Delays to Antibiotics in the Emergency Department and Risk of Mortality in Children With Sepsis.

Importance: Pediatric consensus guidelines recommend antibiotic administration within 1 hour for septic shock and within 3 hours for sepsis without shock. Limited studies exist identifying a specific time past which delays in antibiotic administration are associated with worse outcomes. Objective: To determine a time point for antibiotic administration that is associated with increased risk of mortality among pediatric patients with sepsis. Design, Setting, and Participants: This retrospective cohort study used data from 51 US children's hospitals in the Improving Pediatric Sepsis Outcomes collaborative. Participants included patients aged 29 days to less than 18 years with sepsis recognized within 1 hour of emergency department arrival, from January 1, 2017, through December 31, 2021. Piecewise regression was used to identify the inflection point for sepsis-attributable 3-day mortality, and logistic regression was used to evaluate odds of sepsis-attributable mortality after adjustment for potential confounders. Data analysis was performed from March 2022 to February 2024. Exposure: The number of minutes from emergency department arrival to antibiotic administration. Main Outcomes and Measures: The primary outcome was sepsis-attributable 3-day mortality. Sepsis-attributable 30-day mortality was a secondary outcome. Results: A total of 19 515 cases (median [IQR] age, 6 [2-12] years) were included. The median (IQR) time to antibiotic administration was 69 (47-116) minutes. The estimated time to antibiotic administration at which 3-day sepsis-attributable mortality increased was 330 minutes. Patients who received an antibiotic in less than 330 minutes (19 164 patients) had sepsis-attributable 3-day mortality of 0.5% (93 patients) and 30-day mortality of 0.9% (163 patients). Patients who received antibiotics at 330 minutes or later (351 patients) had 3-day sepsis-attributable mortality of 1.2% (4 patients), 30-day mortality of 2.0% (7 patients), and increased adjusted odds of mortality at both 3 days (odds ratio, 3.44; 95% CI, 1.20-9.93; P = .02) and 30 days (odds ratio, 3.63; 95% CI, 1.59-8.30; P = .002) compared with those who received antibiotics within 330 minutes. Conclusions and Relevance: In this cohort of pediatric patients with sepsis, 3-day and 30-day sepsis-attributable mortality increased with delays in antibiotic administration 330 minutes or longer from emergency department arrival. These findings are consistent with the literature demonstrating increased pediatric sepsis mortality associated with antibiotic administration delay. To guide the balance of appropriate resource allocation with time for adequate diagnostic evaluation, further research is needed into whether there are subpopulations, such as those with shock or bacteremia, that may benefit from earlier antibiotics.

Association Between the COI and Excess Health Care Utilization and Costs for ACSC.

BACKGROUND AND OBJECTIVES: The authors of previous work have associated the Childhood Opportunity Index (COI) with increased hospitalizations for ambulatory care sensitive conditions (ACSC). The burden of this inequity on the health care system is unknown. We sought to understand health care resource expenditure in terms of excess hospitalizations, hospital days, and cost. METHODS: We performed a retrospective cross-sectional study of the Pediatric Health Information Systems database, including inpatient hospitalizations between January 1, 2016 and December 31, 2022 for children <18 years of age. We compared ACSC hospitalizations, mortality, and cost across COI strata. RESULTS: We identified 2 870 121 hospitalizations among 1 969 934 children, of which 44.5% (1 277 568/2 870 121) were for ACSCs. A total of 49.1% (331 083/674 548) of hospitalizations in the very low stratum were potentially preventable, compared with 39.7% (222 037/559 003) in the very high stratum (P < .001). After adjustment, lower COI was associated with higher odds of potentially preventable hospitalization (odds ratio 1.18, 95% confidence interval [CI] 1.17-1.19). Compared with the very high COI stratum, there were a total of 137 550 (95% CI 134 582-140 517) excess hospitalizations across all other strata, resulting in an excess cost of $1.3 billion (95% CI $1.28-1.35 billion). Compared with the very high COI stratum, there were 813 (95% CI 758-871) excess deaths, with >95% from the very low and low COI strata. CONCLUSIONS: Children with lower neighborhood opportunity have increased risk of ACSC hospitalizations. The COI may identify communities in which targeted intervention could reduce health care utilization and costs.

Prevalence of Reintubation Within 24 Hours of Extubation in Bronchiolitis: Retrospective Cohort Study Using the Virtual Pediatric Systems Database.

OBJECTIVES: High-flow nasal cannula and noninvasive positive pressure ventilation are used to support children following liberation from invasive mechanical ventilation. Evidence comparing extubation failure rates between patients randomized to high-flow nasal cannula and noninvasive positive pressure ventilation is available for adult and neonatal patients; however, similar pediatric trials are lacking. In this study, we employed a quality controlled, multicenter PICU database to test the hypothesis that high-flow nasal cannula is associated with higher prevalence of reintubation within 24 hours among patients with bronchiolitis. DESIGN: Secondary analysis of a prior study utilizing the Virtual Pediatric Systems database. SETTING: One-hundred twenty-four participating PICUs. PATIENTS: Children less than 24 months old with a primary diagnosis of bronchiolitis who were admitted to one of 124 PICUs between January 2009 and September 2015 and received invasive mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 759 patients, median age was 2.4 months (1.3-5.4 mo), 41.2% were female, 39.7% had greater than or equal to 1 comorbid condition, and 43.7% were Caucasian. Median PICU length of stay was 8.7 days (interquartile range, 5.8-13.7 d) and survival to PICU discharge was 100%. Median duration of intubation was 5.5 days (3.4-9.0 d) prior to initial extubation. High-flow nasal cannula was used following extubation in most (656 [86.5%]) analyzed subjects. The overall prevalence of reintubation within 24 hours was 5.9% (45 children). Extubation to noninvasive positive pressure ventilation was associated with greater prevalence of reintubation than extubation to high-flow nasal cannula (11.7% vs 5.0%; p = 0.016) and, in an a posteriori model that included Pediatric Index of Mortality 2 score and comorbidities, was associated with increased odds of reintubation (odds ratio, 2.43; 1.11-5.34; p = 0.027). CONCLUSIONS: In this secondary analysis of a multicenter database of children with bronchiolitis, extubation to high-flow nasal cannula was associated with a lower prevalence of reintubation within 24 hours compared with noninvasive positive pressure ventilation in both unmatched and propensity-matched analysis. Prospective trials are needed to determine if post-extubation support modality can mitigate the risk of extubation failure.

Antibiotic Prescription in Young Children With Respiratory Syncytial Virus-Associated Respiratory Failure and Associated Outcomes.

OBJECTIVES: To describe antibiotic prescribing practices during the first 2 days of mechanical ventilation among previously healthy young children with respiratory syncytial virus-associated lower respiratory tract infection and evaluate associations between the prescription of antibiotics at onset of mechanical ventilation with clinical outcomes. DESIGN: Retrospective cohort study. SETTING: Forty-six children's hospitals in the United States. PATIENTS: Children less than 2 years old discharged between 2012 and 2016 with an International Classification of Diseases diagnosis of respiratory syncytial virus-associated lower respiratory tract infection, no identified comorbid conditions, and receipt of mechanical ventilation. INTERVENTIONS: Antibiotic prescription during the first 2 days of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: We compared duration of mechanical ventilation and hospital length of stay between children prescribed antibiotics on both of the first 2 days of mechanical ventilation and children not prescribed antibiotics during the first 2 days of mechanical ventilation. We included 2,107 PICU children with respiratory syncytial virus-associated lower respiratory tract infection (60% male, median age of 1 mo [interquartile range, 1-4 mo]). The overall proportion of antibiotic prescription on both of the first 2 days of mechanical ventilation was 82%, decreasing over the study period (p = 0.004) and varying from 36% to 100% across centers. In the bivariate analysis, antibiotic prescription was associated with a shorter duration of mechanical ventilation (6 d [4-9 d] vs 8 d [6-11 d]; p < 0.001) and a shorter hospital length of stay (11 d [8-16 d] vs 13 d [10-18 d]; p < 0.001). After adjustment for center, demographics, and vasoactive medication prescription, antibiotic prescription was associated with a 1.21-day shorter duration of mechanical ventilation and a 2.07-day shorter length of stay. Ultimately, 95% of children were prescribed antibiotics sometime during hospitalization, but timing, duration, and antibiotic choice varied markedly. CONCLUSIONS: Although highly variable across centers and decreasing over time, the practice of instituting antibiotics after intubation in young children with respiratory syncytial virus-associated lower respiratory tract infection was associated with a shortened clinical course after adjustment for the limited available covariates. A prudent approach to identify and optimally treat bacterial coinfection is needed.

Outcomes of Children With Bronchiolitis Treated With High-Flow Nasal Cannula or Noninvasive Positive Pressure Ventilation.

OBJECTIVES: Initial respiratory support with noninvasive positive pressure ventilation or high-flow nasal cannula may prevent the need for invasive mechanical ventilation in PICU patients with bronchiolitis. However, it is not clear whether the initial choice of respiratory support modality influences the need for subsequent invasive mechanical ventilation. The purpose of this study is to compare the rate of subsequent invasive mechanical ventilation after initial support with noninvasive positive pressure ventilation or high-flow nasal cannula in children with bronchiolitis. DESIGN: Analysis of the Virtual Pediatric Systems database. SETTING: Ninety-two participating PICUs. PATIENTS: Children less than 2 years old admitted to a participating PICU between 2009 and 2015 with a diagnosis of bronchiolitis who were prescribed high-flow nasal cannula or noninvasive positive pressure ventilation as the initial respiratory treatment modality. INTERVENTIONS: None. Subsequent receipt of invasive mechanical ventilation was the primary outcome. MEASUREMENTS AND MAIN RESULTS: We identified 6,496 subjects with a median age 3.9 months (1.7-9.5 mo). Most (59.7%) were male, and 23.4% had an identified comorbidity. After initial support with noninvasive positive pressure ventilation or high-flow nasal cannula, 12.3% of patients subsequently received invasive mechanical ventilation. Invasive mechanical ventilation was more common in patients initially supported with noninvasive positive pressure ventilation compared with high-flow nasal cannula (20.1% vs 11.0%: p < 0.001). In a multivariate logistic regression model that adjusted for age, weight, race, viral etiology, presence of a comorbid diagnosis, and Pediatric Index of Mortality score, initial support with noninvasive positive pressure ventilation was associated with a higher odds of subsequent invasive mechanical ventilation compared with high-flow nasal cannula (odds ratio, 1.53; 95% CI, 1.24-1.88). CONCLUSIONS: In this large, multicenter database study of infants with acute bronchiolitis that received initial respiratory support with high-flow nasal cannula or noninvasive positive pressure ventilation, noninvasive positive pressure ventilation use was associated with higher rates of invasive mechanical ventilation, even after adjusting for demographics, comorbid condition, and severity of illness. A large, prospective, multicenter trial is needed to confirm these findings.

Temporal Changes in Prescription of Neuropharmacologic Drugs and Utilization of Resources Related to Neurologic Morbidity in Mechanically Ventilated Children With Bronchiolitis.

OBJECTIVES: Critically ill children with bronchiolitis may require neuropharmacologic medications and support for neuro-functional sequelae, but current practices are not well described. We aimed to describe recent trends in neuropharmacology and utilization of neuro-rehabilitation resources in mechanically ventilated children with bronchiolitis. DESIGN: Analysis of the multicenter Pediatric Health Information System database. SETTING: Forty-seven U.S. children's hospitals. PATIENTS: PICU patients less than 2 years old with bronchiolitis undergoing mechanical ventilation between 2006 and 2015. INTERVENTIONS: None. Annual rates of utilization of neuropharmacologic medications (sedatives, analgesics, etc) and of neuro-rehabilitation services (physical therapy, neurologic consultation, etc) over the 10-year study period were compared. MEASUREMENTS AND MAIN RESULTS: Neuropharmacologic medications prescribed on greater than or equal to 2 days were extracted. Utilization of MRI of the brain, neurologic consultation, swallow evaluation, occupational therapy, and physical therapy was also extracted. Among 12,508 subjects, the median age was 2.8 months, ~50% had comorbid conditions, and the median duration of mechanical ventilation was 7 days. The percentage of children prescribed greater than or equal to five drugs/drug classes increased over the study period from 36.5% to 55.8% (p < 0.001). There were significant increases over time in utilization of 10 of the 15 individual drugs/drug classes analyzed. More than half of subjects (6,294 [50.3%]) received at least one service that evaluates/treats neurologic morbidity. There were significant increases in the use of greater than or equal to one service (36.3% in 2006 to 59.6% in 2015; p < 0.001) and in the use of greater than or equal to two services (20.8% to 34.8%; p < 0.001). Utilization of each of the five individual resources increased significantly during the study period, but use of vasoactive medications and mortality did not. CONCLUSIONS: Prescription of neuropharmacologic agents increased over time using metrics of both overall drug burden and specific drug usage. Concurrently, the utilization of services that evaluate and/or treat neurologic morbidity was common and also increased over time.

Neurologic and Functional Morbidity in Critically Ill Children With Bronchiolitis.

OBJECTIVES: Neurologic and functional morbidity occurs in ~30% of PICU survivors, and young children may be at particular risk. Bronchiolitis is a common indication for PICU admission among children less than 2 years old. Two single-center studies suggest that greater than 10-25% of critical bronchiolitis survivors have neurologic and functional morbidity but those estimates are 20 years old. We aimed to estimate the burden of neurologic and functional morbidity among more recent bronchiolitis patients using two large, multicenter databases. DESIGN: Analysis of the Pediatric Health Information System and the Virtual Pediatric databases. SETTING: Forty-eight U.S. children's hospitals (Pediatric Health Information System) and 40 international (mostly United States) children's hospitals (Virtual Pediatric Systems). PATIENTS: Previously healthy PICU patients less than 2 years old admitted with bronchiolitis between 2009 and 2015 who survived and did not require extracorporeal membrane oxygenation or cardiopulmonary resuscitation. INTERVENTIONS: None. Neurologic and functional morbidity was defined as a Pediatric Overall Performance Category greater than 1 at PICU discharge (Virtual Pediatric Systems subjects), or a subsequent hospital encounter involving developmental delay, feeding tubes, MRI of the brain, neurologist evaluation, or rehabilitation services (Pediatric Health Information System subjects). MEASUREMENTS AND MAIN RESULTS: Among 3,751 Virtual Pediatric Systems subjects and 9,516 Pediatric Health Information System subjects, ~20% of patients received mechanical ventilation. Evidence of neurologic and functional morbidity was present at PICU discharge in 707 Virtual Pediatric Systems subjects (18.6%) and more chronically in 1,104 Pediatric Health Information System subjects (11.6%). In both cohorts, neurologic and functional morbidity was more common in subjects receiving mechanical ventilation (27.5% vs 16.5% in Virtual Pediatric Systems; 14.5% vs 11.1% in Pediatric Health Information System; both p < 0.001). In multivariate models also including demographics, use of mechanical ventilation was the only variable that was associated with increased neurologic and functional morbidity in both cohorts. CONCLUSIONS: In two large, multicenter databases, neurologic and functional morbidity was common among previously healthy children admitted to the PICU with bronchiolitis. Prospective studies are needed to measure neurologic and functional outcomes using more precise metrics. Identification of modifiable risk factors may subsequently lead to improved outcomes from this common PICU condition.