Antibiotic Indications and Appropriateness in the Pediatric Intensive Care Unit: A 10-Center Point Prevalence Study.

BACKGROUND: Antibiotics are prescribed to most pediatric intensive care unit (PICU) patients, but data describing indications and appropriateness of antibiotic orders in this population are lacking. METHODS: We performed a multicenter point prevalence study that included children admitted to 10 geographically diverse PICUs over 4 study days in 2019. Antibiotic orders were reviewed for indication, and appropriateness was assessed using a standardized rubric. RESULTS: Of 1462 patients admitted to participating PICUs, 843 (58%) had at least 1 antibiotic order. A total of 1277 antibiotic orders were reviewed. Common indications were empiric therapy for suspected bacterial infections without sepsis or septic shock (260 orders, 21%), nonoperative prophylaxis (164 orders, 13%), empiric therapy for sepsis or septic shock (155 orders, 12%), community-acquired pneumonia (CAP; 118 orders, 9%), and post-operative prophylaxis (94 orders, 8%). Appropriateness was assessed for 985 orders for which an evidence-based rubric for appropriateness could be created. Of these, 331 (34%) were classified as inappropriate. Indications with the most orders classified as inappropriate were empiric therapy for suspected bacterial infection without sepsis or septic shock (78 orders, 24%), sepsis or septic shock (55 orders, 17%), CAP (51 orders, 15%), ventilator-associated infections (47 orders, 14%), and post-operative prophylaxis (44 orders, 14%). The proportion of antibiotics classified as inappropriate varied across institutions (range, 19%-43%). CONCLUSIONS: Most PICU patients receive antibiotics. Based on our study, we estimate that one-third of antibiotic orders are inappropriate. Improved antibiotic stewardship and research focused on strategies to optimize antibiotic use in critically ill children are needed.

Pediatric In-Hospital Cardiac Arrest Secondary to Acute Pulmonary Embolism.

OBJECTIVES: Pulmonary embolism is a rarely reported and potentially treatable cause of cardiac arrest in children and adolescents. The objective of this case series is to describe the course of five adolescent patients with in-hospital cardiac arrest secondary to pulmonary embolism. DESIGN: Case series. SETTING: Single, large academic children's hospital. PATIENTS: All patients under the age of 18 years (n = 5) who experienced an in-hospital cardiac arrest due to apparent pulmonary embolism from August 1, 2013, to July 31, 2017. INTERVENTIONS: All five patients received systemic thrombolytic therapy (IV tissue plasminogen activator) during cardiac arrest or periarrest during ongoing resuscitation efforts. MEASUREMENTS AND MAIN RESULTS: Five adolescent patients, 15-17 years old, were treated for pulmonary embolism-related cardiac arrests during the study period. These accounted for 6.3% of all children and 25% of adolescents (12-17 yr old) receiving at least 5 minutes of in-hospital cardiopulmonary resuscitation during the study period. All five had venous thromboembolism risk factors. Two patients had known, extensive venous thrombi at the time of cardiac arrest, and one was undergoing angiography at the time of arrest. The diagnoses of pulmonary embolism were based on clinical suspicion, bedside echocardiography (n = 4), and low end-tidal CO2 levels relative to arterial CO2 values (n = 5). IV tissue plasminogen activator was administered during cardiopulmonary resuscitation in three patients and after the return of spontaneous circulation, in the setting of severe hemodynamic instability, in the other two patients. Four of five patients were successfully resuscitated and survived to hospital discharge. CONCLUSIONS: Pulmonary embolism was recognized as the etiology of multiple adolescent cardiac arrests in this single-center series and may be more common than previously reported. Recognition, high-quality cardiopulmonary resuscitation, and treatment with thrombolytic therapy resulted in survival in four of five patients.

Failure of Invasive Airway Placement on the First Attempt Is Associated With Progression to Cardiac Arrest in Pediatric Acute Respiratory Compromise.

OBJECTIVES: The aim of this study was to describe the proportion of acute respiratory compromise events in hospitalized pediatric patients progressing to cardiopulmonary arrest, and the clinical factors associated with progression of acute respiratory compromise to cardiopulmonary arrest. We hypothesized that failure of invasive airway placement on the first attempt (defined as multiple attempts at tracheal intubation, and/or laryngeal mask airway placement, and/or the creation of a new tracheostomy or cricothyrotomy) is independently associated with progression of acute respiratory compromise to cardiopulmonary arrest. DESIGN: Multicenter, international registry of pediatric in-hospital acute respiratory compromise. SETTING: American Heart Association's Get with the Guidelines-Resuscitation registry (2000-2014). PATIENTS: Children younger than 18 years with an index (first) acute respiratory compromise event. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 2,210 index acute respiratory compromise events, 64% required controlled ventilation, 26% had return of spontaneous ventilation, and 10% progressed to cardiopulmonary arrest. There were 762 acute respiratory compromise events (34%) that did not require an invasive airway, 1,185 acute respiratory compromise events (54%) with successful invasive airway placement on the first attempt, and 263 acute respiratory compromise events (12%) with failure of invasive airway placement on the first attempt. After adjusting for confounding variables, failure of invasive airway placement on the first attempt was independently associated with progression of acute respiratory compromise to cardiopulmonary arrest (adjusted odds ratio 1.8 [95% CIs, 1.2-2.6]). CONCLUSIONS: More than 1 in 10 hospitalized pediatric patients who experienced an acute respiratory compromise event progressed to cardiopulmonary arrest. Failure of invasive airway placement on the first attempt is independently associated with progression of acute respiratory compromise to cardiopulmonary arrest.

Implementation of a critical care outreach team in a children's hospital.

Introduction: Proactive surveillance by a critical care outreach team (CCOT) can promote early recognition of deterioration in hospitalized patients but is uncommon in pediatric rapid response systems (RRSs). After our children's hospital introduced a CCOT in 2019, we aimed to characterize early implementation outcomes. We hypothesized that CCOT rounding would identify additional children at risk for deterioration. Methods: The CCOT, staffed by a dedicated critical care nurse (RN), respiratory therapist, and attending, conducts daily in-person rounds with charge RNs on medical-surgical units, to screen RRS-identified high-risk patients for deterioration. In this prospective study, observers tracked rounds discussion content, participation, and identification of new high-risk patients. We compared 'identified-patient-discussions' (IPD) about RRS-identified patients, and 'new-patient-discussions' (NPD) about new patients with Fisher's exact test. For new patients, we performed thematic analysis of clinical data to identify deterioration related themes. Results: During 348 unit-rounds over 20 days, we observed 383 discussions - 35 (9%) were NPD. Frequent topics were screening for clinical concerns (374/383, 98%), active clinical concerns (147/383, 39%), and watcher activation (66/383, 17%). Most discussions only included standard participants (353/383, 92%). Compared to IPD, NPD more often addressed active concerns (74.3% vs 34.8%, p < 0.01) and staffing resource concerns (5.7% vs 0.6%, p < 0.04), and more often incorporated extra participants (25.7% vs 6%, p < 0.01). In thematic analysis of 33 new patients, most (29/33, 88%) had features of deterioration. Conclusion: A successfully implemented CCOT enhanced identification of clinical deterioration not captured by existing RRS resources. Future work will investigate its impact on operational safety and patient-centered outcomes.

Sex-specific modulation of the medial prefrontal cortex by glutamatergic median raphe neurons.

The current understanding of the neuromodulatory role of the median raphe nucleus (MRN) is primarily based on its putative serotonergic output. However, a significant proportion of raphe neurons are glutamatergic. The present study investigated how glutamatergic MRN input modulates the medial prefrontal cortex (mPFC), a critical component of the fear circuitry. Our studies show that VGLUT3-expressing MRN neurons modulate VGLUT3- and somatostatin-expressing neurons in the mPFC. Consistent with this modulation of mPFC GABAergic neurons, activation of MRN (VGLUT3) neurons suppresses mPFC pyramidal neuron activity and attenuates fear memory in female but not male mice. In agreement with these female-specific effects, we observed sex differences in glutamatergic transmission onto MRN (VGLUT3) neurons and mPFC (VGLUT3) neuron-mediated dual release of glutamate and GABA. Thus, our results demonstrate a cell type-specific modulation of the mPFC by MRN (VGLUT3) neurons and reveal a sex-specific role of this neuromodulation in mPFC synaptic plasticity and fear memory.

Pediatric Sepsis Requiring Intensive Care Admission: Potential Structured Follow-Up Protocols to Identify and Manage New or Exacerbated Medical Conditions.

Pediatric sepsis is a leading cause of morbidity and mortality in children globally. Children who require the pediatric intensive care unit (PICU) are at high risk for new or worsening co-morbidities, as well as readmission. This review describes the current state of protocolized follow-up after pediatric sepsis requiring PICU admission. We searched Medline and EMBASE databases for studies published in English from 2005 to date. Duplicates, review articles, abstracts and poster presentations were excluded; neonatal intensive care unit (NICU) patients were also excluded since neonatal sepsis is variably defined and differs from the pediatric consensus definition. The search yielded 418 studies of which 55 were duplicates; the subsequent 363 studies were screened for inclusion criteria, yielding 31 studies for which full article screening was completed. Subsequently, 23 studies were excluded due to wrong population (9), wrong publication type (10), duplicate data (3) or wrong outcome (1). In total, nine studies were included for which we described study design, setting, population, sample size, outcomes, PICU core outcome domain, and results. There were 4 retrospective cohort studies, 4 prospective cohort studies, 1 retrospective case series and no prospective trials. These studies show the varying trajectories of recovery after discharge, with the common finding that new or worsening morbidities are worse within months of discharge, but may persist. Sepsis survivors may have distinct needs and a different post-PICU trajectory compared to other critically ill children, particularly in quality of life and neurocognitive outcomes. Future research should focus on developing screening protocols and studying protocolized follow-up trials to reduce morbidity after pediatric sepsis.

Sex-specific modulation of the medial prefrontal cortex by glutamatergic median raphe neurons.

A substantial proportion of raphe neurons are glutamatergic. However, little is known about how these glutamatergic neurons modulate the forebrain. We investigated how glutamatergic median raphe nucleus (MRN) input modulates the medial prefrontal cortex (mPFC), a critical component of fear circuitry. We show that vesicular glutamate transporter 3 (VGLUT3)-expressing MRN neurons activate VGLUT3- and somatostatin-expressing neurons in the mPFC. Consistent with this modulation of mPFC GABAergic neurons, activation of MRN (VGLUT3) neurons enhances GABAergic transmission in mPFC pyramidal neurons and attenuates fear memory in female but not male mice. Serotonin plays a key role in MRN (VGLUT3) neuron-mediated GABAergic plasticity in the mPFC. In agreement with these female-specific effects, we observed sex differences in glutamatergic transmission onto MRN (VGLUT3) neurons and in mPFC (VGLUT3) neuron-mediated dual release of glutamate and GABA. Our results demonstrate a cell type-specific modulation of the mPFC by MRN (VGLUT3) neurons and reveal a sex-specific role of this neuromodulation in mPFC synaptic plasticity.

Mixed-methods process evaluation of a respiratory-culture diagnostic stewardship intervention.

OBJECTIVE: To conduct a process evaluation of a respiratory culture diagnostic stewardship intervention. DESIGN: Mixed-methods study. SETTING: Tertiary-care pediatric intensive care unit (PICU). PARTICIPANTS: Critical care, infectious diseases, and pulmonary attending physicians and fellows; PICU nurse practitioners and hospitalist physicians; pediatric residents; and PICU nurses and respiratory therapists. METHODS: This mixed-methods study was conducted concurrently with a diagnostic stewardship intervention to reduce the inappropriate collection of respiratory cultures in mechanically ventilated children. We quantified baseline respiratory culture utilization and indications for ordering using quantitative methods. Semistructured interviews informed by these data and the Consolidated Framework for Implementation Research (CFIR) were then performed, recorded, transcribed, and coded to identify salient themes. Finally, themes identified in these interviews were used to create a cross-sectional survey. RESULTS: The number of cultures collected per day of service varied between attending physicians (range, 2.2-27 cultures per 100 days). In total, 14 interviews were performed, and 87 clinicians completed the survey (response rate, 47%) and 77 nurses or respiratory therapists completed the survey (response rate, 17%). Clinicians varied in their stated practices regarding culture ordering, and these differences both clustered by specialty and were associated with perceived utility of the respiratory culture. Furthermore, group "default" practices, fear, and hierarchy were drivers of culture orders. Barriers to standardization included fear of a missed diagnosis and tension between practice standardization and individual decision making. CONCLUSIONS: We identified significant variation in utilization and perceptions of respiratory cultures as well as several key barriers to implementation of this diagnostic test stewardship intervention.

Frequency of and Risk Factors Associated With Hospital Readmission After Sepsis.

OBJECTIVES: Although children who survive sepsis are at risk for readmission, identification of patient-level variables associated with readmission has been limited by administrative datasets. We determined frequency and cause of readmission within 90 days of discharge and identified patient-level variables associated with readmission using a large, electronic health record-based registry. METHODS: This retrospective observational study included 3464 patients treated for sepsis or septic shock between January 2011 and December 2018 who survived to discharge at a single academic children's hospital. We determined frequency and cause of readmission through 90 days post-discharge and identified patient-level variables associated with readmission. Readmission was defined as inpatient treatment within 90 days post-discharge from a prior sepsis hospitalization. Outcomes were frequency of and reasons for 7-, 30-, and 90-day (primary) readmission. Patient variables were tested for independent associations with readmission using multivariable logistic regression. RESULTS: Following index sepsis hospitalization, frequency of readmission at 7, 30, and 90 days was 7% (95% confidence interval 6%-8%), 20% (18%-21%), and 33% (31%-34%). Variables independently associated with 90-day readmission were age ≤ 1 year, chronic comorbid conditions, lower hemoglobin and higher blood urea nitrogen at sepsis recognition, and persistently low white blood cell count ≤ 2 thous/µL. These variables explained only a small proportion of overall risk (pseudo-R2 range 0.05-0.13) and had moderate predictive validity (area under the receiver operating curve range 0.67-0.72) for readmission. CONCLUSIONS: Children who survive sepsis were frequently readmitted, most often for infections. Risk for readmission was only partly indicated by patient-level variables.

Opportunities to improve diagnosis in emergency transfers to the pediatric intensive care unit.

BACKGROUND: Late recognition of in-hospital deterioration is a source of preventable harm. Emergency transfers (ET), when hospitalized patients require intensive care unit (ICU) interventions within 1 h of ICU transfer, are a proximal measure of late recognition associated with increased mortality and length of stay (LOS). OBJECTIVE: To apply diagnostic process improvement frameworks to identify missed opportunities for improvement in diagnosis (MOID) in ETs and evaluate their association with outcomes. DESIGN, SETTINGS, AND PARTICIPANTS: A single-center retrospective cohort study of ETs, January 2015 to June 2019. ET criteria include intubation, vasopressor initiation, or ≥ $\ge \phantom{\rule{}{0ex}}$ 60 mL/kg fluid resuscitation 1 h before to 1 h after ICU transfer. The primary exposure was the presence of MOID, determined using SaferDx. Cases were screened by an ICU and non-ICU physician. Final determinations were made by an interdisciplinary group. Diagnostic process improvement opportunities were identified. MAIN OUTCOME AND MEASURES: Primary outcomes were in-hospital mortality and posttransfer LOS, analyzed by multivariable regression adjusting for age, service, deterioration category, and pretransfer LOS. RESULTS: MOID was identified in 37 of 129 ETs (29%, 95% confidence interval [CI] 21%-37%). Cases with MOID differed in originating service, but not demographically. Recognizing the urgency of an identified condition was the most common diagnostic process opportunity. ET cases with MOID had higher odds of mortality (odds ratio 5.5; 95% CI 1.5-20.6; p = .01) and longer posttransfer LOS (rate ratio 1.7; 95% CI 1.1-2.6; p = .02). CONCLUSION: MOID are common in ETs and are associated with increased mortality risk and posttransfer LOS. Diagnostic improvement strategies should be leveraged to support earlier recognition of clinical deterioration.

Observing sources of system resilience using in situ alarm simulations.

Alarm fatigue (and resultant alarm nonresponse) threatens the safety of hospitalized patients. Historically threats to patient safety, including alarm fatigue, have been evaluated using a Safety I perspective analyzing rare events such as failure to respond to patients' critical alarms. Safety II approaches call for learning from the everyday adaptations clinicians make to keep patients safe. To identify such sources of resilience in alarm systems, we conducted 59 in situ simulations of a critical hypoxemic-event alarm in medical/surgical and intensive care units at a tertiary care pediatric hospital between December 2019 and May 2022. Response timing, observations of the environment, and postsimulation debrief interviews were captured. Four primary means of successful alarm responses were mapped to domains of Systems Engineering Initiative for Patient Safety framework to inform alarm system design and improvement.

Improving Vancomycin Stewardship in Critically Ill Children.

BACKGROUND AND OBJECTIVES: Inappropriate vancomycin use is common in children's hospitals. We report a quality improvement (QI) intervention to reduce vancomycin use in our tertiary care PICU. METHODS: We retrospectively quantified the prevalence of infections caused by organisms requiring vancomycin therapy, including methicillin-resistant Staphylococcus aureus (MRSA), among patients with suspected bacterial infections. Guided by these data, we performed 3 QI interventions over a 3-year period, including (1) stakeholder education, (2) generation of a consensus-based guideline for empiric vancomycin use, and (3) implementation of this guideline through clinical decision support. Vancomycin use in days of therapy (DOT) per 1000 patient days was measured by using statistical process control charts. Balancing measures included frequency of bacteremia due to an organism requiring vancomycin not covered with empiric therapy, 30-day mortality, and cardiovascular, respiratory, and renal organ dysfunction. RESULTS: Among 1276 episodes of suspected bacterial infection, a total of 19 cases of bacteremia (1.5%) due to organisms requiring vancomycin therapy were identified, including 6 MRSA bacteremias (0.5%). During the 3-year QI project, overall vancomycin DOT per 1000 patient days in the PICU decreased from a baseline mean of 182 DOT per 1000 patient days to 109 DOT per 1000 patient days (a 40% reduction). All balancing measures were unchanged, and all cases of MRSA bacteremia were treated empirically with vancomycin. CONCLUSION: Our interventions reduced overall vancomycin use in the PICU without evidence of harm. Provider education and consensus building surrounding indications for empiric vancomycin use were key strategies.

Early Experience with a Novel Strategy for Assessment of Sepsis Risk: The Shock Huddle.

INTRODUCTION: Severe sepsis/septic shock (SS), a leading cause of death in children, is a complex clinical syndrome that can be challenging to diagnose. To assist with the early and accurate diagnosis of this illness, we instituted an electronic scoring tool and developed a novel strategy for the assessment of currently hospitalized children at risk for SS. METHODS: The Shock Tool was created to alert providers to children at risk for SS. Above a threshold score of 45, patients were evaluated by a team from the pediatric intensive care unit (PICU), led by the Shock Nurse (RN), a specially trained PICU nurse, to assess their need for further therapies. Data related to this evaluation, termed a Shock Huddle, were collected and reviewed with the intensivist fellow on service. RESULTS: Over 1 year, 9,241 hospitalized patients were screened using the Shock Score. There were 206 Shock Huddles on 109 unique patients. Nearly 40% of Shock Huddles included a diagnostic or therapeutic intervention at the time of patient assessment, with the most frequent intervention being a fluid bolus. Shock Huddles resulted in a patient transfer to the PICU 10% of the time. CONCLUSION: Implementation of an electronic medical record-based sepsis recognition tool paired with a novel strategy for rapid assessment of at-risk patients by a Shock RN is feasible and offers an alternative strategy to a traditional medical emergency team for the delivery of sepsis-related care. Further study is needed to describe the impact of this process on patient outcomes.

A pragmatic checklist to identify pediatric ICU patients at risk for cardiac arrest or code bell activation.

BACKGROUND: In-hospital cardiac arrest is a rare event associated with significant morbidity and mortality. The ability to identify the ICU patients at risk for cardiac arrest could allow the clinical team to prepare staff and equipment in anticipation. METHODS: This pilot study was completed at a large tertiary care pediatric intensive care unit to determine the feasibility of a simple checklist of clinical variables to predict deterioration. The daily checklist assessed patient risk for critical deterioration defined as cardiac arrest or code bell activation within 24h of the checklist screen. The Phase I checklist was developed by expert consensus and evaluated to determine standard diagnostic test performance. A modified Phase II checklist was developed to prospectively test the feasibility and bedside provider "number needed to train". RESULTS: For identifying patients requiring code bell activation, both checklists demonstrated a sensitivity of 100% with specificity of 76.0% during Phase I and 97.7% during Phase II. The positive likelihood ratio improved from 4.2 to 43.7. For identifying patients that had a cardiac arrest within 24h, the Phase I and II checklists demonstrated a sensitivity of 100% with specificity again improving from 75.7% to 97.6%. There was an improved positive likelihood ratio from 4.1 in Phase I to 41.9 in Phase II, with improvement of "number needed to train" from 149 to 7.4 providers. CONCLUSIONS: A novel high-risk clinical indicators checklist is feasible and provides timely and accurate identification of the ICU patients at risk for cardiac arrest or code bell activation.