A risk-stratified assessment of biomarker-based acute kidney injury phenotypes in children.

BACKGROUND: The functional acute kidney injury (AKI) diagnostic tests serum creatinine (SCr) and urine output are imprecise and make management challenging. Combining tubular injury biomarkers with functional markers reveal AKI phenotypes that may facilitate personalized care. However, when and in whom to obtain injury biomarkers remains unclear. METHODS: This was a prospective, observational study of patients admitted to a pediatric intensive care unit (PICU). Using the Renal Angina Index (RAI), subjects were screened for the presence (RAI+) or absence (RAI-) of renal angina 12 h post-admission and assigned an AKI phenotype using urinary NGAL (NGAL+: ≥150 ng/ml) and SCr (SCr+: ≥KDIGO Stage 1). Outcomes for each AKI phenotype were assessed and compared by RAI status. RESULTS: In all, 200/247 (81%) subjects were RAI+. RAI+ subjects who were NGAL+ had higher risk of Day 3 AKI, renal replacement therapy use, and mortality and fewer ventilator- and PICU-free days, compared to NGAL-, irrespective of Day 0 SCr. Similar findings were not demonstrated in RAI- subjects, though NGAL+/SCr+ was associated with fewer ventilator- and PICU-free days compared to NGAL-/SCr+. CONCLUSIONS: NGAL- and SCr-based AKI phenotypes provide improved prognostic information in children with renal angina (RAI+) and/or with SCr elevation. These populations may be appropriate for targeted biomarker testing. IMPACT: New consensus recommendations encourage the integration of kidney tubular injury biomarkers such as urinary NGAL with serum creatinine for diagnosis and staging of acute kidney injury; however, no structured testing framework exists guiding when to test and in whom. Urinary NGAL- and serum creatinine-based acute kidney injury phenotypes increase diagnostic precision in critically ill children experiencing renal angina (RAI+) or serum creatinine-defined acute kidney injury. These data provide preliminary evidence for a proposed framework for directed urinary NGAL assessment in the pediatric intensive care unit.

Assessment of a Situation Awareness Quality Improvement Intervention to Reduce Cardiac Arrests in the PICU.

OBJECTIVES: To use improved situation awareness to decrease cardiopulmonary resuscitation events by 25% over 18 months and demonstrate process and outcome sustainability. DESIGN: Structured quality improvement initiative. SETTING: Single-center, 35-bed quaternary-care PICU. PATIENTS: All patients admitted to the PICU from February 1, 2017, to December 31, 2020. INTERVENTIONS: Interventions targeted situation awareness and included bid safety huddles, bedside mitigation signs and huddles, smaller pod-based huddles, and an automated clinical decision support tool to identify high-risk patients. MEASUREMENTS AND MAIN RESULTS: The primary outcome metric, cardiopulmonary resuscitation event rate per 1,000 patient-days, decreased from a baseline of 3.1-1.5 cardiopulmonary resuscitation events per 1,000 patient-days or by 52%. The secondary outcome metric, mortality rate, decreased from a baseline of 6.6 deaths per 1,000 patient-days to 3.6 deaths per 1,000 patient-days. Process metrics included percent of clinical deterioration events predicted, which increased from 40% to 67%, and percent of high-risk patients with shared situation awareness, which increased from 43% to 71%. Balancing metrics included time spent in daily safety huddle, median 0.4 minutes per patient (interquartile range, 0.3-0.5), and a number needed to alert of 16 (95% CI, 14-25). Neither unit acuity as measured by Pediatric Risk of Mortality III scores nor the percent of deaths in patients with do-not-attempt resuscitation orders or electing withdrawal of life-sustaining technologies changed over time. CONCLUSIONS: Interprofessional teams using shared situation awareness may reduce cardiopulmonary resuscitation events and, thereby, improve outcomes.

Trajectory of Mortality and Health-Related Quality of Life Morbidity Following Community-Acquired Pediatric Septic Shock.

OBJECTIVES: In-hospital pediatric sepsis mortality has decreased substantially, but long-term mortality and morbidity among children initially surviving sepsis, is unknown. Accordingly, the Life After Pediatric Sepsis Evaluation investigation was conducted to describe the trajectory of mortality and health-related quality of life morbidity for children encountering community-acquired septic shock. DESIGN: Prospective, cohort-outcome study, conducted 2013-2017. SETTING: Twelve academic PICUs in the United States. PATIENTS: Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support. INTERVENTIONS: Demographic, infection, illness severity, organ dysfunction, and resource utilization data were collected daily during PICU admission. Serial parent proxy-report health-related quality of life assessments were obtained at baseline, 7 days, and 1, 3, 6, and 12 months following PICU admission utilizing the Pediatric Quality of Life Inventory or Stein-Jessop Functional Status Scale. MEASUREMENTS AND MAIN RESULTS: Among 389 children enrolled, mean age was 7.4 ± 5.8 years; 46% were female; 18% were immunocompromised; and 51% demonstrated chronic comorbidities. Baseline Pediatric Overall Performance Category was normal in 38%. Median (Q1-Q3) Pediatric Risk of Mortality and Pediatric Logistic Organ Dysfunction scores at PICU admission were 11.0 (6.0-17.0) and 9.0 (6.0-11.0); durations of vasoactive-inotropic and mechanical ventilation support were 3.0 days (2.0-6.0 d) and 8.0 days (5.0-14.0 d); and durations of PICU and hospital stay were 9.4 days (5.6-15.4 d) and 15.7 days (9.2-26.0 d). At 1, 3, 6, and 12 months following PICU admission for the septic shock event, 8%, 11%, 12%, and 13% of patients had died, while 50%, 37%, 30%, and 35% of surviving patients had not regained their baseline health-related quality of life. CONCLUSIONS: This investigation provides the first longitudinal description of long-term mortality and clinically relevant, health-related quality of life morbidity among children encountering community-acquired septic shock. Although in-hospital mortality was 9%, 35% of survivors demonstrated significant, health-related quality of life deterioration from baseline that persisted at least 1 year following hospitalization for septic shock.

Early Sequential Risk Stratification Assessment to Optimize Fluid Dosing, CRRT Initiation and Discontinuation in Critically Ill Children with Acute Kidney Injury: Taking Focus 2 Process Article.

BACKGROUND: Acute Kidney Injury (AKI) is common in critically ill children and is associated with increased morbidity and mortality. Recognition and management of AKI is often delayed, predisposing patients to risk of clinically significant fluid accumulation (Fluid Overload (FO)). Early recognition and intervention in high risk patients could decrease fluid associated morbidity. We aim to assess an AKI Clinical Decision Algorithm (CDA) using a sequential risk stratification strategy integrating the Renal Angina Index (RAI), urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) and the Furosemide Stress Test (FST) to optimize AKI and FO prediction and management in critically ill children. METHODS/DESIGN: This single center prospective observational cohort study evaluates the AKI CDA in a Pediatric Intensive Care Unit (PICU). Every patient ≥ 3 months old has the risk score RAI calculated automatically at 12 hours of admission. Patients with a RAI ≥ 8 (fulfilling renal angina) have risk further stratified with a urine NGAL and, if positive (NGAL ≥ 150ng/mL), subsequently by their response to a standardized dose of furosemide (namely FST). RAI negative or NGAL negative patients are treated per usual care. FST-responders are managed conservatively, while non-responders receive fluid restrictive strategy and/or continuous renal replacement therapy (CRRT) at 10%-15% of FO. 2100 patients over 3 years will be evaluated to capture 210 patients with severe AKI (KDIGO Stage 2 or 3 AKI), 100 patients with >10% FO, and 50 requiring CRRT. Primary analyses: Standardizing a pediatric FST and assessing prediction accuracy of CDA for severe AKI, FO>10% and CRRT requirement in children. Secondary analyses in patients with AKI: Renal function return to baseline, RRT and mortality within 28 days. DISCUSSION: This will be the first prospective evaluation of feasibility of AKI CDA, integrating individual prediction tools in one cohesive and comprehensive approach, and its prediction of FO>10% and AKI, as well as the first to standardize the FST in the pediatric population. This will increase knowledge on current AKI prediction tools and provide actionable insight for early interventions in critically ill children based on their level of risk.

Venous thromboembolism in hospitalized adolescents: an approach to risk assessment and prophylaxis.

BACKGROUND: Pediatric hospital-acquired venous thromboembolism (VTE) is an increasingly prevalent and morbid disease. A multidisciplinary team at a tertiary children's hospital sought to answer the following clinical question: "Among hospitalized adolescents, does risk assessment and stratified VTE prophylaxis compared with no prophylaxis reduce VTE occurrence without an increase in significant adverse effects?" METHODS: Serial literature searches using key terms were performed in the following databases: Medline, Cochrane Database, CINAHL (Cumulative Index to Nursing and Allied Health), Scopus, EBMR (Evidence Based Medicine Reviews). Pediatric studies were sought preferentially; when pediatric evidence was sparse, adult studies were included. Abstracts and titles were screened, and relevant full articles were reviewed. Studies were rated for quality using a standard rating system. RESULTS: Moderate evidence exists to support VTE risk assessment in adolescents. This evidence comes from pediatric studies that are primarily retrospective in design. The results of the studies are consistent and cite prominent factors such as immobilization and central venous access. There is insufficient evidence to support specific prophylactic strategies in pediatric patients because available pediatric evidence for thromboprophylaxis efficacy and safety is minimal. There is, however, high-quality, consistent evidence demonstrating efficacy and safety of thromboprophylaxis in adults. CONCLUSIONS: On the basis of the best available evidence, we propose a strategy for risk assessment and stratified VTE prophylaxis for hospitalized adolescents. This strategy involves assessing risk factors and considering prophylactic measures based on level of risk. We believe this strategy may reduce risk of VTE and appropriately balances the adverse effect profile of mechanical and pharmacologic prophylactic methods.