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.

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.