Synergistic association of fluid overload and acute kidney injury on outcomes in pediatric cardiac ECMO: a retrospective analysis of the KIDMO database.

BACKGROUND: Acute kidney injury (AKI) and fluid overload (FO) are associated with poor outcomes in children receiving extracorporeal membrane oxygenation (ECMO). Our objective is to evaluate the impact of AKI and FO on pediatric patients receiving ECMO for cardiac pathology. METHODS: We performed a secondary analysis of the six-center Kidney Interventions During Extracorporeal Membrane Oxygenation (KIDMO) database, including only children who underwent ECMO for cardiac pathology. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria. FO was defined as < 10% (FO-) vs. ≥ 10% (FO +) and was evaluated at ECMO initiation, peak during ECMO, and ECMO discontinuation. Primary outcomes were mortality and length of stay (LOS). RESULTS: Data from 191 patients were included. Non-survivors (56%) were more likely to be FO + than survivors at peak ECMO fluid status and ECMO discontinuation. There was a significant interaction between AKI and FO. In the presence of AKI, the adjusted odds of mortality for FO + was 4.79 times greater than FO- (95% CI: 1.52-15.12, p = 0.01). In the presence of FO + , the adjusted odds of mortality for AKI + was 2.7 times higher than AKI- [95%CI: 1.10-6.60; p = 0.03]. Peak FO + was associated with a 55% adjusted relative increase in LOS [95%CI: 1.07-2.26, p = 0.02]. CONCLUSIONS: The association of peak FO + with mortality is present only in the presence of AKI + . Similarly, AKI + is associated with mortality only in the presence of peak FO + . FO + was associated with LOS. Studies targeting fluid management have the potential to improve LOS and mortality outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

Acute Kidney Injury, Fluid Overload, and Renal Replacement Therapy Differ by Underlying Diagnosis in Neonatal Extracorporeal Support and Impact Mortality Disparately.

INTRODUCTION: We aimed to characterize acute kidney injury (AKI), fluid overload (FO), and renal replacement therapy (RRT) utilization by diagnostic categories and examine associations between these complications and mortality by category. METHODS: To test our hypotheses, we conducted a retrospective multicenter, cohort study including 446 neonates (categories: 209 with cardiac disease, 114 with congenital diaphragmatic hernia [CDH], 123 with respiratory disease) requiring extracorporeal membrane oxygenation (ECMO) between January 1, 2007, and December 31, 2011. RESULTS: AKI, FO, and RRT each varied by diagnostic category. AKI and RRT receipt were most common in those neonates with cardiac disease. Subjects with CDH had highest peak %FO (51% vs. 28% cardiac vs. 32% respiratory; p < 0.01). Hospital survival was 55% and varied by diagnostic category (45% cardiac vs. 48% CDH vs. 79% respiratory; p < 0.001). A significant interaction suggested risk of mortality differed by diagnostic category in the presence or absence of AKI. In its absence, diagnosis of CDH (vs. respiratory disease) (OR 3.04, 95% CL 1.14-8.11) independently predicted mortality. In all categories, peak %FO (OR 1.20, 95% CL 1.11-1.30) and RRT receipt (OR 2.12, 95% CL 1.20-3.73) were independently associated with mortality. DISCUSSION/CONCLUSIONS: Physiologically distinct ECMO diagnoses warrant individualized treatment strategies given variable incidence and effects of AKI, FO, and RRT by category on mortality.

Acute kidney injury risk-based screening in pediatric inpatients: a pragmatic randomized trial.

BACKGROUND: Pediatric acute kidney injury (AKI) is common and associated with increased morbidity, mortality, and length of stay. We performed a pragmatic randomized trial testing the hypothesis that AKI risk alerts increase AKI screening. METHODS: All intensive care and ward admissions of children aged 28 days through 21 years without chronic kidney disease from 12/6/2016 to 11/1/2017 were included. The intervention alert displayed if calculated AKI risk was > 50% and no serum creatinine (SCr) was ordered within 24 h. The primary outcome was SCr testing within 48 h of AKI risk > 50%. RESULTS: Among intensive care admissions, 973/1909 (51%) were randomized to the intervention. Among those at risk, more SCr tests were ordered for the intervention group than for controls (418/606, 69% vs. 361/597, 60%, p = 0.002). AKI incidence and severity were the same in intervention and control groups. Among ward admissions, 5492/10997 (50%) were randomized to the intervention, and there were no differences between groups in SCr testing, AKI incidence, or severity of AKI. CONCLUSIONS: Alerts based on real-time prediction of AKI risk increased screening rates in intensive care but not pediatric ward settings. Pragmatic clinical trials provide the opportunity to assess clinical decision support and potentially eliminate ineffective alerts.

Fluid overload and fluid removal in pediatric patients on extracorporeal membrane oxygenation requiring continuous renal replacement therapy: a multicenter retrospective cohort study.

OBJECTIVE: The aim of this study was to characterize continuous renal replacement therapy (CRRT) utilization on extracorporeal membrane oxygenation (ECMO) and to determine the association of both fluid overload (FO) at CRRT initiation and fluid removal during CRRT with mortality in a large multicenter cohort. METHODS: Retrospective chart review of all children < 18 years of age concurrently treated with ECMO and CRRT from January 1, 2007, to December 31, 2011, at six tertiary care children's hospital. Children treated with hemodialysis or peritoneal dialysis were excluded from the FO analysis. MEASUREMENTS AND MAIN RESULTS: A total of 756 of the 1009 children supported with ECMO during the study period had complete FO data. Of these, 357 (47.2%) received either CRRT or were treated with an in-line filter and thus entered into the final analysis. Survival to ECMO decannulation was 66.4% and survival to hospital discharge was 44.3%. CRRT initiation occurred at median of 1 day (IQR 0, 2) after ECMO initiation. Median FO at CRRT initiation was 20.1% (IQR 5, 40) and was significantly lower in ECMO survivors vs. non-survivors (15.3% vs. 30.5% p = 0.005) and in hospital survivors vs. non-survivors (13.5% vs. 25.9%, p = 0.004). Median FO at CRRT discontinuation was significantly lower in ECMO survivors (23% vs. 37.6% p = 0.002) and hospital survivors vs. non-survivors (22.6% vs. 36.1%, p = 0.002). In ECMO survivors, after adjusting for pH at CRRT initiation, non-renal complications, ECMO mode, support type, center, patient age and AKI, FO at CRRT initiation (p = 0.01), and FO at CRRT discontinuation (p = 0.0002) were independently associated with duration of ECMO. In a similar multivariable analysis, FO at CRRT initiation (adjusted adds ratio [aOR] 1.09, 95% CI 1.00-1.18, p = 0.045) and at CRRT discontinuation (aOR 1.11, 95% CI 1.03-1.19, p = 0.01) were independently associated with hospital mortality. CONCLUSIONS: In a multicenter pediatric ECMO cohort, this study demonstrates that severe FO was very common at CRRT initiation. We found an independent association between the degree of FO at CRRT initiation with adverse outcomes including mortality and increased duration of ECMO support. The results suggest that intervening prior to the development of significant FO may be a clinical therapeutic target and warrants further evaluation.

Assessing Competence in Central Venous Catheter Placement by Pediatric Critical Care Fellows: A National Survey Study.

OBJECTIVES: To describe the current approach to initial training, ongoing skill maintenance, and assessment of competence in central venous catheter placement by pediatric critical care medicine fellows, a subset of trainees in whom this skill is required. DESIGN: Cross-sectional internet-based survey with deliberate sampling. SETTING: United States pediatric critical care medicine fellowship programs. SUBJECTS: Pediatric critical care medicine program directors of Accreditation Council for Graduate Medical Education-accredited fellowship programs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A working group of the Education in Pediatric Intensive Care Investigators research collaborative conducted a national study to assess the degree of standardization of training and competence assessment of central venous catheter placement across pediatric critical care medicine fellowship programs. After piloting, the survey was sent to all program directors (n = 67) of Accreditation Council for Graduate Medical Education-accredited pediatric critical care medicine programs between July 2017 and September 2017. The response rate was 85% (57/67). Although 98% of programs provide formalized central venous catheter placement training for first-year fellows, only 42% of programs provide ongoing maintenance training as part of fellowship. Over half (55%) of programs use a global assessment tool and 33% use a checklist-based tool when evaluating fellow central venous catheter placement competence under direct supervision. Only two programs (4%) currently use an assessment tool previously published and validated by the Education in Pediatric Intensive Care group. A majority (82%) of responding program directors believe that a standardized approach to assessment of central venous catheter competency across programs is important. CONCLUSIONS: Despite national mandates for skill competence by many accrediting bodies, no standardized system currently exists across programs for assessing central venous catheter placement. Most pediatric critical care medicine programs use a global assessment and decisions around the ability of a fellow to place a central venous catheter under indirect supervision are largely based upon subjective assessment of performance. Further investigation is needed to determine if this finding is consistent in other specialties/subspecialties, if utilization of standardized assessment methods can improve program directors' abilities to ensure trainee competence in central venous catheter insertion in the setting of variable training approaches, and if these findings are consistent with other procedures across critical care medicine training programs, adult and pediatric.

Therapeutic Plasma Exchange in Children With Thrombocytopenia-Associated Multiple Organ Failure: The Thrombocytopenia-Associated Multiple Organ Failure Network Prospective Experience.

OBJECTIVE: The objective was to compare the resolution of organ dysfunction, 28-day mortality, and biochemical markers in children with thrombocytopenia-associated multiple organ failure who received therapeutic plasma exchange versus no therapeutic plasma exchange. DESIGN: Observational longitudinal cohort study. SETTING: Nine U.S. PICUs. PATIENTS: Eighty-one children with sepsis-induced thrombocytopenia-associated multiple organ failure. INTERVENTIONS: Therapeutic plasma exchange. MEASUREMENTS AND MAIN RESULTS: Adjusted relative risk for 28-day mortality was modeled using standard multivariate regression with propensity score weighting to reduce covariate confounding. Change from baseline Pediatric Logistic Organ Dysfunction scores between therapeutic plasma exchange and no therapeutic plasma exchange differed in temporal pattern during the first week (p = 0.009). By day 4, mean Pediatric Logistic Organ Dysfunction score declined by 7.9 points (95% CI, -10.8 to -5.1) in the therapeutic plasma exchange-treated group compared with no change with no therapeutic plasma exchange. Use of therapeutic plasma exchange was associated with reduced 28-day mortality by multivariate analysis (adjusted relative risk, 0.45; 95% CI, 0.23-0.90; p = 0.02) and by propensity score weighting (adjusted relative risk, 0.46; 95% CI, 0.22-0.97; p = 0.04). CONCLUSIONS: Therapeutic plasma exchange use in thrombocytopenia-associated multiple organ failure was associated with a decrease in organ dysfunction. After accounting for several risk factors, 28-day all-cause mortality was lower in children treated with therapeutic plasma exchange compared with those receiving no therapeutic plasma exchange. A multicenter randomized clinical trial is necessary to determine a causal relationship.

Electronic health record-based predictive models for acute kidney injury screening in pediatric inpatients.

BackgroundAcute kidney injury (AKI) is common in pediatric inpatients and is associated with increased morbidity, mortality, and length of stay. Its early identification can reduce severity.MethodsTo create and validate an electronic health record (EHR)-based AKI screening tool, we generated temporally distinct development and validation cohorts using retrospective data from our tertiary care children's hospital, including children aged 28 days through 21 years with sufficient serum creatinine measurements to determine AKI status. AKI was defined as 1.5-fold or 0.3 mg/dl increase in serum creatinine. Age, medication exposures, platelet count, red blood cell distribution width, serum phosphorus, serum transaminases, hypotension (ICU only), and pH (ICU only) were included in AKI risk prediction models.ResultsFor ICU patients, 791/1,332 (59%) of the development cohort and 470/866 (54%) of the validation cohort had AKI. In external validation, the ICU prediction model had a c-statistic=0.74 (95% confidence interval 0.71-0.77). For non-ICU patients, 722/2,337 (31%) of the development cohort and 469/1,474 (32%) of the validation cohort had AKI, and the prediction model had a c-statistic=0.69 (95% confidence interval 0.66-0.72).ConclusionsAKI screening can be performed using EHR data. The AKI screening tool can be incorporated into EHR systems to identify high-risk patients without serum creatinine data, enabling targeted laboratory testing, early AKI identification, and modification of care.

The Impact of Fluid Overload on Outcomes in Children Treated With Extracorporeal Membrane Oxygenation: A Multicenter Retrospective Cohort Study.

OBJECTIVE: To characterize the epidemiology of fluid overload and its association with mortality and duration of extracorporeal membrane oxygenation in children treated with extracorporeal membrane oxygenation. DESIGN: Retrospective cohort study. SETTING: Six tertiary children's hospital ICUs. PATIENTS: Seven hundred fifty-six children younger than 18 years old treated with extracorporeal membrane oxygenation for greater than or equal to 24 hours from January 1, 2007, to December 31, 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall survival to extracorporeal membrane oxygenation decannulation and hospital discharge was 74.9% (n = 566) and 57.7% (n = 436), respectively. Median fluid overload at extracorporeal membrane oxygenation initiation was 8.8% (interquartile range, 0.3-19.2), and it differed between hospital survivors and non survival, though not between extracorporeal membrane oxygenation survivors and non survivors. Median peak fluid overload on extracorporeal membrane oxygenation was 30.9% (interquartile range, 15.4-54.8). During extracorporeal membrane oxygenation, 84.8% had a peak fluid overload greater than or equal to 10%; 67.2% of patients had a peak fluid overload of greater than or equal to 20% and 29% of patients had a peak fluid overload of greater than or equal to 50%. The median peak fluid overload was lower in patients who survived on extracorporeal membrane oxygenation (27.2% vs 44.4%; p < 0.0001) and survived to hospital discharge (24.8% vs 43.3%; p < 0.0001). After adjusting for acute kidney injury, pH at extracorporeal membrane oxygenation initiation, nonrenal complications, extracorporeal membrane oxygenation mode, support type, center and patient age, the degree of fluid overload at extracorporeal membrane oxygenation initiation (p = 0.05), and the peak fluid overload on extracorporeal membrane oxygenation (p < 0.0001) predicted duration of extracorporeal membrane oxygenation in survivors. Multivariable analysis showed that peak fluid overload on extracorporeal membrane oxygenation (adjusted odds ratio, 1.09; 95% CI, 1.04-1.15) predicted mortality on extracorporeal membrane oxygenation; fluid overload at extracorporeal membrane oxygenation initiation (adjusted odds ratio, 1.13; 95% CI, 1.05-1.22) and peak fluid overload (adjusted odds ratio, 1.18; 95% CI, 1.12-1.24) both predicted hospital morality. CONCLUSIONS: Fluid overload occurs commonly and is independently associated with adverse outcomes including increased mortality and increased duration of extracorporeal membrane oxygenation in a broad pediatric extracorporeal membrane oxygenation population. These results suggest that fluid overload is a potential target for intervention to improve outcomes in children on extracorporeal membrane oxygenation.

Competency milestones for medical students: Design, implementation, and analysis at one medical school.

Competency-based assessment seeks to align measures of performance directly with desired learning outcomes based upon the needs of patients and the healthcare system. Recognizing that assessment methods profoundly influence student motivation and effort, it is critical to measure all desired aspects of performance throughout an individual's medical training. The Accreditation Council for Graduate Medical Education (ACGME) defined domains of competency for residency; the subsequent Milestones Project seeks to describe each learner's progress toward competence within each domain. Because the various clinical disciplines defined unique competencies and milestones within each domain, it is difficult for undergraduate medical education to adopt existing GME milestones language. This paper outlines the process undertaken by one medical school to design, implement and improve competency milestones for medical students. A team of assessment experts developed milestones for a set of focus competencies; these have now been monitored in medical students over two years. A unique digital dashboard enables individual, aggregate and longitudinal views of student progress by domain. Validation and continuous quality improvement cycles are based upon expert review, user feedback, and analysis of variation between students and between assessors. Experience to date indicates that milestone-based assessment has significant potential to guide the development of medical students.

Acute Kidney Injury Incidence in Noncritically Ill Hospitalized Children, Adolescents, and Young Adults: A Retrospective Observational Study.

BACKGROUND: Acute kidney injury (AKI) has been characterized in high-risk pediatric hospital inpatients, in whom AKI is frequent and associated with increased mortality, morbidity, and length of stay. The incidence of AKI among patients not requiring intensive care is unknown. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 13,914 noncritical admissions during 2011 and 2012 at our tertiary referral pediatric hospital were evaluated. Patients younger than 28 days or older than 21 years of age or with chronic kidney disease (CKD) were excluded. Admissions with 2 or more serum creatinine measurements were evaluated. FACTORS: Demographic features, laboratory measurements, medication exposures, and length of stay. OUTCOME: AKI defined as increased serum creatinine level in accordance with KDIGO (Kidney Disease: Improving Global Outcomes) criteria. Based on time of admission, time interval requirements were met in 97% of cases, but KDIGO time window criteria were not strictly enforced to allow implementation using clinically obtained data. RESULTS: 2 or more creatinine measurements (one baseline before or during admission and a second during admission) in 2,374 of 13,914 (17%) patients allowed for AKI evaluation. A serum creatinine difference ≥0.3mg/dL or ≥1.5 times baseline was seen in 722 of 2,374 (30%) patients. A minimum of 5% of all noncritical inpatients without CKD in pediatric wards have an episode of AKI during routine hospital admission. LIMITATIONS: Urine output, glomerular filtration rate, and time interval criteria for AKI were not applied secondary to study design and available data. The evaluated cohort was restricted to patients with 2 or more clinically obtained serum creatinine measurements, and baseline creatinine level may have been measured after the AKI episode. CONCLUSIONS: AKI occurs in at least 5% of all noncritically ill hospitalized children, adolescents, and young adults without known CKD. Physicians should increase their awareness of AKI and improve surveillance strategies with serum creatinine measurements in this population so that exacerbating factors such as nephrotoxic medication exposures may be modified as indicated.

Pediatric acute asthma exacerbations: Evaluation and management from emergency department to intensive care unit.

OBJECTIVE: The goal of this report is to review available modalities for assessing and managing acute asthma exacerbations in pediatric patients, including some that are not included in current expert panel guidelines. While it is not our purpose to provide a comprehensive review of the National Asthma Education and Prevention Program (NAEPP) guidelines, we review NAEPP-recommended treatments to provide the full range of treatments available for managing exacerbations with an emphasis on the continuum of care between the ER and ICU. DATA SOURCES: We searched PubMed using the following search terms in different combinations: asthma, children, pediatric, exacerbation, epidemiology, pathophysiology, guidelines, treatment, management, oxygen, albuterol, ß2-agonist, anticholinergic, theophylline, corticosteroid, magnesium, heliox, BiPAP, ventilation, mechanical ventilation, non-invasive mechanical ventilation and respiratory failure. We attempted to weigh the evidence using the hierarchy in which meta-analyses of randomized controlled trials (RCTs) provide the strongest evidence, followed by individual RCTs, followed by observational studies. We also reviewed the NAEPP and Global Initiative for Asthma expert panel guidelines. RESULTS AND CONCLUSIONS: Asthma is the most common chronic disease of childhood, and acute exacerbations are a significant burden to patients and to public health. Optimal assessment and management of exacerbations, including appropriate escalation of interventions, are essential to minimize morbidity and prevent mortality. While inhaled albuterol and systemic corticosteroids are the mainstay of exacerbation management, escalation may include interventions discussed in this review.

The Incidence of Acute Kidney Injury and Its Effect on Neonatal and Pediatric Extracorporeal Membrane Oxygenation Outcomes: A Multicenter Report From the Kidney Intervention During Extracorporeal Membrane Oxygenation Study Group.

OBJECTIVE: In a population of neonatal and pediatric patients on extracorporeal membrane oxygenation; to describe the prevalence and timing of acute kidney injury utilizing a consensus acute kidney injury definition and investigate the association of acute kidney injury with outcomes (length of extracorporeal membrane oxygenation and mortality). DESIGN: Multicenter retrospective observational cohort study. SETTING: Six pediatric extracorporeal membrane oxygenation centers. PATIENTS: Pediatric patients (age, < 18 yr) on extracorporeal membrane oxygenation at six centers during a period of January 1, 2007, to December 31, 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Complete data were analyzed for 832 patients on extracorporeal membrane oxygenation. Sixty percent of patients had acute kidney injury utilizing the serum creatinine Kidney Disease Improving Global Outcomes criteria (AKI) and 74% had acute kidney injury using the full Kidney Disease Improving Global Outcomes criteria including renal support therapy (AKI). Of those who developed acute kidney injury, it was present at extracorporeal membrane oxygenation initiation in a majority of cases (52% AKI and 65% AKI) and present by 48 hours of extracorporeal membrane oxygenation support in 86% (AKI) and 93% (AKI). When adjusted for patient age, center of support, mode of support, patient complications and preextracorporeal membrane oxygenation pH, the presence of acute kidney injury by either criteria was associated with a significantly longer duration of extracorporeal membrane oxygenation support (AKI, 152 vs 110 hr; AKI, 153 vs 99 hr) and increased adjusted odds of mortality at hospital discharge (AKI: odds ratio, 1.77; 1.22-2.55 and AKI: odds ratio, 2.50; 1.61-3.90). With the addition of renal support therapy to the model, acute kidney injury was associated with a longer duration of extracorporeal membrane oxygenation support (AKI, 149 vs 121 hr) and increased risk of mortality at hospital discharge (AKI: odds ratio, 1.52; 1.04-2.21). CONCLUSION: Acute kidney injury is present in 60-74% of neonatal-pediatric patients supported on extracorporeal membrane oxygenation and is present by 48 hours of extracorporeal membrane oxygenation support in 86-93% of cases. Acute kidney injury has a significant association with increased duration of extracorporeal membrane oxygenation support and increased adjusted odds of mortality at hospital discharge.

Global Trends in Extracorporeal Membranous Oxygenation Use and Survival of Patients With Influenza-Associated Illness.

OBJECTIVES: To determine the overall use of extracorporeal membranous oxygenation for influenza-associated illness and describe risk factors associated with mortality in these patients. DESIGN: Retrospective multicenter cohort analysis. SETTING: The international Extracorporeal Life Support Organization database was queried for patients with influenza-associated illness on extracorporeal membranous oxygenation from 1992 to 2014. PATIENTS: In total, 1,654 patients with influenza-associated illness on extracorporeal membranous oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data collected included age, type of support, duration of support, type of microbial codetection, complications, and survival status at discharge. The primary outcome of interest was survival to hospital discharge. From 1992 to 2014, 1,688 (3%) of the 61,336 extracorporeal membranous oxygenation runs were due to influenza-associated illness reflecting 1,654 unique patients: 30 (2%) were neonates, 521 (31%) were pediatric patients, and 1,103 (67%) were adults. Extracorporeal membranous oxygenation use for influenza-associated illness increased from 1992 to 2014, with a marked increase in use after the 2009 H1N1 pandemic. Survival to hospital discharge of patients with influenza-associated illness on extracorporeal membranous oxygenation was 63% and was not affected by bacterial codetection. However, when patients with Staphylococcus aureus codetection were compared with those with another bacterial codetection, their survival to hospital discharge was significantly lower (52% vs 67%; p < 0.01). In a logistic regression model, the effect of S. aureus on in-hospital mortality varied by age group, with younger patients with S. aureus having increased in-hospital mortality. CONCLUSIONS: Extracorporeal membranous oxygenation use for individuals with influenza increased over time, particularly after the 2009 H1N1 pandemic, most notably among older adults. Survival to hospital discharge for patients with influenza on extracorporeal membranous oxygenation was slightly higher than survival to hospital discharge for respiratory illness due to any cause. Bacterial codetection was common among patients with influenza on extracorporeal membranous oxygenation and was associated with increased days on extracorporeal membranous oxygenation but not increased mortality. Only S. aureus codetection in children was associated with increased in-hospital mortality.

The morbidity and mortality of patients with fungal infections before and during extracorporeal membrane oxygenation support.

OBJECTIVE: To evaluate the prevalence of fungal infections (both pre-cannulation and post-cannulation) while on extracorporeal membrane oxygenation support and the associated morbidity and mortality. DESIGN: Retrospective cohort study. PATIENT AND METHODS: The Extracorporeal Life Support Organization database is an international voluntary registry of clinical data for patients placed on extracorporeal membrane oxygenation. The database was queried for all patients on extracorporeal membrane oxygenation from 1997 to 2009. Patient and extracorporeal membrane oxygenation data collected included age, support type, length of support, infection status and organism code, discharge status, complications, and component failures. Outcomes of interest were mortality, extracorporeal membrane oxygenation-related patient complications, and mechanical component failures. RESULTS: From 1997 to 2009, there were 21,073 patients' extracorporeal membrane oxygenation runs analyzed of which 12,933 were in the neonatal group (0-30 days), 6,073 were in the pediatric group (31 days to <18 yrs old), and 2,067 were in the adult group (≥18 yrs). The prevalence of fungal infection during extracorporeal membrane oxygenation varied by age group and timing of infection and ranged from 0.04% to 5%. Fungal infections pre-extracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation conferred a statistically significant higher relative risk of mortality for all age groups and varied by support type and timing of infection. Extracorporeal membrane oxygenation-related complications and component failures were not statistically significantly affected by infection status. CONCLUSIONS: Fungal infection before or during extracorporeal membrane oxygenation increases the odds of mortality and the magnitude of this effect is dependent upon age-group and timing of infection. This increased mortality was not the result of increased patient or mechanical complications during extracorporeal membrane oxygenation. For patients with fungal infections pre-extracorporeal membrane oxygenation, 82%-89% demonstrated presumed clearance during extracorporeal membrane oxygenation. Although the risk of mortality increased with fungal infections, it does not appear that fungal infection before or during extracorporeal membrane oxygenation is a contraindication to initiation or continuation of support.

Nonrenal indications for continuous renal replacement therapy: A report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group.

OBJECTIVE: Continuous renal replacement therapy is the most often implemented dialysis modality in the pediatric intensive care unit setting for patients with acute kidney injury. However, it also has a role in the management of patients with nonrenal indications such as clearance of drugs and intermediates of disordered cellular metabolism. MEASUREMENTS AND METHODS: Using data from the multicenter Prospective Pediatric Continuous Renal Replacement Therapy Registry, we report a cohort of pediatric patients receiving continuous renal replacement therapy for nonrenal indications. Nonrenal indications were obtained from the combination of "other" category for continuous renal replacement therapy initiation and patient diagnosis (both primary and secondary). This cohort was further divided into three subgroups: inborn errors of metabolism, drug toxicity, and tumor lysis syndrome. RESULTS: From 2000 to 2005, a total of 50 continuous renal replacement therapy events with nonrenal indications for therapy were included in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. Indication-specific survival of the subgroups was 62% (inborn errors of metabolism), 82% (tumor lysis syndrome), and 95% (drug toxicity). The median small solute dose delivered among the subgroups ranged from 2125 to 8213 mL/1.73 m/hr, with 54%-59% receiving solely diffusion-based clearance as continuous venovenous hemodialysis. No association was established between survival and dose delivered, modality of continuous renal replacement therapy, or use of intermittent hemodialysis prior to continuous renal replacement therapy. CONCLUSIONS: Pediatric patients requiring continuous renal replacement therapy for nonrenal indications are a distinct cohort within the population receiving renal replacement therapy with little published experience of outcomes for this group. Survival within this cohort varies by indication for continuous renal replacement therapy and is not associated with continuous renal replacement therapy modality. Additionally, survival is not associated with small solute doses delivered within a cohort receiving >2000 mL/1.73 m/hr. Our data suggest metabolic control is established rapidly in pediatric patients and that acute detoxification may be provided with continuous renal replacement therapy for both the initial and maintenance phases of treatment using either convection or diffusion at appropriate doses.

Effect of Smartphone App-Based Education on Clinician Prescribing Habits in a Learning Health Care System: A Randomized Cluster Crossover Trial.

Importance: Effective methods for engaging clinicians in continuing education for learning-based practice improvement remain unknown. Objective: To determine whether a smartphone-based app using spaced education with retrieval practice is an effective method to increase evidence-based practice. Design, Setting, and Participants: A prospective, unblinded, single-center, crossover randomized clinical trial was conducted at a single academic medical center from January 6 to April 24, 2020. Vanderbilt University Medical Center clinicians prescribing intravenous fluids were invited to participate in this study. Interventions: All clinicians received two 4-week education modules: 1 on prescribing intravenous fluids and 1 on prescribing opioid and nonopioid medications (counterbalancing measure), over a 12-week period. The order of delivery was randomized 1:1 such that 1 group received the fluid management module first, followed by the pain management module after a 4-week break, and the other group received the pain management module first, followed by the fluid management module after a 4-week break. Main Outcomes and Measures: The primary outcome was evidence-based clinician prescribing behavior concerning intravenous fluids in the inpatient setting and pain medication prescribing on discharge from the hospital. Results: A total of 354 participants were enrolled and randomized, with 177 in group 1 (fluid then pain management education) and 177 in group 2 (pain management then fluid education). During the overall study period, 16 868 questions were sent to 349 learners, with 11 783 (70.0%) being opened: 10 885 (92.4%) of those opened were answered and 7175 (65.9%) of those answered were answered correctly. The differences between groups changed significantly over time, indicated by the significant interaction between educational intervention and time (P = .002). Briefly, at baseline evidence-concordant IV fluid ordered 7.2% less frequently in group 1 than group 2 (95% CI, -19.2% to 4.9%). This was reversed after training at 4% higher (95% CI, -8.2% to 16.0%) in group 1 than group 2, a more than doubling in the odds of evidence-concordant ordering (OR, 2.56, 95% CI, 0.80-8.21). Postintervention, all gains had been reversed with less frequent ordering in group 1 than group 2 (-9.5%, 95% CI, -21.6% to 2.7%). There was no measurable change in opioid prescribing behaviors at any time point. Conclusions and Relevance: In this randomized clinical trial, use of smartphone app learning modules resulted in statistically significant short-term improvement in some prescribing behaviors. However, this effect was not sustained over the long-term. Additional research is needed to understand how to sustain improvements in care delivery as a result of continuous professional development at the institutional level. Trial Registration: ClinicalTrials.gov Identifier: NCT03771482.

Fluid Balance Management Informs Renal Replacement Therapy Use During Pediatric Extracorporeal Membrane Oxygenation: A Survey Report From the Kidney Intervention During Extracorporeal Membrane Oxygenation Group.

Fluid overload (FO) and acute kidney injury (AKI) occur commonly in children supported with extracorporeal membrane oxygenation (ECMO). Continuous renal replacement therapy (CRRT) may be used to manage AKI and FO in children on ECMO. In 2012, our group surveyed ECMO centers to begin to understand the practice patterns around CRRT and ECMO. Since then, more centers are initiating ECMO for increasingly diverse indications and an increased volume of research quantifies the detrimental impacts of AKI and FO. We, therefore, investigated practice patterns of CRRT utilization during ECMO in children. A multi-point survey instrument was distributed to 116 international neonatal and pediatric ECMO centers. Sixty of 116 (51.7%) international neonatal and pediatric ECMO centers responded. All reports using CRRT on ECMO, compared with 75% from the 2012 survey. Eighty-five percent use CRRT to treat or prevent FO, an increased from 59%. The modality of CRRT therapy differed between in-line (slow continuous ultrafiltration, 84.4%) and machine-based (continuous venovenous hemodiafiltration, 87.3%) methods. Most (65%) do not have protocols for fluid management, AKI, or CRRT on ECMO. Trialing off CRRT is dictated by physician preference in 90% (54/60), with varying definitions of success. In this survey study, we found that CRRT use during pediatric ECMO has increased since 2012 with fluid management representing the predominant indication for initiation. Despite the expanded utilization of CRRT with ECMO, there remains significant practice variation in terms of method, modality, indication, the timing of initiation, fluid management, and discontinuation.

Acute Kidney Injury and Fluid Overload in Pediatric Extracorporeal Cardio-Pulmonary Resuscitation: A Multicenter Retrospective Cohort Study.

Acute kidney injury (AKI) and fluid overload (FO) are common complications of extracorporeal membrane oxygenation (ECMO). The purpose of this study was to characterize AKI and FO in children receiving extracorporeal cardiopulmonary resuscitation (eCPR). We performed a multicenter retrospective study of children who received eCPR. AKI was assessed during ECMO and FO defined as <10% [FO-] vs. ≥10% [FO+] evaluated at ECMO initiation and discontinuation. A composite exposure, defined by a four-group discrete phenotypic classification [FO-/AKI-, FO-/AKI+, FO+/AKI-, FO+/AKI+] was also evaluated. Primary outcome was mortality and hospital length of stay (LOS) among survivors. 131 patients (median age 29 days (IQR:9, 242 days); 51% men and 82% with underlying cardiac disease) were included. 45.8% survived hospital discharge. FO+ at ECMO discontinuation, but not AKI was associated with mortality [aOR=2.3; 95% CI: 1.07-4.91]. LOS for FO+ patients was twice as long as FO- patients, irrespective of AKI status [(FO+/AKI+ (60 days; IQR: 49-83) vs. FO-/AKI+ (30 days, IQR: 19-48 days); P = 0.01]. FO+ at ECMO initiation and discontinuation was associated with an adjusted 66% and 50% longer length of stay respectively. Prospective studies that target timing and strategy of fluid management, including its removal in children receiving ECPR are greatly needed.