Stephen M. Gorga

OBJECTIVES: Sepsis is a leading cause of morbidity and mortality for critically ill children, yet the pattern of healthcare use before admission for sepsis remains unknown. We measured the proportion and characteristics of healthcare encounters within 7 days before sepsis hospitalizations. DESIGN: Using the Merative MarketScan administrative claims database, we conducted a retrospective observational cohort study to quantify pre-admission healthcare encounters among children hospitalized with sepsis. SETTING: The Merative MarketScan database includes inpatient, outpatient, and emergency medical claims from employer-based insurance plans and Medicaid data from approximately 7 million healthcare consumers across multiple states. PATIENTS: Included patients were 0–18 years old and hospitalized with sepsis between January 1, 2016, and December 31, 2022. Children were required to have 30 days of continuous insurance enrollment before admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our primary outcome was the occurrence of any healthcare encounter in the 7 days before sepsis hospitalization, including outpatient, emergency department, or inpatient visits. Of those encounters, we identified the proportion that were related to infection. We compared hospitalization characteristics, including mechanical ventilation, ICU use, and length of stay, among those with vs. without pre-sepsis healthcare utilization. We identified 6928 pediatric sepsis hospitalizations, of whom 64.3% (4452/6928) had a complex chronic condition with a median age of 10 years (interquartile range, 3–15 yr). Overall, 53.5% (3707/928) of sepsis hospitalizations had a healthcare encounter within 7 days of admission, including 33.7% (2338/6928) with an outpatient visit, 28.2% (1956/6928) with an emergency department visit, and 6.2% (431/6928) with an inpatient hospitalization. Among sepsis hospitalizations with any pre-admission encounter, 38.9% (1445/3707) had an infection-related diagnosis documented at the encounter. There was no difference in mechanical ventilation, ICU use, or length of stay between those with vs. without pre-sepsis healthcare encounters. CONCLUSIONS: Over half of children hospitalized with sepsis were evaluated in the outpatient or emergency department setting in the week preceding admission, with one in five evaluated for infection. Further understanding of these pre-admission encounters may allow for earlier sepsis identification and possibly intervention in the prehospital setting.

The interactions of pulmonary and renal physiology that underlie acute lung injury (ALI) and acute kidney injury (AKI) have been recognized for nearly a century. The understanding of lung-kidney crosstalk has evolved and is recognized as an important factor in patient management and outcomes. We aim to describe the association between fluid accumulation (FA) and ALI with outcomes of critically ill children and young adults requiring continuous renal replacement therapy (CRRT). Planned secondary analysis using data from the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK). ALI severity was defined using the Berlin oxygenation criteria. Fluid accumulation was categorized as ≤ 10%, > 10–20%, and > 20% at CRRT initiation. Illness severity was quantified using the Pediatric Logistic Organ Dysfunction Score 2 (PELOD-2). The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included (1) 28-day mechanical ventilation (IMV) free days, (2) 28-day ICU free days, and (3) major adverse kidney events at 90 days (MAKE90) defined by death, persistent kidney dysfunction (eGFR reduction by 25% of baseline), or new dialysis requirement. This is a multinational retrospective cohort study. Invasively ventilated patients aged 0–25 years from January 2015 to December 2021 requiring CRRT for AKI or FA with ALI. There were no interventions. A total of 312 patients were included in the analysis. ALI was mild in 67 (21.5%), moderate in 142 (45.5%), and severe in 103 (33.0%). Fluid accumulation was ≤ 10% in 166 (53.2%), > 10–20% in 60 (19.2%), and > 20% in 86 (27.6%). The ICU mortality was 44.6% (139/312). In the multivariable analysis, neither ALI nor FA category was associated with mortality or MAKE90. Time to CRRT initiation (aOR 1.04, 95% CI 1.01–1.08) and illness severity (aOR 1.25, 95% CI 1.14–1.37) were associated with mortality. Conclusions : In children and young adults with ALI receiving CRRT for AKI or FA, longer time to CRRT initiation and illness severity at CRRT initiation were associated with mortality. When accounting for multiple factors, neither ALI nor FA at CRRT initiation were associated with MAKE90 or mortality. Our findings warrant further exploration in a prospective cohort. What is Known: • Acute kidney injury (AKI) and acute lung injury (ALI) commonly coexist in critically ill children and are associated with increased morbidity and mortality through bidirectional organ crosstalk. • Fluid accumulation (FA) worsens both AKI and ALI, with higher degrees of FA associated with worse outcomes, with continuous renal replacement therapy (CRRT) frequently used to manage the consequences of AKI and FA. What is New: • In this multicenter international cohort of children and young adults with ALI receiving CRRT, longer time to CRRT initiation and illness severity at CRRT initiation, but neither ALI nor FA at CRRT initiation were associated with mortality were associated with mortality. • These findings suggest that FA thresholds at the start of interventions may be less discriminatory in populations with dynamic processes such as severe multiple organ failure.

Acute kidney injury (AKI) and fluid accumulation (FA) are common during extracorporeal membrane oxygenation (ECMO) support and are associated with increased morbidity and mortality. Despite their clinical importance, contemporary data describing the epidemiology and management of these conditions remain limited. Founded in 2021, the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) seeks to improve outcomes for children requiring extracorporeal organ support. This report describes the design of the WE-ROCK ECMO study, an international, multicenter, retrospective cohort of patients supported with ECMO from 2018 to 2022. We include 1,264 children aged 0–25 years treated at 43 centers across 10 countries. Collected data include demographics, clinical characteristics before ECMO initiation, and detailed information from the first 14 days of ECMO support, including fluid intake and output, diuretic use, and continuous renal replacement therapy (CRRT) practices. Primary outcomes include major adverse kidney events at 90 days (mortality, dialysis dependence, and persistent kidney dysfunction) as well as functional status outcomes. The WE-ROCK ECMO study represents the largest international investigation of kidney and fluid-related variables in pediatric ECMO, providing critical insight into practice variation and the relationships among AKI, FA, CRRT, and clinical outcomes, and establishing a foundation for future interventional trials.

Acute kidney injury (AKI) and acute lung injury (ALI) are common in critically ill neonates, children, and those with severe cardiac disease. Although kidney and lung dysfunction can occur independently, molecular signaling and organ crosstalk significantly influence the function of each organ. Additionally, there is a link between AKI and fluid balance disorders. A bidirectional and synergistic relationship exists between AKI and fluid imbalance, with fluid management potentially becoming compromised before or after AKI. Fluid accumulation can further worsen ALI by impairing gas exchange. Organ crosstalk involves both pro‐inflammatory and anti‐inflammatory cytokines, as well as other modulating factors. Both AKI and ALI have harmful effects in pediatric patients, and AKI can lead to long‐term consequences, especially in premature neonates, who are at much higher risk for bronchopulmonary dysplasia and chronic lung disease following AKI. Unfortunately, supportive treatments for ALI, such as positive pressure ventilation, can increase right ventricular afterload and central venous pressure, which may worsen renal perfusion, creating a cycle of ongoing multiple organ dysfunction. Pediatric research has provided insights into potential treatment strategies for preventing ALI, even without AKI. Prophylactic peritoneal dialysis may help remove pro‐inflammatory cytokines that contribute to AKI and ALI in children undergoing cardiac surgery. Future studies are necessary to explore interventions that can prevent or reduce the harmful effects of kidney and lung injuries in critically ill children.

Acute kidney injury is common among neonates with critical cardiac disease. Risk factors and associations with kidney‐related outcomes are heterogeneous and distinct from other neonates. As survival of children with critical cardiac disease increases to adulthood, the burden of chronic kidney disease is increasing. Thirty percent to 50% of adults with congenital heart disease have impaired kidney function, even in the absence of prior kidney injury episodes. This may be related to the current standardized acute kidney injury criteria, which may not fully capture clinically meaningful kidney injury and long‐term kidney health risks. An improved understanding of which neonates with critical cardiac disease should undergo kidney health follow‐up is imperative. During the National Institutes of Health–supported Neonatal Kidney Health Consensus Workshop to Address Kidney Health meeting conducted in February 2024, a panel of 51 neonatal nephrology experts focused on at‐risk groups: (1) preterm infants, (2) critically ill infants with acute kidney injury, and (3) infants with critical cardiac disease. The critical cardiac disease subgroup, comprising multidisciplinary experts, used a modified Delphi process to achieve consensus on recommendations for kidney health follow‐up. In this report, we review available data on kidney health follow‐up in critical cardiac disease and summarize the 2 consensus‐based recommendations. We introduce novel diagnostic and risk‐stratification tools for acute kidney injury diagnosis in neonates with cardiac disease to guide follow‐up recommendations. Finally, we identify important knowledge gaps, representing areas of focus for future research. These should be prioritized to understand and improve long‐term kidney health in critical cardiac disease.

Intravenous (IV) fluids are commonly administered to critically ill children, but clinicians lack effective guidance for the correct dose and duration of therapy resulting in variation of prescribing habits which harm children. It is unknown if clinicians recognize the amount of IV fluid that patients receive. We aimed to determine clinician's accuracy in the identification of the volume of IV fluids patients will receive over the next 24 hours. Prospective cohort study enrolled all patients admitted to the pediatric intensive care unit (PICU) from May to August 2021 at the University of Michigan's C.S. Mott Children's Hospital PICU. For each patient, clinicians estimated the volume of IV fluid that patients will receive in the next 24 hours. The primary outcome was accuracy of the estimation defined as predicted volume of IV fluids versus actual volume administered within 10 mL/kg or 500 mL depending on patient's weight. We tested for differences in accuracy by clinician type using chi-square tests. There were 259 patients for whom 2,295 surveys were completed by 177 clinicians. Clinicians' estimates were accurate 48.8% of the time with a median difference of 10 (1–26) mL/kg. We found that accuracy varied between clinician type: bedside nurses were most accurate at 64.3%, and attendings were least accurate at 30.5%. PICU clinicians have poor recognition of the amount of IV fluids their patients will receive in the subsequent 24-hour period. Estimate accuracy varied by clinician's role and improved over time, which may suggest opportunities for improvement. ^* Drs. Barbaro and Basu are recognized as senior authors in this manuscript. Received: 23 August 2022 Accepted: 23 September 2022 Article published online: 21 November 2022 © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Objectives This study aimed to test whether early oxygenation failure severity categories (absent/mild/moderate/severe) were associated with health-related quality of life (HRQL) deterioration among children who survived sepsis-related acute respiratory failure. Methods We performed a secondary analysis of a study of community-acquired pediatric septic shock, Life After Pediatric Sepsis Evaluation. The primary outcome was an adjusted decline in HRQL ≥ 25% below baseline as assessed 3 months following admission. Logistic regression models were built to test the association of early oxygenation failure including covariates of age and nonrespiratory Pediatric Logistic Organ Dysfunction-2 score. Secondarily, we tested if there was an adjusted decline in HRQL at 6 and 12 months and functional status at 28 days. Results We identified 291 children who survived to discharge and underwent invasive ventilation. Of those, that 21% (61/291) had mild oxygenation failure, 20% (58/291) had moderate, and 17% (50/291) had severe oxygenation failure. Fifteen percent of children exhibited a decline in HRQL of at least 25% from their baseline at the 3-month follow-up time point. We did not identify an association between the adjusted severity of oxygenation failure and decline in HRQL ≥ 25% at 3-, 6-, or 12-month follow-up. Children with oxygenation failure were more likely to exhibit a decline in functional status from baseline to hospital discharge, but results were similar across severity categories. Conclusion Our findings that children of all oxygenation categories are at risk of HRQL decline suggest that those with mild lung injury should not be excluded from comprehensive follow-up, but more work is needed to identify those at the highest risk.

Background: Fluid overload and acute kidney injury are common and associated with poor outcomes among critically ill children. The prodrome of renal angina stratifies patients by risk for severe acute kidney injury, but the predictive discrimination for fluid overload is unknown. Methods: Post-hoc analysis of patients admitted to a tertiary care pediatric intensive care unit (PICU). The primary outcome was the performance of renal angina fulfillment on day of ICU admission to predict fluid overload ≥15% on Day 3. Results: 77/139 children (55%) fulfilled renal angina (RA+). After adjusting for covariates, RA+ was associated with increased odds of fluid overload on Day 3 (adjusted odds ratio (aOR) 5.1, 95% CI 1.23–21.2, p = 0.025, versus RA-). RA- resulted in a 90% negative predictive value for fluid overload on Day 3. Median fluid overload was significantly higher in RA+ patients with severe acute kidney injury compared to RA+ patients without severe acute kidney injury (% fluid overload on Day 3: 8.8% vs. 0.73%, p = 0.002). Conclusion: Among critically ill children, fulfillment of renal angina was associated with increased odds of fluid overload versus the absence of renal angina and a higher fluid overload among patients who developed acute kidney injury. Renal angina directed risk classification may identify patients at highest risk for fluid accumulation. Expanded study in larger populations is warranted.

Recent increases in COVID-19 cases are associated to infections among a younger population in the US.¹ In a focused survey administered prior to vaccine emergency use authorizations (EUAs), 2 in 5 US youths reported willingness to vaccinate against COVID-19, whereas 1 in 3 were uncertain.² Since then, the US has implemented a mass immunization campaign.³ Widespread vaccine uptake among youth is essential to achieve adequate community immunization levels to attenuate the COVID-19 pandemic.⁴ We therefore collected the thoughts and opinions from a diverse sample of US youth after the initiation of mass immunization campaigns regarding COVID-19 vaccine acceptability, perceived barriers to vaccination, and anticipated changes in behavior.