Association of Diagnostic Stewardship for Blood Cultures in Critically Ill Children With Culture Rates, Antibiotic Use, and Patient Outcomes: Results of the Bright STAR Collaborative.

Importance: Blood culture overuse in the pediatric intensive care unit (PICU) can lead to unnecessary antibiotic use and contribute to antibiotic resistance. Optimizing blood culture practices through diagnostic stewardship may reduce unnecessary blood cultures and antibiotics. Objective: To evaluate the association of a 14-site multidisciplinary PICU blood culture collaborative with culture rates, antibiotic use, and patient outcomes. Design, Setting, and Participants: This prospective quality improvement (QI) collaborative involved 14 PICUs across the United States from 2017 to 2020 for the Bright STAR (Testing Stewardship for Antibiotic Reduction) collaborative. Data were collected from each participating PICU and from the Children's Hospital Association Pediatric Health Information System for prespecified primary and secondary outcomes. Exposures: A local QI program focusing on blood culture practices in the PICU (facilitated by a larger QI collaborative). Main Outcomes and Measures: The primary outcome was blood culture rates (per 1000 patient-days/mo). Secondary outcomes included broad-spectrum antibiotic use (total days of therapy and new initiations of broad-spectrum antibiotics ≥3 days after PICU admission) and PICU rates of central line-associated bloodstream infection (CLABSI), Clostridioides difficile infection, mortality, readmission, length of stay, sepsis, and severe sepsis/septic shock. Results: Across the 14 PICUs, the blood culture rate was 149.4 per 1000 patient-days/mo preimplementation and 100.5 per 1000 patient-days/mo postimplementation, for a 33% relative reduction (95% CI, 26%-39%). Comparing the periods before and after implementation, the rate of broad-spectrum antibiotic use decreased from 506 days to 440 days per 1000 patient-days/mo, respectively, a 13% relative reduction (95% CI, 7%-19%). The broad-spectrum antibiotic initiation rate decreased from 58.1 to 53.6 initiations/1000 patient-days/mo, an 8% relative reduction (95% CI, 4%-11%). Rates of CLABSI decreased from 1.8 to 1.1 per 1000 central venous line days/mo, a 36% relative reduction (95% CI, 20%-49%). Mortality, length of stay, readmission, sepsis, and severe sepsis/septic shock were similar before and after implementation. Conclusions and Relevance: Multidisciplinary diagnostic stewardship interventions can reduce blood culture and antibiotic use in the PICU. Future work will determine optimal strategies for wider-scale dissemination of diagnostic stewardship in this setting while monitoring patient safety and balancing measures.

Stroke in pediatric ECMO patients: analysis of the National Inpatient Sample (NIS) database.

BACKGROUND: The rates, outcomes, and long-term trends of stroke complicating the use of extracorporeal membrane oxygenation (ECMO) have been inconsistently reported. We compared the outcomes of pediatric ECMO patients with and without stroke and described the frequency trends between 2000 and 2017. METHODS: Using the National Inpatient Sample (NIS) database, pediatric patients (age ≤18 years) who received ECMO were identified using ICD-9&10 codes. Binary, regression, and trend analyses were performed to compare patients with and without stroke. RESULTS: A total of 114,477,997 records were reviewed. Overall, 28,695 (0.025%) ECMO patients were identified of which 2982 (10.4%) had stroke, which were further classified as hemorrhagic (n = 1464), ischemic (n = 1280), or combined (n = 238). Mortality was higher in the hemorrhagic and combined groups compared to patients with ischemic stroke and patients without stroke. Length of stay (LOS) was significantly longer in stroke vs. no-stroke patients. Hypertension and septicemia were more encountered in the hemorrhagic group, whereas the combined group demonstrated higher frequency of cardiac arrest and seizures. CONCLUSIONS: Over the years, there is an apparent increase in the diagnosis of stroke. All types of stroke in ECMO patients are associated with increased LOS, although mortality is increased in hemorrhagic and combined stroke only. IMPACT: Stroke is a commonly seen complication in pediatric patients supported by ECMO. Understanding the trends will help in identifying modifiable risk factors that predict poor outcomes in this patient population.

Simplified Pediatric Index of Mortality 3 Score by Explainable Machine Learning Algorithm.

Pediatric Index of Mortality 3 is a validated tool including 11 variables for the assessment of mortality risk in PICU patients. With the recent advances in explainable machine learning algorithms, we aimed to assess feasibility of application of these machine learning models to simplify the Pediatric Index of Mortality 3 scoring system in order to decrease time and labor required for data collection and entry for Pediatric Index of Mortality 3. DESIGN: Single-center, retrospective cohort study. Data from the Virtual Pediatric Systems for patients admitted to Cleveland Clinic Children`s PICU between January 2008 and December 2019 was obtained. Light Gradient Boosting Machine Regressor (a gradient boosting decision tree algorithm) was used for building the machine learning models. Variable importance was analyzed by SHapley Additive exPlanations. All of the 11 Pediatric Index of Mortality 3 variables were used as input variables in the machine learning models to predict Pediatric Index of Mortality 3 risk of mortality as the outcome variable. Mean absolute error, root mean squared error, and R-squared were calculated for each of the 11 machine learning models as model performance parameters. SETTING: Quaternary children's hospital. PATIENTS: PICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Five-thousand sixty-eight patients were analyzed. The machine learning models were able to maintain similar predictive error until the number of input variables decreased to four. The machine learning model with five input variables (mechanical ventilation in the first hour of PICU admission, very-high-risk diagnosis, surgical recovery from a noncardiac procedure, low-risk diagnosis, and base excess) produced lowest mean root mean squared error of 1.49 (95% CI, 1.05-1.93) and highest R-squared of 0.73 (95% CI, 0.6-0.86) with mean absolute error of 0.43 (95% CI, 0.35-0.5) among all the 11 machine learning models. CONCLUSIONS: Explainable machine learning methods were feasible in simplifying the Pediatric Index of Mortality 3 scoring system with similar risk of mortality predictions compared to the original Pediatric Index of Mortality 3 model tested in a single-center dataset.

Evaluation of Bivalirudin As an Alternative to Heparin for Systemic Anticoagulation in Pediatric Extracorporeal Membrane Oxygenation.

OBJECTIVES: Heparin is the universal anticoagulant for patients receiving extracorporeal membrane oxygenation support. However, heparin has many disadvantages, especially in young children, who develop heparin resistance. Recently our center has used bivalirudin, a direct thrombin inhibitor, for systemic anticoagulation in pediatric extracorporeal life support. Bivalirudin binds directly to thrombin with no need for antithrombin III and it inhibits both circulating and clot-bound thrombin. In this study, we sought to evaluate our experience with bivalirudin in pediatric extracorporeal life support. DESIGN: Retrospective chart review study of patients receiving extracorporeal membrane oxygenation support between October 2014 and May 2018. SETTING: Tertiary, academic PICU. PATIENTS: Sixteen patients receiving heparin and 16 patients receiving bivalirudin on extracorporeal life support were included in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients in the bivalirudin group had a median age of 31 months versus 59 months in the heparin group (p = 0.41). Recovery and extracorporeal membrane oxygenation decannulation were similar in both groups (56% in the heparin group and 62% in the bivalirudin group; p = 0.62). Time to reach goal therapeutic anticoagulation level was shorter in the bivalirudin group (11 vs 29 hr; p = 0.01). Bleeding events were fewer in the bivalirudin group, and there was no difference in the rate of thrombotic events between the two groups. Comprehensive cost analysis that includes anticoagulant, laboratories, and antithrombin III cost, showed that heparin anticoagulation therapy total cost was significantly higher than bivalirudin (1,184 dollars per day in heparin group vs 494 dollars per day in bivalirudin group; p = 0.03). Bivalirudin dose required to maintain target anticoagulation will increase over time, and this is associated with an increase in creatinine clearance and an increase in fibrinogen serum levels. CONCLUSIONS: This study showed that the use of bivalirudin in pediatric extracorporeal membrane oxygenation support is feasible, safe, reliable, and cost-effective in comparison to heparin. Further prospective randomized clinical trials are necessary to confirm our observations.

Bivalirudin Anticoagulation for an Infant with Hyperbilirubinemia and Elevated Plasma-Free Hemoglobin on ECMO.

Heparin has been used for decades as an anticoagulant in patients on mechanical circulatory support, which includes extracorporeal membrane oxygenation (ECMO) and ventricular assist devices. Bivalirudin is a direct thrombin inhibitor that can be used as an alternative anticoagulant in neonates and infants demonstrating inaccurate heparin monitoring. We report a case of a 2-month-old male child who was placed on ECMO for severe acute respiratory distress syndrome. His ECMO course was complicated by severe hemolysis and hyperbilirubinemia, which precluded accurate monitoring of heparin activity. Bivalirudin was successfully used for anticoagulation in this patient.