Azithromycin for Pediatric Critical Asthma: A Multicenter Retrospective Cohort Study.

OBJECTIVES: To characterize the prescribing trends and clinical outcomes related to azithromycin (AZI) among children hospitalized for critical asthma (CA). METHODS: We performed a multicenter, retrospective cohort study using the Pediatric Health Information Systems registry of children 3 to 17 years of age hospitalized in a PICU for CA from January 2011 to December 2022. We excluded for alternative indications for AZI (eg, atypical pneumonia, B. pertussis infection, acute otitis media, acute sinusitis, pharyngitis/tonsillitis, and urethritis). The primary outcome was AZI prescribing rate by hospital and calendar year (trends assessed by Joinpoint regression). Cohorts with and without AZI exposure were further characterized by demographics, CA treatments, and inpatient outcomes using descriptive and comparative (ie, χ2 and Wilcoxon rank tests) statistics. RESULTS: Of the 47 797 children studied, 9901 (20.7%) were prescribed AZI with a downward annual trend noted from 34.7% in 2011% to 12.4% in 2022 (-1.7% per year, R2 = 0.91). Median institutional AZI prescribing rate was 19.2% (interquartile range [IQR] 11.7%-28%; total range 5.6%-60%). Compared with children not prescribed AZI, those prescribed AZI were older (median 8.3 [IQR 5.7-11.6] vs 7.3 [4.9-10.8] years, P < .001) and experienced a more severe clinical trajectory with greater rates of bilevel positive airway pressure ventilation (19.7% vs 12.6%, P < .001), invasive ventilation (22.1% vs 13.5%, P < .001), extracorporeal life support (0.8% vs 0.1%, P < .001), and median length of stay (4 [IQR 3-6] vs 3 [IQR 2-4] days, P < .001). CONCLUSIONS: Between 2011 and 2022, 20.7% of children hospitalized for CA were prescribed AZI notwithstanding the absence of trial-derived efficacy or safety data for this indication and population.

Vitamin K Prescribing Trends Among Critically Ill Children Hospitalized for Sepsis: A Multicenter Observational Cohort Study.

Objective: Vitamin K (VK) is commonly prescribed for pediatric sepsis-induced coagulopathy without trial-derived evidence to support its use for this indication. The purpose of this study was to characterize national prescribing trends for VK in this population. Patients and Methods: This is a multicenter retrospective cohort study using the Pediatric Health Information System registry including children 0 to 17 years of age hospitalized for sepsis in the pediatric intensive care unit from January 2016 through December 2022. The primary outcome was overall, annual, and center-specific VK prescribing rates. Descriptive data included demographics, length of stay, and rates of VK deficiency, hepatic insufficiency, red blood cell (RBC) transfusion, venous thromboembolism (VTE), and mortality. VK prescribing trends were assessed using Joinpoint regression. Descriptive statistics employed included Wilcoxon rank-sum, student's t, and chi-square tests. Results: Of the 31 221 encounters studied, 4539 (14.6%) were prescribed VK (median center-specific rate: 14.2%; interquartile range [IQR]: 8.8-21%) with a linear annual trend decreasing from 17.3% in 2016 to 13.3% in 2022 (-0.6%/year, r2 = .661). Those prescribed VK had greater rates of hepatic dysfunction (20.5% vs 3.1%), RBC transfusion (26.5% vs 11.2%), VTE (12.5% vs 4.6%), mortality (17.1% vs 4.4%), and median length of stay (16 [IQR: 8-33] vs 8 [4-15] days) (all P < .001). VK deficiency was diagnosed in 0.2% of encounters. Conclusions: In this multicenter retrospective cohort, VK prescribing was common among critically ill children diagnosed with sepsis. Phased trials are needed to demonstrate clinical efficacy and safety for VK in this population.

Noninvasive Respiratory Support for Pediatric Critical Asthma: A Multicenter Cohort Study.

BACKGROUND: Noninvasive respiratory support (NRS) for pediatric critical asthma includes CPAP; bi-level positive airway pressure (BPAP); and heated, humidified, high-flow nasal cannula (HFNC). We used the Virtual Pediatric System database to estimate NRS by prescribing rates for pediatric critical asthma and characterize patient clinical features and in-patient outcomes by the initial NRS device applied. METHODS: We performed a retrospective cohort study from 125 participating pediatric ICUs among children 2-17 years of age hospitalized for critical asthma and prescribed NRS from 2017 through 2021. The primary outcomes were NRS modality prescribing rates and trends. Secondary outcomes were descriptive and included demographics, comorbidities, severity of illness indices, and NRS failure rates (defined as escalation from the initial NRS modality to invasive ventilation, HFNC to BPAP or CPAP, or CPAP to BPAP). RESULTS: Of the 10,083 encounters studied, the initial NRS modalities prescribed varied widely by hospital center (HFNC: 69.7 ± 29.6%; BPAP: 27.2 ± 7.1%; CPAP: 3.1 ± 5.9%). The mean rates of HFNC use increased from 59.7% in 2017 to 71.9% in 2021 (+2.5%/y). In contrast, BPAP (-1.6%/y) and CPAP (-0.8%/y) utilization declined throughout the study period. Older children who were obese and with a higher Pediatric Risk of Mortality III-Probability of Mortality score were more frequently prescribed BPAP and CPAP compared with HFNC. Those children on HFNC experienced higher noninvasive respiratory support failure rates versus BPAP (7.3% vs 2.4%; P < .001) but a lower subsequent invasive ventilation rate versus BPAP (0.8% vs 2.4%; P < .001). CONCLUSIONS: In this multi-center cohort study, we observed that children with critical asthma are increasingly exposed to HFNC compared with BPAP and CPAP. Rates of HFNC failure were greater than those of BPAP failure, but a majority were transitioned to BPAP without subsequent invasive ventilation. The next steps include prospective trials, including practical end points such as patient comfort and optimal delivery of nebulized treatments to distinguish device superiority and suitable NRS utilization.

Child Opportunity Index and Pediatric Intensive Care Outcomes: A Multicenter Retrospective Study in the United States.

OBJECTIVES: To evaluate for associations between a child's neighborhood, as categorized by Child Opportunity Index (COI 2.0), and 1) PICU mortality, 2) severity of illness at PICU admission, and 3) PICU length of stay (LOS). DESIGN: Retrospective cohort study. SETTING: Fifteen PICUs in the United States. PATIENTS: Children younger than 18 years admitted from 2019 to 2020, excluding those after cardiac procedures. Nationally-normed COI category (very low, low, moderate, high, very high) was determined for each admission by census tract, and clinical features were obtained from the Virtual Pediatric Systems LLC (Los Angeles, CA) data from each site. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 33,901 index PICU admissions during the time period, median patient age was 4.9 years and PICU mortality was 2.1%. There was a higher percentage of admissions from the very low COI category (27.3%) than other COI categories (17.2-19.5%, p < 0.0001). Patient admissions from the high and very high COI categories had a lower median Pediatric Index of Mortality 3 risk of mortality (0.70) than those from the very low, low, and moderate COI groups (0.71) ( p < 0.001). PICU mortality was lowest in the very high (1.7%) and high (1.9%) COI groups and highest in the moderate group (2.5%), followed by very low (2.3%) and low (2.2%) ( p = 0.001 across categories). Median PICU LOS was between 1.37 and 1.50 days in all COI categories. Multivariable regression revealed adjusted odds of PICU mortality of 1.30 (95% CI, 0.94-1.79; p = 0.11) for children from a very low versus very high COI neighborhood, with an odds ratio [OR] of 0.996 (95% CI, 0.993-1.00; p = 0.05) for mortality for COI as an ordinal value from 0 to 100. Children without insurance coverage had an OR for mortality of 3.58 (95% CI, 2.46-5.20; p < 0.0001) as compared with those with commercial insurance. CONCLUSIONS: Children admitted to a cohort of U.S. PICUs were often from very low COI neighborhoods. Children from very high COI neighborhoods had the lowest risk of mortality and observed mortality; however, odds of mortality were not statistically different by COI category in a multivariable model. Children without insurance coverage had significantly higher odds of PICU mortality regardless of neighborhood.

Hospital-Acquired Venous Thromboembolism and Invasive Mechanical Ventilation: A Report From the Children's Hospital Acquired Thrombosis Consortium.

OBJECTIVES: To determine if the duration of invasive mechanical ventilation (IMV) was associated with hospital-acquired venous thromboembolism (HA-VTE) among critically ill children. DESIGN: A multicenter, matched case-control study as a secondary analysis of Children's Hospital Acquired Thrombosis (CHAT) Consortium registry. SETTING: PICUs within U.S. CHAT Consortium participating centers. PATIENTS: Children younger than 21 years old admitted to a PICU receiving IMV for greater than or equal to 1 day duration from January 2012 to March 2022 were included for study. Cases with HA-VTE were matched 1:2 to controls without HA-VTE by patient age groups: younger than 1, 1-12, and older than 12 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was IMV duration in days. Descriptive data included demographics, anthropometrics, HA-VTE characteristics (i.e., type, location, and timing), central venous catheterization data, thromboprophylaxis practices, and Braden Q mobility scores. Descriptive, comparative, and associative (multivariate conditional logistic regression for HA-VTE) statistics were employed. A total of 152 cases were matched to 304 controls. Cases with HA-VTE were diagnosed at a median of 7 days (interquartile range [IQR], 3-16 d) after IMV. The HA-VTE were limb deep venous thromboses in 130 of 152 (85.5%) and frequently central venous catheterization-related (111/152, 73%). Cases with HA-VTE experienced a longer length of stay (median, 34 d [IQR, 18-62 d] vs. 11.5 d [IQR, 6-21 d]; p < 0.001) and IMV duration (median, 7 d [IQR, 4-15 d] vs. 4 d [IQR, 1-7 d]; p < 0.001) as compared with controls. In a multivariate logistic model, greater IMV duration (adjusted odds ratio, 1.09; 95% CI, 1.01-1.17; p = 0.023) was independently associated with HA-VTE. CONCLUSIONS: Among critically ill children undergoing IMV, HA-VTE was associated with greater IMV duration. If prospectively validated, IMV duration should be included as part of prothrombotic risk stratification and future pediatric thromboprophylaxis trials.

Pediatric Extracorporeal Membrane Oxygenation Anticoagulation and Monitoring: Where We Were and Where Are We Now?

Extracorporeal membrane oxygenation (ECMO) support in neonates and pediatric patients has continued to advance. In addition to technologic progress, there is a growing interest in the anticoagulation agents and laboratory monitoring strategies used in children requiring ECMO support. This review summarizes current available evidence and provides guidance for clinicians regarding anticoagulation agents and monitoring.

Association of the Child Opportunity Index and Inpatient Illness Severity in the United States, 2018-2019.

OBJECTIVE: Children residing in impoverished neighborhoods have reduced access to health care resources. Our objective was to identify potential associations between Child Opportunity Index (COI), a composite score of neighborhood characteristics, and inpatient severity of illness and clinical trajectory among United States (US) children. METHODS: This retrospective cohort study assessed data using the Pediatric Health Information System Registry from 2018 to 2019. Primary exposure variable was COI level (range: very low [CO1 1], low [COI 2], moderate [COI 3], high [COI 4], and very high [COI 5]). Markers of inpatient clinical severity included index mortality, Pediatric Intensive Care Unit (PICU) admission, invasive mechanical ventilation (IMV), and hospital length of stay (LOS). Subgroup analysis of COI and clinical outcome variation by United States Census Geographic Regions was conducted. Adjusted regression analysis was utilized to understand associations between COI and inpatient clinical severity outcomes. RESULTS: Of the 132,130 encounters, 44% resided in very low or low COI neighborhoods. In adjusted models, very low COI was associated with increased mortality (aOR: 1.35, 95% CI: 1.05-1.74, P = .018), PICU admission (aOR: 1.06, 95% CI: 1.02-1.11, P = 0.014), IMV (aOR: 1.12, 95% CI: 1.04-1.21, P = .002), and higher hospital LOS (P = .045). Regional variation by COI depicted the East North Central region having the highest rate of mortality (20.5%), P < .001, and PICU admissions (23%), P = .014. CONCLUSIONS: Our multicenter, retrospective study highlights the interaction between neighborhood-level deprivation and worsened health disparities, indicating a need for prospective study.

Hospital-acquired venous thromboembolism during invasive mechanical ventilation in children: a single-center, retrospective cohort study.

BACKGROUND: Invasive mechanical ventilation (IMV) has been independently associated with hospital-acquired venous thromboembolism (HA-VTE) among critically ill children, including extremity deep venous thrombosis and pulmonary embolism. OBJECTIVES: We aimed to characterize the frequency and timing of HA-VTE following IMV exposure. METHODS: This was a single-center, retrospective cohort study including children aged <18 years, hospitalized in a pediatric intensive care unit, undergoing mechanical ventilation for >24 hours from October 2020 through April 2022. Encounters with an existing tracheostomy or receiving treatment for HA-VTE prior to endotracheal intubation were excluded. The primary outcomes characterized clinically-relevant HA-VTE, including timing after intubation, location, and the presence of known hypercoagulability risk factors. Secondary outcomes were IMV exposure magnitude, defined by IMV duration and ventilator parameters (ie, volumetric, barometric, and oxygenation indices). RESULTS: Of 170 consecutive, eligible encounters, 18 (10.6%) experienced HA-VTE at a median of 4 days (IQR, 1.4-6.4) following endotracheal intubation. Those with HA-VTE had an increased frequency of a prior venous thromboembolism (27.8% vs 8.6%, P = .027). No differences in frequency of other HA-VTE risk factors (ie, acute immobility, hematologic malignancy, sepsis, and COVID-19-related illness), presence of a concurrent central venous catheter, or the magnitude of IMV exposure were noted. CONCLUSION: Children undergoing IMV experience HA-VTE at markedly higher rates than previously estimated in the general pediatric intensive care unit population after endotracheal intubation. While prospective validation is needed, these findings are an important step toward informing the development of risk-stratified thromboprophylaxis trials in critically ill children.

Dexamethasone versus methylprednisolone for critical asthma: A single center, open-label, parallel-group clinical trial.

BACKGROUND: Evidence for the use of dexamethasone for pediatric critical asthma is limited. We sought to compare the clinical efficacy and safety of dexamethasone versus methylprednisolone among children hospitalized in the pediatric intensive care unit (PICU) for critical asthma. METHODS: A prospective, single center, open-label, two-arm, parallel-group, nonrandomized trial among children ages 5-17 years hospitalized within the PICU from April 2019 to December 2021 for critical asthma consented to receive methylprednisolone (standard care) or dexamethasone (intervention) at a 2:1 allocation ratio, respectively. The intervention arm received intravenous dexamethasone 0.25 mg/kg/dose (max: 15 mg/dose) every 6 h for 48 h and the standard care arm intravenous methylprednisolone 1 mg/kg/dose every 6 h (max dose: 60 mg/dose) for 5 days. Study endpoints were clinical efficacy (i.e., length of stay [LOS], continuous albuterol duration, and a composite of adjunctive asthma interventions) and safety (i.e., corticosteroid-related adverse events). RESULTS: Ninety-two participants were analyzed of whom 31 were allocated to the intervention arm and 61 the standard care arm. No differences in demographics, clinical characteristics, or acute/chronic asthma severity indices were observed. Regarding efficacy and safety endpoints, no differences in hospital LOS, continuous albuterol duration, adjunctive asthma intervention rates, or corticosteroid-related adverse events were noted. Compared to the intervention arm, participants in the standard care arm more frequently were prescribed corticosteroids at discharge (72% vs. 13%, p < 0.001). CONCLUSIONS: Among children hospitalized for critical asthma, dexamethasone appears safe and warrants further investigation to fully assess clinical efficacy and potential advantages over commonly applied agents such as methylprednisolone.

Hemorrhagic Disease of the Newborn: A Case Series Illustrating Preventable Harm.

Newborns are susceptible to postnatal Vitamin K deficiencies from limited placental transfer, gastrointestinal absorption, and bioavailability in breast milk and formula preparations. For over 50 years, the American Academy of Pediatrics has recommended prophylactic vitamin K to prevent hemorrhagic disease in newborns. Yet, public skepticism contributes to increasing refusal rates. We present three cases of vitamin K-dependent bleeding following parental refusal of postnatal prophylaxis. Two patients experienced intracranial hemorrhage with resultant neurological devastation and mortality, respectively. The third child presented with symptomatic hematuria. Perinatal providers must partner with families and advocate vitamin K prophylaxis to limit unnecessary morbidity and mortality.

Performance Characteristics of a Machine-Learning Tool to Predict 7-Day Hospital Readmissions.

OBJECTIVES: To develop an institutional machine-learning (ML) tool that utilizes demographic, socioeconomic, and medical information to stratify risk for 7-day readmission after hospital discharge; assess the validity and reliability of the tool; and demonstrate its discriminatory capacity to predict readmissions. PATIENTS AND METHODS: We performed a combined single-center, cross-sectional, and prospective study of pediatric hospitalists assessing the face and content validity of the developed readmission ML tool. The cross-sectional analyses used data from questionnaire Likert scale responses regarding face and content validity. Prospectively, we compared the discriminatory capacity of provider readmission risk versus the ML tool to predict 7-day readmissions assessed via area under the receiver operating characteristic curve analyses. RESULTS: Overall, 80% (15 of 20) of hospitalists reported being somewhat to very confident with their ability to accurately predict readmission risk; 53% reported that an ML tool would influence clinical decision-making (face validity). The ML tool variable exhibiting the highest content validity was history of previous 7-day readmission. Prospective provider assessment of risk of 413 discharges showed minimal agreement with the ML tool (κ = 0.104 [95% confidence interval 0.028-0.179]). Both provider gestalt and ML calculations poorly predicted 7-day readmissions (area under the receiver operating characteristic curve: 0.67 vs 0.52; P = .11). CONCLUSIONS: An ML tool for predicting 7-day hospital readmissions after discharge from the general pediatric ward had limited face and content validity among pediatric hospitalists. Both provider and ML-based determinations of readmission risk were of limited discriminatory value. Before incorporating similar tools into real-time discharge planning, model calibration efforts are needed.

Heliox Prescribing Trends for Pediatric Critical Asthma.

BACKGROUND: Children with asthma exacerbations requiring pediatric ICU (PICU) admission, known as critical asthma (CA), are prescribed a variety of therapeutic interventions including heliox. Delivered invasively and noninvasively, heliox is employed to enhance deposition of aerosolized medications, improve obstructive pulmonary pathophysiology, and avoid complications associated with invasive mechanical ventilation. We used the Virtual Pediatric Systems database to update estimates of heliox prescription and explore for relationships between heliox and mechanical ventilation frequency and duration. METHODS: We performed a retrospective cohort study using data from 97 PICUs among children 3-17 y of age admitted for CA from 2013-2019. The primary outcome was heliox prescribing rates and trends. Subgroup analyses assessed mechanical ventilation rates and duration by heliox exposure. RESULTS: Of 43,238 subjects studied, 1,070 (2.5%) were prescribed heliox. Mean heliox prescribing rates fell from 4.11% in 2013 to 2.37% in 2019. Heliox use was greater from centers in the South (2.6%) and Midwest (3.3%) as compared to the West (1.6%) and Northeast United States (1.6%, P < .001). In the subgroup assessing mechanical ventilation frequency, mechanical ventilation rates were 273/39,739 (0.7%) and greater for those provided heliox (1.9% vs 0.7%, P < .001). In the subgroup assessing mechanical ventilation duration, no differences in median mechanical ventilation duration were observed (4.94 [interquartile range [IQR] 3.04-6.36] vs 4.63 [IQR 3.11-7.30] d; P = .35) for those with and without heliox. In exploratory adjusted models, noninvasive heliox was not associated with mechanical ventilation. Mortality was rare (206/43,238 [0.47%]) and predominantly among subjects intubated prehospitalization (188/206 [91.3%]). CONCLUSIONS: Heliox as adjunctive therapy for children with CA is uncommon (2.5%) and not associated with mechanical ventilation or decreased mechanical ventilation duration in adjusted models. Updated estimates provided herein inform prospective controlled trial development to better define the role of heliox for CA.

Enoxaparin Thromboprophylaxis in Children Hospitalized for COVID-19: A Phase 2 Trial.

BACKGROUND: Evidence regarding the safety and efficacy of anticoagulant thromboprophylaxis among pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) is limited. We sought to evaluate safety, dose-finding, and preliminary efficacy of twice-daily enoxaparin as primary thromboprophylaxis among children hospitalized for symptomatic COVID-19, including primary respiratory infection and multisystem inflammatory syndrome in children (MISC). METHODS: We performed a phase 2, multicenter, prospective, open-label, single-arm clinical trial of twice-daily enoxaparin (initial dose: 0.5mg/kg per dose; max: 60mg; target anti-Xa activity: 0.20-0.49IU/mL) as primary thromboprophylaxis for children <18 years of age hospitalized for symptomatic COVID-19. Study endpoints included: cumulative incidence of International Society of Thrombosis and Haemostasis-defined clinically relevant bleeding; enoxaparin dose-requirements; and cumulative incidence of venous thromboembolism within 30-days of hospital discharge. Descriptive statistics summarized endpoint estimates that were further evaluated by participant age (±12 years) and clinical presentation. RESULTS: Forty children were enrolled and 38 met analyses criteria. None experienced clinically relevant bleeding. Median (interquartile range) dose to achieve target anti-Xa levels was 0.5 mg/kg (0.48-0.54). Dose-requirement did not differ by age (0.5 [0.46-0.52] mg/kg for age ≥12 years versus 0.52 [0.49-0.55] mg/kg for age <12 years, P = .51) but was greater for participants with MISC (0.52 [0.5-0.61] mg/kg) as compared with primary COVID-19 (0.48 [0.39-0.51] mg/kg, P = .010). Two children (5.3%) developed central-venous catheter-related venous thromboembolism. No serious adverse events were related to trial intervention. CONCLUSIONS: Among children hospitalized for COVID-19, thromboprophylaxis with twice-daily enoxaparin appears safe and warrants further investigation to assess efficacy.

Dexamethasone for Pediatric Critical Asthma: A Multicenter Descriptive Study.

BACKGROUND: Systemic corticosteroids are vital to critical asthma management. While intravenous methylprednisolone is routinely used in the pediatric intensive care unit (PICU) setting, recent data supports dexamethasone as an alternative. Using the Pediatric Health Information System (PHIS) registry, we assessed trends and variation in corticosteroid prescribing among children hospitalized for critical asthma. METHODS: We performed a multicenter retrospective cohort study using PHIS data among children 3-17 years of age admitted for critical asthma from 2011 through 2019. Primary outcomes were corticosteroid prescribing rates by year and participating sites. Exploratory outcomes were corticosteroid-related adverse effects, rates of adjunctive pharmaceutical and respiratory interventions, mortality and length of stay. RESULTS: Of the 49 children's hospitals assessed, 26 907 encounters were included for study. Mean dexamethasone exposure rates were 18.1 ± 2.4% where 2.4 ± 1.2% represented dexamethasone-alone prescribing. Dexamethasone alone prescribing exhibited a linear trend (annual increase of 0.5 ± 0.1% annually R2 = 0.845) without correlation to cumulative site critical asthma admission rates. Compared to encounters prescribed solely methylprednisolone or a combination of dexamethasone and methylprednisolone, subjects provided dexamethasone alone had reduced asthma severity indices, length of stay, and exposure rates to adjunctive asthma interventions. Adverse events were rare and the dexamethasone-alone group less frequently experienced gastritis and hyperglycemia. CONCLUSIONS: In this multicenter retrospective study from 49 children's hospitals, dexamethasone prescribing rates appear increasing for pediatric critical asthma. Observed variability in corticosteroid prescribing implies a continued need for controlled prospective comparative analyses to define ideal corticosteroid regimens for pediatric critical asthma.

Heliox for Pediatric Critical Asthma: A Multicenter, Retrospective, Registry-Based Descriptive Study.

BACKGROUND: In cases of critical asthma (CA), heliox may be applied as an adjunctive rescue therapy to avoid invasive mechanical ventilation (MV), improve deposition of aerosolized medications, and enhance laminar airflow through obstructed airways. Using the Pediatric Health Information System (PHIS) registry, we evaluate heliox prescribing and explored for differences in MV rates and hospital length of stay (LOS) among children with and without heliox exposure. METHODS: We performed a retrospective cohort study using PHIS data from 42 pediatric intensive care units among children 5-17 years of age admitted for CA from 2010 through 2019. Primary outcomes were heliox prescribing rates and trends. Secondary outcomes were invasive MV rates and LOS assessed in a subgroup of children receiving ≥ 1 adjunctive intervention(s). RESULTS: Of the 19,780 studied, heliox was prescribed in 12.5% and linearly declined from 16.1% in 2010 to 5.6% in 2019. The overall MV rate was 12.8% and was lower in subjects receiving heliox alone (4.9%) compared to heliox plus alternative adjunctive therapies [31.2%] or children receiving non-heliox adjunctive therapies [22.1%], P < .01). Accounting for MV, no difference in LOS was observed. In exploratory adjusted models, MV free hospitalization was associated with heliox-only exposure (OR: 0.33, 95% CI: 0.17-0.63, P < .01) and exposure to multiple adjunctive therapies was associated with MV (OR: 2.48, 95% CI: 1.56-3.94, P < .01). CONCLUSIONS: In this multicenter retrospective study from 42 children's hospitals, heliox prescribing for CA declined over the last decade. Subjects receiving multiple adjunctive therapies more commonly required invasive MV perhaps indicating a greater severity of illness. At this time, prospective trials needed to identify the role of heliox for pediatric CA.

High-flow nasal cannula and bilevel positive airway pressure for pediatric status asthmaticus: a single center, retrospective descriptive and comparative cohort study.

INTRODUCTION: We aimed to describe patient characteristics and clinical outcomes for children hospitalized for status asthmaticus (SA) receiving high-flow nasal cannula (HFNC) or bilevel positive airway pressure (BiPAP). METHODS: We performed a single center, retrospective cohort study among 39 children admitted for SA aged 5-17 years from January 2016 to May 2019 to a quaternary pediatric intensive care unit (PICU). Cohorts were defined by BiPAP versus HFNC exposure and assessed to determine if differences existed in demographics, anthropometrics, comorbidities, asthma severity indices, historical factors, duration of noninvasive ventilation, and asthma-related clinical outcomes (i.e. length of stay, mechanical ventilation rates, exposure to concurrent sedatives/anxiolysis, and rate of adjunctive therapy exposure). RESULTS: Thirty-three percent (n = 13) received HFNC (33%) and 67% (n = 26) BiPAP. Children receiving BiPAP had greater age (10.9 ± 3.7 vs. 6.8 ± 2.2 years, P < 0.01), asthma severity (proportion with severe NHLBI classification: 38% vs. 0%, P < 0.01; median pediatric asthma severity score: 13[12,14] vs. 10[9,12], P < 0.01), previous PICU admissions (62% vs. 15%, P = 0.01), frequency of prescribed anxiolysis/sedation (42% vs. 8%, P = 0.02), and median duration of continuous albuterol (1.7[1,3.1] vs. 0.9[0.7,1.6] days, P = 0.03) compared to those on HFNC. Those on HFNC more commonly were treated comorbid bacterial pneumonia (69% vs. 19%, P < 0.01). No differences in NIV duration, mortality, mechanical ventilation rates, or LOS were observed. CONCLUSIONS: Our data suggest a trial of BiPAP or HFNC appears well tolerated in children with SA. Prospective trials are needed to establish modality superiority and identify patient or clinical characteristics that prompt use of HFNC over BiPAP.

Predicting Flow Rate Escalation for Pediatric Patients on High Flow Nasal Cannula Using Machine Learning.

Background: High flow nasal cannula (HFNC) is commonly used as non-invasive respiratory support in critically ill children. There are limited data to inform consensus on optimal device parameters, determinants of successful patient response, and indications for escalation of support. Clinical scores, such as the respiratory rate-oxygenation (ROX) index, have been described as a means to predict HFNC non-response, but are limited to evaluating for escalations to invasive mechanical ventilation (MV). In the presence of apparent HFNC non-response, a clinician may choose to increase the HFNC flow rate to hypothetically prevent further respiratory deterioration, transition to an alternative non-invasive interface, or intubation for MV. To date, no models have been assessed to predict subsequent escalations of HFNC flow rates after HFNC initiation. Objective: To evaluate the abilities of tree-based machine learning algorithms to predict HFNC flow rate escalations. Methods: We performed a retrospective, cohort study assessing children admitted for acute respiratory failure under 24 months of age placed on HFNC in the Johns Hopkins Children's Center pediatric intensive care unit from January 2019 through January 2020. We excluded encounters with gaps in recorded clinical data, encounters in which MV treatment occurred prior to HFNC, and cases electively intubated in the operating room. The primary study outcome was discriminatory capacity of generated machine learning algorithms to predict HFNC flow rate escalations as compared to each other and ROX indices using area under the receiver operating characteristic (AUROC) analyses. In an exploratory fashion, model feature importance rankings were assessed by comparing Shapley values. Results: Our gradient boosting model with a time window of 8 h and lead time of 1 h before HFNC flow rate escalation achieved an AUROC with a 95% confidence interval of 0.810 ± 0.003. In comparison, the ROX index achieved an AUROC of 0.525 ± 0.000. Conclusion: In this single-center, retrospective cohort study assessing children under 24 months of age receiving HFNC for acute respiratory failure, tree-based machine learning models outperformed the ROX index in predicting subsequent flow rate escalations. Further validation studies are needed to ensure generalizability for bedside application.

Volatile anesthetic agents for life-threatening pediatric asthma: A multicenter retrospective cohort study and narrative review.

BACKGROUND: Volatile anesthetic agents are described as rescue therapy for children invasively ventilated for critical asthma. Yet, data are currently limited to case series. AIMS: Using the Virtual Pediatric Systems database, we assessed children admitted to a pediatric intensive care unit invasively ventilated for life-threatening asthma and hypothesized ventilation duration and mortality rates would be lower for subjects exposed to volatile anesthetics compared with those without exposure. METHODS: We performed a multicenter retrospective cohort study among nine institutions including children 5-17 years of age invasively ventilated for asthma from 2013 to 2019 with and without exposure to volatile anesthetics. Primary outcomes were ventilation duration and mortality. Secondary outcomes included patient characteristics, length of stay, and anesthetic-related adverse events. A subgroup analysis was performed evaluating children intubated ≥2 days. RESULTS: Of 203 children included in study, there were 29 (14.3%) with and 174 (85.7%) without exposure to volatiles. No differences in odds of mortality (1.1, 95% CI: 0.3-3.9, p > .999) were observed. Subjects receiving volatiles experienced greater median difference in length of stay (4.8, 95% CI: 1.9-7.8 days, p < .001), ventilation duration (2.3, 95% CI: 1-3.3 days, p < .001), and odds of extracorporeal life support (9.1, 95% CI: 1.9-43.2, p = .009) than those without volatile exposure. For those ventilated ≥2 days, no differences were detected in mortality, ventilation duration, length of stay, arrhythmias, or acute renal failure. However, the odds of extracorporeal life support remained greater for those receiving volatiles (7.6, 95% CI: 1.3-44.5, p = .027). No children experienced malignant hyperthermia or hepatic failure after volatile exposure. CONCLUSIONS: For intubated children for asthma, no differences in mechanical ventilation duration or mortality between those with and without volatile anesthetic exposure were observed. Although volatiles may represent a viable rescue therapy for severe cases of asthma, definitive, and prospective trials are still needed.

Venous Thromboembolism among Critically Ill Children: A Narrative Review.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality among hospitalized patients, including children. In recent years, it has become clear that hospitalization and critical illness bestow an increased VTE risk in pediatrics and relate to mortality and life-limiting comorbidities. For critically ill children, reported rates of VTE vary by study sampling techniques, presence of inherited or acquired thrombophilia, acute and chronic immobility, underlying illness prompting hospitalization, and clinical factors related to illness severity such as central venous catheterization, length of stay, mechanical ventilation, and patient age. Accordingly, critically ill children with new signs of venous congestion, acute inflammation, or unexplained acute organ dysfunction should be routinely evaluated for VTE. This narrative review summarizes recent and historical literature regarding risk factors, prevention, presentation, treatment, and outcomes of VTE in critically ill children. In addition, we identify knowledge gaps and priorities for future collaborative research on this vital condition. Special attention is given to the clinical trial opportunities, challenges, and ongoing efforts in thromboprophylaxis in critically ill children, including those hospitalized for disease related to novel coronavirus (COVID-19) and multisystem inflammatory disease in children.