Therapeutic Plasma Exchange Is Associated With Improved Major Adverse Kidney Events in Children and Young Adults With Thrombocytopenia at the Time of Continuous Kidney Replacement Therapy Initiation.

Therapeutic plasma exchange (TPE) has been shown to improve organ dysfunction and survival in patients with thrombotic microangiopathy and thrombocytopenia associated with multiple organ failure. There are no known therapies for the prevention of major adverse kidney events after continuous kidney replacement therapy (CKRT). The primary objective of this study was to evaluate the effect of TPE on the rate of adverse kidney events in children and young adults with thrombocytopenia at the time of CKRT initiation. DESIGN: Retrospective cohort. SETTING: Two large quaternary care pediatric hospitals. PATIENTS: All patients less than or equal to 26 years old who received CKRT between 2014 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We defined thrombocytopenia as a platelet count less than or equal to 100,000 (cell/mm3) at the time of CKRT initiation. We ascertained major adverse kidney events at 90 days (MAKE90) after CKRT initiation as the composite of death, need for kidney replacement therapy, or a greater than or equal to 25% decline in estimated glomerular filtration rate from baseline. We performed multivariable logistic regression and propensity score weighting to analyze the relationship between the use of TPE and MAKE90. After excluding patients with a diagnosis of thrombotic thrombocytopenia purpura and atypical hemolytic uremic syndrome (n = 6) and with thrombocytopenia due to a chronic illness (n = 2), 284 of 413 total patients (68.8%) had thrombocytopenia at CKRT initiation (51% female). Of the patients with thrombocytopenia, the median (interquartile range) age was 69 months (13-128 mo). MAKE90 occurred in 69.0% and 41.5% received TPE. The use of TPE was independently associated with reduced MAKE90 by multivariable analysis (odds ratio [OR], 0.35; 95% CI, 0.20-0.60) and by propensity score weighting (adjusted OR, 0.31; 95% CI, 0.16-0.59). CONCLUSIONS: Thrombocytopenia is common in children and young adults at CKRT initiation and is associated with increased MAKE90. In this subset of patients, our data show benefit of TPE in reducing the rate of MAKE90.

An Evaluation of Antimicrobial Prescribing and Risk-adjusted Mortality.

The Centers for Disease Control and Prevention recommends tracking risk-adjusted antimicrobial prescribing. Prior studies have used prescribing variation to drive quality improvement initiatives without adjusting for severity of illness. The present study aimed to determine the relationship between antimicrobial prescribing and risk-adjusted ICU mortality in the Pediatric Health Information Systems (PHIS) database, assessed by IBM-Watson risk of mortality. A nested analysis sought to assess an alternative risk model incorporating laboratory data from federated electronic health records. METHODS: Retrospective cohort study of pediatric ICU patients in PHIS between 1/1/2010 and 12/31/2019, excluding patients admitted to a neonatal ICU, and a nested study of PHIS+ from 1/1/2010 to 12/31/2012. Hospital antimicrobial prescription volumes were assessed for association with risk-adjusted mortality. RESULTS: The cohort included 953,821 ICU encounters (23,851 [2.7%] nonsurvivors). There was 4-fold center-level variability in antimicrobial use. ICU antimicrobial use was not correlated with risk-adjusted mortality assessed using IBM-Watson. A risk model incorporating laboratory data available in PHIS+ significantly outperformed IBM-Watson (c-statistic 0.940 [95% confidence interval 0.933-0.947] versus 0.891 [0.881-0.901]; P < 0.001, area under the precision recall curve 0.561 versus 0.297). Risk-adjusted mortality was inversely associated with antimicrobial prescribing in this smaller cohort using both the PHIS+ and Watson models (P = 0.05 and P < 0.01, respectively). CONCLUSIONS: Antimicrobial prescribing among pediatric ICUs in the PHIS database is variable and not associated with risk-adjusted mortality as assessed by IBM-Watson. Expanding existing administrative databases to include laboratory data can achieve more meaningful insights when assessing multicenter antibiotic prescribing practices.

Association of Acute Kidney Injury With Subsequent Sepsis in Critically Ill Children.

OBJECTIVES: Acute kidney injury is a major cause of morbidity and mortality in critically ill children. A growing body of evidence has shown that acute kidney injury affects immune function, yet little is known about the association between acute kidney injury and subsequent infection in pediatric patients. Our objective was to examine the association of non-septic acute kidney injury with the development of subsequent sepsis in critically ill children. DESIGN: A single-center retrospective cohort study. SETTING: The pediatric and cardiac ICUs at a tertiary pediatric care center. PATIENTS: All patients 0-18 years old without a history of chronic kidney disease, who did not have sepsis prior to or within the initial 48 hours of ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed data for 5,538 children (median age, 5.3 yr; 58.2% male), and identified 255 (4.6%) with stage 2 or 3 acute kidney injury. Suspected sepsis occurred in 46 children (18%) with stage 2 or 3 acute kidney injury compared to 286 children (5.4%) with stage 1 or no acute kidney injury. On adjusted analysis, children with stage 2 or 3 acute kidney injury had 2.05 times greater odds of developing sepsis compared to those with stage 1 or no acute kidney injury (95% CI, 1.39-3.03; p < 0.001). Looking at acute kidney injury severity, children with stage 2 and 3 acute kidney injury had a 1.79-fold (95% CI, 1.15-2.79; p = 0.01) and 3.24-fold (95% CI, 1.55-6.80; p = 0.002) increased odds of developing suspected sepsis, respectively. CONCLUSIONS: Acute kidney injury is associated with an increased risk for subsequent infection in critically ill children. These results further support the concept of acute kidney injury as a clinically relevant immunocompromised state.

Remote Ischemic Preconditioning in the PICU: A Simple Concept With a Complex Past.

OBJECTIVE: In this study, we will review the most recently proposed mechanisms for remote ischemic preconditioning and summarize the past 10 years of clinical studies, as well as potential reasons for why, despite over 20 years of research on remote ischemic preconditioning, it is not routinely used in the pediatric critical care patient. In addition, future directions for remote ischemic preconditioning research will be discussed. DATA SOURCES: We searched the PubMed database for relevant literature. STUDY SELECTION AND DATA EXTRACTION: In PubMed, the search terms "ischemic preconditioning" and "remote preconditioning" were used. Randomized controlled trials published from 2006 until the present time that used a blood pressure cuff to induce remote ischemic preconditioning were included. We also reviewed the reference lists of the articles found in the PubMed search and included those thought to contribute to the objectives. All studies pertaining to remote ischemic preconditioning that included pediatric patients were reviewed. DATA SYNTHESIS AND CONCLUSIONS: Differences in study outcomes in the effect of remote ischemic preconditioning on organ protection have been reported and may have played a large role in limiting the translation of findings into routine clinical practice. Ongoing efforts to protocolize the remote ischemic preconditioning technique in large multicenter trials with clearly delineated patient risk groups, including the use of biomarkers for enrichment, may help to ultimately determine if this procedure can be safely and effectively used for critically ill children.