this patient population. Second, our center special- of adults admitted to pediatric intensive care units. JAMA Pediatr. 2013;
izes in caring for adults with CHD and other comorbidities, with 167:436–443.
patients 18 years or older comprising approximately 10% of all
10. Edwards JD, Vasilevskis EE, Yoo EJ, et al. Adults with childhood-onset
hospital days during the study period; therefore, the results may
chronic conditions admitted to US pediatric and adult intensive care units.
be less generalizable to pediatric centers that care for fewer young
J Crit Care. 2015;30:201–206.
adult patients.
The majority of adult patients with IHCA at a pediatric qua- 11. Goodman DM, Hall M, Levin A, et al. Adults with chronic health
ternary center had preexisting comorbidities, the most common of conditions originating in childhood: inpatient experience in children's
hospitals. Pediatrics. 2011;128:5–13.
which was congenital heart disease. Overall survival to discharge
after IHCA was similar to that reported in the general pediatric 12. Alten JA, Klugman D, Raymond TT, et al. Epidemiology and outcomes of
population. However, survival to discharge was lower in the sub- cardiac arrest in pediatric cardiac intensive care units. Pediatr Crit Care
group of patients 25 years or older when compared with those Med. 2017;18:935–943.
aged 18 to 24 years. These findings support the need for further 13. Lowry AW, Knudson JD, Cabrera AG, et al. Cardiopulmonary resuscitation
understanding of this patient population to optimize IHCA and in hospitalized children with cardiovascular disease: estimated prevalence
postarrest care. In addition, further studies of resuscitation involv- and outcomes from the kids' inpatient database. Pediatr Crit Care Med.
ing this patient population could address an important knowledge 2013;14:248–255.
gap—whether adults being treated for IHCA on pediatric services 14. Berg RA, Nadkarni VM, Clark AE, et al. Incidence and outcomes of
receive care according to American Heart Association Advanced cardiopulmonary resuscitation in PICUs. Crit Care Med. 2016;
Cardiac Life Support guidelines, Pediatric Advanced Life Support 44:798–808.
guidelines, or a hybrid approach. 15. Virani SS, Alonso A, Benjamin EJ, et al. Heart disease and stroke statistics
—2020 update: a report from the American Heart Association. Circulation.
2020;141:e139–e596.
REFERENCES 16. Wiberg S, Holmberg MJ, Donnino MW, et al. Age-dependent trends in
1. Holmberg MJ, Ross CE, Fitzmaurice GM, et al. Annual incidence of adult survival after adult in-hospital cardiac arrest. Resuscitation. 2020;151:
and pediatric in-hospital cardiac arrest in the United States. Circ 189–196.
Cardiovasc Qual Outcomes. 2019;12:e005580. 17. Chan PS, Nallamothu BK, Krumholz HM, et al. Long-term outcomes in
2. Nadkarni VM, Larkin GL, Peberdy MA, et al. First documented rhythm elderly survivors of in-hospital cardiac arrest. N Engl J Med. 2013;
and clinical outcome from in-hospital cardiac arrest among children and 368:1019–1026.
adults. JAMA. 2006;295:50–57. 18. Andersen LW, Holmberg MJ, Berg KM, et al. In-hospital cardiac arrest: a
3. Berg RA, Sutton RM, Holubkov R, et al. Ratio of PICU versus ward review. JAMA. 2019;321:1200–1210.
cardiopulmonary resuscitation events is increasing. Crit Care Med. 2013; 19. Ramachandran SK, Mhyre J, Kheterpal S, et al. Predictors of survival from
41:2292–2297. perioperative cardiopulmonary arrests: a retrospective analysis of 2,524
4. Girotra S, Spertus JA, Li Y, et al. Survival trends in pediatric in-hospital events from the Get With The Guidelines—Resuscitation registry.
cardiac arrests: an analysis from Get With The Guidelines—Resuscitation. Anesthesiology. 2013;119:1322–1339.
Circ Cardiovasc Qual Outcomes. 2013;6:42–49. 20. Odegard KC, DiNardo JA, Kussman BD, et al. The frequency of
5. Girotra S, Nallamothu BK, Spertus JA, et al. Trends in survival after in- anesthesia-related cardiac arrests in patients with congenital heart disease
hospital cardiac arrest. N Engl J Med. 2012;367:1912–1920. undergoing cardiac surgery. Anesth Analg. 2007;105:335–343.

ORIGINAL ARTICLE
Initial Pain Assessment and Management in Pediatric Burn

Patients Presenting to a Major Trauma Center in Saudi Arabia
Abdulmajeed Alrashoud, MBBS,* Ayesha Imtiaz, MBBS,* Mohammed Masmali, MBBS,*
Abdullah Zayedi, MBBS,* Paul A. Jennings, PhD,†‡ Abdullah Akkam, MBBS,* and Biswadev Mitra, PhD§||¶
injuries.2,3 The majority of the children with burns have less than
Background: Pediatric burn injury is a traumatic experience for af- 10% total body surface area (TBSA) affected, with only a minor-
fected children and their families. Burn pain is frequently undertreated ity having more than 10% TBSA involvement.3–6
and may adversely affect patient experience and outcomes. The aim of this There is a paucity of pediatric trauma research from countries
study was to investigate the current practice of initial pediatric burn pain around the Arabian gulf.7 Among countries around the Arabian
assessment and management at a major trauma center in Riyadh, Kingdom gulf, pediatric burn injuries have a high incidence reported to be
of Saudi Arabia. 4.9/1000 patients per year,3 and 25% of all burn injury patients in
Methods: We conducted a retrospective cohort study that included children the United Arab Emirates and 44% in Iraq have been reported to
14 years and younger who visited King Saud Medical City in the Kingdom be children.8,9 In a previous report on the topic from Saudi Arabia
of Saudi Arabia with a presenting complaint of burn injury from January 01, of all pediatric burn patients, infants and toddlers were the most
2017 to August 30, 2018. Variables were reported using descriptive statistics commonly injured followed by the adolescent-age group. Scald
as appropriate. and flame injuries were the most common (98%), frequently caused
Results: The 309 patients who were analyzed were classified into 3 age by an incident in the house (97.5%).10
groups ranging from 0 to younger than 3 years (61%), 3 to 7 years (24%), Pediatric burn injury is a traumatic experience, not only for
and older than 7 years (15%). They included 145 (47%) female and 164 children but also for their families. One of the chief factors that
(53%) male patients. Pain levels of 182 patients (59%) were documented contribute to this traumatic experience is pain, and it must be dealt
using an age-appropriate tool. In 75 children (24%), pain levels were docu- with promptly and adequately. Regardless of the cause, size, and
mented using an alternate tool, and the tool used was not defined for 44 chil- depth of burns, all burn victims experience pain. Adequate pain
dren (14%). Pain assessment was not documented for 8 children. Of those management is every burn patient's right and the responsibility of
with an age-appropriate tool, the median initial pain score was 4 (interquartile health professionals. It must not be based on personal beliefs, but
range [IQR], 2–4). Analgesia was recorded to have been administered to 139 rather on scientific evidence. Successful pain management depends
patients (45%), within a median time of 50 minutes (IQR, 17–154 minutes) on continuous and accurate assessment.11,12
to first analgesia. Among patients who had appropriate assessment of pain, Assessment and management of pain are not always easy and
92 (50.3%) received analgesia compared with 52 (41.3%) who did not have accurate, and it is all the more difficult in children because of differ-
appropriate assessment (P = 0.12). Among patients who had appropriate pain ences in cognitive development.13 Burn pain in children is frequently
assessment, time to analgesia was 42 minutes (IQR, 15–132 minutes) com- undertreated and may result in noncompliance with management and
pared with 53 minutes (IQR, 17–189 minutes) among patients who did not consequently result in prolonged healing. Undertreated pain has also
have appropriate assessment (P = 0.48). been associated with a higher risk of atelectasis and posttraumatic
Discussion: Most pediatric patients presenting with burns had pain assess- stress disorders.14,15 It can have long-term effects on pain sensitiv-
ment, but a substantial proportion of children were not managed using rec- ity, immune functioning, and on attitudes and behaviors toward
ommended age-specific tools. The use of age-specific tools was not neces- health care.16,17
sarily associated with delivery of analgesia. For pediatric burns, prompt Improved treatment of burn pain can spare these children some
delivery of analgesia should be prioritized with pain assessment using degree of suffering as well as potential long-term medical and
age-appropriate tools being recommended, but optional. psychiatric problems that result from this trauma. The aim of this
Key Words: assessment, burns, pain study was to investigate the current practice of initial burn pain as-
sessment and management at a major trauma center in Riyadh,
Kingdom of Saudi Arabia.
B urn injuries are common in children under 10 years of age with

thermal burns reported as the most common mechanism (scalds
account for >60% of these) followed by electrical and chemical in-
METHODS
juries.1,2 Younger children are more susceptible to scald burns Setting
compared with older children who are more likely to sustain flame
Riyadh, the capital city of Saudi Arabia, has a population of
approximately 8 million, with 34% of the population within the
From the *Pediatric Emergency Department, Children's Hospital, King Saud pediatric-age group (<14 years old). In Riyadh, there are 16 govern-
Medical City, Riyadh, Saudi Arabia; †Ambulance Victoria; ‡Department of mental hospitals, of which 8 receive trauma patients. All of them ac-
Community Emergency Health and Paramedic Practice, Monash University; commodate pediatric trauma with pediatric intensive care unit care.
§Emergency & Trauma Centre, The Alfred Hospital; ||Department of Epidemi-
ology & Preventive Medicine, Monash University; and ¶National Trauma Re-
This study analyzed data from the King Saud Medical City
search Institute, Melbourne, Victoria, Australia. (KSMC), a tertiary care center in Riyadh for medicine and surgery
Disclosure: The authors declare no conflict of interest. specializing in spinal and neurosurgery. It has 1500 beds, of which
Reprints: Biswadev Mitra, PhD, National Trauma Research Institute, The 180 beds are in the intensive care unit. By virtue of the bed capac-
Alfred Hospital, 55 Commercial Rd, Melbourne, Victoria 3004, Australia
(e‐mail: Biswadev.mitra@monash.edu).
ity and patient load, KSMC is by far the largest hospital of Saudi
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. Arabia. King Saud Medical City's emergency department (ED) is
ISSN: 0749-5161 one of the busiest in the country, with more than 140,000 presentations

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Pain Assessment and Management in Burn Patients
TABLE 1. Pain Assessment Tools for Pediatric Burns Patients
Behavioral Pain Scale Used for unconscious, ventilated, sedated patients

Face-Leg-Activity-Cry-Consolability For children aged 1 mo to 7 y and for the cognitively impaired
Wong-Baker Pain Scale For patients aged >7 y
Numerical Rating Scale For adult, fully conscious patients
Premature Infant Pain Profile For premature to 1-mo corrected gestational age
per year. Trauma patients presenting to KSMC, pediatric or other- RESULTS

wise, are received in a single ED.
There were 309 eligible patients who presented with burns
Design injury during the study period. Patients were categorized into 3
We conducted a retrospective cohort study that included chil- age groups ranging from 0 to younger than 3 years (61%), 3 to
dren 14 years and younger who presented to the trauma center of 7 years (24%), and older than 7 years (15%). They included 145
King Saud Medical City with a presenting complaint of burn injury (47%) female and 164 (53%) male patients. Pain levels of 182 pa-
from January 1, 2017, to August 30, 2018. tients (59%) were documented using an age-appropriate tool. In
All pediatric burn patients were identified through KSMC 75 children (24%), pain levels were documented using an alternate
medical records and ED registry data. Data were extracted by inves- tool, and the tool used was not defined for 44 children (14%). Pain
tigators using explicit chart review, reviewed by a second investigator, assessment was not documented for 8 children (3%). Pain assess-
and cross checked against data medical records for accuracy. Demo- ment scales subgrouped by age are listed in Table 2.
graphics, triage category (Canadian ED triage categories),18 initial The distribution of patients subgrouped by appropriateness
heart rate at presentation, mechanism of injury, degree of burn, and of pain assessment is listed in Table 3. Younger patients and those
TBSA affected were collected as additional explanatory variables. triaged to a higher category seemed to have more frequent use of
The depth of burns and TBSA were assessed and recorded by adult appropriate pain scales. Most patients were injured by scalds, and
emergency physicians or plastic surgeons. Pain assessment was car-
ried out at triage; the type of pain tool that was used and time to first
analgesia administered were the outcome variables. Pain assessment
tools recommended by age category are listed in Table 1. TABLE 3. Comparison of Patient Subgrouped by
Age-Appropriate Pain Assessment
Analysis Appropriate Alternate Tool
Continuous, near-normal distributed data were summarized using Pain Scale (n = 183) or No Tool (n = 126) P
mean (SD) and compared using Student t test. Ordinal or skewed data
were summarized using median (interquartile range [IQR]) and com- Age group 0.052
pared using Wilcoxon rank-sum test. Count data were summarized <3 y 122 67
using proportions and compared using the χ2 test or Fisher's exact test 3–7 y 36 37
if value in a cell was less than 5. P < 0.05 was defined to be statistically >7 y 25 22
significant. Delivery of analgesia was compared among patients man- Male sex 99 (54.1%) 65 (51.6%) 0.66
aged with appropriate tool using Kaplan-Meier survival functions, After-hours 122 (66.7%) 84 (66.7%) 0.99
with patients censored at time of first delivery of analgesia. presentation
Triage category* 0.001
Ethics 1 3 2
The study was reviewed and approved by King Saud Medical 2 49 19
City Institutional Review Board (approval no. H1R1-25).
3 125 94
4 0 6
TABLE 2. Pain Assessment Tools Used Subgrouped by Age Initial heart rate, 121 (SD 23) 118 (SD 20) 0.13
beats/min
Age Groups, y Mechanism of injury* 0.06
Pain Assessment Tool <3 3–7 >7 Total Scald 143 83
Flame 17 21
BPS 1 2 2 5
Chemical 5 5
FLACC 120 34 4 158
Electrical 1 4
NRS 16 9 22 47
Other 8 4
PIPP 6 0 0 6
Missing 10 6
WBPS 12 19 10 41
Degree of burns* 0.60
Not Defined 28 9 7 44
1 11 10
Not documented 5 1 2 8
2 138 90
Total 188 74 47 309
3 6 6
BPS indicates Behavioral Pain Scale; FLACC, Face-Leg-Activity-Cry- 4 1 2
Consolability; not defined, pain was assessed but the type of tool was not % TBSA burned 7 (IQR, 3–13) 7 (IQR, 3–11) 0.58
mentioned; NRS, Numerical Rating Scale; PIPP, Premature Infant Pain
Profile; WBPS, Wong-Baker Pain Scale. *Categories contain missing data.

Alrashoud et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
there was no association of appropriateness of pain scales with the cannot verbalize or who are cognitively impaired. Fear, anxiety,
mechanism of injury, degree, and extent of burns. and stress due to the hospital environment and medical personnel
There were 144 patients (46.7%) who were provided analgesia can influence the expression of pain, and these are not accounted
in the ED. The most common initial analgesia administered was infor separately in the pain scales. In addition to this, expression of
travenous morphine in 49 patients (15.9%), followed by paracetamol pain can be influenced by the child's sex and culture.
in 38 patients (12.3%) and intravenous fentanyl in 37 patients More so than in the adult population, it is important to recog-
(12.0%). There was no association between appropriateness of pain nize pain as one of the rapidly treatable entities in the ED. Barriers
scale used and type of analgesia (P = 0.33). Among patients who to analgesia delivery may be underrecognition of the presence of
had appropriate assessment of pain, 92 (50.3%) received analgesia pain, underestimating its severity and the level of distress that it
compared with 52 (41.3%) who did not have appropriate assessment can cause to the patient, the fear of masking signs, or irrational fears
(P = 0.12). Among patients who had appropriate pain assessment, of addiction to analgesics from isolated administration in the setting
median time to analgesia was 42 (IQR, 15–132 minutes) compared of trauma. These can be overcome by training the medical person-
with 53 minutes (IQR, 17–189 minutes) among patients who did not nel to recognize, acknowledge, classify pain, and rapidly initiate the
have appropriate assessment (P = 0.48). Time to analgesia subgrouped administration of analgesia.
by appropriateness of pain assessment is listed in Figure 1. Findings of this study support the practice of assessment of
pain to be prioritized after delivery of initial analgesia. The value
of pain assessment cannot be understated and should remain an in-
DISCUSSION
tegral part of management, but in the setting of burns injury, we
Among pediatric burn patients who presented to the largest recommend ongoing reassessment of pain after initial treatment
trauma center in Saudi Arabia, almost all (99%) had documented to identify the need for escalation or de-escalation of pain man-
pain assessment at triage, although many were assessed using tools agement. The use of analgesic ladders with initial management
that were not appropriate for age or clinical condition. Analgesia de- of mild to moderate pain with acetaminophen and nonsteroidal
livery was inconsistent but not associated with appropriateness of anti-inflammatory drugs is recommended, with escalation to opi-
pain assessment. These findings emphasize the need for focus on oids reserved for those with severe pain or in cases unresponsive
delivery of analgesia with the use and documentation of pain scales to first-line analgesics.
recommended, but an optional step. This study was limited by being a retrospective review of pro-
This study also highlights the substantial burden of pediatric spectively collected data and having relied on quality of documenta-
burns, with the majority of the infant-toddler–age group sustain- tion that may not always correlate with the quality of care delivered.
ing scald injuries. Male and female patients were almost equally Other limitations of the study were that it was a single-center study.
affected, with a large proportion of patients arriving after-hours, Pain assessment was not repeated after analgesia administration
most likely reflecting recreational activities outside of school. to assess its effect and has been planned for further quality im-
Self-reporting by patients in conjunction with assessment of provement activities.
caregivers and health care providers may be the most reliable pain
assessment.19 Assessment of pain in children can be challenging
and can be done using observational/behavioral pain scales or by CONCLUSIONS
self-reporting, depending on the age and cognitive development. It Most pediatric patients with burns who presented to the trauma
is more difficult to assess pain accurately in younger children who center had pain assessment, but a substantial proportion did not
FIGURE 1. Time to delivery of analgesia subgrouped by appropriate pain score utilization.

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Pain Assessment and Management in Burn Patients
receive recommended assessment and analgesia. Analgesia admin- 8. Grivna M, Eid HO, Abu-Zidan FM. Epidemiology of burns in the United
istration and time to first analgesia were not associated with the Arab Emirates: lessons for prevention. Burns. 2014;40:500–505.
appropriateness of pain assessment. This study reinforced the sub- 9. Kadir AR. Paediatric burns in Sulaimani, Iraq. Ann Burns Fire Disasters.
stantial pain experienced by pediatric patients with burns injury 2007;20:121–125.
and the importance of prompt delivery of analgesia. Age-specific 10. Jamal YS, Ardawi MS, Ashy AR, et al. Paediatric burn injuries in the
pain assessment should be considered to inform appropriate analge- Jeddah area of Saudi Arabia: a study of 197 patients. Burns. 1990;16:
sia administration. 36–40.
11. Blakeney PE, Rosenberg L, Rosenberg M, et al. Psychosocial care of
REFERENCES persons with severe burns. Burns. 2008;34:433–440.
1. Riedlinger DI, Jennings PA, Edgar DW, et al. Scald burns in children aged 12. Ryan CM, Lee A, Kazis LE, et al. Recovery trajectories after burn injury in
14 and younger in Australia and New Zealand—an analysis based on the young adults: does burn size matter? J Burn Care Res. 2015;36:118–129.
Burn Registry of Australia and New Zealand (BRANZ). Burns. 2015;41: 13. Bonham A. Managing procedural pain in children with burns. Part 1:
462–468. assessment of pain in children. Int J Trauma Nurs. 1996;2:68–73.
2. Gandhi M, Thomson C, Lord D, et al. Management of pain in children with 14. Bayat A, Ramaiah R, Bhananker SM. Analgesia and sedation for children
burns. Int J Pediatr. 2010;2010:825657. undergoing burn wound care. Expert Rev Neurother. 2010;10:1747–1759.
3. Alharthy N, Al Mutairi M, AlQueflie S, et al. Pattern of burns identified in 15. Bittner EA, Shank E, Woodson L, et al. Acute and perioperative care of the
the pediatrics emergency department at King Abdul-Aziz Medical City: burn-injured patient. Anesthesiology. 2015;122:448–464.
Riyadh. J Nat Sci Biol Med. 2016;7:16–21. 16. American Academy of Pediatrics. Committee on Psychosocial Aspects of
4. Dhopte A, Tiwari VK, Patel P, et al. Epidemiology of pediatric burns and Child and Family Health; Task Force on Pain in Infants, Children, and
future prevention strategies—a study of 475 patients from a high-volume Adolescents. The assessment and management of acute pain in infants,
burn center in North India. Burns Trauma. 2017;5:1. children, and adolescents. Pediatrics. 2001;108:793–797.
5. Lee CJ, Mahendraraj K, Houng A, et al. Pediatric burns: a single institution 17. Kahsay H. Assessment and treatment of pain in pediatric patients.
retrospective review of incidence, etiology, and outcomes in 2273 burn Curr Pediatr Res. 2017.
patients (1995–2013). J Burn Care Res. 2016;37:e579–e585. 18. Gravel J, Fitzpatrick E, Gouin S, et al. Performance of the Canadian Triage
6. Li H, Wang S, Tan J, et al. Epidemiology of pediatric burns in Southwest and Acuity Scale for children: a multicenter database study. Ann Emerg
China from 2011 to 2015. Burns. 2017;43:1306–1317. Med. 2013;61:27–32.e3.
7. Hefny AF, Grivna M, Abbas AK, et al. Pediatric trauma research in the Gulf 19. Uspal N, Black KD, Cico SJ. Pediatric pain management in the emergency
Cooperation Council countries. Asian J Surg. 2012;35:74–80. department. Pediatr Emerg Med Pract. 2019;16:1–24.

ORIGINAL ARTICLE
Time of Observation in Xenobiotic Ingestions in Children

Is 6 Hours Too Long?
Maya Capua, MD,* Maire Amlicke, BS,† Emily Esposito, BA,‡ Joshua Belfer, MD,† Mitchell Bellis, MD,§
Daria Falkowitz, DO,†|| and David Teng, MD†
in young children are typically secondary to exploratory behavior

Objectives: Children endure a prolonged observation after xenobiotic in- rather than suicidal intent, tend to only include 1 xenobiotic agent,
gestions, despite low associated morbidity and mortality. The primary ob- and present sooner for medical evaluation.1,3,4 Although pediatric
jective was to describe the management and outcomes of acute xenobiotic toxic exposures account for more than half of all reported human
exposures in asymptomatic pediatric patients presenting to the emergency toxic exposures, they constitute less than 3% of ingestion-related
department (ED). A secondary objective was to explore the impact of vital fatalities with an acute mortality rate of <0.0004%.2,5 This sug-
signs on the patients' management and outcomes. gests that the severity of exposures varies greatly, and the majority
Methods: We conducted a retrospective review of asymptomatic children of ingestions are not life-threatening. The variability in morbidity
(younger than 18 years) presenting to a pediatric ED after a toxic ingestion and mortality may impact the physician's approach to the pediatric
from 2014 to 2018. Ingestions of hydrocarbons, acetaminophen, salicylates, unintentional ingestion.
sulfonylureas, caustic, and/or extended release agents were excluded. Demo- Most patients, adult or pediatric, who present after the ingestion
graphic and clinical data were abstracted. of an immediate-release xenobiotic are observed for 6 hours, which is
Results: Of 2817 charts, we identified 109 asymptomatic patients with a based on the time-to-peak of the substance. This is based primarily on
mean age of 4.7 years. The average observation from registration to dispo- the principle that individual pharmacokinetics/pharmacodynamics of
sition was 4.06 hours. Five patients were admitted and were subsequently a xenobiotic and, more specifically, the time-to-peak effects deter-
discharged within 24 hours. Of the discharged patients, 2 returned within mine the duration necessary for observation.6 Most of these inges-
72 hours and were subsequently discharged home. A total of 321 asymptom- tions can be safely observed in the emergency department (ED)
atic patients presented with ≥1 abnormal vital signs (mean age, 6.6 years) for 6 hours with little concern for delayed presentation of toxicity.6
and were observed in the ED for an average of 4.54 hours. They had a higher However, some studies suggest that this observation period may
percentage of ingestions related to suicide attempts (odds ratio, 6.8). Twenty- not be necessary. A prospective study in adult patients by Hol-
two were admitted. Of those discharged home, 11 returned to the ED within lander et al6 found that a large subset of intentional overdose pa-
72 hours; all were subsequently discharged home. tients who were observed for 6 hours could have been medically
Conclusions: Prolonged observations may not be necessary after inges- cleared within 2 to 4 hours of presentation. Similarly, a published
tions in asymptomatic children. Vital sign abnormalities at presentation did abstract by Ojo et al7 found that asymptomatic patients arriving
not impact disposition. Prospective studies are needed to determine the after ingestion rarely developed new symptoms.
safety and efficacy of this shortened observation. To evaluate the efficacy of the 6-hour observation period, the pri-
Key Words: ingestion, observation, xenobiotic mary aim of this study was to describe the management and outcomes
of acute xenobiotic exposures in asymptomatic pediatric patients. We
hypothesize that, if patients are asymptomatic upon arrival to the ED,
their observation period is unlikely to impact their disposition. As a
P ediatric toxic ingestions are a common cause of injury among
children and account for approximately 60% of all human
toxic exposures reported to North American poison control cen-
secondary aim, we will explore the impact of vital signs (VSs) on
the outcome and management of these asymptomatic patients.
ters.1 The 2018 Annual Report of the American Association of
Poison Control Centers' National Poison Data System found that METHODS
children younger than 20 years had more than 4.3 times the num-
We conducted a retrospective chart review of patients youn-
ber of toxic exposures reported (1483 per 100,000) as compared
ger than 18 years, who presented to an urban tertiary care pediatric
with adults (340 per 100,000).2 Adolescents who present for med-
ED after developing a concern for a potentially toxic ingestion
ical care after an ingestion are at a higher risk of morbidity and
from May 2014 to December 2018. Patients were identified based
mortality compared with young children, especially those younger
on their International Classification of Diseases, Ninth or Tenth
than of 5 years.1,3 This may be attributed to the fact that ingestions
Revision (ICD-9/10), codes for toxic ingestions. We did not in-
clude any encounters with ICD-9/10 codes that were incorrectly
From the *Division of Pediatric Emergency Medicine, The Hospital for Sick classified as a toxic ingestion (labeled as “bad code” in Fig. 1),
Children, Toronto, Ontario, Canada; †Division of Pediatric Emergency Medi-
cine, Cohen Children's Medical Center, New Hyde Park, NY; ‡St. George's
as well as any patients lacking sufficient physician documentation
University Medical School, West Indies, Grenada; }New York-Presbyterian (labeled as “no note” in Fig. 1). Lastly, we did not include any pa-
Brooklyn Methodist Hospital, Brooklyn, NY; and ||Hackensack University tients who were transferred from outside institutions (labeled as
Medical Center, Hackensack, NJ. “transfers” in Fig. 1), as we could not reliably evaluate their pre-
Reprints: Maya Capua, MD, Division of Emergency Medicine, The Hospital for
senting VSs or any initial interventions.
Sick Children Toronto, ON M5G 1X8, Canada (e‐mail: mayacapua@ Ingestions of caustic substances, hydrocarbons, acetamino-
gmail.com). phen, salicylates, and sulfonylureas were not included because
Supplemental digital content is available for this article. Direct URL citations these agents already have established treatment algorithms.8–10
Cases known to involve extended release agents were also not in-
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. cluded because these substances require longer observations.1 We
ISSN: 0749-5161 also did not include any patients who were not normoglycemic if

Pediatric Emergency Care • Volume 39, Number 1, January 2023 Time of Observation in Xenobiotic Ingestions
FIGURE 1. Breakdown of included encounters. Note: If there were multiple drug ingestions not included, the authors only counted them once
(eg, ranking for inclusion: extended release >acetaminophen >caustic).
obtained on presentation (point of care blood glucose between <70 The study was approved by the Northwell Health Institu-
or >150 mg/dL). Of the remaining patients, only those who were tional Review Board.
asymptomatic on presentation were included. Asymptomatic was
defined as no documented evidence of potential toxodromic symp-
toms (altered mental status, respiratory distress, emesis, or acute rash) RESULTS
in the physician documentation and normal VSs at triage. We defined We reviewed 2817 patient charts, and based on the inclusion
normal VSs by the Harriet Lane Handbook (see Figure 2, Supple- criteria previously, 109 patients (3.9%) were determined to be
mental Digital Content 1, http://links.lww.com/PEC/A913), which asymptomatic with normal VSs upon presentation to the ED. The
provided a narrow range of normal values to control for any sub- mean age of this cohort was 4.7 years, with a median age of 2.7 years
jectivity related to the interpretation of those values.11 (interquartile range, 1.8–5.8 years; Table 1). A total of 103 ingestions
Study data were then abstracted from each patient’s chart, in- (94.5%) were of known agents, and 6 (5.5%) were ingestions of un-
cluding demographics, self-assigned race/ethnicity, past medical known substances. The most common ingestions were nonsteroidal
history, ingested agent, time of ingestion, presenting VSs, inter- anti-inflammatory drugs (NSAIDs) (13.6%) and cardiac medications
ventions, and length of stay. (9.7%), and 2 ingestions were disclosed as secondary to suicide
As part of our secondary analysis, we evaluated a subset of attempts. Furthermore, there were 8 coingestions (Table 2).
patients with abnormal VSs as the only outlying variable. We then The average time from ingestion to registration for asymp-
compared this group of asymptomatic ingestions with abnormal tomatic patients with normal VSs was 2.3 hours. Upon arrival,
VSs upon presentation, with the original group of asymptomatic 24 patients received an intervention within the first 60 minutes,
patients with normal VSs to evaluate the impact of VSs on the out- which included laboratory tests, electrocardiograms, medication
come and management of these patients. administration, and/or imaging studies (Fig. 2). No patients were

Capua et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
within 72 hours for an unrelated complaint of a nasal foreign body.

TABLE 1. Demographics In the rest of this cohort (89 patients), there was 1 additional 72-hour
return visit. This was for a patient who had ingested multiple laxative
Normal VSs Abnormal VSs
chew tablets and returned with 2 episodes of emesis and 3 loose
(n = 109) (n = 321) stools. The child was subsequently discharged from the ED without
any additional interventions.
Characteristics n (% of Group) n (% of Group)
As part of our secondary analysis, we evaluated a subset of pa-
Sex tients with abnormal VSs as the only outlying variable. Of the 2817 re-
Female 32 (29.4) 168 (52.3) viewed charts, 321 patients (11.4%) were asymptomatic but presented
Male 77 (70.6) 153 (47.7) to the ED with at least 1 abnormal VS.11 The mean age of this cohort
Age, y was 6.6 years old, with a median age of 3.1 years (interquartile range,
0–4 75 (68.8) 192 (59.8) 1.9–13.8 years; Table 1). The most common VS abnormality was
blood pressure (82%), and no patients had abnormal oxygen saturation
5–9 20 (18.3) 33 (10.3)
upon presentation (Fig. 3). The most common ingestions were also
10–15 5 (4.6) 51 (15.9) NSAIDs (13.2%) and cardiac medications (7.3%). Furthermore, 18
16–18 9 (8.3) 45 (14.0) (5.9%) were ingestions of unknown substances, and 26 were
Mean age 4.70 6.64 coingestions (Table 2). A higher percentage of ingestions were catego-
Median age 2.71 (IQR*, 3.12 (IQR*, rized as secondary to a disclosed suicide attempt in this group (n = 36
1.82–5.83) 1.85–13.82) [11.2%]; odds ratio (OR), 6.8; 95% confidence interval, 1.6–28.6).
Race/ethnicity The average time from ingestion to registration for asymp-
Unknown 2 (1.8) 13 (4.0) tomatic patients with abnormal VSs was 2.7 hours. Within the first
White, non-Hispanic 47 (43.1) 125 (38.8) 60 minutes, 128 patients (39.9%) received an intervention (Fig. 4),
Hispanic 1 (0.9) 1 (0.3) and 1 patient was admitted for telemetry (see Table 3, Supplemental
Black, African American 31 (28.4) 84 (26.2) Digital Content 2, http://links.lww.com/PEC/A914). Between 60 and
Asian 13 (11.9) 43 (13.4) 120 minutes, 90 patients (28%) received an intervention, and there
were no admissions. Between 120 and 180 minutes, 45 patients
American Indian 0 (0.0) 1 (0.3)
(14%) received an intervention, and 4 patients were admitted (Sup-
Pacific Islander 0 (0.0) 0 (0.0) plemental Digital Content, Supplementary Table 3, http://links.lww.
Other 15 (13.8) 54 (16.8) com/PEC/A914). Three of the admissions were for monitoring after
*IQR indicates interquartile range. ingestions of unknown substances, and 1 was for an ingestion of
levothyroxine and phenobarbital. Between 180 and 240 minutes,
38 patients (11.8%) received an intervention, and 5 patients were
admitted during this period. Between 60 and 120 minutes, 12 admitted (see Table 3, Supplemental Digital Content 2, http://
patients received an intervention, and 1 patient who ingested links.lww.com/PEC/A914). Between 240 and 300 minutes, 23 pa-
cabergoline was admitted for monitoring based on extended phar- tients (7.2%) received an intervention, and 1 patient with an
macokinetics. Between 120 and 180 minutes, 12 patients received
an intervention, and no patients were admitted.
Between 180 and 240 minutes, 8 patients received an inter- TABLE 2. Distribution of Ingested Xenobiotic Agents
vention, and 3 patients were admitted. The first patient was admit-
ted for 24-hour telemetry monitoring because of the ingestion of Normal VSs Abnormal VSs
an unknown substance after consultation with a medical toxicolo- (n = 109) (n = 321)
gist. The second patient was admitted for monitoring after an in-
gestion of clonidine, because of an episode of hypoxia with perioral Drug Category n (% of Group) n (% of Group)
cyanosis. The patient responded to tactile stimulation, and VSs sub- Alcohol 4 (3.9) 2 (0.66)
sequently normalized in the ED. The third admission in this group
Antiepileptic 3 (2.9) 8 (2.6)
was secondary to a disclosed suicide attempt with escitalopram and
eszopiclone ingestions and was admitted for telemetry monitoring Antihistamine 5 (4.9) 21 (6.9)
and the potential for delayed QT prolongation. Antipsychotic 0 (0) 10 (3.3)
Between 240 and 300 minutes, 3 patients received an interven- Benzodiazepines 4 (3.9) 16 (5.3)
tion, and no patients were admitted. Between 300 and 360 minutes, Bupropion 0 (0) 0 (0)
4 patients received an intervention, and no patients were admitted. Cardiac (CCB, BB, cardiac 10 (9.7) 22 (7.3)
After 360 minutes, there were no additional interventions; however, glycosides)
1 patient with an unknown ingested agent was admitted 7.8 hours Drugs of abuse 5 (4.9) 18 (5.9)
after ED presentation for telemetry based on the recommendations Hormones 7 (6.8) 8 (2.6)
of the consulting medical toxicologist. NSAIDs 14 (13.6) 40 (13.2)
Overall, patients were observed in the ED from registration Opioids 2 (1.9) 9 (3.0)
to disposition for an average of 4.1 hours and 6.0 hours postingestion. SSRI 3 (2.9) 7 (2.3)
Four of the 5 patients were admitted within 4 hours of presentation.
Vitamins 9 (8.7) 7 (2.3)
All 5 admitted patients had no additional acute events during admis-
sion and were discharged home within 24 hours. Other 37 (35.9) 135 (44.5)
One hundred four asymptomatic patients were discharged. Known 103 303
Of this group, 15 (14%) were discharged within 120 minutes of Unknown 6 18
registration, and the predominant xenobiotic ingestions in this rap- BB indicates β blocker; CCB, calcium channel blocker; SSRI, selective
idly assessed and discharged group were dessicants (3 of 15) and serotonin reuptake inhibitors.
vitamins (2 of 15). One of these 15 patients returned to the ED

FIGURE 2. Interventions performed on asymptomatic patients with normal VSs.
unknown ingestion was admitted after an episode of hypoxia and these 55 patients returned to the ED within 72 hours, all of which
transient hypotension. Between 300 and 360 minutes, 13 patients were rat poison ingestions and were instructed to follow-up for re-
(4%) received an intervention, and 2 patients were admitted for peat laboratories. In the rest of this cohort (244 patients), 8 addi-
observation. After 360 minutes, 16 patients (5%) received an in- tional patients returned to the ED within 72 hours. Three patients re-
tervention, and 9 patients were admitted (see Table 3, Supplemen- turned with symptoms of emesis and/or diarrhea after their inges-
tal Digital Content 2, http://links.lww.com/PEC/A914). tion of furosemide, metoprolol, and guanfacine, respectively, and
These patients were observed in the ED from registration to the symptoms were deemed unlikely related to the ingestion. All
disposition for an average of 4.5 hours and 7.1 hours from time were subsequently discharged from the ED. An additional 3 patients
of ingestion. Twenty-two (6.8%) were admitted. Ninety-five per- were advised to come back for repeat laboratories and/or additional
cent (21 of 22) of admitted patients were discharged within 24 hours consultations within the 72-hour window: 1 ingested valproic acid
of admission. One patient was admitted for 48 hours and subse- and 2 ingested rat poison (super warfarins such as brodifacoum).
quently transferred to a psychiatric facility for further management. All of these patients were ultimately discharged home again. Fi-
There was no significant difference in the OR for admission when nally, 2 patients came back within the 72-hour window for psychi-
comparing patients with normal VSs to those with abnormal VSs atric and/or behavior health evaluations, unrelated to the ingestion.
(OR, 1.5; 95% confidence interval, 0.57–4.15).
Two hundred ninety-nine asymptomatic patients with abnor-
mal VSs were discharged home. Of this group, 55 (18%) were DISCUSSION
discharged within 120 minutes of registration, and the predomi- Pediatric toxic ingestions are a common cause of injury, yet
nant xenobiotic ingestions in this rapidly assessed and discharged those that are secondary to exploratory behavior in infants or young
group were rat poison (7 of 55) and NSAIDS (3 of 55). Three of children rarely result in morbidity or mortality.1 Although there are
FIGURE 3. Distribution of abnormal VSs.

Capua et al Pediatric Emergency Care • Volume 39, Number 1, January 2023
FIGURE 4. Interventions performed on asymptomatic patients with abnormal VSs.
studies in adult literature that assess the observation period after an There were 22 admissions (7%) within our cohort of patients
ingestion, the authors did not encounter any similar studies in pedi- with abnormal VSs. There was no significant difference in the OR
atrics or any widely accepted evidence for the duration of observa- for admission when comparing patients with normal VSs with those
tion in asymptomatic pediatric patients.6 with abnormal VSs. This could be attributed to 2 main factors—the
There were 2817 charts reviewed, yielding a cohort of 109 first is that admission, as an outcome variable, is subjective, and ad-
asymptomatic patients with normal VSs upon presentation to the mission thresholds may differ between providers. The second ex-
ED. A second cohort, based on our secondary objective, included planation is that VSs, when interpreted in isolation, may be poor
321 asymptomatic patients presenting with abnormal VSs. A higher predictors of life-threatening conditions in pediatric patients. Partic-
percentage of our patients presented to the ED with abnormal VSs, ularly in the ED, toxicity, anxiety, and the uncooperative pediatric
making it difficult to compare the 2 groups. Accordingly, we ana- patient may contribute to abnormalities in VSs. One study found
lyzed each group individually and subsequently compared rates of that nonhospitalized children, including those in the ED at triage
admissions/discharges/returns. The majority of diagnostic interven- and in primary care settings, had higher heart rates than hospitalized
tions such as laboratory tests, electrocardiograms, imaging, and/or children even when accounting for body temperature.12 This was
medication administrations occurred within the first 2 hours after even more notable in children younger than 2 years.12 The authors
presentation, but there was no clear association between interven- attributed some of those differences to the emotional stress of young
tion and admission (see Figure 2, Supplemental Digital Content children who are ill and being assessed by strangers, and the effect
1, http://links.lww.com/PEC/A913). of this stress on heart rate. In addition, the study's narrow range of
normal VSs may have impacted this result, as the 2 groups may
not have actually represented markedly different populations upon
presentation. For these reasons, the authors sought to describe the
Admissions reasons for admission, as well as the clinical course, to provide con-
There were 5 admitted patients (4.6%) in the asymptomatic text to the disposition decisions.
group with normal VSs. Four (80%) of the admissions were deter- Of the 36 patients who disclosed suicidality in the context of
mined within 4 hours of presentation, consistent with our hypoth- their ingestion, 7 (19.4%) were admitted. Therefore, patients who
esis that providers can identify most patients requiring admission disclose suicidality after an ingestion likely represent a vulnerable
or further medical interventions in less than 6 hours. One patient population with unreliable history and may require longer obser-
was not admitted until 7.8 hours postregistration. After chart re- vations and/or admissions, even if the psychiatric concerns have
view, there were several features of this case, which limit its appli- been addressed.
cability to the rest of the study. First, this child had an unwitnessed
ingestion of an unknown substance. Additional history later re- Discharges
vealed medications in the home, including a β blocker and a sul-
fonylurea. This child was ultimately admitted for monitoring for Disposition is a critical part of ED management. Although the
bradycardia or hypoglycemia. As stated in the methods, disclosed investigators of this study are evaluating if a shorter observation
sulfonylurea ingestions were not included in this study because of time would be appropriate, it is also critical to ensure safety when
their preestablished treatment algorithms and prolonged pharma- discharging a patient. Return visits may be one indicator of potential
cokinetics.1 However, because of the nature of this unknown in- medical management errors associated with inappropriate assess-
gestion, it was included in the cohort initially. In this case, the risk ment or treatment.13 Our study demonstrated that none of the
of a sulfonylurea ingestion, although quite low, warranted admis- discharged patients, regardless of their VSs or admission status,
sion for monitoring by the toxicology team. Over the course of required any unanticipated medical interventions postdischarge.
the admission, this child had no acute events and was discharged This supports the disposition decisions made by providers.
within 24 hours. Because of the retrospective nature of this study,
the authors were unable to determine if the providers had planned Limitations
this disposition earlier in the clinical course or if there was a change Our study had several limitations. First, because this was a
after 7 hours of observation when the medications were disclosed. retrospective chart review, we were limited by the information

available in the medical chart. We were unable to determine the none of the discharged patients, in either group, required any un-
reasoning for certain clinical decisions, including the time a pa- anticipated medical interventions postdischarge. Patients who dis-
tient was medically cleared for discharge or why a patient received close suicidal intent upon presentation represent a potentially at-
specific treatments or interventions. We also could not be certain risk and sometimes unreliable group and should be monitored ac-
that time of admission was captured with the level of precision re- cordingly. Prospective studies evaluating the shortened observa-
quired for a time-to-event analysis; therefore, we instead calculated tion period in asymptomatic patients are needed and will help cli-
OR of admission between our groups. Similarly, when selecting the nicians determine necessary observation periods, as prolonged
relevant encounters, we found multiple unrelated ICD-9/10 codes length of stay in an ED comes with additional risks and costs.
likely due to the variability in the wording of discharge diagnoses.
The data were also limited to include those cases where documenta-
tion was able to obtained, with 649 potential subjects excluded for ACKNOWLEDGMENT
lack of complete documentation (denoted as “no note” in Fig. 1). Thank you to Dr Jane Cerise, from the Feinstein Institute for
The authors were unable to determine if these patients would have Medical Research, for her assistance and contribution to the sta-
otherwise fit the inclusion criteria and, as such, cannot postulate on tistical analyses in this study.
whether they would have impacted the data set. In addition, given
the retrospective nature of this study, we were only able to account
for patients who return to care within the hospital network. However, REFERENCES
given the catchment area of the hospital network, this likely repre- 1. Fine JS. Pediatric Principles. In: Nelson LS, Howland MA, Lewin NA,
sented the majority of return visits requiring acute care interventions. et al, eds. Goldfrank's Toxicologic Emergencies. 11th ed. New York, NY:
Second, there is an innate limitation when evaluating ingestions McGraw-Hill; 2019:447–460.
in pediatric populations who cannot reliably disclose the ingested 2. Gummin DD, Mowry JB, Spyker DA, et al. 2018 Annual report of the
agent. Investigators rely predominantly on secondary history from a American Association of Poison Control Centers' National Poison Data
caretaker, and there may be secondary gain from withholding infor- System (NPDS): 36th annual report. Clin Toxicol (Phila). 2019;57:
mation because of fear of allegations of child endangerment or negli- 1220–1413.
gence. Similarly, investigators cannot be certain that the patient actu- 3. Reyes L, Tews M, Paik M. Peds Poisonings. The Clerkship Directors in
ally ingested the alleged substance. Nonetheless, the investigators Emergency Medicine (CDEM). Updated 2015. Available at: https://www.
used the most consistent information available to them. saem.org/cdem/education/online-education/peds-em-curriculum/
Finally, the authors recognize that using abnormal VSs as a approach-to/ingestion. Accessed June 24, 2020.
method of identifying a potentially at-risk patient group is met
4. Hoffman RJ, Osterhoudt KC. Evaluation and management of pediatric
with challenges. Vital sign norms are highly variable and are con- poisonings. Pediatr Case Rev. 2002;2:51–63.
stantly changing because of the scope of patients presenting to the
ED. A recent study from Sepanski et al14 found that heart and re- 5. Wang GS, Deakyne S, Bajaj L, et al. The limited utility of screening
spiratory rates from 1.2 million nonadmitted patients presenting to laboratory tests and electrocardiograms in the management of unintentional
asymptomatic pediatric ingestions. J Emerg Med. 2013;45:34–38.
their EDs were higher than previously published norms in the Pe-
diatric Advanced Life Support guidelines. Furthermore, they ad- 6. Hollander JE, McCracken G, Johnson S, et al. Emergency department
vocated for using centile ranges rather than dichotomous “nor- observation of poisoned patients: how long is necessary? Acad Emerg Med.
mal” and “abnormal” cutoffs.14 Another study by Fleming et al15 1999;6:887–894.
found that existing reference ranges for heart rates and respiratory 7. Ojo AO, Alam S, Shenoi R. Outcomes of unintentional pediatric ingestions
rates in children were inconsistent, and the ranges did not agree in a pediatric emergency department observation unit: which ingestion is
with centile charts derived from their systematic review of obser- most likely to lead to an admission? Ann Emerg Med. 2014;64:S141–S142.
vational studies. Nonetheless, given the lack of a widely accepted 8. Rumack BH, Matthew H. Acetaminophen poisoning and toxicity.
source for normal VSs, the authors decided to use the guidelines Pediatrics. 1975;55:871–876.
based on The Harriet Lane Handbook. The authors acknowledged 9. Crain EF, Gershel JC, Mezey AP. Caustic ingestions. Symptoms as
that this may provide a falsely high number of patients with abnor- predictors of esophageal injury. Am J Dis Child. 1984;138:863–865.
mal VSs but would be unlikely to miss those with VS changes that
10. Done AK. Salicylate intoxication. Significance of measurements of
may not meet the “abnormal” values in other published ranges.
salicylate in blood in cases of acute ingestion. Pediatrics. 1960;26:
This would lead to increasing the sensitivity at the cost of the spec- 800–807.
ificity of the patient population.
11. Engorn B, Flerlage J. The Harriet Lane Handbook. 20th ed. Philadelphia,
PA: Elsevier; 2015.
CONCLUSIONS
12. Daymont C, Bonafide CP, Brady PW. Heart rates in hospitalized children
Xenobiotic ingestions (not involving acetaminophen, salicy-
by age and body temperature. Pediatrics. 2015;135:e1173–e1181.
lates, hydrocarbons, caustic substances, and/or extended release
medications) in asymptomatic pediatric patients are often observed 13. Logue EP, Ali S, Spiers J, et al. Characteristics of patients and families who
for 6 hours postingestion based on pharmacokinetics. Of 910 toxic make early return visits to the pediatric emergency department. Open
exposures presenting to the ED of this pediatric hospital, about one Access Emerg Med. 2013;5:9–15.
third will have a predetermined, defined evaluation pathway and 14. Sepanski RJ, Godambe SA, Zaritsky AL. Pediatric vital sign distribution
about one fifth will be symptomatic. Out of the remaining cases, derived from a multi-centered emergency department database. Front
when children are asymptomatic at presentation or only have minor Pediatr. 2018;6:66.
VS abnormalities, it is unlikely that their observation in the ED 15. Fleming S, Thompson M, Stevens R, et al. Normal ranges of heart rate and
will alter their disposition. Our current study suggests that such respiratory rate in children from birth to 18 years of age: a systematic
extended observation periods may not be necessary. Furthermore, review of observational studies. Lancet. 2011;377:1011–1018.

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ORIGINAL ARTICLE

Immunization Status and the Management of Febrile

Conclusions: Higher rates of laboratory testing and interventions were

Pediatric Emergency Care • Volume 39, Number 1, January 2023 www.pec-online.com 1

FIGURE 1. Flow diagram of encounters included in chart review.

2 www.pec-online.com © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

TABLE 2. Differences in Management

FI (n = 721) UnderI (n = 44) UnI (n = 23) P OR (95% CI)*

© 2022 The Author(s). Published by Wolters Kluwer Health, Inc. www.pec-online.com 3

4 www.pec-online.com © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

© 2022 The Author(s). Published by Wolters Kluwer Health, Inc. www.pec-online.com 5

Pharmacogenomic Profiling of Pediatric Patients on

Key Words: combinatorial pharmacogenomic testing, psychiatric disorders,

6 www.pec-online.com Pediatric Emergency Care • Volume 39, Number 1, January 2023

METHODS Data Collection and Analysis

© 2022 The Author(s). Published by Wolters Kluwer Health, Inc. www.pec-online.com 7

of relative improvement of the underlying psychiatric disorder

RESULTS in the study. Twenty-five percent of the samples were African

FIGURE 1. Patient enrollment diagram.

8 www.pec-online.com © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

© 2022 The Author(s). Published by Wolters Kluwer Health, Inc. www.pec-online.com 9

10 www.pec-online.com © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

© 2022 The Author(s). Published by Wolters Kluwer Health, Inc. www.pec-online.com 11

12 www.pec-online.com © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Utilizing Near-Infrared Spectroscopy to Identify Pediatric

direct interventions to optimize patient outcomes. Currently, the

Pediatric Emergency Care • Volume 39, Number 1, January 2023 www.pec-online.com 13

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

14 www.pec-online.com © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Statistical Analysis Subgroup Analyses

© 2022 Wolters Kluwer Health, Inc. All rights reserved. www.pec-online.com 15

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

FIGURE 2. Consort diagram.

16 www.pec-online.com © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

© 2022 Wolters Kluwer Health, Inc. All rights reserved. www.pec-online.com 17

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

18 www.pec-online.com © 2022 Wolters Kluwer Health, Inc. All rights reserved.

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© 2022 Wolters Kluwer Health, Inc. All rights reserved. www.pec-online.com 19

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Characteristics of Pediatric Patient Transfers From General

Objective: Each year, approximately 300,000 pediatric patients are trans-

20 www.pec-online.com Pediatric Emergency Care • Volume 39, Number 1, January 2023

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Patient Characteristics RESULTS

General Hospital General Hospital General Hospitals With

© 2022 Wolters Kluwer Health, Inc. All rights reserved. www.pec-online.com 21

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

22 www.pec-online.com © 2022 Wolters Kluwer Health, Inc. All rights reserved.

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TABLE 2. Characteristics of Patients Transferred Based on Hospital Type*

© 2022 Wolters Kluwer Health, Inc. All rights reserved. www.pec-online.com 23

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

24 www.pec-online.com © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Unadjusted OR (95% CI) Adjusted OR (95% CI)

© 2022 Wolters Kluwer Health, Inc. All rights reserved. www.pec-online.com 25

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.