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Pediatric emergency medicine literature 2020

Journal logoUnlabelled imageAmerican Journal of Emergency Medicine 43 (2021) 123-133

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American Journal of Emergency Medicine

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Pediatric emergency medicine literature 2020

Frank Petruzella, MD a, Joshua S. Easter, MD b,?

a Department of Emergency Medicine, Virginia Commonwealth University, Box 980401, Richmond, Virginia 23298-0401, United States of America

b Department of Emergency Medicine, University of Virginia, 200 Jeanette Lancaster Way, Charlottesville, VA 22903, United States of America

a r t i c l e i n f o

Article history:

Received 2 January 2021

Received in revised form 6 January 2021 Accepted 9 January 2021

Keywords: Pediatric trauma Resuscitation Fever

Asthma Seizure

a b s t r a c t

Most children are treated at general Emergency Departments (EDs) and not specialized pediatric EDs. Therefore, it is crucial for emergency medicine physicians to be aware of recent developments in pediatric emergency med- icine. Often impactful articles on pediatric emergency medicine are not published in the journals regularly stud- ied by general emergency medicine physicians. We selected ten studies that we found impactful, robust, and relevant for practicing general emergency physicians. This review includes studies of status epilepticus, cardiac arrest, asthma, infant fever, wound care, rapid sequence intubation, coronavirus, and trauma.

(C) 2021

  1. Introduction

Most children are treated at general Emergency Departments (EDs) and not specialized pediatric EDs. Therefore, it is crucial for emergency medicine physicians to be aware of recent developments in pediatric emergency medicine. Often impactful articles on pediatric emergency medicine are not published in the journals regularly studied by general emergency medicine physicians. We selected ten studies that we found impactful, robust, and relevant for practicing general emergency physi- cians. This review includes studies of status epilepticus, cardiac arrest, asthma, infant fever, wound care, rapid sequence intubation, coronavi- rus, and trauma. Table 1 includes a summary of the articles and key findings.

  1. Pharmacotherapy for status epilepticus

Chamberlain J. et al. Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomized controlled trial. Lancet. 2020; 395: 12171124.

Benzodiazepines are first-line therapy for status epilepticus, but

when they fail, the literature does not give provide a clear choice for the most effective second-line medication. Prompt cessation of seizures is crucial, as prolonged Seizure activity is neurotoxic, and prolonged sei- zures are also more difficult to terminate. The Established Status Epilep- ticus Treatment Trial (ESETT) was a double-blind, randomized control

* Corresponding author.

E-mail address: [email protected] (J.S. Easter).

trial conducted at 58 EDs in the United States, showing levetiracetam, fosphenytoin, and valproate had similar success in terminating benzodiazepine-refractory convulsive status epilepticus [1]. The study included patients from 2 to 94 years of age, but the results were not stratified by age.

The current study by Chamberlain et al. was largely a secondary

analysis of patients in the ESETT trial that compared the efficacy of the different pharmacotherapies in children <18 years, adults 18-65 years, and elderly patients >65 years. All patients had persis- tent or recurrent convulsions in the ED for at least 5 min after receiv- ing adequate doses of benzodiazepines (e.g., lorazepam 0.1 mg/kg IV, diazepam IV 0.3 mg/kg, or midazolam 0.3 mg/kg IM for children

<32 kg; lorazepam 4 mg IV, diazepam 10 mg IV, or midazolam 10 mg IM for adults and heavier children). Patients were randomized to 60 mg/kg of levetiracetam (maximum 4500 mg), 20 mg PE/kg fosphenytoin (maximum 1500 mg PE), or 40 mg/kg of valproate (maximum 3000 mg). The primary outcome measure was cessation of clinically apparent seizures with improved responsiveness at 60 min after anti-epileptic administration as determined by the blinded treating clinician. Secondary outcomes included the inci- dence of adverse events, such as life-threatening hypotension, arrhythmia, need for endotracheal intubation, and death. Patients re-presenting to the ED for status epilepticus were enrolled more than once in the trial but only their first enrollment data were included when comparing the different therapies.

The study included 462 patients with status epilepticus, and 55% were children. In contrast to adults, status epilepticus in children was more likely to be unprovoked (47% vs 23%) and occur in the setting of a febrile illness (40% vs 1%). Anti-epileptics were more likely to

https://doi.org/10.1016/j.ajem.2021.01.013

0735-6757/(C) 2021

Table 1

Summary of articles and key findings.

Article Clinical

topic

Study type Key findings

Chamberlain J. et al. Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomized controlled trial. Lancet. 2020; 395: 1217-1124.

Hoyme D. et al., Improved survival to hospital discharge in pediatric in-hospital cardiac arrest using 2 J/kg as first defibrillation dose for initial pulseless ventricular arrhythmia. Resuscitation. 2020; 153: 88-96.

Status epilepticus

Cardiac arrest

Multicenter, double-blind, randomized controlled trial

Planned analysis of multicenter, prospective observational study

-Levetiracetam, fosphenytoin, and valproate had similar efficacy in terminating status epilepticus refractory to benzodiazepines

-Fosphenytoin was associated with higher frequency of intubation

-Half of cases of status epilepticus in children were terminated by administration of an anti-epileptic

-For children <12 years of age, those receiving defibrillation doses of 1.7-2.5 J/kg were more likely to survive

-For children >12 years of age, defibrillation dose was not associated with likelihood of survival

-Supports the American Heart Association recommendation of 2 J/kg for initial defibrillation

Schuh S. et al. Effect of nebulized magnesium vs placebo added to albuterol on hospitalization among children with refractory acute asthma treated in the emergency department: a randomized clinical trial. JAMA. 2020; 324(20): 2038-47.

Lyons T. et al. Performance of the modified boston and philadelphia criteria for invasive bacterial infections. Pediatrics 2020, April; 145 (4):e20193538.

Asthma Multicenter, double-blind,

randomized controlled trial

Infant Fever Analysis of multicenter

cohort study

-Nebulized magnesium did not reduce the Need for hospitalization or Asthma severity scores compared to placebo in children with asthma exacerbations refractory to initial beta agonists and steroids

-The Boston and Philadelphia criteria misclassified nearly one third of children with bacteremia or meningitis as low risk and appropriate for discharge

-The Boston and Philadelphia had better diagnostic accuracy for identifying children with urinary tract infections

Seiler M. et al. Non-Operative treatment versus suture refixation of the nail plate in pediatric fingernail avulsion injuries. J Hand Surg Eur Vol. 2020 Oct 22:1753193420965390.

Wound Care

Single center cohort study -Not replacing an avulsed nail was non-inferior to suturing the

nail in place

-Replacing an avulsed nail was more likely to require procedural sedation

Conway JA, et al. Ketamine Use for Tracheal Intubation in Critically Ill Children Is Associated With a Lower Occurrence of Adverse Hemodynamic Events. Crit Care Med. 2020 Jun;48(6): e489-e497.

Rapid Sequence Intubation

Retrospective analysis of data from multicenter, prospective cohort study

-Ketamine was associated with fewer adverse events than other Induction agents

-Higher doses of ketamine (>1.5 mg/kg) had less adverse events than lower doses

Schutzman S. et al. The infant scalp score: a validated tool to stratify risk of traumatic brain injury in infants with isolated scalp hematoma. Academic Emergency Medicine. 2020; 00:0:1-6.

Jonat B. et al. Multisystem inflammatory syndrome in children Associated With Coronavirus Disease 2019 in a Children’s Hospital in New York City: Patient Characteristics and an Institutional Protocol for Evaluation, Management, and Follow-Up. Pediatr Crit Care Med. 2020 Sep 29.

Head injury Retrospective analysis of

data from multicenter prospective cohort study

SARS-CoV-2 Prospective single center cohort study

-Size and location of a scalp hematoma can be used to determine risk of brain injury in infants

-No children with scalp risk scores <5 had important injuries

-Implementation of a protocol to identify and treat MIS-C syndrome in children with SARS-CoV-2 reduced time to treatment and may reduce length of stay in the hospital

-The proposed protocol included administration of antibiotics, anticoagulants, steroids, and IVIG for all patients

Goyal T. et al. racial and ethnic differences in Emergency Department Pain Management of Children With Fractures. Pediatrics. 2020 May;145(5).

healthcare disparities

Retrospective analysis of multicenter prospective cohort study

-African American and Hispanic children with long bone frac- tures were more likely to receive any pain medication than white children

-White children were more likely to receive opioid pain medication and optimal reductions in their pain

Polites S. et al. Timing and volume of crystalloid and blood products in pediatric trauma: An Eastern Association for the Surgery of Trauma Multicenter prospective observational study. J Trauma Acute Care Surg. 2020;89: 36-42.

Trauma Prospective Multicenter cohort study

-Half of children requiring >1 crystalloid bolus received blood products

-More than 1 crystalloid bolus was associated with increased duration of mechanical ventilation, intensive care, and hospitalization

terminate status in children (51%) than adults (45%) or the elderly (39%). There were no differences in efficacy between the anti-epileptic medications. In addition, there were no differences based on age (Table 2). 17% of children required intubation compared to 25% of adults and 28% of elderly patients. Children receiving fosphenytoin (33%) were more likely to require endotracheal intubation compared to valproate (11%) or levetiracetam (8%). This effect was not present for adults. There were no differences in other adverse effects in groups receiving the three anti-epileptics.

Table 2

Efficacy of anti-epileptics in terminating status epilepticus in children, adults, and the elderly.

Levetiracetam Fosphenytoin Valproate

While this is the largest trial of these second-line therapies for status epilepticus, the study was underpowered to detect differences in adverse events between groups. The number of elderly patients was also low, limiting conclusions in this subgroup. In addition, while the study protocol was based on the American Epilepsy Society guidelines for status epilepticus, the doses and timing of medication administration may have deviated from common prac- tice in the ED. [2,3]

In this large randomized control trial, children were more likely to have unprovoked or febrile status epilepticus compared to adults. They were also more likely to respond to anti-epileptic medications. However, similar to adults there were no differences in effectiveness at terminating status epilepticus between levetiracetam, fosphenytoin, and valproate in children. While children receiving fosphenytoin were more likely to require endotracheal intubation, other studies have not replicated this finding [4,5]. Other serious adverse events were similar

%

(95% CI)

%

(95% CI)

%

(95% CI)

between groups. With the similar efficacy of levetiracetam and

Children

52

(41-62)

49

(38-61)

52

(41-63)

valproate to fosphenytoin, we recommend their use initially in the man-

Adults

44

(33-55)

46

(34-59)

46

(34-58)

agement of children with status epilepticus that does not resolve with

Elderly

37

(19-59)

35

(17-59)

47

(25-70)

benzodiazepines.

  1. Cardiac arrest

Hoyme D. et al., Improved survival to hospital discharge in pediatric in- hospital cardiac arrest using 2 J/kg as first defibrillation dose for initial pulseless ventricular arrhythmia. Resuscitation. 2020; 153: 8896.

The Shockable rhythms of ventricular fibrillation and pulseless

ventricular tachycardia are less common in children than adults but still arise in one quarter of pediatric resuscitations. Similar to adults, children with shockable rhythms are more likely to survive compared to children with Non-shockable rhythms. Prompt defibrillation termi- nates the ventricular arrhythmia by applying asynchronous current to the heart.

The ideal dose of energy to maximize the likelihood of restoring a perfusing rhythm is unclear. The American Heart Association’s pediatric advanced life support (PALS) guidelines recommend administering 2-4 J /kg. Meanwhile, the European, Australian, and New Zealand Resus- citation Councils recommend 4 J/kg. Larger energy doses may ensure sufficient delivery of energy to the heart to terminate an arrhythmia but may also increase damage to the myocardium. Animal studies have only found significant damage with extremely large amounts of energy (>10 J/kg) [6,7]. Prior studies in humans have identified poten- tial benefits to larger energy doses [8]. However, they are limited by small sample sizes with heterogeneity in the presenting rhythm and age of the subjects.

In this study, Hoyme et al. measured the association between various defibrillation energy doses and survival. They included children

<=18 years of age in the Get With the Guidelines Resuscitation database

from 2000 to 2016 suffering in-hospital cardiac arrest with an initial presenting rhythm of ventricular fibrillation or pulseless ventricular tachycardia. The American Heart Association oversees the Get With the Guidelines database, which prospectively enrolls children with car- diac arrest from multiple hospitals. As the American Heart Association guidelines recommend weight-based dosing only for pre-pubertal chil- dren, the authors focused primarily on children <=12 years of age. With defibrillators only capable of delivering discrete doses of energy, the authors considered doses of 1.7-2.5 J/kg to reflect intent to deliver approximately 2 J/kg. They compared this Dose range to smaller and larger energy doses. Survival to hospital discharge was the primary outcome measure, with a secondary outcome of return of circulation. The authors attempted to control for confounders by including patient (e.g., demographics and co-morbidities), arrest (e.g., etiology, witnessed, rhythm), and Environmental factors (e.g., location, time of day) in a multivariate model.

During 17 years, 1624 children with in-hospital cardiac arrest and an initial rhythm of ventricular fibrillation or pulseless ventricular tachy- cardia were enrolled in the database, but complete data were only available for 422 children, with 301 of these children <=12 years of age. The mean patient age was 3 years. 57% of children had ventricular fibril- lation, and on average they were defibrillated within 4 min of their arrest. 41% of children received an energy of 1.7-2.5 J/kg, 31% received

<1.7 J/kg, and 28% received >2.5 J/kg.

For children <=12 years, those given doses outside the 1.7-2.5 J/kg range were less likely to survive compared to children given 1.7-2.5 J/ kg (adjusted OR = 0.64; 95% CI: 0.44-0.89). When the cohort was di- vided into smaller samples to compare doses <1.7 J/kg (adjusted OR = 0.73; 95% CI: 0.47-1.2) or > 2.5 J/kg (adjusted OR = 0.55; 95%

CI: 0.29-1.0) to the 1.7-2.5 J/kg range, the confidence intervals for the odds ratios broadened and crossed 1.0. There were no differences between doses in the likelihood of return of circulation. There were also no differences based on defibrillation dose in outcomes for children

>12 years of age; although, a sub-analysis including children <18 years with initial ventricular fibrillation showed doses >2.5 J/kg were associ- ated with decreased survival (adjusted OR = 0.44; 95% CI: 0.23-0.84). There are several important limitations. First, the study transpired over 17 years and therefore encompassed many advances in resuscita- tion care that have improved survival. A larger proportion of children

in the low defibrillation dose group were from recent years, and this may have impacted their outcomes. Children receiving defibrillation doses outside the range recommended by the American Heart Associa- tion may also have been more prone to receiving other resuscitation measures that deviated from guidelines, including those guidelines with robust evidence to support their use. This may have reduced their survival. The authors focused on the initial presenting rhythm. Often ventricular fibrillation or pulseless ventricular tachycardia arise in the midst of prolonged Pediatric resuscitations, and it is unclear if the findings from this study would apply to children in these situations. The authors also did not assess the dose of subsequent defibrillations. There was a substantial amount of missing data, and missing cases had lower survival. Finally, it is important for emergency physicians to note that two thirds of these arrests transpired in the intensive care unit, with nearly three quarters of patients already on mechanical ven- tilation. It is unclear if the results would be the same for children arrest- ing in the ED or pre-hospital setting.

This is the largest study of pediatric defibrillation dose for cardiac ar- rest. In children <12 years of age, defibrillation doses approximating the AHA recommendation of 2 J/kg were associated with improved survival. The study lacked sufficient power to determine the exact ideal energy dose. While the authors did not find significant differences in outcomes between defibrillation doses when including adolescents, the American Heart Association recommends administering standard adult defibrilla- tion doses for adolescents. Further studies are needed to determine the ideal energy dose in the ED, but this study provides the strongest evi- dence to date, supporting the Initial administration of 2 J/kg to defibril- late children presenting with ventricular fibrillation or pulseless ventricular tachycardia.

  1. Inhaled magnesium for refractory asthma exacerbations

Schuh S. et al. Effect of nebulized magnesium vs placebo added to albu- terol on hospitalization among children with refractory acute asthma treated in the emergency department: a randomized clinical trial. JAMA. 2020; 324(20): 203847.

Many children with severe asthma fail to respond to treatment with

inhaled beta agonists and corticosteroids. inhaled magnesium sulfate induces bronchodilation, improving lung function. A multicenter study in the United Kingdom found that inhaled magnesium improvED asthma severity scores for children in the ED, and the British Thoracic Society recommends administration of nebulized magnesium for chil- dren with severe asthma and hypoxemia [9,10]. A 2017 Cochrane re- view of 25 studies, including studies of adults and children, concluded that nebulized magnesium may reduce hospitalizations, particularly in patients with severe asthma exacerbations [11]. However, the Cochrane review noted that the overall poor quality of the data limits this conclu- sion, particularly for children.

In this randomized, double blind, placebo controlled trial, Schuh et al. studied the effect of inhaled magnesium on the need for hospital- ization in 818 children 2 to 17 years of age in 7 Canadian EDs. All chil- dren received standard of care therapy with an oral corticosteroid and 3 consecutive treatments of inhaled albuterol and ipratropium bromide via inhaler or nebulizer. If they did not improve after one hour, children with moderate to severe exacerbations of their asthma, as defined by Pediatric Respiratory Assessment Measures (PRAM) score of >=5, were enrolled. Children were randomized to 3 consecutive nebulizations with either albuterol and 600 mg (1.2 ml) of magnesium sulfate or albu- terol and 5.5% saline. The primary outcome was the need for hosp- italization, as determined by the emergency physician. Secondary outcomes included improvements in PRAM score and adverse events. The trial was powered to detect a 10% difference in need for hospitaliza- tion between groups.

Enrolled children were relatively sick, with a median PRAM score in the ED after one hour of Standard therapy of 6. One quarter (24%) had been admitted for asthma in the last year, and 10% had previously

been admitted to the ICU. However, the patients were not critically ill, as children requiring emergent airway management or receiving intrave- nous magnesium during the first hour of treatment were excluded. Nearly half of children (46%) were hospitalized within 24 h of enroll- ment. There were no significant differences between patients receiving inhaled magnesium (44%) and placebo (48%) in frequency of admission within 24 h. There also were no differences in return for medical care within 72 h. There were no significant differences in PRAM scores, respi- ratory rate, oxygen saturations, or attributable serious adverse events between the groups. A subgroup analysis of children with severe exac- erbations (PRAM score >= 8) also did not show any difference between inhaled magnesium and placebo.

The most significant limitation of this study is that the decision to admit patients was not standardized. Physicians independently deter- mined the need for admission, and this may have impacted the primary outcome. However, it is unlikely this would systematically bias the re- sults; patients were randomized to the intervention, and physicians were blinded to the intervention. In addition, inhaled magnesium showed no significant benefit with objective outcome measures, such as oxygen saturation and respiratory rate.

This large, robust randomized controlled trial showed no benefit to inhaled magnesium for children in the ED with asthma exacerbations refractory to treatment with inhaled beta agonists and corticosteroids. Based on these results, we recommend employing alternate therapies, such as intravenous magnesium or terbutaline, for moderate to severe asthma exacerbations that fail initial standard therapy. Unlike inhaled magnesium, small studies suggest that intravenous magnesium reduces the need for admission and the duration of hospitalization for severe asthma exacerbations [12].

  1. Neonatal fever

Lyons T. et al. Performance of the modified boston and philadelphia criteria for invasive bacterial infections. Pediatrics 2020, April; 145 (4): e20193538.

Fever in infants under 60 days of age is a diagnostic challenge in the ED, given that physical examination alone cannot reliably delineate be- nign viral infections from serious bacterial infections [13-15]. As a result, febrile infants in this age range often undergo blood, urine and cerebro- spinal fluid (CSF) testing to evaluate for bacterial infections. Many will also be admitted and receive parenteral antibiotics until cultures are deemed negative, typically at 48 h. There have been several attempts to develop criteria to risk stratify these patients to avoid unnecessary admissions and antibiotic use. Two of the more widely used criteria are the Boston and Philadelphia criteria [16,17]. Developed in the early 1990s, both criteria use peripheral white blood cell count , CSF WBC, and the presence of pyuria to identify infants at low risk for having bacterial infection. The epidemiology of serious bacterial in- fections in this patient population has changed dramatically since these criteria were validated, with herd immunity from conjugated Haemophilus influenza and pneumococcal vaccine use, as well as maternal group B Streptococcus (GBS) prophylaxis [18-23].

In this study, Lyons et al. assessed the diagnostic accuracy of the Bos- ton and Philadelphia criteria to identify children at low risk for invasive bacterial infections. The study was a planned secondary analysis of data that was originally obtained for the Pediatric Emergency Medicine Col- laborative Research Committee herpes simplex virus study. The original study was a retrospective, cross-sectional study of infants evaluated for meningitis. It included data from 23 EDs in the United State and Canada from 2005 to 2013. For this study, a secondary analysis was performed

on data from patients aged 29 to 60 days with CSF and blood culture ob-

Urine microscopy performed, particularly children with a negative screening urinalysis (Table 3). When applying the modified criteria to patient data, if any of the high risk predictors was present, the patient was no longer considered low risk for bacterial infection.

The primary outcome was performance of the criteria with respect to invasive bacterial infection, which was defined as either blood or CSF culture growing pathogenic bacteria. Secondary outcome was per- formance of criteria with regards to any bacterial infection, which was defined as bacteremia, meningitis, or a urinary tract infection . UTI was defined as any urine culture growing >=50,000 colony-forming units of a pathogenic bacteria or a urine culture with >=10,000 CFUs of a pathogenic bacteria and pyuria (>10 WBC per high-power field [hpf], or positive Leukocyte esterase).

The study included 10,928 infants who met inclusion criteria. Of these, 264 (2.4%) had invasive bacterial infection, with 193 (1.8%) hav- ing bacteremia, and 71 (0.6%) having Bacterial meningitis. Adequate laboratory data was present in 76% of infants to apply the modified Bos- ton criteria, and 74% of infants to apply the modified Philadelphia criteria. No significant differences were found in clinical or laboratory characteristics between the cohorts. Secondary outcome analysis was performed on 10,286 infants who had a urine culture documented.

When the modified criteria were applied to the cohorts to identify bacteremia or meningitis, the modified Boston criteria had a sensitivity of 63% (95% CI 56-69%) and a specificity 59% (95% CI 58-60%). The mod- ified Philadelphia criteria had a sensitivity of 72% (95% CI 65-78%), and a specificity of 46% (95% CI 45-47%). They showed similar positive and negative predictive values (PPV, NPV), with Boston and Philadelphia criteria having NPVs of 98% and 98% and PPVs of 3.9% and 3.5%, respec- tively. Both criteria performed somewhat better when evaluating for urinary tract infection in addition to bacteremia or meningitis, with the Boston criteria having a sensitivity of 79% (95% CI 77-82%) and spec- ificity of 65% (95% CI 64-66%), and the Philadelphia criteria having a sensitivity of 86% (95% CI 84-88%), and specificity of 51% (95% CI

50-53%).

There were several limitations that impact the conclusions from this study. As the study was retrospective, the authors were unable to deter- mine several factors that were criteria in the original Boston and Phila- delphia criteria, including infants’ overall appearance, physical examination findings, and comorbidities. Similarly, they were only able to include infants with blood and CSF culture results, and so were unable to analyze data from ~700 infants. Finally, the authors acknowl- edge that the original criteria were not developed to identify invasive bacterial infections, but rather to detect infants a low risk who could be managed as outpatients. They note that this study cannot determine if those infants with bacteremia or meningitis, who were classified as low risk could have been safely discharged and managed as outpatients. When used to identify bacterial infections in febrile infants, this study of a large, multinational cohort found that the Boston and Phila- delphia criteria do not perform well. In patients with bacteremia or meningitis, both criteria misclassified approximately one third of these infants as being low risk, and therefore appropriate for discharge. While the overall prevalence of bacteremia or meningitis in this study (2.4%) is similar to prior derivation studies (0-5%), the authors posit that the difference between historical performance of the criteria and

Table 3

Modified Boston and Philadelphia high risk predictors of bacterial infection.

Boston Philadelphia

Blood WBC >=20,000 per mm3 WBC >=15,000 per mm3

tained within 24 h of ED arrival. Patients admitted to the ICU were ex-

Urine WBCs >10 per hpf (or)

Positive leukocyte esterase

WBCs >10 per hpf (or)

Positive leukocyte esterase

cluded, as the original criteria were developed to evaluate well appearing infants. Both the Boston and Philadelphia criteria were mod- ified in order to apply them to the study population; both original criteria require urine microscopy, and not all patients in the study had

CSF WBCs >=10 per hpf WBCs >=8 per hpf (or) Positive CSF gram strain

Abbreviations: CSF = cerebrospinal fluid; WBC = white blood cell count; hpf = high power field.

the performance in this study may be due to the changing epidemiology of bacterial infections in infants. Derivation studies for both Boston and Philadelphia criteria showed 11-25% of infections were caused by

H. influenza, and 11-15% by S. pneumonia, whereas the current study re- ported only 1% and 5% of bacterial infections were caused by each re- spectively [16,17,20,22-24]. This change in epidemiology could lead to a difference in immune response, which both criteria rely on heavily. Future studies should be directed at developing better risk stratification criteria, considering the current pathogens leading to invasive bacterial illness in children.

  1. Fingertip injuries

Seiler M. et al. Non-operative treatment versus suture refixation of the nail plate in pediatric fingernail avulsion injuries. J Hand Surg Eur Vol. 2020 Oct 22:1753193420965390.

Fingertip injuries with fingernail avulsions are one the most com- mon hand injuries seen in children in EDs [25-27]. Risk of nailbed injury and resultant nail deformities is higher with severe injuries, such as displaced fractures and substantial nailbed lacerations. With isolated nail plate avulsion without these Significant injuries, current recom- mendations still include suturing the avulsed nail plate back in place, with the proximal edge under the eponychial fold [27-29]. Given the age of the patients in which this injury commonly occurs and the com- plexity of the procedure, this often requires procedural sedation to en- sure success.

In this study, Seiler et al. report the results of a prospective, single center cohort study comparing non-operative management of isolated nail plate avulsion with the traditional management of replacing the nail in the epnychial fold in Switzerland. Patients aged 1 to 16 years with proximal or complete fingernail avulsion were included. Exclusion criteria included signs of severe injury, such as displaced phalanx frac- ture or nailbed laceration with gap >1 mm as well as delayed presenta- tion (>24 h after injury). Given the patient population and parental preferences where the study took place, the authors concluded that ran- domization of treatment would have been unacceptable to parents. Therefore, after thorough explanation of treatment options, parents were asked to choose a treatment option. Patients in the operative group had either the nail or a silicone substitute (if the nail was lost) su- tured in place with non-absorbable sutures that were removed after 3 weeks. Patients in the non-operative group had the wound cleansed and disinfected with chlorhexidine and despanthenol, then dressed with a non-adherent ointment dressing. If the nail was incompletely avulsed, the proximal end was shortened prior to dressing. Non- displaced fractures were splinted with a forearm based palmar hand splint. Patients were seen in follow up at 5, 10 and 21 days, and then at 6 months.

The primary outcome was the appearance of the new nail as judged using the Nail Appearance Score (NAS) at the 6 month follow up visit [30]. This score takes into account 6 different criteria and averages them to determine a final score between 1 (worst possible outcome), and 4 (normal nail). The primary outcome was calculated by averaging the scores assigned by two physicians who were blinded to the treat- ment groups. Secondary outcomes included patient and parental satis- faction with the new nail, as well as signs of local infection. The study was designed to test for non-inferiority between the operative and non-operative groups with regard to the primary outcome. The non- operative group was considered non-inferior to the operative group if the Nail Appearance Score for the operative group was no more than 1/3 of a point better on average than the non-operative group.

During a three year period, 50 patients were enrolled, 38 into the non-operative group, and 12 into the operative group. Groups did not differ in age, gender, or presence of fracture on X-ray, although a higher percentage of patients had proximal partial avulsion rather than com- plete avulsion in the operative group vs non-operative group (92% vs 58% respectively; p = 0.039). Four patients in the operative group

received ketamine sedation vs one patient in the non-operative group (p = 0.009). Overall, both groups did well at follow up, with a mean Nail Appearance Score of 3.96 (95% CI: [3.93; 3.99]) for the operative group, and 3.98 (95% CI: [3.97; 3.99]) for the non-operative group. The authors conclude that the non-operative management is not inferior to standard management. There was also no difference in parent and patient satisfaction with the outcome as judged by a 4 point Patient and Parental Nail Satisfaction Score (PNSS), with the operative group and non-operative group reporting a score of 3.92 (95% CI: 3.65-3.99) and 3.98 (95% CI: 3.87-4.00) respectively. There were no signs of local infection in either group.

There were several limitations to this study. The first, and most sig- nificant limitation was that the study was not randomized, thus making the data susceptible to selection bias. It was also performed at a single institution, perhaps making it difficult to generalize. The study was small, and as such was underpowered to determine whether a differ- ence exists between groups, limiting the authors to a non-inferiority analysis. In addition, while the authors considered parental satisfaction about the final appearance of the nail, they did not assess satisfaction with the initial ED treatment, where non-operative management would likely prove superior. Finally, the study is difficult to compare with other previous studies, as the authors note that there is no univer- sally accepted scoring system for nail outcomes.

In this small, prospective cohort study, the outcomes of fingernail avulsions were excellent in all patients, whether managed by conserva- tive methods, or by traditional operative repair. Statistically, operative repair was not superior to non-operative repair. In addition, patients re- ceiving operative treatment were more likely to necessitate procedural sedation, which carries added risk, resource use, and cost. For simple nail avulsion injuries, we recommend discussing the benefits and risks of both treatment options with parents, and together deciding about op- erative or non-operative management.

  1. Rapid sequence intubation

Conway JA, et al. Ketamine Use for Tracheal Intubation in Critically Ill Children Is Associated With a Lower Occurrence of Adverse Hemodynamic Events. Crit Care Med. 2020 Jun;48(6):e489-e497.

In the ED, critically ill children often require tracheal intubation. The combination of vasodilation and decreased preload caused by most in- duction agents coupled with the increased intrathoracic pressure from initiation of positive pressure ventilation has the potential for serious complications, including hypotension, dysrhythmias, cardiac arrest, and death. In the setting of a critically ill patient with hemodynamic in- stability, these risks are potentially greater, and induction agents and doses are typically chosen based on the potential mitigation of these complications.

Through antagonism of the N-methyl-D-aspartate receptor, keta- mine causes analgesia, dissociative anesthesia, and sedative effects. While it does produce decreased myocardial contractility, it is a sympa- thomimetic, blocking norepinephrine reuptake, resulting in preserva- tion of systemic vascular resistance and therefore hemodynamic status. Based on this, ketamine is often recommended as the induction agent of choice for hemodynamically unstable children [31-33]. Al- though this recommendation is based on the physiologic response to ketamine, there is limited data supporting it in children, and several adult studies suggest persistent or worsening hemodynamic instability with ketamine [34-36].

In this study, Conway et al. compared the occurrence of adverse he- modynamic tracheal intubation associated events between patients un- dergoing ketamine induction (either ketamine alone or in combination with other medications) versus all other induction agents. The study was a retrospective analysis of data from the National Emergency Air- way Registry for Children, which prospectively enrolled children under- going intubations in pediatric intensive care units from 2013 to 2017. The primary outcome was occurrence of adverse events (dysrhythmias,

hypotension requiring intervention, hypertension requiring interven- tion, or cardiac arrest) occurring within 20 min of an intubation. The au- thors also looked at the subgroup of children undergoing intubation for pre-intubation hemodynamic instability/shock compared to children with other indications for intubation. Ketamine dose was broken into quartiles, and a dose dependent effect was measured by quartile. The authors sought to limit confounding by adjusting for patient, provider, and practice characteristics through multivariate logistic regression.

The authors analyzed 10,750 intubation events, with 3436 (32%) in- cluding ketamine as an induction agent. Mean ketamine dose for induc- tion was 1.9 mg/kg (+-1.1 mg/kg). Ketamine induction was used for 41% of intubations with hemodynamic instability. Ketamine was associated with increased use of video laryngoscopy (24% with ketamine vs 19% without ketamine, p < 0.001), and resident physicians were less likely to attempt intubation with ketamine induction (9.7% with ketamine vs 15% without ketamine, p < 0.001). Analysis of the primary outcome showed adverse events arose in 5.5% of intubations. Hypotension was observed in 3.3%, cardiac arrest in 1.4%, and dysrhythmias in 1.3%. Keta- mine was associated with decreased odds of adverse events overall (un- adjusted OR = 0.75; 95% CI, 0.62-0.90). This effect persisted when controlling for patient and Provider characteristics, site, device used, and Neuromuscular blockade (adjusted OR = 0.74, 95% CI, 0.58-0.95). The lower frequency of adverse events with ketamine also persisted in children intubated for pre-intubation hemodynamic instability. When examining ketamine dosing, higher doses (mean dose >1.5 mg/kg) were associated with lower adverse events compared to mean doses of 0.88 mg/kg (unadjusted OR = 0.64; 95% CI, 0.49-0.84).

There are several limitations to this study. As with any retrospective

cohort study, there are limitations to which data points are available for analysis. The authors note that this data set does not provide detailed pre-intubation clinical information, including the degree of preexisting hemodynamic instability, vasopressor use, and vital signs at the time of intubation. Another limitation was that data were self-reported, which raises the risk of reporting bias and inaccuracies. The authors attempted to mitigate this by conducting site-specific data checks and compliance plans. The retrospective nature of this study also makes it particularly vulnerable to selection bias, e.g., many practitioners chose ketamine specifically for patients whom they ascertained were at risk of hemodynamic instability. A prospective randomized controlled trial would be able to mitigate this bias. Lastly, this study looks at inductions for intubation only in an intensive care unit (ICU) setting. Ketamine’s ability to preserve hemodynamic stability is due to sympathomimetic effect stemming from inhibition of norepinephrine reuptake, and there- fore is only possible in a state of catecholamine repletion. In the ED set- ting it is possible that patients would have greater catecholamine reserves than patients in the ICU. It is therefore possible that the protec- tive effect of ketamine would actually be greater in ED patients.

This is the largest study of ketamine induction in children, and it showed ketamine induction is associated with fewer adverse events when compared to other agents. This effect is seen irrespective of whether the patient has baseline hemodynamic instability. This protec- tive effect appears to be dose related, with higher doses associated with less adverse events. Although future prospective randomized controlled trials are needed to validate these findings, particularly in the ED setting and in unique cohorts (e.g., patients with sepsis), these findings support the use of ketamine induction for intubation in children with hemody- namic instability.

  1. Traumatic scalp hematomas in infants

Schutzman S. et al. The infant scalp score: a validated tool to stratify risk of traumatic brain injury in infants with isolated scalp hematoma. Aca- demic Emergency Medicine. 2020; 00:0:16.

Infants with head trauma are difficult to assess in the ED, as they

cannot communicate readily. They are also at high risk from the

radiation associated with CT to identify injuries. Several prediction models have been derived and externally validated to assist clinicians with determining the need for CT for these patients [37-40]. Each of these prediction models include scalp hematomas as a risk factor for brain injury. For example, the Pediatric Emergency Care Applied Re- search Network (PECARN) model classifies an infant with a scalp hema- toma as moderate risk, recommending observation or CT (Fig. 1). This recommendation is less useful than when the PECARN model classifies children as low or high risk and provides a definitive recommendation about the need for CT. Often children in the moderate risk category un- dergo CT despite infrequently harboring significant brain injuries [41,42].

The study by Schutzman et al. aimed to provide additional risk strat- ification for infants falling into this moderate risk category as a result of a scalp hematoma. Prior to the publication of the PECARN prediction model, the authors derived a risk score for infants with scalp hemato- mas based on the size and location of the hematoma as well as the infant’s age (Table 4) [43]. Younger age, larger hematoma size, and a temporal or parietal location harbored higher risk of brain injury. This derivation study was limited by a small sample size.

In the current study, the authors reviewed data for infants <1 year of age from the PECARN derivation study, which prospectively enrolled children presenting within 24 h of Blunt head trauma with Glasgow Coma Scale scores of 14-15. Schutzman et al. focused on those infants from PECARN with isolated scalp hematomas without other risk factors from the PECARN model, i.e., the infants did not have altered mental sta- tus, abnormal behavior per the parent, loss of consciousness, seizure, vomiting, neurologic deficit, or palpable Skull fractures. The authors cal- culated the scalp score utilizing characteristics of the hematoma re- ported by the treating clinicians as part of the original PECARN study. The primary outcome was clinically important brain injury, which in- cluded death, need for neurosurgery, intubation for >=24 h, or hospitali- zation for >=2 nights. The presence of any traumatic injury on CT was a secondary outcome. CTs were obtained at the discretion of the treating clinician. Study personnel successfully contacted 79% of patients not un- dergoing CT for follow-up to determine if a clinically important injury had occurred.

The authors validated the risk score in the 1289 infants from the PECARN study sample with isolated scalp hematomas and no other concerning signs or symptoms. Two thirds of these patients were 6-12 months of age, 36% underwent CT, 0.9% had clinically important brain injuries, and 4.6% had any injuries on CT. Greater scalp scores were associated with increased risk of brain injury (Fig. 2). 68% of in- fants had scalp risk scores <5, and none of these infants had clinically important injuries, yielding a sensitivity of 100% (95% CI: 74-100%) and specificity of 69% (95% CI: 66-71%). Nearly half of infants had scores

<4, and none of these children had any injury on CT. Interestingly, 23% of the CTs obtained on infants in the original PECARN study were on children with scalp scores <4. This study demonstrates that these pa- tients with scores <4 were at Very low risk of injury, and they likely could have been safely discharged without CT acquisition.

The primary limitation of this study is the sample size. While the cur- rent study was much larger than the original scalp score study, it only included 12 infants with clinically important brain injuries. As a result, the confidence interval for the sensitivity of the score is wide, with a lower bound of 74% for a scalp score of <5. Another potential issue is that identification of hematomas may be difficult, as demonstrated by the intermediate Interobserver agreement on the presence of hemato- mas (? = 0.66) It is also crucial to recognize that the scalp risk score does not apply for children with head injuries potentially arising in the setting of non-accidental trauma.

The scalp score helps to risk stratify infants with isolated scalp he- matomas after head trauma. It is particularly useful when a child is clas- sified as medium risk by the PECARN model based on the presence of a scalp hematoma. Calculation of the scalp risk score allows clinicians to

Image of Fig. 1

Fig. 1. PECARN model for head injury in infants [37].

determine the risk of injury more accurately. Nearly half of children will have risk scores <5 and have very low risk of clinically important inju- ries. Lower scalp scores are associated with even lower risk of injury, and we rarely obtain CT for children with scores <4. Meanwhile, youn- ger infants with large hematomas in their temporal or parietal regions have higher scalp scores and may need to undergo CT.

  1. Multisystem inflammatory syndrome in children

Jonat B. et al. Multisystem Inflammatory Syndrome in Children Associ- ated With Coronavirus Disease 2019 in a Children’s Hospital in New York City: Patient Characteristics and an Institutional Protocol for Evaluation, Management, and Follow-Up. Pediatr Crit Care Med. 2020 Sep 29.

In March 2020, as the first surge of the severe acute respiratory syn- drome coronavirus 2 (SARS-CoV-2) pandemic spread globally, a novel inflammatory syndrome temporally associated with SARS-CoV-2 infec- tion and specific to children began to be reported. This illness was ulti- mately designated as multisystem inflammatory syndrome in children by the United States Centers for Disease Control (CDC) [44- 46]. While phenotypically similar to Kawasaki disease, MIS-C is distinct in that it appears to affect a wider age range of patients. In addition to the typical Kawasaki Disease symptoms, it often manifests with gastro- intestinal symptoms, and may present with neurological symptoms, myocardial depression, and shock. Since the recognition of MIS-C, guidelines have been developed for the identification and evaluation of the disorder, but there is little evidence to guide treatment [47,48].

In this study Jonat et al. developed and implemented a clinical proto- col for suspected MIS-C at a quaternary care pediatric referral center. They aimed to improve timely recognition of MIS-C, risk stratify pa- tients, and reduce coronary artery injury, hemodynamic instability, and end organ injury. The protocol was developed based largely on ex- pert opinion from various pediatric subspecialties. Patients were screened using the New York State Department of Health case definition

Table 4

Risk score for brain injury is determined by summing points for age, size, and location of the scalp hematoma.

Risk Score Points

Age (months)

Size (cm)

Location of hematoma

0

>12

N/A

Frontal

1

6-11

<1

Occipital

2

3-5

1-3

Temporal or Parietal

3

0-2

>3

N/A

criteria, which considers clinical, laboratory, epidemiological and viral testing characteristics. Children <21 years of age were included if they displayed fever >38o C and signs of severe systemic inflammatory pro- cesses (hypotension, cardiac disease, or end-organ damage) or two of the following less severe signs: maculopapular rash; bilateral non- purulent conjunctivitis; inflammation of the mouth, hands, or feet; or diarrhea, vomiting, or abdominal pain). Children with other more likely causes for their symptoms (e.g., bacterial sepsis or other viral infection) were excluded. Children with confirmed SARS-CoV-2 by PCR or serum antibodies, typically underwent laboratory and viral testing, including systemic inflammation markers (complete blood count, C-reactive pro- tein, erythrocyte sedimentation rate, fibrinogen, D-dimer, ferritin, lactic acid dehydrogenase, interleukin 6, or procalcitonin), markers of end- Organ function, cardiac function, and testing to rule out other infectious causes of symptoms. In addition, all patients had chest radiography and echocardiography as part of their initial evaluation. Once identified, suspected and confirmed cases of MIS-C were stratified as mild, moder- ate, or severe based on inotropic support (Vasoactive-Inotropic Score [VIS]), respiratory support and evidence of organ injury. In some pa- tients with mild disease, minimal inflammation, no cardiac involve- ment, and no shock, treatment was deferred in favor of observation and serial testing.

Fig. 3 depicts the treatment algorithm. All patients treated for

MIS-C received broad-spectrum antibiotics, proton pump inh- ibitors, anticoagulation with low-molecular-weight heparin or

Image of Fig. 2

Fig. 2. Percent risk of having a clinically important brain injury by scalp score in infants.

low-dose aspirin, and 2 g/kg dose of Intravenous immunoglobulin . Intensity of further immunomodulation with methylpred- nisolone and/or anakinra, as well as a repeat dose of IVIG was dic- tated based on the clinical severity of symptoms and initial response to therapy. All patients underwent varying lengths of ste- roid taper as determined by the duration and intensity of their ini- tial treatment course.

The authors report data for 54 patients admitted for MIS-C from mid-March to early June 2020; 26 were admitted before and 28 after implementation of the protocol. Demographic characteristics were sim- ilar between the pre- and post-protocol groups with regard to age, sex, race, and ethnicity. Presenting symptoms were similar among the groups as well, with GI symptoms being the most common (83%), followed by rash (76%), and conjunctivitis (57%). Pre-protocol patients had higher median C-reactive protein (224 mg/L pre- vs. 108 mg/L post-protocol; p = 0.04), interleukin-6 (266 pg/mL pre- vs. 76 pg/mL post-protocol p = 0.03), and N-terminal-pro B-type natriuretic peptide (5968 pg/mL pre- vs. 559 pg/mL post-protocol; p < 0.01).

No difference was found in rate of glucocorticoid or IVIG use between groups, but the authors did find a reduction in time to admin- istration of the first dose of IVIG in the post-protocol group (33 h pre-protocol vs. 20 h post-protocol; p = 0.02). They also report a trend toward reduction in median time to first glucocorticoid dose

(26 h (range 1-285) pre-protocol vs. 11 h (range 1-46) post-protocol; p = 0.05). A higher percent of pre-protocol patients were admitted to the Pediatric Intensive Care Unit (PICU) than post-protocol patients (73% vs. 43% respectively; p = 0.02). Patients in the pre-protocol group had significantly longer PICU lengths of stay and overall hospital length of stay, with pre-protocol patients staying in the PICU a median of 5 days and the hospital a median of 6 days vs. 3 days in the PICU and 3 days in the hospital in the post-protocol group (p < 0.01). All patients in both groups survived to discharge.

While the data suggest that implementation of this treatment protocol resulted in a reduction in treatment delay and a decrease in hospital length of stay, the authors discuss several caveats and po- tential limitations to these findings. First, all patients with MIS-C at their institution had pediatric cardiology, pediatric infectious dis- ease, and pediatric rheumatology consults, emphasizing the multi- disciplinary approach that these patients necessitate. Secondly, while the decrease in PICU admission and overall length of stay re- ported were associated with a decrease in Time to administration of immunomodulators, the authors do mention potential con- founders of this association. Patients in the pre-protocol group ap- peared more severely ill at the time of presentation, as evidenced by higher inflammatory markers. Given that MIS-C is a novel pro- cess, it may be that the post-protocol group had decreased length

Image of Fig. 3

Fig. 3. Management of children with concern for multisystem inflammatory syndrome.

of stay and PICU admission secondary not to administration of IVIG and/or glucocorticoids earlier in the hospitalization, but rather ear- lier in the disease course. As clinicians gained experience with diag- nosing and treating MIS-C, they likely demonstrated earlier recognition of signs and symptoms of the disease process, and could have initiated treatment for patients earlier in the course of ill- ness, mitigating poor outcomes. Finally, a Hawthorne effect among physicians may have induced a change in behavior simply through the knowledge that their behavior was being studied. Finally, the study was not powered to detect differences in mortality.

Although this protocol focuses primarily on inpatient management of MIS-C, these patients will present initially to the ED for evaluation and treatment. As with any illness, early treatment relies on early recog- nition and diagnosis, which in the case of a novel disease process can be difficult. This may prove especially challenging for those practicing in the ED or urgent care setting, where respiratory illness and undifferen- tiated fever are among the most common reasons for pediatric patients to seek care. We encourage maintaining a high index of suspicion for MIS-C, initiating a work-up, including the tests outlined above to iden- tify these patients quickly, allowing for prompt admission or transfer, and timely initiation of potentially beneficial therapy, such as steroids and IVIG.

  1. Racial and ethnic differences in pain control

Goyal T. et al. Racial and Ethnic Differences in Emergency Department Pain Management of Children With Fractures. Pediatrics. 2020 May;145 (5):e20193370.

Pain is the most common reason for patients to present to the ED. The assessment and management of pain is different in children com- pared to adults, and children are more often undertreated for pain [49-52]. In addition, racial and Ethnic disparities in pain management have been demonstrated for specific pediatric cohorts, such as undiffer- entiated abdominal pain and acute appendicitis [53,54]. When evaluat- ing the management of pain associated with Long-bone fractures, the data has been more mixed, with some small or single center studies showing racial and ethnic disparities [55-57].

In this multicenter retrospective cohort study, Goyal et al. analyzed data from the Pediatric Emergency Care Applied Research Network to assess differences in pain management based on race and ethnicity amongst children with long-bone fractures. The study included 7 pedi- atric EDs over a geographically diverse area. Data was included for pa- tients <18 years old presenting to the ED with long-bone fractures, including fractures of the radius, ulna, humerus, clavicle, femur, tibia, or fibula. They excluded visits that did not have pain scores recorded, or if the scores recorded indicated mild pain only. They also excluded children who were assigned an Emergency Severity Index of 1 (critically ill) or 5 (non-urgent) at ED triage. The study outcomes were receipt of any pain medication or receipt of Opioid pain medications. They also measured overall reduction in pain (reduction of >=2 points on the pain score within 90 min of the highest pain score) and optimal reduction in pain (reduction of pain to mild or no pain within 90 min of the highest pain score). Patients were classified as non-Hispanic African

American, non-Hispanic white, Hispanic, or other. The authors con- trolled for several potential confounding variables, including other de- mographic variables, injury severity, ED disposition, site, and clinician. Over a three year period, there were 34,544 ED visits for long-bone fracture treatment, including 21,069 visits with moderate to severe pain scores. Overall, 86% of children received at least one dose of pain medication. When adjusted for confounders, the authors found that non-Hispanic African American and Hispanic children were more likely to receive any analgesia than non-Hispanic white children, but they were less likely to receive Opioid analgesia (Table 5). For 8533 visits a re- assessment of pain was documented. Analysis of these visits showed that 89% of patients had a reduction of their pain score of >=2 points within 90 min, and nearly two thirds (62%) of patients had optimal pain reduction documented within 90 min of the highest pain score. Multivariable adjustment of the clinical outcomes data showed that when compared to non-Hispanic white children, non-Hispanic African American and Hispanic children were more likely to achieve a >= 2 point reduction in pain, but were less likely to achieve optimal reduc-

tion in pain (Table 5).

There are several limitations to this study. First, the parent or patient may have declinED analgesia, and this was not measured. It is possible that there may have been a systematic difference in frequency of refusal of medications based on race or ethnicity. Secondly, only a small per- centage of the total number of visits had a pain reassessment docu- mented, placing the data at risk of ascertainment bias. Notably, there was no disparity between racial and ethnic groups as to which patients had reassessments documented, thus mitigating this risk. Finally, med- ications administered before the ED visit were not measured. If there were differences along racial and ethnic lines in pretreatment prior to the visit, this also may have impacted the outcomes.

This large multicenter study demonstrated racial and ethnic differ- ences in the management of pain in a cohort of children with long bone fractures. When these differences are looked at individually, they seem somewhat contradictory, with minority children being more likely to receive any analgesia and have a Clinically meaningful decrease in pain score, but less likely to receive opioids and achieve optimal pain relief. The authors acknowledge the fact that the reasons for these find- ings are unclear, and posit that perhaps the decreased likelihood of opi- oid administration had a role in the lack of achieving optimal pain reduction in minority children. If true, then it would suggest that while improvements have been made with regard to treating pain in minority populations, more attention may need to be focused on opti- mal analgesia in these patients in the future.

  1. Resuscitation of injured children

Polites S. et al. Timing and volume of crystalloid and blood products in pediatric trauma: An Eastern Association for the Surgery of Trauma multi- center prospective observational study. J Trauma Acute Care Surg. 2020;89: 3642.

Hemorrhagic shock in injured children results in substantial morbid-

ity and mortality. Intravenous crystalloid dilutes clotting factors and platelets, increasing coagulopathy, potentially increasing morbidity.

Table 5

Association of race and ethnicity with treatment of pain for children with Long bone fractures.

Race/Ethnicity Any Analgesic Opioid Analgesic >=2 Point Pain Reduction Optimal Pain Reduction

%

aOR

(95% CI)

%

aOR

(95% CI)

%

aOR

(95% CI)

%

aOR

(95% CI)

White

85

Ref

53

Ref

88

Ref

65

Ref

African American

90

1.7

(1.5-2.0)

40

0.86

(0.77-0.95)

90

1.4

(1.1-1.8)

57

0.78

(0.67-0.90)

Hispanic

86

1.3

(1.2-1.5)

36

0.86

(0.76-0.96)

92

1.4

(1.0-1.8)

60

0.80

(0.67-0.95)

Abbreviations: Ref = reference.

Studies in adults with trauma related shock have shown administration of intravenous crystalloid increases mortality [58,59]. As a result, trauma resuscitation in adults has shifted toward early administration of blood products and not crystalloid boluses. Retrospective studies in children have shown high volume crystalloid infusions with trauma re- lated shock are associated with increased duration of hospitalization, in- tensive care, and mechanical ventilation [60,61].

In this study Polites et al. conducted a 24 center prospective observa- tional study of children <18 years of age with signs of trauma related shock, as defined by an elevated age adjusted Shock Index at the scene of the trauma. The age adjusted shock index is calculated by dividing the heart rate by the systolic blood pressure; the normal range of the calculated shock index is higher for Younger children, who have higher basal heart rates [62]. Children transferred from other hospitals were excluded. The authors compared the amounts and form of resuscitation, including crystalloid boluses and blood products. The primary outcome was survival to hospital discharge, and secondary outcomes were dura- tion of hospitalization and mechanical ventilation. Logistic regression models assessed the association between crystalloid boluses before transfusion of blood products and outcomes, including potential con- founders such as injury severity, massive transfusion protocol activa- tion, and time to transfusion.

The study included 712 children with elevated shock indices, and 88% suffered Blunt injuries. Nearly half (44%) received at least one crys- talloid bolus with a median time to infusion of 28 min (IQR, 13-129). Nearly one quarter of children (23%) received multiple crystalloid bo- luses. Increased crystalloid boluses were associated with increased ad- ministration of blood products. 21% of children received blood products with a median time to transfusion of 50 min (IQR, 15-203). Pa- tients undergoing transfusion were more severely injured (ISS 26 vs. 5, p < 0.001) and more likely to die (23% vs. 0.7%, p < 0.001). Over one quarter (28%) of children undergoing transfusion received blood before any crystalloid bolus. Logistic regression showed no association of re- suscitation strategy with survival to hospital discharge (p = 0.51). In contrast, compared to children receiving <1 crystalloid bolus, children receiving subsequent boluses had increased duration of mechanical ventilation, intensive care, and hospitalization (Table 6).

The largest limitation to this study is that many of the included chil- dren likely were not in shock. While adjusting the shock index for age improves the diagnostic accuracy of the index, it is still not highly pre- dictive of shock [63,64]. This selection bias may have impacted the abil- ity of the study to detect mortality differences, as many children did not have shock and were unlikely to die regardless of the chosen resuscita- tion strategy. In addition, as a Multicenter observational study, there were potentially unmeasured confounders, such as the ratio of blood products given, transport time from the scene to the ED, or the thresh- old to initiate volume resuscitation. A prospective trial is needed to compare the impact of different resuscitation strategies.

This is the largest prospective study of volume resuscitation in in- jured children with shock. It confirms the results of prior retrospective studies, showing that after controlling for injury severity, multiple crys- talloid boluses are associated with increased duration of hospitalization and mechanical ventilation. Increased crystalloid boluses were not asso- ciated with decreased transfusion, suggesting crystalloid infusion does

Table 6 Association of fluid boluses before transfusion of blood products with the duration of me- chanical ventilation, intensive care, and hospitalization.

not obviate the need for blood products. While the study did not directly compare resuscitation strategies, we recommend that for injured chil- dren with signs of shock, clinicians should consider early transfusion and shift to administration of blood products, if additional volume re- suscitation is required after an initial fluid bolus.

Funding

None.

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  1. Centers for Disease Control and Prevention (CDC). Progress toward eliminating Hae-

Crystalloid bolus

Ventilation > 3 days ICU > 6 days Hospitalization > 14 days

aOR 95% CI aOR 95% CI aOR 95% CI

mophilus influenzae type b disease among infants and children-United States, 1987-1997. MMWR Morb Mortal Wkly Rep. 1998;47(46):993-8.

[21] Centers for Disease Control and Prevention (CDC). Perinatal group B streptococcal

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<1

Reference

1

2.4

1.0-5.8

2.0 0.9-4.5 1.4

0.65-3.1

2

3.2

1.3-8.0

2.4 1.0-5.6 3.0

1.3-6.5

>2

3.9

1.4-10.8

8.5 3.4-21 6.4

2.7-15

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