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.

Confidence-weighted Testing as an Impactful Education Intervention within a Pediatric Sepsis Quality Improvement Initiative.

INTRODUCTION: Confidence-weighted testing assesses learners' beliefs about their knowledge and skills. As part of a hospital-wide quality improvement initiative to enhance care for pediatric patients with suspected sepsis, we developed a novel intervention using confidence-weighted testing to identify institutional areas of misinformation and knowledge gaps while also providing real-time feedback to individual learners. METHODS: We developed pediatric sepsis eLearning modules incorporating confidence-weighted testing. We distributed them to nurses, advanced practitioners, and physicians in emergency departments and acute care/non-intensive care unit inpatient settings in our hospital system. We analyzed completion and response data over 2 years following module distribution. Our outcomes included completion, confidently held misinformation (CHM; when a learner answers a question confidently but incorrectly), struggle (when a learner repeatedly answers a question incorrectly or with low confidence), and mastery (when a learner initially answers a question correctly and confidently). RESULTS: Eighty-three percent of assigned learners completed the modules (1,463/1,754). Although nurses had significantly more misinformation and struggled more than physicians and advanced practitioners, learners of all roles achieved 100% mastery as part of module completion. The greatest CHM and struggle were found in serum lactate interpretation's nuances and the hemodynamic shock states commonly seen in sepsis. CONCLUSIONS: Our novel application of confidence-weighted testing enhanced learning by correcting learners' misinformation. It also identified systems issues and institutional knowledge gaps as targets for future improvement.

IVIG Compared With IVIG Plus Infliximab in Multisystem Inflammatory Syndrome in Children.

OBJECTIVES: To compare initial treatment with intravenous immunoglobulin (IVIG) versus IVIG plus infliximab in multisystem inflammatory syndrome in children (MIS-C). METHODS: Single-center retrospective cohort study of patients with MIS-C who met Centers for Disease Control and Prevention criteria and received treatment from April 2020 to February 2021. Patients were included and compared on the basis of initial therapy of either IVIG alone or IVIG plus infliximab. The primary outcome was need for additional therapy 24 hours or more after treatment initiation. RESULTS: Seventy-two children with MIS-C met inclusion criteria. Additional therapy was needed in 13 of 20 (65%) who received IVIG alone and 16 of 52 (31%) who received IVIG plus infliximab (P = .01). The median (interquartile range) ICU lengths of stay were 3.3 (2.2 to 3.8) and 1.8 (1.1 to 2.1) days, respectively (P = .001). New or worsened left ventricular dysfunction developed in 4 of 20 (20%) and 2 of 52 (4%) (P = .05), and new vasoactive medication requirement developed in 3 of 20 (15%) and 2 of 52 (4%), respectively (P = .13). The median percentage changes in the C-reactive protein level at 24 hours posttreatment compared with pretreatment were 0% (-29% to 66%) and -46% (-62% to -15%) (P < .001); and at 48 hours posttreatment, -5% (-41% to 57%) and -70% (-79% to -49%) respectively (P < .001). There was no significant difference in hospital length of stay, time to fever resolution, vasoactive medication duration, or need for diuretics. CONCLUSIONS: Patients with MIS-C initially treated with IVIG plus infliximab compared with those treated with IVIG alone were less likely to require additional therapy and had decreased ICU length of stay, decreased development of left ventricular dysfunction, and more rapid decline in C-reactive protein levels.

An Acute Care Sepsis Response System Targeting Improved Antibiotic Administration.

BACKGROUND AND OBJECTIVES: Pediatric sepsis quality improvement in emergency departments has been well described and associated with improved survival. Acute care (non-ICU inpatient) units differ in important ways, and optimal approaches to improving sepsis processes and outcomes in this setting are not yet known. Our objective was to increase the proportion of acute care sepsis cases in our health system with initial antibiotic order-to-administration time ≤60 minutes by 20% from a baseline of 43% to 52% by December 2020. METHODS: Employing the Model for Improvement with broad stakeholder engagement, we developed and implemented interventions aimed at effective intervention for sepsis cases on acute care units. We analyzed process and outcome metrics over time using statistical process control charts. We used descriptive statistics to explore differences in antibiotic order-to-administration time and inform ongoing improvement. RESULTS: We cared for 187 patients with sepsis over the course of our initiative. The proportion within our goal antibiotic order-to-administration time rose from 43% to 64% with evidence of special cause variation after our interventions. Of all patients, 66% experienced ICU transfer and 4% died. CONCLUSIONS: We successfully decreased antibiotic order-to-administration time. We also introduced a novel model for sepsis response systems that integrates interventions designed for the complexities of acute care settings. We demonstrated impactful local improvements in the acute care setting where quality improvement reports and success have previously been limited.

Characteristics of Pediatric Rapid Response Systems: Results From a Survey of PRIS Hospitals.

BACKGROUND: Many hospitals use rapid response systems (RRSs) to identify and intervene on hospitalized children at risk for deterioration. OBJECTIVES: To describe RRS characteristics across hospitals in the Pediatric Research in Inpatient Settings (PRIS) network. METHODS: We developed the survey through a series of prospective respondent, expert, and cognitive interviews. One institutional expert per PRIS hospital (n = 109) was asked to complete the web survey. We summarized responses using descriptive statistics with a secondary analysis of univariate associations between RRS characteristics and perceived effectiveness. RESULTS: The response rate was 72% (79 of 109). Respondents represented diverse hospital types and were primarily physicians (97%) with leadership roles in care escalation. Many hospitals used an early warning score (77%) for identification with variable characteristics (46% automated versus 54% full or partially manual calculation; inputs included vital signs [98%], physical examination findings [88%], diagnoses [23%], medications [19%], and diagnostic tests [14%]). Few incorporated a validated prediction model (9%). Similarly, many RRSs used a rapid response team for intervention (93%) with variable team composition (respiratory therapists [94%], ICU nurses [93%], ICU providers [67%], and pharmacists [27%]). Some used the early warning score to trigger the rapid response team (50%). Only a few staffed a clinician to proactively surveil hospitalized children for risk of deterioration (18%), and these tended to be larger hospitals (annual admissions 12 000 vs 6000, P = .007). Most responding experts stated their RRSs improved patient outcomes (92%). CONCLUSIONS: RRS characteristics varied across PRIS hospitals.

AutoPEWS: Automating Pediatric Early Warning Score Calculation Improves Accuracy Without Sacrificing Predictive Ability.

INTRODUCTION: Pediatric early warning scores (PEWS) identify hospitalized children at risk for deterioration. Manual calculation is prone to human error. Electronic health records (EHRs) enable automated calculation, removing human error. This study's objective was to compare the accuracy of automated EHR-based PEWS calculation (AutoPEWS) to manual calculation and evaluate the non-inferiority of AutoPEWS in predicting deterioration. METHODS: We performed a retrospective cohort study inclusive of non-intensive care unit inpatients at a freestanding children's hospital over 4.5 months in Fall 2018. AutoPEWS mapped the historical manual PEWS scoring rubric to frequently used EHR documentation. We determined accuracy by comparing the expected respiratory subset score based on the current respiratory rate to the actual respiratory score of AutoPEWS and the manual PEWS. The agreement was determined using kappa statistics. We used predicted probabilities from a generalized linear mixed model to calculate areas under the curve for each combination of scores (AutoPEWS, manual) and deterioration outcome (rapid response team activation, unplanned intensive care unit transfer, critical deterioration event). We compared the adjusted difference in areas under the curves between the scores. Non-inferiority was defined as a difference of <0.05. RESULTS: There were 23,514 total PEWS representative of 5,384 patients. AutoPEWS respiratory scores were 99.97% accurate, while the manual PEWS respiratory scores were 86% accurate. AutoPEWS were higher overall than the manual PEWS (mean 0.65 versus 0.34). They showed a fair-to-good agreement (weighted kappa 0.42). Non-inferiority of AutoPEWS compared with the manual PEWS was demonstrated for all deterioration outcomes. CONCLUSIONS: Automation of PEWS calculation improved accuracy without sacrificing predictive ability.