Trends in Incidence and Drug Prescriptions for Croup in Children Under 5 Years of Age: A 2002-2019 Population-Based Study.

BACKGROUND: Tracking national croup trends can provide important insights for childhood health management. This study aimed to analyze the incidence and drug prescription trends in Korean children over a two-decade period. METHODS: This population-based study encompassed 479,783 children aged < 5 years from 2002-2019, utilizing the National Health Insurance Service-National Sample Cohort. We identified participants with a primary croup diagnosis who were admitted to or visited the emergency room. Age-specific and age-adjusted incidence rates/10,000 person-years were calculated. We assessed using orthogonal polynomial contrasts and stratified by various factors (sex, age, residential area, economic status, comorbidities, and healthcare facility types). We observed changes in the use of five medications: inhaled steroids, systemic steroids, inhaled epinephrine, antibiotics, and short-acting bronchodilators. Generalized binomial logistic regression was used to analyze factors influencing prescription strategies. RESULTS: In 2002, the croup-related visits were 16.1/10,000 person-years, increasing to 98.3 in 2019 (P for trend < 0.001). This trend persisted, regardless of age, sex, region, and economic status. Children with comorbid atopic dermatitis or asthma maintained consistent croup rates, while those without comorbidities increased. Treatment trends showed decreasing antibiotic (73-47%) and oxygen use (21.3-3.4%), with increasing nebulized epinephrine (9.3-41.5%) and multiple drug prescriptions (67.8-80.3%). Primary care centers exhibited a greater increase in prescription usage and hospitalization duration than did tertiary healthcare institutions. CONCLUSION: Over the past two decades, croup incidence has risen, accompanied by increased epinephrine use and decreased antibiotic prescriptions. Longer hospitalization and higher medication use were mainly observed in primary care facilities.

Outdoor Cold Air Versus Room Temperature Exposure for Croup Symptoms: A Randomized Controlled Trial.

OBJECTIVES: Croup is the most common cause of acute upper airway obstruction in children. The benefits of treating croup with steroids are well established, with an onset of effect 30 minutes after administration. We investigated whether a 30-minute exposure to outdoor cold air might improve mild to moderate croup symptoms before the onset of action of steroids. METHODS: This open-label, single-center, randomized controlled trial, enrolled children aged 3 months to 10 years with croup and a Westley Croup Score (WCS) ≥2 attending a tertiary pediatric emergency department. Participants were randomized (1:1) to either a 30-minute exposure to outdoor cold (<10°C) atmospheric air or to indoor ambient room air immediately after triage and administration of a single-dose oral dexamethasone. The primary endpoint was a decrease in WCS ≥2 points from baseline at 30 minutes. Analyses were intention to treat. RESULTS: A total of 118 participants were randomly assigned to be exposed to outdoor cold air (n = 59) or indoor room temperature (n = 59). Twenty-nine of 59 children (49.2%) in the outdoor group and 14 of 59 (23.7%) in the indoor group showed a decrease in WCS ≥2 points from baseline at 30 minutes after triage (risk difference 25.4% [95% confidence interval 7.0-43.9], P = .007). Patients with moderate croup benefited the most from the intervention at 30 minutes (risk difference 46.1% [20.6-71.5], P < .001). CONCLUSIONS: A 30-minute exposure to outdoor cold air (<10°C), as an adjunct to oral dexamethasone, is beneficial for reducing the intensity of clinical symptoms in children with croup, especially when moderate.

Impact of Clinical Guidelines on Hospital Utilization in Children With Croup.

OBJECTIVES: To assess the impact of croup guidelines on healthcare utilization and association between guideline-recommended racemic epinephrine (RE) treatments and admission. METHODS: Cross-sectional study of children ≥3 months to ≤8 years with croup diagnosis (International Classification of Diseases, 10th Revision) from 38 hospitals within the Pediatric Health Information System between January 1, 2019 and June 30, 2022. Guidelines were categorized by minimum number of RE treatments recommended before admission. Exclusion criteria included complex chronic or croup mimicking conditions, alternate respiratory diagnoses, and direct admissions or transfers. Primary outcomes were admission rates and standardized costs. Outcomes were compared by guideline availability and different admission thresholds. Mixed effects regression was adjusted for age, sex, race, payer, previous croup encounters, and year. RESULTS: Twenty hospitals (52.6%) had guidelines. Fourteen recommended 2 RE treatments and 3 recommended 3 RE treatment before admission. Among 121 284 croup encounters, overall mean admission rate was 5.7% (range 0.6% to 18.5%). Hospitals with guidelines demonstrated lower unadjusted admission rate (4.6% vs 6.6%; mean difference -2.0, 95% confidence interval -2.3 to -1.7) and higher costs ($704 vs $651; mean difference 53, 95% confidence interval 43 to 63) compared with hospitals without guidelines. Hospitals with guidelines recommending 3 RE treatments demonstrated similar unadjusted mean admission rate (5.1%) and lower costs ($658 vs $713) compared with hospitals with guidelines recommending 2 RE treatments. After adjustment, all above-mentioned differences were not statistically significant. CONCLUSIONS: Many children's hospitals lack guidelines for croup. Admission rates and costs were not significantly different between hospitals with or without guidelines after adjusting for confounders.

Variation in Organizational Clinical Practice Guidelines for Croup.

BACKGROUND: Croup is one of the most common respiratory complaints in pediatric emergency departments (EDs), yet little is known about clinical practice guidelines (CPGs) for this condition. OBJECTIVES: To describe variation in CPGs across US children's hospitals. METHODS: We describe the prevalence and features of CPGs among hospitals that submit data to the Pediatric Health Information System. Each hospital was contacted between January 10, 2022, and April 25, 2022, for their most recent croup CPG and any revisions. Characteristics reported were based on the most recent CPG revision. Characteristics included treatment recommendations, utilization measures, ED observation times, and admission criteria. Interrater reliability between reviewers was reported as percentage agreement. RESULTS: Thirty-eight hospitals (79.2%) responded to our query, of which 20 (52.6%) had croup CPGs. Interrater reliability was moderate-high for categorizing the indication for racemic epinephrine (RE) (19 of 20; 95%), the minimum number of RE doses recommended before admission (15 of 20; 75%), and ED observation time (19 of 20; 95%), and was 100% for all other characteristics. Three CPGs (15.0%) recommended 1 RE dose, 14 (70.0%) recommended 2 RE doses, and 3 (15.0%) recommended 3 RE doses before hospital admission. Thirteen (65%) CPGs recommended RE for stridor at rest, whereas 7 (30%) recommended RE for any degree of stridor. Fourteen (70%) CPGs recommended an ED observation time <2 hours, 3 (15%) recommended 2 to 4 hours, and 2 (10%) recommended >4 hours. Few CPGs (15%) recommended use of standardized croup clinical scores. CONCLUSIONS: Substantial variation exists among croup CPGs. Our results may inform future efforts to standardize croup CPGs across centers.

Predictors of Inpatient Racemic Epinephrine Use in Patients Admitted With Croup.

OBJECTIVE: Many patients hospitalized for croup receive no additional racemic epinephrine (RE) postadmission. We analyzed the association between inpatient racemic epinephrine (RE) use and demographic and emergency department (ED) parameters including timing between RE doses with a goal of identifying patients who may be low risk for ED discharge. METHODS: We completed a retrospective cohort study of previously healthy patients ages 2 months to <7 years old who were admitted with a diagnosis of croup from 2016 to 2019 at a freestanding tertiary-care children's hospital. Patients were eligible for this study if they received at least 1 RE treatment before admission. RESULTS: The cohort included 238 patients; 59 (24.7%) patients received additional RE during admission. The number of RE doses in the ED (P = .99) and the median time between RE doses (P = .71) were not different between inpatient RE and no inpatient RE groups. Younger patients (P = .045) and patients with tachypnea for age (odds ratio [OR] 2.33; 95% confidence interval = 1.2-4.4) were more likely to require RE during admission. Median length of hospitalization for patients receiving inpatient RE was significantly longer (38 hours vs 16.7 hours, P < .001), whereas readmit rates were similar between groups (5.1% vs 3.9%, P = .71). CONCLUSIONS: Fewer than 25% of admitted patients received inpatient RE. Age and tachypnea for age were associated with inpatient RE use. Reassessment of admission thresholds for multidose RE use may be warranted to prevent unnecessary hospitalizations.

Glucocorticoids for croup in children.

BACKGROUND: Glucocorticoids are the mainstay for the treatment of croup. The existing evidence demonstrates that glucocorticoids are effective in the treatment of croup in children. However, updating the evidence on their clinical relevance in croup is imperative. This is an update to a review first published in 1999, and updated in 2004, 2011, and 2018. OBJECTIVES: To investigate the effects and safety of glucocorticoids in the treatment of croup in children aged 18 years and below. SEARCH METHODS: We searched the Cochrane Library, which includes the Cochrane Central Register of Controlled Trials (CENTRAL; 2022 Issue 9), Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1946 to 4 March 2022), Embase (Ovid) (1974 to 4 March 2022). We also searched the WHO ICTRP and ClinicalTrials.gov on 4 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children (aged 18 years and below) with croup. We assessed the effect of glucocorticoids compared to the following: placebo, any other pharmacologic agents, any other glucocorticoids, any combination of other glucocorticoids, given by different modes of administration, or given in different doses. The included studies must have assessed at least one of our primary outcomes (defined as the change in croup score or return visits, (re)admissions to the hospital or both) or secondary outcomes (defined as the length of stay in hospital or emergency departments, patient improvement, use of additional treatments, or adverse events). DATA COLLECTION AND ANALYSIS: Review authors independently extracted data, with another review author verified. We entered the data into Review Manager 5 for meta-analysis. Two review authors independently assessed studies for risk of bias using the Cochrane risk of bias tool. Two review authors assessed the certainty of the evidence for the primary outcomes using the GRADE approach. MAIN RESULTS: This updated review includes 45 RCTs with a total of 5888 children, an increase of two RCTs with 1323 children since the last update. We also identified one ongoing study and one study awaiting classification. We assessed most studies (98%) as at high or unclear risk of bias.  Any glucocorticoid compared to placebo  Compared to placebo, glucocorticoids may result in greater reductions in croup score after two hours (standardised mean difference (SMD) -0.65, 95% confidence interval (CI) -1.13 to -0.18; 7 RCTs, 426 children; low-certainty evidence); six hours (SMD -0.76, 95% CI -1.12 to -0.40; 11 RCTs, 959 children; low-certainty evidence); and 12 hours (SMD -1.03, 95% CI -1.53 to -0.53; 8 RCTs, 571 children; low-certainty evidence). The evidence for change in croup score after 24 hours is very uncertain (SMD -0.86, 95% CI -1.40 to -0.31; 8 RCTs, 351 children; very low-certainty evidence).  One glucocorticoid compared to another glucocorticoid There was little to no difference between prednisolone and dexamethasone for reduction in croup score at two-hour post-baseline score (SMD 0.06, 95% CI -0.06 to 0.18; 1 RCT, 1231 children; high-certainty evidence). There was likely little to no difference between prednisolone and dexamethasone for reduction in croup score at six-hour post-baseline score (SMD 0.21, 95% CI -0.21 to 0.62; 1 RCT, 99 children; moderate-certainty evidence). However, dexamethasone probably reduced the return visits or (re)admissions for croup by almost half (risk ratio (RR) 0.55, 95% CI 0.28 to 1.11; 4 RCTs, 1537 children; moderate-certainty evidence), and showed a 28% reduction in the use of supplemental glucocorticoids as an additional treatment (RR 0.72, 95% CI 0.53 to 0.97; 2 RCTs, 926 children).  Dexamethasone given in different doses Compared to 0.15 mg/kg, 0.60 mg/kg dexamethasone probably reduced the severity of croup as assessed by the croup scoring scale at 24-hour postbaseline score (SMD 0.63, 95% CI 0.16 to 1.10; 1 RCT, 72 children; moderate-certainty evidence); however, this was not the case at two hours (SMD -0.27, 95% CI -0.76 to 0.22; 2 RCTs, 861 children; high-certainty evidence). There was probably no reduction at six hours (SMD -0.45, 95% CI -1.26 to 0.35; 3 RCTs, 178 children; moderate-certainty evidence), and the evidence at 12 hours is very uncertain (SMD -0.60, 95% CI -4.39 to 3.19; 2 RCTs, 113 children; very low-certainty evidence). There was little to no difference between doses of dexamethasone in return visits or (re)admissions of children or both (RR 0.91, 95% CI 0.71 to 1.17; 3 RCTs, 949 children; high-certainty evidence) or length of stay in the hospital or emergency department (mean difference 0.12, 95% CI -0.32 to 0.56; 2 RCTs, 892 children). The need for additional treatments, such as epinephrine (RR 0.78, 95% CI 0.34 to 1.75; 2 RCTs, 885 children); intubation (risk difference 0.00, 95% CI -0.00 to 0.00; 2 RCTs, 861 children); or use of supplemental glucocorticoids (RR 0.77, 95% CI 0.51 to 1.15; 2 RCTs, 617 children), also did not differ between doses of dexamethasone.  There were moderate to high levels of heterogeneity in the analyses for most comparisons. Adverse events were observed for some of the comparisons reported in the review. AUTHORS' CONCLUSIONS: The evidence that glucocorticoids reduce symptoms of croup at two hours, shorten hospital stays, and reduce the rate of return visits or (re)admissions has not changed in this update. A smaller dose of 0.15 mg/kg of dexamethasone may be as effective as the standard dose of 0.60 mg/kg. More RCTs are needed to strengthen the evidence for effectiveness of low-dose dexamethasone at 0.15 mg/kg to treat croup.

Variation in Emergency Department Use of Racemic Epinephrine and Associated Outcomes for Croup.

OBJECTIVES: Racemic epinephrine (RE) is commonly administered for croup in the emergency department (ED). Our objectives were to examine variation in RE use between EDs, to determine whether ED variation in RE use is associated with hospital or patient factors, and to evaluate the associations between the rates of hospital-specific ED RE use and patient outcomes. METHODS: We performed a retrospective cohort study using the Pediatric Heath Information System of children aged 3 months to 10 years with croup in the ED. We used mixed-effects regression to calculate risk-standardized proportions of patients receiving RE in each ED and to analyze the relationship between risk-standardized institutional RE use and individual patient odds of hospital admission, ICU admission, and ED revisits. RESULTS: We analyzed 231 683 patient visits from 39 hospitals. ED administration of RE varied from 14% to 48% of visits (median, 24.5%; interquartile range, 20.0%-27.8%). A total of 8.6% of patients were hospitalized and 1% were admitted to the ICU. After standardizing for case mix and site effects, increasing ED use of RE per site was associated with increasing patient odds of hospital admission (odds ratio [OR], 1.39-95%; confidence interval [CI], 1.01-1.91), but not ICU admission (OR, 1.39; 95% CI, 0.99-1.97) or ED revisit (OR, 1.00; 95% CI, 0.92-1.09). CONCLUSIONS: In this large, observational study, RE administration varied widely across EDs. Increased RE use by site was associated with increased odds of hospital admission for individual patients when controlling for patient factors. These results suggest further standardization of RE use in children with croup is warranted.

Utilization of intranasal ipratropium bromide in the prevention of recurrent croup events: Is it effective?

OBJECTIVE: Recurrent croup (RC) is a common problem in the pediatric population. We theorize that reduced rhinorrhea and post-nasal drip as well as suppressed cough receptor activity by the anticholinergic, intranasal ipratropium bromide (IB), may lead to reduced inflammation and edema of the subglottis, decreasing RC symptoms. The aim of this study is to determine the effectiveness of IB in improving symptoms of RC and in reducing the need for alternative forms of management. METHOD: A retrospective chart review combined with survey data of patients with RC was conducted to assess demographic data, comorbidities, and treatment outcomes. Pediatric patients less than 10 years of age diagnosed with RC through the department of pediatric otolaryngology between 2018 and 2020 were included. Results were compared between one group treated with IB for RC and a second group treated with medications other than IB. RESULTS: Among the 67 patients treated for RC, 34 completed survey data and were included in the study. Overall, patients who were treated with IB for RC had 1.83 less croup episodes per year (p = 0.046), a 0.5-point improvement in child symptoms (p = 0.017) and 1.3 fewer doses of steroids per year than the patients not treated with IB (p = 0.018). Patients treated with IB were significantly more likely to answer "yes," that the use of medication helped improve symptoms (p < 0.01). CONCLUSION: Intranasal IB is a novel therapeutic option that may reduce RC events, improve patient symptoms and reduce steroid use. Further prospective studies are needed to definitively characterize the benefits of IB in the treatment of RC.

Comparative Effectiveness of Dexamethasone Versus Prednisone in Children Hospitalized With Acute Croup.

OBJECTIVES: To compare the effectiveness of dexamethasone versus prednisone or prednisolone on hospital resource utilization for children hospitalized with acute croup. METHODS: This is a retrospective cohort study of the Pediatric Health Information System database on children aged 6 months to <6 years who were hospitalized with acute croup between January 1, 2015 and December 31, 2019. Children with a chronic complex condition, transferred from outside hospital, and/or received direction admission to ICU were excluded. Propensity score matching was used to compare length of stay (in hours), escalation of care to ICU, and the need for bronchoscopy with exposure to dexamethasone versus prednisone or prednisolone. We also compared rates of 7 day return to the emergency department and readmissions. RESULTS: A total of 11 740 hospitalizations met inclusion criteria; dexamethasone was used in 95.9%; prednisone or prednisolone was used in 4.1%. In the matched cohort (n = 960), the length of stay was not significantly different between the dexamethasone and prednisone or prednisolone groups (21.3 vs 18.5 hours, P = .35). Although the rates bronchoscopy did not differ between the 2 groups, the dexamethasone cohort was more likely to require ICU transfer (P = .007). The rates of 7-day emergency department returns (2.3% vs 1.3%, P = .24) and readmissions (3.1% vs. 2.1%, P = .37) were low and not statistically different. CONCLUSIONS: Hospital resource utilization did not differ significantly for children receiving dexamethasone or prednisone or prednisolone for acute croup. Both corticosteroids may be considered reasonable choices for the treatment of children hospitalized with acute croup.

Prediction Model for Croup Admission Need.

OBJECTIVES: This study aims to generate a predictive model stratifying the probability of requiring hospitalization and inpatient respiratory intervention for croup patients presenting to the emergency department (ED), and secondarily to compare the model's performance with that of ED providers. METHODS: Retrospective data was collected on croup patients presenting to the EDs of 2 pediatric and 1 community hospital from 2019 to 2020, including demographics, preexisting conditions, and history of croup. The ED length of stay, previous dexamethasone administration, time to ED dexamethasone, number of ED racemic epinephrine doses, viral testing, and ED revisits were also recorded. Westley croup scores were derived at ED presentation and final disposition. For admitted patients, any respiratory interventions were recorded. Admission need was defined as either admitted and required an inpatient intervention or not admitted with ED revisit. A prediction model for admission need was fit using L1-penalized logistic regression. RESULTS: We included 2951 patients in the study, 68 (2.3%) of which needed admission. The model's predictors were disposition Westley croup scores, number of ED racemic epinephrine doses, previous dexamethasone administration, and history of intubation. The model's sensitivity was 66%, specificity was 91%, positive predictive value was 15%, and negative predictive value was 99%. ED providers' performance had a sensitivity of 72%, a specificity of 94%, a positive predictive value of 23%, and a negative predictive value of 99%. CONCLUSIONS: The croup admission need predictive model appears to support clinical decision making in the ED, with the potential to improve decision making when pediatric expertise is limited.

Multicentre study revealed significant gaps between evidence-based recommendations for using corticosteroids for croup and clinical practice.

AIM: Adherence to croup management recommendations has been poorly investigated. This study aimed to describe the treatment patterns in two paediatric emergency departments and analyse the adherence to recommendations. METHODS: We conducted a retrospective chart review of children diagnosed with croup in two Italian paediatric emergency departments in 2017. Data on clinical presentation, corticosteroid administration and home therapy were collected. Length of stay, hospitalisation and re-access rates were compared among different corticosteroid treatment groups. RESULTS: We enrolled 632 patients (61.1% males) with a mean age of 42.8 ± 55.1 months. Corticosteroids were administered to 403 (63.8%) children in the emergency departments. Dexamethasone was administered to 1 (0.4%) patient. Inhaled and oral corticosteroids were given to 342 (54.1%) and 226 (35.8%) patients, respectively. Home therapy was prescribed for 603 (95.4%) patients, either with inhaled (86.2%) and/or oral (43.8%) corticosteroids. The re-access rate was 2.8%. The actual pharmaceutical costs were an estimated 10 times higher than they would have been if the recommendations had been followed. CONCLUSION: A significant gap between the evidence and clinical practice for croup treatment was observed. Improving adherence to the recommendations could lead to clinical and economic benefits.

Two Case Reports of Life-Threatening Croup Caused by the SARS-CoV-2 Omicron BA.2 Variant in Pediatric Patients.

Croup is a common upper airway infection characterized by a barking cough, stridor, and hoarseness. It is usually caused by viral infection. A small number of croup caused by coronavirus disease 2019 (COVID-19) has been reported in children before the omicron variant surge. Previously reported cases indicated that croup caused by COVID-19 can be treated in the same manner as those with other viral causes. We describe two cases (9-month-old girl and 11-month-old boy) of previously healthy infants who presented with a barking cough and chest retraction and required endotracheal intubation and cardiopulmonary resuscitation. Despite receiving dexamethasone and nebulized racemic epinephrine (NRE) treatment for croup in the emergency department, these patients still developed acute respiratory failure. Reverse transcription polymerase chain reaction (RT-PCR) of nasopharyngeal samples revealed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron BA.2 variant (Stealth omicron) and no other common respiratory viral pathogens. Both patients were treated with mechanical ventilation, dexamethasone, and NRE in the pediatric intensive care unit. The duration of intubation was 112 hours and 80 hours, respectively. Both patients were discharged without complications. To the best of our knowledge, this is the first report of life-threatening croup produced by the omicron BA.2 variant and confirmed by RT-PCR. We suggest that this SARS-CoV-2 variant may cause severe croup that may not improve with conventional treatment, even in children without underlying diseases.

Retrospective Evaluation of Return Rates in Pediatric Patients Treated With Inhaled Racemic Epinephrine for Croup.

OBJECTIVES: To determine if the length of observation (< 2 hours vs ≥ 2 hours) following treatment of croup with inhaled racemic epinephrine in the emergency department (ED) is associated with return rates (within 48 hours after treatment) in pediatric patients. METHODS: We conducted a retrospective review of patients' medical records from February 2010 through June 2018 for pediatric patients (male and female, ≤ 12 years of age) diagnosed with croup in the ED, treated with racemic epinephrine, and discharged from the ED. RESULTS: We evaluated patients observed for less than 1 hour, 1 to 2 hours, and greater than 2 hours to determine difference in return rates within 48 hours. For patients with mild croup symptoms, 2% observed for less than 1 hour returned; 5% observed for 1 to 2 hours returned, and 3% observed for greater than 2 hours returned. Of the patients with moderate croup symptoms, 29% observed for less than 1 hour returned, 20% observed for 1 to 2 hours returned, and 20% observed for greater than 2 hours returned. A majority who returned for follow-up were not retreated with racemic epinephrine. CONCLUSION: Based on our study results, we can conclude that observing patients following treatment of croup with inhaled racemic epinephrine in the ED for less than 2 hours did not increase their risk of deterioration or need to return. Our data did not show that a longer observation time resulted in lower return rates within 48 hours.

Variation in Prehospital Protocols for Pediatric Respiratory Distress Management in the United States.

OBJECTIVE: This study aimed to compare statewide emergency medical services protocols for the management of pediatric respiratory distress. METHODS: We performed a descriptive study of emergency medical services protocols for the management of pediatric respiratory distress in the United States, excluding those without model or mandatory protocols. We compared medication recommendations for specific disease processes, including asthma, croup, epiglottitis, anaphylaxis, generalized respiratory distress, intubation, and drug assisted intubation. RESULTS: Thirty-four state protocols were included. All had protocols to address the management of pediatric respiratory distress. There was high agreement in albuterol use for bronchospasm and epinephrine use in anaphylaxis. Epinephrine was recommended in all anaphylaxis protocols, 27 croup protocols (79%), and 3 epiglottitis protocols (9%). Six states (18%) called for albuterol in patients with generalized respiratory distress. Steroid recommendations and indications had variance among states; 26 states (76%) allowed steroid use in patients with asthma, 19 states (56%) recommended steroid use in anaphylaxis, and 11 (32%) recommended steroid use in croup protocols. The route for steroid administration also varied among protocols. Five states (15%) allowed continuous positive airway pressure application in pediatric patients, whereas endotracheal intubation and rapid sequence intubations had varying requirements as well as recommendations for use. Twelve (35%) listed impending or current respiratory failure as an indication, whereas other states had specific markers, such as Glasgow Coma Scale or oxygen saturation, as indications. CONCLUSIONS: All included states had specific recommendations for the management of pediatric respiratory distress. There was consistency in recommendations for albuterol use for wheezing and epinephrine use for anaphylaxis. However, there was wide variability in other uses for epinephrine, steroid administration, continuous positive airway pressure use, and specific treatments for croup and epiglottitis. The findings of this study provide a base for important future evidence-based protocol developments and changes in prehospital pediatric respiratory distress treatment.

Variation in Dexamethasone Dosing and Use Outcomes for Inpatient Croup.

OBJECTIVES: Evaluate the association between dexamethasone dosing and outcomes for children hospitalized with croup. METHODS: This study was nested within a multisite prospective cohort study of children aged 6 months to 6 years admitted to 1 of 5 US children's hospitals between July 2014 and June /2016. Multivariable linear and logistic mixed-effects regression models were used to examine the association between the number of dexamethasone doses (1 vs >1) and outcomes (length of stay [LOS], cost, and 30-day same-cause reuse). All multivariable analyses included a site-specific random effect to account for clustering within hospital and were adjusted for age, sex, race and ethnicity, presenting severity, medical complexity, insurance, caregiver education, and hospital. In cost analyses, we controlled for LOS. RESULTS: Among 234 children hospitalized with croup, patient characteristics did not differ by number of doses. The proportion receiving >1 dose varied by hospital (range 27.9%-57.1%). In adjusted analyses, >1 dose was not associated with same-cause reuse (odds ratio 0.87 [95% confidence interval (CI): 0.26 to 2.95]) but was associated with 45% longer LOS (relative risk = 1.45 [95% CI: 1.30 to 1.62]). When we controlled for LOS, >1 dose was not associated with differential cost ($-31.2 [95% CI $-424.4 to $362.0]). Eighty-two (35%) children received dexamethasone before presentation. CONCLUSIONS: We found significant interhospital variation in dexamethasone dosing and LOS. When we controlled for severity on presentation, >1 dexamethasone dose was associated with longer LOS but not reuse. Although incomplete adjustment for severity is one possible explanation, some providers may routinely keep children hospitalized to administer multiple dexamethasone doses.

Heliox for croup in children.

BACKGROUND: Croup is an acute viral respiratory infection with upper airway mucosal inflammation that may cause respiratory distress. Most cases are mild. Moderate to severe croup may require treatment with corticosteroids (the benefits of which are often delayed) and nebulised epinephrine (adrenaline) (the benefits of which may be short-lived and which can cause dose-related adverse effects including tachycardia, arrhythmias, and hypertension). Rarely, croup results in respiratory failure necessitating emergency intubation and ventilation. A mixture of helium and oxygen (heliox) may prevent morbidity and mortality in ventilated neonates by reducing the viscosity of the inhaled air. It is currently used during emergency transport of children with severe croup. Anecdotal evidence suggests that it relieves respiratory distress. This review updates versions published in 2010, 2013, and 2018. OBJECTIVES: To examine the effect of heliox compared to oxygen or other active interventions, placebo, or no treatment on relieving signs and symptoms in children with croup as determined by a croup score and rates of admission and intubation. SEARCH METHODS: We searched CENTRAL, which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE, Embase, CINAHL, Web of Science, and LILACS, on 15 April 2021. We also searched the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/) and ClinicalTrials.gov (clinicaltrials.gov) on 15 April 2021. We contacted the British Oxygen Company, a leading supplier of heliox. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing the effect of heliox in comparison with placebo, no treatment, or any active intervention(s) in children with croup. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Data that could not be pooled for statistical analysis were reported descriptively. MAIN RESULTS: We included 3 RCTs involving a total of 91 children aged between 6 months and 4 years. Study duration was from 7 to 16 months, and all studies were conducted in emergency departments. Two studies were conducted in the USA and one in Spain. Heliox was administered as a mixture of 70% heliox and 30% oxygen. Risk of bias was low in two studies and high in one study because of its open-label design. We did not identify any new trials for this 2021 update. One study of 15 children with mild croup compared heliox with 30% humidified oxygen administered for 20 minutes. There may be no difference in croup score changes between groups at 20 minutes (mean difference (MD) -0.83, 95% confidence interval (CI) -2.36 to 0.70) (Westley croup score, scale range 0 to 16). The mean croup score at 20 minutes postintervention may not differ between groups (MD -0.57, 95% CI -1.46 to 0.32). There may be no difference between groups in mean respiratory rate (MD 6.40, 95% CI -1.38 to 14.18) and mean heart rate (MD 14.50, 95% CI -8.49 to 37.49) at 20 minutes. The evidence for all outcomes in this comparison was of low certainty, downgraded for serious imprecision. All children were discharged, but information on hospitalisation, intubation, or re-presenting to emergency departments was not reported. In another study, 47 children with moderate croup received one dose of oral dexamethasone (0.3 mg/kg) with either heliox for 60 minutes or no treatment. Heliox may slightly improve Taussig croup scores (scale range 0 to 15) at 60 minutes postintervention (MD -1.10, 95% CI -1.96 to -0.24), but there may be no difference between groups at 120 minutes (MD -0.70, 95% CI -1.56 to 0.16). Children treated with heliox may have lower mean Taussig croup scores at 60 minutes (MD -1.11, 95% CI -2.05 to -0.17) but not at 120 minutes (MD -0.71, 95% CI -1.72 to 0.30). Children treated with heliox may have lower mean respiratory rates at 60 minutes (MD -4.94, 95% CI -9.66 to -0.22), but there may be no difference at 120 minutes (MD -3.17, 95% CI -7.83 to 1.49). There may be a difference in hospitalisation rates between groups (odds ratio 0.46, 95% CI 0.04 to 5.41). We assessed the evidence for all outcomes in this comparison as of low certainty, downgraded due to imprecision and high risk of bias related to an open-label design. Information on heart rate and intubation was not reported. In the third study, 29 children with moderate to severe croup all received continuous cool mist and intramuscular dexamethasone (0.6 mg/kg). They were then randomised to receive either heliox (given as a mixture of 70% helium and 30% oxygen) plus one to two doses of nebulised saline or 100% oxygen plus nebulised epinephrine (adrenaline), with gas therapy administered continuously for three hours. Heliox may slightly improve croup scores at 90 minutes postintervention, but may result in little or no difference overall using repeated-measures analysis. We assessed the evidence for all outcomes in this comparison as of low certainty, downgraded due to high risk of bias related to inadequate reporting. Information on hospitalisation or re-presenting to the emergency department was not reported. The included studies did not report on adverse events, intensive care admissions, or parental anxiety. We could not pool the available data because each comparison included data from only one study. AUTHORS' CONCLUSIONS: Given the very limited available evidence, uncertainty remains regarding the effectiveness and safety of heliox. Heliox may not be more effective than 30% humidified oxygen for children with mild croup, but may be beneficial in the short term for children with moderate croup treated with dexamethasone. The effect of heliox may be similar to 100% oxygen given with one or two doses of adrenaline. Adverse events were not reported, and it is unclear if these were monitored in the included studies. Adequately powered RCTs comparing heliox with standard treatments are needed to further assess the role of heliox in the treatment of children with moderate to severe croup.

Croup Admissions: Can We Shrink the Elephant in the Room?

OBJECTIVE: This pilot study aims to identify potential predictors of postadmission interventions of hospitalized croup patients and derive a risk model aimed at reducing hospitalizations for croup. METHODS: Data were collected on all croup hospitalizations for patients aged 1 month to 17 years admitted through a community hospital's emergency department (ED) between 2012 and 2017. Potential predictors were obtained from the electronic medical records including demographics, vital signs, ED length of stay, preintervention and postintervention Westley Croup Score (WCS), number of racemic epinephrine nebulizations administered, time to dexamethasone administration, preexisting conditions, and additional interventions during hospitalization. Statistical analysis used the outcome "patient received racemic epinephrine after hospital admission (yes/no)" to identify characteristics of the child or ED visit associated with that outcome. Preliminary analyses using stepwise logistic regression, tree models, and random forests suggested predictors, interactions among predictors, and the form of their association with the outcome. A final analysis used logistic regression. RESULTS: A total of 116 croup admissions were included, of which 19 (16%) received racemic epinephrine posthospitalization. These characteristics were identified as having some predictive power: sex, preexisting conditions, and preintervention and postintervention WCS, along with the interaction between sex and postintervention WCS. Logistic regression estimated an equation describing the probability of postadmission intervention, permitting the choice among admission thresholds giving different sensitivities and specificities. CONCLUSIONS: There appear to be promising predictors in croup patients presenting to the ED, which might help stratify risk for interventions after the ED encounter and thus reduce the number of potentially avoidable admissions.

Endogenous Glucocorticoid Response to Single-Dose Dexamethasone for Croup in Children: A Pharmacodynamic Study.

OBJECTIVES: Dexamethasone is associated with adrenal insufficiency in adults and children with chronic disease. This association has not been studied after single-dose oral dexamethasone, the standard of care for children with croup. We hypothesized that single-dose oral dexamethasone in children with croup is associated with a transient decrease in endogenous glucocorticoids. METHODS: We conducted a prospective, 2-arm, pharmacodynamic study of single-dose oral dexamethasone 0.6 mg/kg (maximum, 12 mg) in children older than 2 years with croup compared with controls (children with febrile upper respiratory tract infections who did not receive dexamethasone). Primary outcome was urinary 6ß-hydroxycortisol-cortisol ratio. RESULTS: Twenty-seven children were analyzed (22 with croup and 5 with upper respiratory tract infections). Median 6ß-hydroxycortisol-cortisol ratios before dexamethasone, the following morning, and on days 1, 3, and 7 were 2.8, 2.2, 2.0, 2.8, and 2.6, respectively. Among controls, the median 6ß-hydroxycortisol-cortisol ratios at the same time intervals was 1.9, 1.5, 1.8, 2.5, and 1.7, respectively. There were no significant differences in the change from time 0 between groups at any time point. There were no serious adverse events or infectious complications. CONCLUSIONS: Single-dose oral dexamethasone is not associated with decreased endogenous corticosteroid levels in children with croup. Future studies should use criterion standard tests to rule out suppression of the hypothalamic-pituitary-adrenal axis and be powered sufficiently to identify adverse clinical outcomes.