Background Barth syndrome (BTHS) is a rare genetic disease, with no approved curative therapies, characterized by abnormally developed cardiolipin, resulting in mitochondrial dysfunction. Cardiomyopathy, a common clinical manifestation of BTHS, often appears in infancy. Elamipretide, an investigational drug that binds to cardiolipin on the inner mitochondrial membrane, leads to improved membrane stability, enhanced adenosine triphosphate production, and reduced reactive oxygen species. This patient case aims to further support elamipretide's role in treating BTHS infants.Case summary We present an infant diagnosed in utero with BTHS who demonstrated a moderately dilated left ventricle (LV) with an LV ejection fraction (LVEF) of 20% at birth. He was transferred to a tertiary children's hospital where he was intubated and administered medications for haemodynamic support. After several weeks, the patient was extubated and his LVEF improved, although still below normal. On day of life (DOL) 34, therapy with daily IV elamipretide (0.25 mg/kg increased to 0.5 mg/kg on DOL39) began, followed by standard-of-care oral heart failure medications. Subsequent echocardiograms demonstrated improvement of LVEF to near-normal levels. He was weaned off oxygen completely on DOL49 and discharged home on DOL61 on daily subcutaneous elamipretide 0.5 mg/kg and oral heart failure medications. His most recent echocardiogram showed improvement of LVEF to 60%.Discussion Our case suggests that elamipretide may have contributed to the improvement of LV function in this BTHS infant, supporting elamipretide's early use in BTHS. Our findings align with the previous studies in which elamipretide treatment demonstrated normalization of mitochondrial function and improvement in LV function.

INTRODUCTION:Contemporary rates of survival after pediatric in-hospital CPR events and trends in survival over the last 20 years have not been compared based on illness category. We hypothesized that survival to hospital discharge for surgical-cardiac category is higher than the non-cardiac category, and rates of survival after in-hospital CPR increased over time in all categories. METHODS:The AHA Get With The Guidelines®-Resuscitation registry was queried for index CPR events in children < 18 years of age from 2000 to 2021. Categories were surgical-cardiac (in-hospital CPR event following cardiac surgery); medical-cardiac (CPR event in non-surgical cardiac disease); and non-cardiac (CPR event in patients without cardiac disease). The primary outcome was survival to hospital discharge. We compared eras 2000-2004, 2005-2009, 2010-2014, and 2015-2021 with mixed logistic regression models, including event year as a continuous predictor and site as a random effect. RESULTS:Of 16,241 index events, in-hospital CPR event rates by illness category were: 19 % surgical-cardiac, 18 % medical-cardiac, and 63 % non-cardiac. Surgical-cardiac category had the highest rate of survival to hospital discharge compared to medical-cardiac and non-cardiac categories (56 % vs. 44 % vs. 46 %; p < 0.001). After controlling for age, location of event, and hospital size, the odds of survival were highest for surgical-cardiac category (aOR 1.28, 95 % CI 1.17-1.41) and lower for medical-cardiac category (aOR 0.90, 0.82-0.98), compared to the non-cardiac category. Odds of survival increased for all illness categories from the 2000-2004 era to the 2015-2021 era. Rates of improvement differed among illness categories with medical-cardiac having the lowest increased odds per era. Surgical-cardiac patients had the highest rates of extracorporeal resuscitation (ECPR) (20 % across the cohort), though the greatest increase in ECPR utilization was in the non-cardiac population (52 % increased odds per era). CONCLUSIONS:Over the last 20 years, both survival to hospital discharge and ECPR use has increased in all in-hospital CPR event illness categories. Children with surgical-cardiac CPR event have higher odds of survival to hospital discharge compared to non-cardiac CPR event categories, whereas odds of survival were lowest with medical-cardiac CPR events.

ImportanceThe Pediatric Cardiac Critical Care Consortium (PC4) cardiac arrest prevention (CAP) quality improvement (QI) project facilitated a decreased in-hospital cardiac arrest (IHCA) incidence rate across multiple hospitals. The sustainability of this outcome has not been determined.ObjectiveTo examine the IHCA incidence rate at participating hospitals after the QI project ended and discern which factors best aligned with sustained improvement.Design, Setting, and ParticipantsThis observational cohort study compared IHCA data from the CAP era (July 1, 2018, to December 31, 2019) with data from the 2-year follow-up era (March 1, 2020, to February 28, 2022). Data were obtained from pediatric cardiac intensive care units (CICUs) from 17 PC4 CAP–participating hospitals.InterventionThe CAP practice bundle was designed to facilitate local practice integration, with the intention to implement, adapt, and continue CAP processes beyond the CAP era. A web-based survey was administered 2 years after the end of the project to estimate CAP-specific QI work.Main Outcomes and MeasuresRisk-adjusted IHCA incidence rates across all admissions were compared between study eras. The survey generated a novel hospital-specific QI sustainability score, which is generally reflective of the sum of local CAP work performed.ResultsThere were no clinically important differences in demographic and admission characteristics between the 13 082 CAP era admissions and 16 284 follow-up admissions (total mean [SD] age, 5.1 [8.4] years; 56.1% male). Risk-adjusted IHCA incidences were not different between the CAP vs follow-up eras (2.8% vs 2.8%; odds ratio, 1.03; 95% CI, 0.89-1.19), suggesting sustained prevention improvement. There was also no difference between eras in risk-adjusted IHCA incidence within medical, surgical, or high-risk subgroups. A lower hospital QI sustainability score was correlated with higher odds for IHCA in the follow-up vs CAP era (correlation coefficient, −0.58; P = .02). Five hospitals had increases of 1% or greater in risk-adjusted IHCA rates in the follow-up era; these hospitals had significantly lower QI sustainability scores and were less likely to have adopted sustainability elements during the CAP era or report persistent engagement for CAP-related QI processes during follow-up.Conclusions and RelevanceIn this cohort study of all CICU admissions across 17 hospitals, IHCA prevention was feasible and sustainable; the established reduction in risk-adjusted IHCA rate was maintained for at least 2 years after the end of the CAP project. Both implementation strategies and continued engagement in CAP processes during the follow-up era were associated with sustained improvement.

Newborns with coarctation of the aorta are a potentially vulnerable population whose diagnosis could have been impacted by the COVID-19 pandemic. The objectives of this study were to assess if there was delayed diagnosis of infants with coarctation and if they had higher acuity prior to repair after the start of the pandemic. The Pediatric Health Information Systems database was queried for patients less than three months of age who underwent surgical repair or palliation of coarctation of the aorta. Patients were divided into three time periods: (1) pre-COVID (October 2017–December 2019), (2) early COVID (January 2020–December 2020), and (3) late COVID (January 2021–December 2021). The outcomes were age at repair and pre-procedure acuity. Among the 4885 patients, the median time to repair was 10 days during all time periods. Use of pre-procedure mechanical ventilation, vasopressors, and extracorporeal membranous oxygenation did not increase after the start of the pandemic. Median length of hospital stay increased after the start of the pandemic and did not return to baseline (22 days, 24 days, and 25 days, sequentially, p < 0.01). When analyzing patients who presented to the surgical hospital after 3 days of life, there were no differences in age at repair, pre-procedural acuity, or other outcomes. Age at repair of coarctation of the aorta and acuity did not change after the start of the COVID-19 pandemic. This suggests that the safeguards in place to ensure timely diagnosis of critical heart disease were adequate during this time of disruption.

IntroductionThis study was designed to measure the concentration and activity of urinary proteases that activate renal epithelial sodium channel (ENaC) mediated Na+ transport in infants with congenital heart disease, a potential mechanism for fluid retention.MethodsUrine samples from infants undergoing cardiac surgery were collected at three time points: T1) pre-operatively, T2) 6–8 h after surgery, and T3) 24 h after diuretics. Urine was collected from five heathy infant controls. The urine was tested for four proteases and whole-cell patch-clamp testing was conducted in renal collecting duct M-1 cells to test whether patient urine increased Na+ currents consistent with ENaC activation.ResultsHeavy chain of plasminogen, furin, and prostasin were significantly higher in cardiac patients prior to surgery compared to controls. There was no difference in most proteases before and after surgery. Urine from cardiac patients produced a significantly greater increase in Na+ inward currents compared to healthy controls.ConclusionUrine from infants with congenital heart disease is richer in proteases and has the potential to increase activation of ENaC in the nephron to enhance Na+ reabsorption, which may lead to fluid retention in this population.

Congenital heart disease (CHD) is the most common birth defect, occurring in roughly 40,000 U.S. births annually. Malnutrition and feeding intolerance (FI) in CHD range from 30% to 42% and are associated with longer hospitalization and increased mortality. Cardiopulmonary bypass (CPB) required for surgical repair of CHD induces a systemic inflammatory response worsening intestinal dysbiosis and leading to intestinal epithelial barrier dysfunction (EBD), possibly contributing to postoperative FI. The objective of this study was to determine the relationship of postoperative FI with intestinal microbiome, short-chain fatty acids (SCFAs), and EBD in pediatric CHD after cardiac surgery. This was a prospective study of patients aged 0-15 years undergoing cardiac surgery with CPB. Samples were collected preoperatively and postoperatively to evaluate the gut microbiome, plasma EBD markers, short-chain fatty acids (SCFAs), and plasma cytokines. Clinical data were collected to calculate a FI score and evaluate patient status postoperatively. We enrolled 26 CPB patients and identified FI (n = 13). Patients with FI had unique microbial shifts with the reduced SCFA-producing organisms Rothia, Clostridium innocuum, and Intestinimonas. Patients who developed FI had associated elevations in the plasma EBD markers claudin-2 (P < 0.05), claudin-3 (P < 0.01), and fatty acid binding protein (P < 0.01). Patients with FI had reduced plasma and stool SCFAs. Mediation analysis showed the microbiome functional shift was associated with reductions in stool butyric and propionic acid in patients with FI. In conclusion, we provide novel evidence that intestinal dysbiosis, markers of EBD, and SCFA depletion are associated with FI. These data will help identify mechanisms and therapeutics to improve clinical outcomes following pediatric cardiac surgery.NEW & NOTEWORTHY Feeding intolerance contributes to postoperative morbidity following pediatric cardiac surgery. The intestinal microbiome and milieu play a vital role in gut function. Short-chain fatty acids are gut and cardioprotective metabolites produced by commensal bacteria and help maintain appropriate barrier function. Depletion of these metabolites and barrier dysfunction contribute to postoperative feeding intolerance following cardiac surgery. Identifying mechanistic targets to improve the intestinal milieu with the goal of improved nutrition and clinical outcomes is critical.

This study aimed to examine the impact of timing of extubation on feeding outcomes in neonates after surgery for congenital heart disease. This was a single-center retrospective study between December 2014 and June 2020. Patients were divided into three categories: extubated in the OR (immediate), extubated in the intensive care unit (ICU) between 0 and 3 days post-procedure (early), and extubated >3 days post-procedure (delayed). Comparing the immediate and early groups, we found no difference in time to first enteral feed (1.3 days (1.0-3.4) vs. 2.3 days (1.1-3.3), p = 0.27). There was no difference in time to first oral feed (2.0 days (1.1-4.5) vs. 3.1 days (1.8-4.4), p = 0.34) and time to goal feed (6.0 days (3.2-8.3) vs. 6.9 days (5.0-9.0), p = 0.15)). There was no difference in all oral feeds at one year: 88% vs. 98%, p = 0.16. The delayed extubation group performed significantly worse on all measures. Immediate and early extubation displayed no differences in feeding outcomes and length of stay in this study, while delayed extubation performed worse on all measures. Thus, we believe that clinicians should emphasize extubation within 3 days post-surgery to improve feeding outcomes while minimizing time hospitalized.

ABSTRACTIntroductionContemporary rates of survival after pediatric in-hospital cardiac arrest (IHCA) and trends in survival over the last 20 years have not been compared based on illness category. We hypothesized that survival to hospital discharge for surgical-cardiac category is higher than the non-cardiac category, and rates of survival after IHCA increased over time in all categories.MethodsThe AHA Get With The Guidelines®-Resuscitation registry was queried for index IHCA events in children <18 years of age from 2000-2021. Categories were surgical-cardiac (IHCA following cardiac surgery); medical-cardiac (IHCA in non-surgical cardiac disease); and non-cardiac (IHCA in patients without cardiac disease). The primary outcome was survival to hospital discharge. We compared eras 2000-2004, 2005-2009, 2010-2014, and 2015-2021 with mixed logistic regression models, including event year as a continuous predictor and site as a random effect.ResultsOf 17,696 index events, IHCA rates by illness category were: 18% surgical-cardiac, 18% medical-cardiac, and 64% non-cardiac. Surgical-cardiac category had the highest rate of survival to discharge compared to medical-cardiac and non-cardiac categories (56% vs. 43% vs. 46%; p<0.001). After controlling for age, location of event, and hospital size, the odds of survival were highest for surgical-cardiac category (aOR 1.28, 95% CI 1.16-1.40) and lower for medical-cardiac category (aOR 0.87, 0.80-0.95), compared to the non-cardiac category. Odds of survival increased for all illness categories from the 2000-2004 era to the 2015-2021 era. Rates of improvement differed among illness categories with medical-cardiac having the lowest increased odds per era. Surgical-cardiac patients had the highest rates of extracorporeal resuscitation (ECPR) (20% across the cohort), though the greatest increase in ECPR utilization was in the non-cardiac population (44% increased odds per era).ConclusionsOver the last 20 years, both survival to hospital discharge and ECPR use has increased in all IHCA illness categories. Children with surgical-cardiac IHCA have higher odds of survival to hospital discharge compared to non-cardiac IHCA categories, whereas odds of survival were lowest with medical-cardiac IHCA.

Objectives: To describe epinephrine dosing distribution using time-stamped data and assess the impact of dosing strategy on survival after ECPR in children. Methods: This was a retrospective study at five pediatric hospitals of children <18 years with an in-hospital ECPR event. Mean number of epinephr-ine doses was calculated for each 10-minute CPR interval and compared between survivors and non-survivors. Patients were also divided by dosing strategy into a frequent epinephrine group (dosing interval of & LE;5 min/dose throughout the first 30 minutes of the event), and a limited epinephrine group (dosing interval of & LE;5 min/dose for the first 10 minutes then >5 min/dose for the time between 10 and 30 minutes). Results: A total of 191 patients were included. Epinephrine was not evenly distributed throughout ECPR, with 66% of doses being given during the first half of the event. Mean number of epinephrine doses was similar between survivors and non-survivors the first 10 minutes (2.7 doses). After 10 minutes, survivors received fewer doses than non-survivors during each subsequent 10-minute interval. Adjusted survival was not different between strategy groups [OR of survival for frequent epinephrine strategy: 0.78 (95% CI 0.36-1.69), p = 0.53]. Conclusions: Survivors received fewer doses than non-survivors after the first 10 minutes of CPR and although there was no statistical difference in survival based on dosing strategy, the findings of this study question the conventional approach to EPCR analysis that assumes dosing is evenly distributed.

EBV-immortalized B-lymphoblastoid cell lines are used as models for cellular transformation and as antigen-presenting cells in immunological assays. LCLs vary in surface markers and other phenotypic properties, but it is not known how this heterogeneity relates to the EBV life cycle. To explore correlations, we examined 62 LCLs for cellular and viral phenotypes. LCLs generated from pediatric and adult donors could similarly be categorized as either low in EBV copy number or fluctuating within a high range. High-copy status accompanied higher lytic viral gene expression and lower latent gene expression. Inhibiting lytic EBV replication did not affect cellular phenotype or lytic switch protein expression, indicating that an LCL's lytic permissivity was a stable property. Among the cellular genes overexpressed in permissive LCLs were unfolded protein response genes and plasma cell markers. Among genes overexpressed in non-permissive LCLs were transcription factors involved in maintaining B cell lineage, in particular EBF1. This study suggests previously undetected mechanisms by which cellular pathways influence the lytic reactivation of EBV.

Critical Care Medicine: January 2022 - Volume 50 - Issue 1 - p 187 doi: 10.1097/01.ccm.0000807916.93303.90

Background: Although AHA guidelines recommend a fixed epinephrine (epi) dosing frequency during cardiac arrest, it is unknown if a fixed dosing practice is both utilized and effective for EPCR events in children. We hypothesized that 1) epi dosing would not be uniformly distributed during ECPR events and 2) a strategy of limiting epi doses during ECPR would be associated with better survival to hospital discharge (SHD). Methods: This was a multicenter retrospective cohort study of ECPR after in-hospital cardiac arrest in children (< 18 years) between 2012 - 2019. Patient and arrest event details as well as epi dose and time-stamps were recorded. In patients with a CPR duration of ≥ 30 minutes, dosing strategies were categorized as either “frequent epi” (FE; average epi dosing interval of ≤ 5 mins/dose during the first 30 mins of CPR) or “limited epi” (LE; average dosing interval of ≤ 5 mins/dose for the first 10 mins followed by > 5 mins/dose through 30 mins). The primary outcome was SHD. Results: A total of 191 patients from 5 centers were included; overall SHD was 43% (82/191). Epi doses were not evenly distributed, with 66% (919/1385) of doses being given during the first half of CPR. Mean number of epi doses was similar between survivors and non-survivors in the first 10 mins (2.7 doses). After 10 mins, survivors received fewer doses than non-survivors per each 10 min interval (Figure). In the subset of patients that received ≥ 30 mins of CPR (n=147) the LE group had higher SHD [48% (14/52) vs. 27% (46/95), p=0.01] and improved odds of SHD after adjusting for age, sex, illness category, time of day, first pulseless rhythm and CPR duration [OR (95% CI) 4.2 (1.5-11.7); p =0.008]. Conclusion: In contrast to AHA guidelines, epi dosing was not evenly distributed during events in this multicenter study of pediatric in-hospital ECPR. For children with CPR duration ≥ 30 minutes a strategy of limiting epi doses was associated with improved SHD.

Introduction: Contemporary rates of survival after pediatric in-hospital cardiac arrest (IHCA) and trends in survival over the last 20 years have not been compared based on illness category. We hypothesized that (1) survival to hospital discharge for surgical-cardiac category is higher than the non-cardiac category, and (2) rates of survival after IHCA increased over time in all categories. Methods: The AHA Get With The Guidelines ® -Resuscitation database was queried for index IHCA events (excluding delivery room and neonatal intensive care unit) in children <18 years of age from 2000-2021. Categories were defined as: surgical-cardiac, IHCA following cardiac surgery; medical-cardiac, IHCA in non-surgical cardiac disease; and non-cardiac, IHCA in patients without cardiac disease. The primary outcome was survival to hospital discharge. We compared eras 2000-2004, 2005-2009, 2010-2014, and 2015-2021 with mixed logistic regression models, including event year as a continuous predictor and site as a random effect. Results: Of 17,696 index events, IHCA by illness category were: 18% surgical-cardiac, 18% medical-cardiac, and 64% non-cardiac. Surgical-cardiac category had the highest rate of survival to discharge compared to medical-cardiac and non-cardiac categories (56.1% vs. 43.4% vs. 46.3%; p<0.001). After controlling for age, location of event, and hospital size, the odds of survival were higher for surgical-cardiac category (aOR 1.28 (1.16, 1.40)) and lower for medical-cardiac category (aOR 0.87 (0.80, 0.95)), compared to the non-cardiac category. Odds of survival increased for all illness categories across eras. Between the 2000-2004 and 2015-2021 eras, survival in surgical-cardiac subjects increased from 45.6% to 62.3% with odds of survival increasing by 24% per era, (OR 1.24 (95% CI 1.15, 1.35), and survival for medical-cardiac subjects increased from 36.6% to 47.0%, with 14% increased odds per era (OR 1.14 (1.06, 1.23)). Conclusions: Over the last 20 years, children with surgical-cardiac IHCA have substantially higher odds of survival to hospital discharge compared to non-cardiac IHCA categories, whereas odds of survival were worse with medical-cardiac IHCA. Survival to hospital discharge has increased in all IHCA illness categories.

Breath-holding spells are common in childhood and can be associated with bradycardia and pulselessness. This report details severe breath-holding spells complicating postoperative management after atrial septal defect closure. The patient required cardiopulmonary resuscitation despite the use of a temporary pacemaker to prevent bradycardia. After multiple episodes of chest compressions, the decision was made to not intervene immediately to pulselessness and the patient was able to recover without further intervention.

The use of sodium chloride (NaCl) supplementation in children being prescribed diuretics is controversial due to concerns that supplementation could lead to fluid retention. This is a single-center retrospective study in which fluid balance and diuretic dosing was examined in children prescribed enteral NaCl supplements for hyponatremia while receiving loop diuretics. The aim of this study was to determine whether significant fluid retention occurred with the addition of NaCl. Fifty-five patients with 68 events were studied. The median age was 5.2 months, and 82% were hospitalized for cardiac disease. Daily fluid balance the seven days prior to NaCl supplementation was lower than the seven days after, with measurement of: median 17 mL/kg/day (7–26) vs. 22 mL/kg/day (13–35) (p = 0.0003). There was no change in patient weight after supplementation (p = 0.63). There was no difference in the median loop diuretic dose before and after supplementation, with the diuretic dose in furosemide equivalents of 3.2 mL/kg/day (2.3–4.4) vs. 3.2 mL/kg/day (2.2–4.7) (p = 0.50). There was no difference in the proportion of patients receiving thiazide diuretics after supplementation (56% before vs. 50% after (p = 0.10)). NaCl supplementation in children receiving loop diuretics increased calculated fluid balance, but weight was unchanged, and this was not associated with an increase in diuretic needs, suggesting clinicians did not consider the increase in fluid balance to be clinically significant.

ImportancePreventing in-hospital cardiac arrest (IHCA) likely represents an effective strategy to improve outcomes for critically ill patients, but feasibility of IHCA prevention remains unclear.ObjectiveTo determine whether a low-technology cardiac arrest prevention (CAP) practice bundle decreases IHCA rate.Design, Setting, and ParticipantsPediatric cardiac intensive care unit (CICU) teams from the Pediatric Cardiac Critical Care Consortium (PC4) formed a collaborative learning network to implement the CAP bundle consistent with the Institute for Healthcare Improvement framework; 15 hospitals implemented the bundle voluntarily. Risk-adjusted IHCA incidence rates were analyzed across 2 time periods, 12 months (baseline) and 18 months after CAP implementation (intervention) using difference-in-differences (DID) regression to compare 15 CAP and 16 control PC4 hospitals that chose not to participate in CAP but had IHCA rates tracked in the PC4 registry. Patients deemed at high risk for IHCA, based on a priori evidence-based criteria and empirical hospital-specific criteria, were selected to receive the CAP bundle. Data were collected from July 2018 to December 2019, and data were analyzed from March to August 2020.InterventionsCAP bundle included 5 elements developed to promote increased situational awareness and communication among bedside clinicians to recognize and mitigate deterioration in high-risk patients.Main Outcomes and MeasuresRisk-adjusted IHCA incidence rate across all CICU admissions (IHCA events divided by all admissions).ResultsThe bundle was activated in 2664 of 10 510 CAP hospital admissions (25.3%); admission characteristics were similar across study periods. There was a 30% relative reduction in risk-adjusted IHCA incidence rate at CAP hospitals (intervention period: 2.6%; 95% CI, 2.2-2.9; baseline: 3.7%; 95% CI, 3.1-4.0), but no change at control hospitals (intervention period: 2.7%; 95% CI, 2.3-2.9; baseline: 2.7%; 95% CI, 2.2-3.0). DID analysis confirmed significantly reduced odds of IHCA among all admissions at CAP hospitals compared with control hospitals during the intervention period vs baseline (odds ratio, 0.72; 95% CI, 0.56-0.91; P = .01). DID odds ratios were 0.72 (95% CI, 0.53-0.98) for the surgical subgroup, 0.74 (95% CI, 0.48-1.14) for the medical subgroup, and 0.72 (95% CI, 0.50-1.03) for the high-risk admission subgroup at CAP hospitals after intervention. All-cause risk-adjusted mortality rate did not change after intervention.Conclusions and RelevanceImplementation of this CAP bundle led to significant IHCA reduction across multiple pediatric CICUs. Future studies may determine if this bundle can be effective in other critically ill populations.

OBJECTIVES:Assess trends in inpatient acute gastroenteritis (AGE) management across children's hospitals and identify elements of AGE management associated with resource use. METHODS:We examined inpatient stays for children 6 months to 18 years hospitalized with AGE from 2009 to 2018 using the Pediatric Health Information System database. We characterized demographics, hospital-level resource use (ie, medications, laboratories, and imaging), and outcomes (ie, cost per case, 14-day revisit rates, and length of stay [LOS]). We compared demographic characteristics and resource use between 2009 to 2013 and 2014 to 2018 using χ2 and Wilcoxon rank-sum tests. We grouped hospitals on the basis of 2009 use of each resource and trended use over time using logistic regression. Annual change in mean cost and LOS were estimated by using models of log-transformed data. RESULTS:Across 32 354 hospitalizations at 38 hospitals, there was a high use of electrolyte testing (85.4%) and intravenous fluids (84.1%) without substantial changes over time. There were significant reductions in the majority of laboratory, medication, and imaging resources across hospitals over the study period. The most notable reductions were for rotavirus and stool testing. Many hospitals saw a decrease in LOS, with only 3 noting an increased revisit rate. Reductions in cost per case over time were most associated with decreases in imaging, laboratory testing, and LOS. CONCLUSIONS:Significant variation in resource use for children hospitalized with AGE coupled with high use of resources discouraged in AGE guidelines highlights potential opportunities to improve resource use that may be addressed in future AGE guidelines and quality improvement initiatives.