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Characterize the use of inhaled nitric oxide (iNO) for pediatric cardiac patients and assess the relationship between patient characteristics before iNO initiation and outcomes following cardiac surgery.Observational cohort study.PICU and cardiac ICUs in seven Collaborative Pediatric Critical Care Research Network hospitals.Consecutive patients, less than 18 years old, mechanically ventilated before or within 24 hours of iNO initiation. iNO was started for a cardiac indication and excluded newborns with congenital diaphragmatic hernia, meconium aspiration syndrome, and persistent pulmonary hypertension, or when iNO started at an outside institution.None.Four-hundred seven patients with iNO initiation based on cardiac dysfunction. Cardiac dysfunction patients were administered iNO for a median of 4 days (2-7 d). There was significant morbidity with 51 of 407 (13%) requiring extracorporeal membrane oxygenation and 27 of 407 (7%) requiring renal replacement therapy after iNO initiation, and a 28-day mortality of 46 of 407 (11%). Of the 366 (90%) survivors, 64 of 366 patients (17%) had new morbidity as assessed by Functional Status Scale. Among the postoperative cardiac surgical group (n = 301), 37 of 301 (12%) had a superior cavopulmonary connection and nine of 301 (3%) had a Fontan procedure. Based on echocardiographic variables prior to iNO (n = 160) in the postoperative surgical group, right ventricle dysfunction was associated with 28-day and hospital mortalities (both, p0.001) and ventilator-free days (p = 0.003); tricuspid valve regurgitation was only associated with ventilator-free days (p0.001), whereas pulmonary hypertension was not associated with mortality or ventilator-free days.Pediatric patients in whom iNO was initiated for a cardiac indication had a high mortality rate and significant morbidity. Right ventricular dysfunction, but not the presence of pulmonary hypertension on echocardiogram, was associated with ventilator-free days and mortality.

Purpose Our understanding of inborn errors of immunity is increasing; however, their contribution to pediatric sepsis is unknown. Methods We used whole-exome sequencing (WES) to characterize variants in genes related to monogenic immunologic disorders in 330 children admitted to intensive care for severe sepsis. We defined candidate variants as rare variants classified as pathogenic or potentially pathogenic in QIAGEN’s Human Gene Mutation Database or novel null variants in a disease-consistent inheritance pattern. We investigated variant correlation with infection and inflammatory phenotype. Results More than one in two children overall and three of four African American children had immunodeficiency-associated variants. Children with variants had increased odds of isolating a blood or urinary pathogen (blood: OR 2.82, 95% CI: 1.12–7.10, p = 0.023, urine: OR: 8.23, 95% CI: 1.06–64.11, p = 0.016) and demonstrating increased inflammation with hyperferritinemia (ferritin $$\ge 500$$ ≥ 500 ng/mL, OR: 2.16, 95% CI: 1.28–3.66, p = 0.004), lymphopenia (lymphocyte count p = 0.027), thrombocytopenia (platelet count p = 0.013), and CRP greater than 10 mg/dl (OR: 1.71, 95% CI: 1.10–2.68, p = 0.017). They also had increased odds of requiring extracorporeal membrane oxygenation (ECMO, OR: 4.19, 95% CI: 1.21–14.5, p = 0.019). Conclusion Herein, we describe the genetic findings in this severe pediatric sepsis cohort and their microbiologic and immunologic significance, providing evidence for the phenotypic effect of these variants and rationale for screening children with life-threatening infections for potential inborn errors of immunity.

Comparing first and second wave MIS-C cohorts at our quaternary pediatric institution, second wave were older, presented more frequently with shortness of breath, higher maximum troponin and N-terminal BNP, and more frequently required advanced respiratory and inotropic support. Despite increased severity in the second cohort, both cohorts had similar rates of coronary artery abnormalities, systolic dysfunction, and length of stay.

The objective of the study was to describe the complexity of diagnosis and evaluation of Zika-exposed pregnant women/fetuses and infants in a U.S. Congenital Zika Program. Pregnant women/fetuses and/or infants referred for clinical evaluation to the Congenital Zika Program at Children’s National (Washington, DC) from January 2016 to June 2018 were included. We recorded the timing of maternal Zika-virus (ZIKV) exposure and ZIKV laboratory testing results. Based on laboratory testing, cases were either confirmed, possible, or unlikely ZIKV infection. Prenatal and postnatal imaging by ultrasound and/or magnetic resonance imaging (MRI) were categorized as normal, nonspecific, or as findings of congenital Zika syndrome (CZS). Of 81 women–fetus/infant pairs evaluated, 72 (89%) had confirmed ZIKV exposure; 18% of women were symptomatic; only a minority presented for evaluation within the time frame for laboratory detection. Zika virus could only be confirmed in 29 (40%) cases, was possible in 26 (36%) cases, and was excluded in 17 (24%) cases. Five cases (7%) had prenatal ultrasound and MRI findings of CZS, but in only three was ZIKV confirmed by laboratory testing. Because of timing of exposure to presentation, ZIKV infection could not be excluded in many cases. Neuroimaging found CZS in 7% of cases, and in many patients, there were nonspecific imaging findings that warrant long-term follow-up. Overall, adherence to postnatal recommended follow-up evaluations was modest, representing a barrier to care. These challenges may be instructive to future pediatric multidisciplinary clinics for congenital infectious/noninfectious threats to pregnant women and their infants.

OBJECTIVES To describe coronavirus disease 2019 (COVID-19)–related pediatric hospitalizations during a period of B.1.617.2 (Δ) variant predominance and to determine age-specific factors associated with severe illness. METHODS We abstracted data from medical charts to conduct a cross-sectional study of patients aged RESULTS Of 947 hospitalized patients, 759 (80.1%) had COVID-19, of whom 287 (37.8%) had severe illness. Factors associated with severe illness included coinfection with respiratory syncytial virus (RSV) (PR 3.64) and bacteria (PR 1.88) in infants; RSV coinfection in patients aged 1 to 4 years (PR 1.96); and obesity in patients aged 5 to 11 (PR 2.20) and 12 to 17 years (PR 2.48). Having ≥2 underlying medical conditions was associated with severe illness in patients aged CONCLUSIONS Among patients hospitalized for COVID-19, factors associated with severe illness included RSV coinfection in those aged

AIM: The mathematical method used to calculate chest compression (CC) rate during cardiopulmonary resuscitation varies in the literature and across device manufacturers. The objective of this study was to determine the variability in calculated CC rates by applying four published methods to the same dataset. METHODS: This study was a secondary investigation of the first 200 pediatric cardiac arrest events with invasive arterial line waveform data in the ICU-RESUScitation Project (NCT02837497). Instantaneous CC rates were calculated during periods of uninterrupted CCs. The defined minimum interruption length affects rate calculation (e.g., if an interruption is defined as a break in CCs ≥ 2 seconds, the lowest possible calculated rate is 30 CCs/min). Average rates were calculated by four methods: 1) rate with an interruption defined as ≥ 1 second; 2) interruption ≥ 2 seconds; 3) interruption ≥ 3 seconds; 4) method #3 excluding top and bottom quartiles of calculated rates. American Heart Association Guideline-compliant rate was defined as 100–120 CCs/min. A clinically important change was defined as ± 5 CCs/min. The percentage of events and epochs (30 second periods) that changed Guideline-compliant status was calculated. RESULTS: Across calculation methods, mean CC rates (118.7 – 119.5/min) were similar. Comparing all methods, 14 events (7%) and 114 epochs (6%) changed Guideline-compliant status. CONCLUSION: Using four published methods for calculating CC rate, average rates were similar, but 7% of events changed Guideline-compliant status. These data suggest that a uniform calculation method (interruption ≥ 1 second) should be adopted to decrease variability in resuscitation science.

Risk factors for mortality in children with refractory pediatric septic shock who are supported with extracorporeal life support (ECLS) are largely unknown. Therefore, we performed univariable and multivariable analyses to determine risk factors for mortality among children (

Objectives To characterize contemporary use of inhaled nitric oxide in pediatric acute respiratory failure and to assess relationships between clinical variables and outcomes. We sought to study the relationship of inhaled nitric oxide response to patient characteristics including right ventricular dysfunction and clinician responsiveness to improved oxygenation. We hypothesize that prompt clinician responsiveness to minimize hyperoxia would be associated with improved outcomes. Design An observational cohort study. Setting Eight sites of the Collaborative Pediatric Critical Care Research Network. Patients One hundred fifty-one patients who received inhaled nitric oxide for a primary respiratory indication. Measurements and main results Clinical data were abstracted from the medical record beginning at inhaled nitric oxide initiation and continuing until the earliest of 28 days, ICU discharge, or death. Ventilator-free days, oxygenation index, and Functional Status Scale were calculated. Echocardiographic reports were abstracted assessing for pulmonary hypertension, right ventricular dysfunction, and other cardiovascular parameters. Clinician responsiveness to improved oxygenation was determined. One hundred thirty patients (86%) who received inhaled nitric oxide had improved oxygenation by 24 hours. PICU mortality was 29.8%, while a new morbidity was identified in 19.8% of survivors. Among patients who had echocardiograms, 27.9% had evidence of pulmonary hypertension, 23.1% had right ventricular systolic dysfunction, and 22.1% had an atrial communication. Moderate or severe right ventricular dysfunction was associated with higher mortality. Clinicians responded to an improvement in oxygenation by decreasing FIO2 to less than 0.6 within 24 hours in 71% of patients. Timely clinician responsiveness to improved oxygenation with inhaled nitric oxide was associated with more ventilator-free days but not less cardiac arrests, mortality, or additional morbidity. Conclusions Clinician responsiveness to improved oxygenation was associated with less ventilator days. Algorithms to standardize ventilator management may improve signal to noise ratios in future trials enabling better assessment of the effect of inhaled nitric oxide on patient outcomes. Additionally, confining studies to more selective patient populations such as those with right ventricular dysfunction may be required.

BACKGROUND AND OBJECTIVES: Chart reviews are frequently used for research, care assessments, and quality improvement activities despite an absence of data on reliability and validity. We aim to describe a structured chart review methodology and to establish its validity and reliability. METHODS: A generalizable structured chart review methodology was designed to evaluate causes of morbidity or mortality and to identify potential therapeutic advances. The review process consisted of a 2-tiered approach with a primary review completed by a site physician and a short secondary review completed by a central physician. A total of 327 randomly selected cases of known mortality or new morbidities were reviewed. Validity was assessed by using postreview surveys with a Likert scale. Reliability was assessed by percent agreement and interrater reliability. RESULTS: The primary reviewers agreed or strongly agreed in 94.9% of reviews that the information to form a conclusion about pathophysiological processes and therapeutic advances could be adequately found. They agreed or strongly agreed in 93.2% of the reviews that conclusions were easy to make, and confidence in the process was 94.2%. Secondary reviewers made modifications to 36.6% of cases. Duplicate reviews (n = 41) revealed excellent percent agreement for the causes (80.5%–100%) and therapeutic advances (68.3%–100%). κ statistics were strong for the pathophysiological categories but weaker for the therapeutic categories. CONCLUSIONS: A structured chart review by knowledgeable primary reviewers, followed by a brief secondary review, can be valid and reliable.

BACKGROUND: Little is known about the epidemiology of and outcomes related to red blood cell (RBC) transfusion in septic children across multiple centers. We performed propensity-adjusted secondary analyses of the Biomarker Phenotyping of Pediatric Sepsis and Multiple Organ Failure (PHENOMS) study to test the hypothesis that early RBC transfusion is associated with fewer organ failure-free days in pediatric severe sepsis. METHODS: 401 children were enrolled in the parent study. Children were excluded from these analyses if they received extracorporeal membrane oxygenation (n = 22) or died (n = 1) before sepsis day 2. Propensity-adjusted analyses compared children who received RBC transfusion on or before sepsis day 2 (early RBC transfusion) with those who did not. Logistic regression was used to model the propensity to receive early RBC transfusion. A weighted cohort was constructed using stabilized inverse probability of treatment weights. Variables in the weighted cohort with absolute standardized differences > 0.15 were added to final multivariable models. RESULTS: 50% of children received at least one RBC transfusion. The majority (68%) of first transfusions were on or before sepsis day 2. Early RBC transfusion was not independently associated with organ failure-free (−0.34 [95%CI: − 2, 1.3] days) or PICU-free days (−0.63 [−2.3, 1.1]), but was associated with the secondary outcome of higher mortality (aOR 2.9 [1.1, 7.9]). CONCLUSIONS: RBC transfusion is common in pediatric severe sepsis and may be associated with adverse outcomes. Future studies are needed to clarify these associations, to understand patient-specific transfusion risks, and to develop more precise transfusion strategies.

Objectives:To describe the incidence of seasonal respiratory viral infections (s-RVIs) before and during the coronavirus disease 2019 (COVID-19) pandemic and to compare virus-specific patient outcomes in pediatric patients.Design:A retrospective cross-sectional study including patient admissions to the Children’s National Hospital between October 1, 2015, and December 31, 2020.Results:Among 12,451 patient admissions between March 15 and December 31, 2020 (cohort 1), 8,162 (66%) were tested for severe acute respiratory coronavirus virus 2 (SARS-CoV-2), and 249 (2.0%) were positive. Among 10,986 patient admissions between April 1 and December 31, 2020 (cohort 2), 844 (8%) were tested for s-RV upon admission and 160 were positive. Thus, 1.5% of patient admissions were associated with laboratory-confirmed s-RVIs. Among the 49,901 patient admissions during a viral season between October 1, 2015, and March 31, 2020 (cohort 3), 7,539 (15%) were tested for s-RV upon admission and 4,531 were positive; thus, 9.0% of patient admissions were associated with laboratory-confirmed s-RVIs. hHRV/rENT was the most detected virus, but the detection rate decreased substantially (31% vs 18%; P < .001) during the COVID-19 pandemic. No patients had RSV, influenza, hMPV, hPIV, or hCoV detected upon admission after April 21, 2020. The 3 patient cohorts had no statistically significant difference in the percentage of ICU admissions (10.8% vs 15.0% vs 14.2%; P > .05) or death at discharge (0.8% vs 0.6% vs 0.5%; P > .05).Conclusions:Compared to COVID-19, s-RVI cases were associated with a higher proportion of inpatient admissions but were similar in ICU admission and death rates in hospitalized pediatric patients. Public health interventions for preventing COVID-19 were highly effective in preventing pediatrics s-RVIs.

The SARS-CoV-2 virus has emerged as a global pandemic, severely impacting everyday life. Significant resources have been dedicated towards profiling the viral genome in the adult population. We present an analysis of viral genomes acquired from pediatric patients presenting to Children’s National Hospital in Washington D.C, including 24 with primary SARS CoV2 infection and 3 with Multisystem Inflammatory Syndrome in Children (MIS-C) undergoing treatment at our facility. Viral genome analysis using next generation sequencing indicated that approximately 81% of the analyzed strains were of the GH clade, 7% of the cases belonged to the GR clade, and 12% of the cases belonged to S, V, or G clades. One sample, acquired from a neonatal patient, presented with the highest viral RNA load of all patients evaluated at our center. Viral sequencing of this sample identified a SARS-CoV-2 spike variant, S:N679S. Analysis of data deposited in the GISAID global database of viral sequences shows the S:N679S variant is present in eight other sequenced samples within the US mid-Atlantic region. The similarity of the regional sequences suggests transmission and persistence of the SARS-CoV-2 variant within the Capitol region, raising the importance of increasing the frequency of SARS-CoV-2 genomic surveillance.IMPORTANCEA variant in the SARS-CoV-2 spike protein was identified in a febrile neonate who was hospitalized with COVID-19. This patient exhibited the highest viral RNA load of any COVID-19 patient tested at our center. Viral sequencing identified a spike protein variant, S:N679S, which is proximal to the cleavage site at residue 681. The SARS-CoV-2 surface spike is a protein trimer (three subunits) which serves as the key target for antibody therapies and vaccine development. Study of viral sequences from the GISAID database revealed eight related sequences from the US mid-Atlantic region. The identification of this variant in a very young patient, its critical location in the spike polyprotein, and the evidence that it has been detected in other patients in our region underscores the need for increased viral sequencing to monitor variant prevalence and emergence, which may have a direct impact on recommended public health measures and vaccination strategies.

Background: Elevated maternal psychological distress during pregnancy is linked to adverse short- and long-term outcomes in the offspring. The potential deleterious effects of intensified levels of maternal distress during the COVID-19 pandemic on the developing fetal brain are currently unknown. Methods: We prospectively enrolled 202 pregnant women: 65 with negative COVID-19 diagnoses during the pandemic who underwent 92 fetal MRI scans, and 137 pre-pandemic controls who had 182 MRI scans. Multi-plane, multi-phase single shot fast spin echo T2-weighted images were acquired on a GE 1.5T MRI Scanner. High-resolution 3D models of the fetal brains were reconstructed, and volumes of six brain tissue types were calculated: cortical gray matter (CGM), white matter (WM), cerebellum, deep gray matter (DGM), brainstem, and hippocampus. Cortical folding measures, including brain surface area, local gyrification index (LGI), and sulcal depth were determined. At each MRI scan, maternal distress was assessed using validated stress, anxiety and depression scales. Generalized estimating equations (GEEs) were utilized to compare maternal distress measures, brain volume and cortical folding differences between pandemic and pre-pandemic cohorts. Findings: Stress and depression scores were significantly higher in the pandemic cohort (14.2 vs. 10.4 for stress; 5.9 vs. 4.2 for depression; p

OBJECTIVES: More children are surviving critical illness but are at risk of residual or new health conditions. An evidence-informed and stakeholder-recommended core outcome set is lacking for pediatric critical care outcomes. Our objective was to create a multinational, multistakeholder-recommended pediatric critical care core outcome set for inclusion in clinical and research programs. DESIGN: A two-round modified Delphi electronic survey was conducted with 333 invited research, clinical, and family/advocate stakeholders. Stakeholders completing the first round were invited to participate in the second. Outcomes scoring greater than 69% "critical" and less than 15% "not important" advanced to round 2 with write-in outcomes considered. The Steering Committee held a virtual consensus conference to determine the final components. SETTING: Multinational survey. PATIENTS: Stakeholder participants from six continents representing clinicians, researchers, and family/advocates. MEASUREMENTS AND MAIN RESULTS: Overall response rates were 75% and 82% for each round. Participants voted on seven Global Domains and 45 Specific Outcomes in round 1, and six Global Domains and 30 Specific Outcomes in round 2. Using overall (three stakeholder groups combined) results, consensus was defined as outcomes scoring greater than 90% "critical" and less than 15% "not important" and were included in the final PICU core outcome set: four Global Domains (Cognitive, Emotional, Physical, and Overall Health) and four Specific Outcomes (Child Health-Related Quality of Life, Pain, Survival, and Communication). Families (n = 21) suggested additional critically important outcomes that did not meet consensus, which were included in the PICU core outcome set-extended. CONCLUSIONS: The PICU core outcome set and PICU core outcome set-extended are multistakeholder-recommended resources for clinical and research programs that seek to improve outcomes for children with critical illness and their families.

Introduction: A novel pediatric disease, MIS-C, has emerged during the COVID -19 pandemic. The majority of cases were reported from European and Northeastern US centers. We present our experience of MIS-C with cardiac findings from a large tertiary pediatric cardiac center. Methods: We conducted a retrospective study of all MIS-C patients evaluated and treated from 03/29/2020 to 6/18/2020 at our center. Demographics, clinical, echo and ECG data were extracted from the echo database and EHR. Abnormal cardiac findings during the acute phase were defined as coronary artery abnormality (CAA), decreased ejection fraction (EF) and rhythm abnormality. CAAs were defined as dilation (z-score of > 2 to ≤ 2.49) or aneurysm (2.5 to < 5) as well as reviewed for qualitative changes. Results: 32 children, 17 (53%) males have been treated for MIS-C. The median (IQR) age was 9 (7 - 13) years. Underlying medical conditions were noted in 9 (28%) patients including 2 with cardiac conditions (one with previous history of atypical Kawasaki Disease (KD) and one with previous history of pericardial effusion s/p pericardial window). Ten (31%) patients had abnormal cardiac findings; 4 had isolated CAA, 3 had combined CAA and low EF and 2 had isolated low EF. One patient had aneurysms in all 3 CA’s, 2 patients had abnormalities in 2 CA’s (LMCA and RCA aneurysms in 1 and LMCA aneurysm and LAD dilation in 1 patient), and 4 patients had single CAA (RCA dilation in 1, LAD aneurysm in 1, and LAD dilation in 2 patients). No patient with CAA had morphologic evidence of saccular or fusiform changes. CAA persisted on subsequent echo in 3 patients and normalized in 3 patients. EF normalized on subsequent echo in 3 patients. One of the patients with isolated low EF was also found to have intermittent high grade atrioventricular (AV) block. The 10 th patient had normal echo but 1st degree AV block, sinus bradycardia, and long QTc. No arrhythmia was noted. No mortality occurred and overall length of stay was 13.6±9 days. Conclusion: Our MIS-C patients had a high rate of cardiac findings in the acute phase which exceeded rates historically observed in the setting of KD. Further long term study is needed to assess if the cardiac abnormalities persist, improve with immune modulation or are associated with major cardiac events.

OBJECTIVES To serially evaluate health-related quality of life during the first year after community-acquired septic shock in children with preexisting severe developmental disabilities and explore factors associated with health-related quality of life changes in these children. DESIGN Secondary analysis of the Life after Pediatric Sepsis Evaluation investigation. SETTING Twelve academic PICU in the United States. PATIENTS Children greater than or equal to 1 month and less than 18 years old identified by their family caregiver (e.g., parent/guardian) as having severe developmental disability prior to septic shock. INTERVENTIONS Family caregivers completed the Stein-Jessop Functional Status II-R Short Form as a measure of their child's health-related quality of life at baseline (reflecting preadmission status), day 7, and months 1, 3, 6, and 12 following PICU admission. Stein-Jessop Functional Status II-R Short Form scores were linearly transformed to a 0-100 scale, with higher scores indicating better health-related quality of life. MEASUREMENTS AND MAIN RESULTS Of 392 Life after Pediatric Sepsis Evaluation participants, 137 were identified by their caregiver as having a severe developmental disability. Sixteen children (11.6%) with severe disability died during the 12 months following septic shock. Among 121 survivors, Stein-Jessop Functional Status II-R Short Form scores declined from preadmission baseline to day 7 (70.7 ± 16.1 vs 55.6 ± 19.2; p < 0.001). Stein-Jessop Functional Status II-R Short Form scores remained below baseline through month 12 (59.1 ± 21.0, p < 0.001 vs baseline). After adjusting for baseline Stein-Jessop Functional Status II-R Short Form, the caregiver being a single parent/guardian was associated with lower month 3 Stein-Jessop Functional Status II-R Short Form scores (p = 0.041). No other baseline child or caregiver characteristic, or critical illness-related factors were significantly associated with month 3 Stein-Jessop Functional Status II-R Short Form scores. CONCLUSIONS Health-related quality of life among children with severe developmental disability remains, on average, below baseline during the first year following community-acquired septic shock. Children with severe disability and septic shock that are in single parent families are at increased risk. Clinical awareness of the potential for decline in health-related quality of life among disabled children is essential to prevent this adverse outcome from being missed.

This cohort study compares the clinical features of coronavirus disease 2019 (COVID-19) with those of influenza A and B in US children., Key Points Question What are the similarities and differences in clinical features between coronavirus disease 2019 (COVID-19) and seasonal influenza in US children? Findings In this cohort study of 315 children with COVID-19 and 1402 children with seasonal influenza, there were no statistically significant differences in the rates of hospitalization, admission to the intensive care unit, and mechanical ventilator use between the 2 groups. More patients with COVID-19 than with seasonal influenza reported fever, diarrhea or vomiting, headache, body ache, or chest pain at the time of diagnosis. Meaning The findings suggest that prevention of both COVID-19 and seasonal influenza in US children is prudent and urgent for the well-being of this population., Importance Compared with seasonal influenza, the clinical features and epidemiologic characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus 2019 (COVID-19) in US children remain largely unknown. Objective To describe the similarities and differences in clinical features between COVID-19 and seasonal influenza in US children. Design, Setting, and Participants This retrospective cohort study included children who were diagnosed with laboratory-confirmed COVID-19 between March 25 and May 15, 2020, and children diagnosed with seasonal influenza between October 1, 2019, and June 6, 2020, at Children’s National Hospital in the District of Columbia. Exposures COVID-19 or influenza A or B. Main Outcomes and Measures Rates of hospitalization, admission to the intensive care unit, and mechanical ventilator use and the association between underlying medical conditions, clinical symptoms, and COVID-19 vs seasonal influenza. Results The study included 315 patients diagnosed with COVID-19 (164 [52%] male; median age, 8.3 years [range, 0.03-35.6 years]) and 1402 patients diagnosed with seasonal influenza (743 [53%] male; median age, 3.9 years [range, 0.04-40.4 years]). Patients with COVID-19 and those with seasonal influenza had a similar hospitalization rate (54 [17%] vs 291 [21%], P = .15), intensive care unit admission rate (18 [6%] vs 98 [7%], P = .42), and use of mechanical ventilators (10 [3%] vs 27 [2%], P = .17). More patients hospitalized with COVID-19 than with seasonal influenza reported fever (41 [76%] vs 159 [55%], P = .005), diarrhea or vomiting (14 [26%] vs 36 [12%], P = .01), headache (6 [11%] vs 9 [3%], P = .01), body ache or myalgia (12 [22%] vs 20 [7%], P = .001), and chest pain (6 [11%] vs 9 [3%], P = .01). Differences between patients hospitalized with COVID-19 vs influenza who reported cough (24 [48%] vs 90 [31%], P = .05) and shortness of breath (16 [30%] vs 59 [20%], P = .13) were not statistically significant. Conclusions and Relevance In this cohort study of US children with COVID-19 or seasonal influenza, there was no difference in hospitalization rates, intensive care unit admission rates, and mechanical ventilator use between the 2 groups. More patients hospitalized with COVID-19 than with seasonal influenza reported clinical symptoms at the time of diagnosis.

OBJECTIVES To evaluate the physical and psychosocial domains of health-related quality of life among children during the first year following community-acquired septic shock, and explore factors associated with poor physical and psychosocial health-related quality of life outcomes. DESIGN Secondary analysis of the Life After Pediatric Sepsis Evaluation. SETTING Twelve academic PICUs in the United States. PATIENTS Children greater than or equal to 1 month and less than 18 years old who were perceived to be without severe developmental disability by their family caregiver at baseline and who survived hospitalization for community-acquired septic shock. INTERVENTIONS Family caregivers completed the Pediatric Quality of Life Inventory for children 2-18 years old or the Pediatric Quality of Life Inventory Infant Scales for children less than 2 years old at baseline (reflecting preadmission status), day 7, and months 1, 3, 6, and 12 following PICU admission. Higher Pediatric Quality of Life Inventory Physical and Psychosocial Health Summary Scores indicate better health-related quality of life. MEASUREMENTS AND MAIN RESULTS Of 204 children, 58 (28.2%) had a complex chronic comorbid condition. Children with complex chronic comorbid conditions had lower baseline physical health-related quality of life (62.7 ± 22.6 vs 84.1 ± 19.7; p < 0.001) and psychosocial health-related quality of life (68.4 ± 14.1 vs 81.2 ± 15.3; p < 0.001) than reference norms, whereas children without such conditions had baseline scores similar to reference norms. Children with complex chronic comorbid conditions recovered to their baseline health-related quality of life, whereas children without such conditions did not (physical health-related quality of life 75.3 ± 23.7 vs 83.2 ± 20.1; p = 0.008 and psychosocial health-related quality of life 74.5 ± 18.7 vs 80.5 ± 17.9; p = 0.006). Age less than 2 years was independently associated with higher month 12 physical health-related quality of life, and abnormal neurologic examination and neurologic injury suspected by a healthcare provider during the PICU course were independently associated with lower month 12 physical health-related quality of life. Treatment of increased intracranial pressure and medical device use at month 1 were independently associated with lower month 12 psychosocial health-related quality of life. CONCLUSIONS Physical and psychosocial health-related quality of life were reduced among children during the first year following community-acquired septic shock compared with reference norms, although many recovered to baseline. Risk factors for poor health-related quality of life included neurologic complications during the hospitalization and dependence on a medical device 1 month postadmission.

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.

Importance Prenatal maternal psychological distress can result in detrimental mother and child outcomes. Maternal stress increases with receipt of a prenatal diagnosis of fetal congenital heart disease (CHD); however, the association between maternal stress and the developing brain in fetuses with CHD is unknown. Objective To determine the association of maternal psychological distress with brain development in fetuses with CHD. Design, Setting, and Participants This longitudinal, prospective, case-control study consecutively recruited 48 pregnant women carrying fetuses with CHD and 92 healthy volunteers with low-risk pregnancies from the Children’s National Health System between January 2016 and September 2018. Data were analyzed between January 2016 and June 2019. Exposures Fetal CHD and maternal stress, anxiety, and depression. Main Outcomes and Measures Maternal stress, anxiety, and depression were measured using the Perceived Stress Scale, Spielberger State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale, respectively. Volumes of fetal total brain, cerebrum, left and right hippocampus, cerebellum, and brainstem were determined from 3-dimensionally reconstructed T2-weighted magnetic resonance imaging (MRI) scans. Results This study included 223 MRI scans from 140 fetuses (74 MRIs from 48 fetuses with CHD and 149 MRIs from 92 healthy fetuses) between 21 and 40 weeks’ gestation. Among 48 women carrying fetuses with CHD, 31 (65%) tested positive for stress, 21 (44%) for anxiety, and 14 (29%) for depression. Among 92 pregnant women carrying healthy fetuses, 25 (27%) tested positive for stress, 24 (26%) for anxiety, and 8 (9%) for depression. Depression scores were higher among 17 women carrying fetuses with single-ventricle CHD vs 31 women carrying fetuses with 2-ventricle CHD (3.8; 95% CI, 0.3 to 7.3). Maternal stress and anxiety were associated with smaller left hippocampal (stress: −0.003 cm3; 95% CI, −0.005 to −0.001 cm3), right hippocampal (stress: −0.004; 95% CI, −0.007 to −0.002; trait anxiety: −0.003; 95% CI, −0.005 to −0.001), and cerebellar (stress: −0.06; 95% CI, −0.09 to −0.02) volumes only among women with fetal CHD. Impaired hippocampal regions were noted in the medial aspect of left hippocampal head and inferior aspect of right hippocampal head and body. Impaired cerebellar regions were noted in the anterior superior aspect of vermal and paravermal regions and the left cerebellar lobe. Conclusions and Relevance These findings suggested that psychological distress among women carrying fetuses with CHD is prevalent and is associated with impaired fetal cerebellar and hippocampal development. These data underscore the importance of universal screening for maternal psychological distress, integrated prenatal mental health support, and targeted early cognitive-behavioral interventions given that stress is a potentially modifiable risk factor in this high-risk population.

Objectives ICU length of stay is an important measure of resource use and economic performance. Our primary aims were to characterize the utilization of PICU beds and to develop a new model for PICU length of stay. Design Prospective cohort. The main outcomes were factors associated with PICU length of stay and the performance of a regression model for length of stay. Setting Eight PICUs. Patients Randomly selected patients (newborn to 18 yr) from eight PICUs were enrolled from December 4, 2011, to April 7, 2013. Data consisted of descriptive, diagnostic, physiologic, and therapeutic information. Interventions None. Measurements and main results The mean length of stay for was 5.0 days (SD, 11.1), with a median of 2.0 days. The 50.6% of patients with length of stay less than 2 days consumed only 11.1% of the days of care, whereas the 19.6% of patients with length of stay 4.9-19 days and the 4.6% with length of stay greater than or equal to 19 days consumed 35.7% and 37.6% of the days of care, respectively. Longer length of stay was observed in younger children, those with cardiorespiratory disease, postintervention cardiac patients, and those who were sicker assessed by Pediatric Risk of Mortality scores receiving more intensive therapies. Patients in the cardiac ICU stayed longer than those in the medical ICU. The length of stay model using descriptive, diagnostic, severity, and therapeutic factors performed well (patient-level R-squared of 0.42 and institution-level R-squared of 0.76). Standardized (observed divided by expected) length of stay ratios at the individual sites ranged from 0.87 to 1.09. Conclusions PICU bed utilization was dominated by a minority of patients. The 5% of patients staying the longest used almost 40% of the bed days. The multivariate length of stay model used descriptive, diagnostic, therapeutic, and severity factors and has potential applicability for internal and external benchmarking.

OBJECTIVES To determine the frequency of hyperoxia and hypocapnia during pediatric extracorporeal membrane oxygenation and their relationships to complications, mortality, and functional status among survivors. DESIGN Secondary analysis of data collected prospectively by the Collaborative Pediatric Critical Care Research Network. SETTING Eight Collaborative Pediatric Critical Care Research Network-affiliated hospitals. PATIENTS Age less than 19 years and treated with extracorporeal membrane oxygenation. INTERVENTIONS Hyperoxia was defined as highest PaO2 greater than 200 Torr (27 kPa) and hypocapnia as lowest PaCO2 less than 30 Torr (3.9 kPa) during the first 48 hours of extracorporeal membrane oxygenation. Functional status at hospital discharge was evaluated among survivors using the Functional Status Scale. MEASUREMENTS AND MAIN RESULTS Of 484 patients, 420 (86.7%) had venoarterial extracorporeal membrane oxygenation and 64 (13.2%) venovenous; 69 (14.2%) had extracorporeal membrane oxygenation initiated during cardiopulmonary resuscitation. Hyperoxia occurred in 331 (68.4%) and hypocapnia in 98 (20.2%). Hyperoxic patients had higher mortality than patients without hyperoxia (167 [50.5%] vs 48 [31.4%]; p < 0.001), but no difference in functional status among survivors. Hypocapnic patients were more likely to have a neurologic event (49 [50.0%] vs 143 (37.0%]; p = 0.021) or hepatic dysfunction (49 [50.0%] vs 121 [31.3%]; p < 0.001) than patients without hypocapnia, but no difference in mortality or functional status among survivors. On multivariable analysis, factors independently associated with increased mortality included highest PaO2 and highest blood lactate concentration in the first 48 hours of extracorporeal membrane oxygenation, congenital diaphragmatic hernia, and being a preterm neonate. Factors independently associated with lower mortality included meconium aspiration syndrome. CONCLUSIONS Hyperoxia is common during pediatric extracorporeal membrane oxygenation and associated with mortality. Hypocapnia appears to occur less often and although associated with complications, an association with mortality was not observed.

Although pediatric intensivists philosophically embrace lung protective ventilation for acute lung injury and acute respiratory distress syndrome, we hypothesized that ventilator management varies. We assessed ventilator management by evaluating changes to ventilator settings in response to blood gases, pulse oximetry, or end-tidal CO2. We also assessed the potential impact that a pediatric mechanical ventilation protocol adapted from National Heart Lung and Blood Institute acute respiratory distress syndrome network protocols could have on reducing variability by comparing actual changes in ventilator settings to those recommended by the protocol.Prospective observational study.Eight tertiary care U.S. PICUs, October 2011 to April 2012.One hundred twenty patients (age range 17 d to 18 yr) with acute lung injury/acute respiratory distress syndrome.Two thousand hundred arterial and capillary blood gases, 3,964 oxygen saturation by pulse oximetry, and 2,757 end-tidal CO2 values were associated with 3,983 ventilator settings. Ventilation mode at study onset was pressure control 60%, volume control 19%, pressure-regulated volume control 18%, and high-frequency oscillatory ventilation 3%. Clinicians changed FIO2 by ±5 or ±10% increments every 8 hours. Positive end-expiratory pressure was limited at ~10 cm H2O as oxygenation worsened, lower than would have been recommended by the protocol. In the first 72 hours of mechanical ventilation, maximum tidal volume/kg using predicted versus actual body weight was 10.3 (8.5-12.9) (median [interquartile range]) versus 9.2 mL/kg (7.6-12.0) (p0.001). Intensivists made changes similar to protocol recommendations 29% of the time, opposite to the protocol's recommendation 12% of the time and no changes 56% of the time.Ventilator management varies substantially in children with acute respiratory distress syndrome. Opportunities exist to minimize variability and potentially injurious ventilator settings by using a pediatric mechanical ventilation protocol offering adequately explicit instructions for given clinical situations. An accepted protocol could also reduce confounding by mechanical ventilation management in a clinical trial.

Objectives To examine issues regarding the granularity (size/scale) and potential acceptability of recommendations in a ventilator management protocol for children with pediatric acute respiratory distress syndrome. Design Survey/questionnaire. Setting The eight PICUs in the Collaborative Pediatric Critical Care Research Network. Participants One hundred twenty-two physicians (attendings and fellows). Interventions None. Measurements and main results We used an online questionnaire to examine attitudes and assessed recommendations with 50 clinical scenarios. Overall 80% of scenario recommendations were accepted. Acceptance did not vary by provider characteristics but did vary by ventilator mode (high-frequency oscillatory ventilation 83%, pressure-regulated volume control 82%, pressure control 75%; p = 0.002) and variable adjusted (ranging from 88% for peak inspiratory pressure and 86% for FIO2 changes to 69% for positive end-expiratory pressure changes). Acceptance did not vary based on child size/age. There was a preference for smaller positive end-expiratory pressure changes but no clear granularity preference for other variables. Conclusions Although overall acceptance rate for scenarios was good, there was little consensus regarding the size/scale of ventilator setting changes for children with pediatric acute respiratory distress syndrome. An acceptable protocol could support robust evaluation of ventilator management strategies. Further studies are needed to determine if adherence to an explicit protocol leads to better outcomes.

To describe functional status at hospital discharge for neonatal and pediatric patients treated with extracorporeal membrane oxygenation, and identify factors associated with functional status and mortality. Secondary analysis of observational data collected by the Collaborative Pediatric Critical Care Research Network between December 2012 and September 2014. Eight hospitals affiliated with the Collaborative Pediatric Critical Care Research Network. Patients were less than 19 years old and treated with extracorporeal membrane oxygenation. Functional status was evaluated among survivors using the Functional Status Scale. Total Functional Status Scale scores range from 6 to 30 and are categorized as 6–7 (good), 8–9 (mildly abnormal), 10–15 (moderately abnormal), 16–21 (severely abnormal), and greater than 21 (very severely abnormal). Of 514 patients, 267 (52%) were neonates (≤ 30 d old). Indication for extracorporeal membrane oxygenation was respiratory for 237 (46%), cardiac for 207 (40%), and extracorporeal cardiopulmonary resuscitation for 70 (14%). Among 282 survivors, 89 (32%) had good, 112 (40%) mildly abnormal, 67 (24%) moderately abnormal, and 14 (5%) severely or very severely abnormal function at hospital discharge. Among neonates, development of renal failure and longer hospitalization were independently associated with worse Functional Status Scale. Chronic conditions, prematurity, venoarterial extracorporeal membrane oxygenation, increased red cell transfusion in the first 24 hours of extracorporeal membrane oxygenation, and longer extracorporeal membrane oxygenation duration were independently associated with mortality. Among pediatric patients, chronic neurologic conditions, tracheostomy or home ventilator, extracorporeal cardiopulmonary resuscitation, hepatic dysfunction, and longer ICU stay were independently associated with worse Functional Status Scale. Chronic cardiac conditions, hepatic dysfunction, and neurologic or thrombotic complications were independently associated with mortality. Achieving blood lactate concentration less than or equal to 2 mmol/L during extracorporeal membrane oxygenation was independently associated with survival in both neonatal and pediatric patients. In this study, about half of extracorporeal membrane oxygenation patients survived with good, mildly abnormal, or moderately abnormal function at hospital discharge. Patient and extracorporeal membrane oxygenation-related factors are associated with functional status and mortality.

To develop a prognostic model for predicting mortality at time of extracorporeal membrane oxygenation initiation for children which is important for determining center-specific risk-adjusted outcomes.Multivariable logistic regression using a large national cohort of pediatric extracorporeal membrane oxygenation patients.The ICUs of the eight tertiary care children's hospitals of the Collaborative Pediatric Critical Care Research Network.Five-hundred fourteen children (19 yr old), enrolled with an initial extracorporeal membrane oxygenation run for any indication between January 2012 and September 2014.None.A total of 514 first extracorporeal membrane oxygenation runs were analyzed with an overall mortality of 45% (n = 232). Weighted logistic regression was used for model selection and internal validation was performed using cross validation. The variables included in the Pediatric Extracorporeal Membrane Oxygenation Prediction model were age (pre-term neonate, full-term neonate, infant, child, and adolescent), indication for extracorporeal membrane oxygenation (extracorporeal cardiopulmonary resuscitation, cardiac, or respiratory), meconium aspiration, congenital diaphragmatic hernia, documented blood stream infection, arterial blood pH, partial thromboplastin time, and international normalized ratio. The highest risk of mortality was associated with the presence of a documented blood stream infection (odds ratio, 5.26; CI, 1.90-14.57) followed by extracorporeal cardiopulmonary resuscitation (odds ratio, 4.36; CI, 2.23-8.51). The C-statistic was 0.75 (95% CI, 0.70-0.80).The Pediatric Extracorporeal Membrane Oxygenation Prediction model represents a model for predicting in-hospital mortality among children receiving extracorporeal membrane oxygenation support for any indication. Consequently, it holds promise as the first comprehensive pediatric extracorporeal membrane oxygenation risk stratification model which is important for benchmarking extracorporeal membrane oxygenation outcomes across many centers.

Objectives:To determine the incidence of cardiopulmonary resuscitation in PICUs and subsequent outcomes.Design, Setting, and Patients:Multicenter prospective observational study of children younger than 18 years old randomly selected and intensively followed from PICU admission to hospital discharge

Background Children and young adults were initially reported as largely spared from severe complications of SARS-CoV-2 infection, but the impact to this population has been significant. Methods This observational retrospective cohort study includes 420 symptomatic children and young adults with lab confirmed SARS-CoV-2 infection treated between March 15 and June 16, 2020 at Children’s National Hospital in Washington DC. We identified and compared cohorts of non-hospitalized (N=324) and hospitalized (N=96) patients, including non-critically ill (N=64) and critically ill hospitalized (N=32) patients. Clinical and demographic data were extracted from medical records Results Of 420 SARS-CoV-2-infected symptomatic patients, 23% required hospitalization, of which 67% were non-critically ill and 33% were critically ill. All age groups were represented in the symptomatic cohort, with a median age of 8.6 years. Patients > 15 years of age represented 44% of critical care admissions. Males and females were equally represented in all cohorts. Underlying medical conditions were present in 36%, but more common in hospitalized (59 %) and critically ill (66 %) patients. The most frequent underlying diagnosis overall was asthma (16 %), but also included neurologic (6 %), diabetes (3 %), obesity (3 %), cardiac (3 %), hematologic (3 %) and oncologic (1 %) conditions. The majority (66 %) of SARS-CoV-2 infected patients presented with respiratory symptoms with or without fever. Other symptoms were also present, including diarrhea/vomiting (21 %), myalgia (11 %), chest pain (8 %) and loss of sense of smell or taste (7%). Hospitalized patients required varying levels of respiratory support, including mechanical ventilation, BiPAP, RAM cannula and HFNC. Additional presentations included diabetic hyperglycemia, sickle cell vaso-occlusive crisis, vascular complications, and multisystem inflammation. Treatment included remdesivir, convalescent plasma, tocilizumab and other therapies. Conclusion Although children/young adults have been less affected than elderly adults, the impact of SARS-CoV2 on this population has been significant in Washington DC and informs other regions anticipating their surge. Disclosures Andrea Hahn, MD, MS, Johnson and Johnson (Consultant)

Background Background: Multi-system Inflammatory Syndrome of Children (MIS-C) has recently emerged internationally as a serious inflammatory complication of SARS-CoV-2 infection with significant morbidity for the pediatric population. Methods This observational retrospective cohort study includes 33 children meeting CDC criteria for MIS-C treated between March 15 and June 17, 2020 at Children’s National Hospital in Washington DC. Clinical and demographic data were extracted from medical records and are summarized. Results Of 33 hospitalized MIS-C patients, 42% were critically ill, and 58% were non-critically ill. The median age was 8.9 years (0.7–18.7 years). More males (58 %) than females (43 %) were represented in the MIS-C cohort. The majority (75%) of children had no underlying medical condition. Criteria for incomplete or complete Kawasaki Disease (KD) were present in 39% of patients, while an additional 9% had some features of KD. However the remaining 52% of MIS-C patients presented with other sub-phenotypes including prominent severe abdominal pain and/or nonspecific multiorgan dysfunction. 30% presented with shock requiring volume and/or inotropic support. SARS-CoV-2 antibodies were present in 61% of patients. Virus was detectable by PCR in 36% of patients. At the time of initial evaluation, 39% (13/33) of children had identified cardiac abnormalities including myocardial dysfunction (5/33; 15%), coronary ectasia (4/33; 12%), coronary aneurysm (3/33; 9%), or pericardial effusion 5/33; 15%) either alone or in combination. Cytokine profiling identified elevation of several cytokines in this cohort, including IL-6. Treatment has included intravenous immunoglobulin, aspirin, anakinra and other immunomodulatory therapies, with overall rapid response to therapy. No deaths have occurred. Conclusion The emergence of MIS-C late in the surge of SARS-CoV-2 circulation in the Washington DC metropolitan region has added to the already significant burden of hospitalized and critically ill children in our region. A significant percentage of these children present with cardiac dysfunction and abnormalities, whether or not with KD features at presentation. Detailed characterization of immune responses and long term outcome of these patients is a priority. Disclosures Andrea Hahn, MD, MS, Johnson and Johnson (Consultant)

Despite worldwide spread of severe acute respiratory syndrome coronavirus-2, few publications have reported the potential for severe disease in the pediatric population. We report 177 infected children and young adults, including 44 hospitalized and 9 critically ill patients, with a comparison of patient characteristics between infected hospitalized and nonhospitalized cohorts, as well as critically ill and noncritically ill cohorts. Children 15 years of age were over-represented among hospitalized patients (P = .07). Adolescents and young adults were over-represented among the critically ill cohort (P = .02).

To describe factors associated with hemolysis during pediatric extracorporeal membrane oxygenation and the relationships between hemolysis, complications, and mortality.Secondary analysis of data collected prospectively by the Collaborative Pediatric Critical Care Research Network between December 2012 and September 2014.Three Collaborative Pediatric Critical Care Research Network-affiliated hospitals.Age less than 19 years and treated with extracorporeal membrane oxygenation.None.Hemolysis was defined based on peak plasma free hemoglobin levels during extracorporeal membrane oxygenation and categorized as none (0.001 g/L), mild (0.001 to0.5 g/L), moderate (0.5 to1.0 g/L), or severe (≥ 1.0 g/L). Of 216 patients, four (1.9%) had no hemolysis, 67 (31.0%) had mild, 51 (23.6%) had moderate, and 94 (43.5%) had severe. On multivariable analysis, variables independently associated with higher daily plasma free hemoglobin concentration included the use of in-line hemofiltration or other continuous renal replacement therapy, higher hemoglobin concentration, higher total bilirubin concentration, lower mean heparin infusion dose, lower body weight, and lower platelet count. Using multivariable Cox modeling, daily plasma free hemoglobin was independently associated with development of renal failure during extracorporeal membrane oxygenation (defined as creatinine2 mg/dL [176.8 μmol/L] or use of in-line hemofiltration or continuous renal replacement therapy) (hazard ratio, 1.04; 95% CI, 1.02-1.06; p0.001), but not mortality (hazard ratio, 1.01; 95% CI, 0.99-1.04; p = 0.389).Hemolysis is common during pediatric extracorporeal membrane oxygenation. Hemolysis may contribute to the development of renal failure, and therapies used to manage renal failure such as in-line hemofiltration and other forms of continuous renal replacement therapy may contribute to hemolysis. Hemolysis was not associated with mortality after controlling for other factors. Monitoring for hemolysis should be a routine part of extracorporeal membrane oxygenation practice, and efforts to reduce hemolysis may improve patient care.

Background Early identification of children at risk for cardiac arrest would allow for skill training associated with improved outcomes and provides a prevention opportunity. Objective Develop and assess a predictive model for cardiopulmonary arrest using data available in the first 4 h. Methods Data from PICU patients from 8 institutions included descriptive, severity of illness, cardiac arrest, and outcomes. Results Of the 10074 patients, 120 satisfying inclusion criteria sustained a cardiac arrest and 67 (55.9%) died. In univariate analysis, patients with cardiac arrest prior to admission were over 6 times and those with cardiac arrests during the first 4 h were over 50 times more likely to have a subsequent arrest. The multivariate logistic regression model performance was excellent (area under the ROC curve = 0.85 and Hosmer-Lemeshow statistic, p = 0.35). The variables with the highest odds ratio’s for sustaining a cardiac arrest in the multivariable model were admission from an inpatient unit (8.23 (CI: 4.35–15.54)), and cardiac arrest in the first 4 h (6.48 (CI: 2.07–20.36). The average risk predicted by the model was highest (11.6%) among children sustaining an arrest during hours >4–12 and continued to be high even for days after the risk assessment period; the average predicted risk was 9.5% for arrests that occurred after 8 PICU days. Conclusions Patients at high risk of cardiac arrest can be identified with routinely available data after 4 h. The cardiac arrest may occur relatively close to the risk assessment period or days later.

Introduction: Our objectives are to (1) describe the pathogens, site, timing and risk factors for acquired infection during neonatal and pediatric ECMO and (2) explore the association between acquired infection and mortality. Methods: Secondary analysis of prospective data collected by the Collaborative Pediatric Critical Care Research Network between December 2012 and September 2014. Clinical factors associated with acquired infection were assessed with multivariable Cox regression. Factors associated with mortality were assessed with logistic regression. Results: Of 481 patients, 247 (51.3%) were neonates and 400 (83.2%) received venoarterial ECMO. Eighty (16.6%) patients acquired one or more infections during ECMO; 60 (12.5%) patients had bacterial, 21 (4.4%) had fungal and 11 (2.3%) had viral infections. The site of infection included respiratory for 53 (11.0%) patients, bloodstream for 21 (4.4%), urine for 20 (4.2%) and other for 7 (1.5%). Candida species were most common. Median time to infection was 5.2 days (IQR 2.3, 9.6). On multivariable analysis, a greater number of procedures for ECMO cannula placement was independently associated with increased risk of acquired infection during ECMO (Hazard Ratio 2.13 (95% CI 1.22, 3.72), pConclusion: ECMO procedures and location may contribute to acquired infection risk; however, acquired infection did not predict mortality in this study.

Background: On the basis of laboratory cardiopulmonary resuscitation (CPR) investigations and limited adult data demonstrating that survival depends on attaining adequate arterial diastolic blood pressure (DBP) during CPR, the American Heart Association recommends using blood pressure to guide pediatric CPR. However, evidence-based blood pressure targets during pediatric CPR remain an important knowledge gap for CPR guidelines. Methods: All children ≥37 weeks’ gestation and Results: Blinded investigators analyzed blood pressure waveforms during CPR from 164 children, including 60% P =0.007) and survival with favorable neurological outcome (adjusted relative risk, 1.6; 95% confidence interval, 1.1–2.5; P =0.02). Conclusions: These data demonstrate that mean DBP ≥25 mm Hg during CPR in infants and ≥30 mm Hg in children ≥1 year old was associated with greater likelihood of survival to hospital discharge and survival with favorable neurological outcome.

Pertussis can cause life-threatening illness in infants. Data regarding neurodevelopment after pertussis remain scant. The aim of this study was to assess cognitive development of infants with critical pertussis 1 year after PICU discharge.Prospective cohort study.Eight hospitals comprising the Eunice Kennedy Shriver National Institute for Child Health and Human Development Collaborative Pediatric Critical Care Research Network and 18 additional sites across the United States.Eligible patients had laboratory confirmation of pertussis infection, were less than 1 year old, and were admitted to the PICU for at least 24 hours.The Mullen Scales of Early Learning was administered at a 1-year follow-up visit. Functional status was determined by examination and parental interview.Of 196 eligible patients, 111 (57%) completed the Mullen Scales of Early Learning. The mean scores for visual reception, receptive language, and expressive language domains were significantly lower than the norms (p0.001), but not fine and gross motor domains. Forty-one patients (37%) had abnormal scores in at least one domain and 10 (9%) had an Early Learning Composite score 2 or more SDs below the population norms. Older age (p0.003) and Hispanic ethnicity (p0.008) were associated with lower mean Early Learning Composite score, but presenting symptoms and PICU course were not.Infants who survive critical pertussis often have neurodevelopmental deficits. These infants may benefit from routine neurodevelopmental screening.

Pulmonary hypertension is associated with diverse cardiac, pulmonary, and systemic diseases in neonates, infants, and older children and contributes to significant morbidity and mortality. However, current approaches to caring for pediatric patients with pulmonary hypertension have been limited by the lack of consensus guidelines from experts in the field. In a joint effort from the American Heart Association and American Thoracic Society, a panel of experienced clinicians and clinician-scientists was assembled to review the current literature and to make recommendations on the diagnosis, evaluation, and treatment of pediatric pulmonary hypertension. This publication presents the results of extensive literature reviews, discussions, and formal scoring of recommendations for the care of children with pulmonary hypertension.

Assessments of care including quality assessments adjusted for physiological status should include the development of new morbidities as well as mortalities. We hypothesized that morbidity, like mortality, is associated with physiological dysfunction and could be predicted simultaneously with mortality.Prospective cohort study from December 4, 2011, to April 7, 2013.General and cardiac/cardiovascular PICUs at seven sites.Randomly selected PICU patients from their first PICU admission.None.Among 10,078 admissions, the unadjusted morbidity rates (measured with the Functional Status Scale and defined as an increase of ≥ 3 from preillness to hospital discharge) were 4.6% (site range, 2.6-7.7%) and unadjusted mortality rates were 2.7% (site range, 1.3-5.0%). Morbidity and mortality were significantly (p0.001) associated with physiological instability (measured with the Pediatric Risk of Mortality III score) in dichotomous (survival and death) and trichotomous (survival without new morbidity, survival with new morbidity, and death) models without covariate adjustments. Morbidity risk increased with increasing Pediatric Risk of Mortality III scores and then decreased at the highest Pediatric Risk of Mortality III values as potential morbidities became mortalities. The trichotomous model with covariate adjustments included age, admission source, diagnostic factors, baseline Functional Status Scale, and the Pediatric Risk of Mortality III score. The three-level goodness-of-fit test indicated satisfactory performance for the derivation and validation sets (p0.20). Predictive ability assessed with the volume under the surface was 0.50 ± 0.019 (derivation) and 0.50 ± 0.034 (validation) (vs chance performance = 0.17). Site-level standardized morbidity ratios were more variable than standardized mortality ratios.New morbidities were associated with physiological status and can be modeled simultaneously with mortality. Trichotomous outcome models including both morbidity and mortality based on physiological status are suitable for research studies and quality and other outcome assessments. This approach may be applicable to other assessments presently based only on mortality.

Objectives To examine the feasibility of deploying a virtual web service for sharing data within a research network, and to evaluate the impact on data consistency and quality. Material and Methods Virtual machines (VMs) encapsulated an open-source, semantically and syntactically interoperable secure web service infrastructure along with a shadow database. The VMs were deployed to 8 Collaborative Pediatric Critical Care Research Network Clinical Centers. Results Virtual web services could be deployed in hours. The interoperability of the web services reduced format misalignment from 56% to 1% and demonstrated that 99% of the data consistently transferred using the data dictionary and 1% needed human curation. Conclusions Use of virtualized open-source secure web service technology could enable direct electronic abstraction of data from hospital databases for research purposes.

T he STARTS-1 and -2 trials (Sildenafil in Treatment-Naive Children, Aged 1 to 17 Years, With Pulmonary Arterial Hypertension) and subsequent 2012 US Food and Drug Administration (FDA) product labeling for sildenafil use in pediatric patients with pulmonary hypertension highlight many of the challenges to the development and approval of medications for children. This experience served as the impetus for direct collaboration between FDA representatives and the Joint Council on Congenital Heart Disease (JCCHD) (representing the pediatric cardiology leadership of the American College of Cardiology, the American Heart Association, and the American Academy of Pediatrics) to improve communication and realign missions with regard to pediatric drug trials. These discussions led to the joint FDA/JCCHD development of this statement, which describes the current environment and identifies possible future directions for reducing barriers to pediatric drug trials. There are many challenges to the development and approval of medications for children. The STARTS-1 and -2 trials, which are described briefly in the next section, highlight many of the challenges in pediatric trial design and approval of medications for children, especially those with rare diseases. Through a series of conversations between the FDA and JCCHD that had their origin around review of the effect of the STARTS-1 and -2 trials and subsequent regulatory response on clinical practice, it became clear that better communication and alignment of goals surrounding pediatric drug trials were needed. This paper serves as unique opportunity to bring leaders of the pediatric cardiology community and FDA together as 1 voice. Fewer than 50% of drugs approved for use in the United States have sufficient data to support labeling for dosing, safety, and efficacy in children.1,2 Several studies estimate at least 40% and up to 100% of hospitalized children are prescribed at least 1 medication that is used “off-label.”3 …

Extracorporeal membrane oxygenation (ECMO) is used for respiratory and cardiac failure in children but is complicated by bleeding and thrombosis.(1) To measure the incidence of bleeding (blood loss requiring transfusion or intracranial hemorrhage) and thrombosis during ECMO support; (2) to identify factors associated with these complications; and (3) to determine the impact of these complications on patient outcome.This was a prospective, observational cohort study in pediatric, cardiac, and neonatal intensive care units in eight hospitals, carried out from December 2012 to September 2014.ECMO was used on 514 consecutive patients under age 19 years. Demographics, anticoagulation practices, severity of illness, circuitry components, bleeding, thrombotic events, and outcome were recorded. Survival was 54.9%. Bleeding occurred in 70.2%, including intracranial hemorrhage in 16%, and was independently associated with higher daily risk of mortality. Circuit component changes were required in 31.1%, and patient-related clots occurred in 12.8%. Laboratory sampling contributed to transfusion requirement in 56.6%, and was the sole reason for at least one transfusion in 42.2% of patients. Pump type was not associated with bleeding, thrombosis, hemolysis, or mortality. Hemolysis was predictive of subsequent thrombotic events. Neither hemolysis nor thrombotic events increased the risk of mortality.The incidences of bleeding and thrombosis are high during ECMO support. Laboratory sampling is a major contributor to transfusion during ECMO. Strategies to reduce the daily risk of bleeding and thrombosis, and different thresholds for transfusion, may be appropriate subjects of future trials to improve outcomes of children requiring this supportive therapy.

Parent–physician bereavement meetings may benefit parents by facilitating sense making, which is associated with healthy adjustment after a traumatic event. Prior research suggests a reciprocal relationship between sense making and positive emotions. We analyzed parents’ use of emotion words during bereavement meetings to better understand parents’ emotional reactions during the meeting and how their emotional reactions related to their appraisals of the meeting. Parents’ use of positive emotion words increased, suggesting the meetings help parents make sense of the death. Parents’ use of positive emotion words was negatively related to their own and/or their spouse’s appraisals of the meeting, suggesting that parents who have a positive emotional experience during the meeting may also have a short-term negative reaction. Language analysis can be an effective tool to understand individuals’ ongoing emotions and meaning making processes during interventions to reduce adverse consequences of a traumatic event, such as a child’s death.

Background— We sought to determine whether empirical nesiritide or milrinone would improve the early postoperative course after Fontan surgery. We hypothesized that compared with milrinone or placebo, patients assigned to receive nesiritide would have improved early postoperative outcomes. Methods and Results— In a single-center, randomized, double-blinded, placebo-controlled, multi-arm parallel-group clinical trial, patients undergoing primary Fontan surgery were assigned to receive nesiritide, milrinone, or placebo. A loading dose of study drug was administered on cardiopulmonary bypass followed by a continuous infusion for ≥12 hours and ≤5 days after cardiac intensive care unit admission. The primary outcome was days alive and out of the hospital within 30 days of surgery. Secondary outcomes included measures of cardiovascular function, renal function, resource use, and adverse events. Among 106 enrolled subjects, 35, 36, and 35 were randomized to the nesiritide, milrinone, and placebo groups, respectively, and all were analyzed based on intention to treat. Demographics, patient characteristics, and operative factors were similar among treatment groups. No significant treatment group differences were found for median days alive and out of the hospital within 30 days of surgery (nesiritide, 20 [minimum to maximum, 0–24]; milrinone, 18 [0–23]; placebo, 20 [0–23]; P =0.38). Treatment groups did not significantly differ in cardiac index, arrhythmias, peak lactate, inotropic scores, urine output, duration of mechanical ventilation, intensive care or chest tube drainage, or adverse events. Conclusions— Compared with placebo, empirical perioperative nesiritide or milrinone infusions are not associated with improved early clinical outcomes after Fontan surgery. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00543309.

OBJECTIVES: Ongoing adult sepsis clinical trials are assessing therapies that target three inflammation phenotypes including 1) immunoparalysis associated, 2) thrombotic microangiopathy driven thrombocytopenia associated, and 3) sequential liver failure associated multiple organ failure. These three phenotypes have not been assessed in the pediatric multicenter setting. We tested the hypothesis that these phenotypes are associated with increased macrophage activation syndrome and mortality in pediatric sepsis. DESIGN: Prospective severe sepsis cohort study comparing children with multiple organ failure and any of these phenotypes to children with multiple organ failure without these phenotypes and children with single organ failure. SETTING: Nine PICUs in the Eunice Kennedy Shriver National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. PATIENTS: Children with severe sepsis and indwelling arterial or central venous catheters. INTERVENTIONS: Clinical data collection and twice weekly blood sampling until PICU day 28 or discharge. MEASUREMENTS AND MAIN RESULTS: Of 401 severe sepsis cases enrolled, 112 (28%) developed single organ failure (0% macrophage activation syndrome 0/112; < 1% mortality 1/112), whereas 289 (72%) developed multiple organ failure (9% macrophage activation syndrome 24/289; 15% mortality 43/289). Overall mortality was higher in children with multiple organ and the phenotypes (24/101 vs 20/300; relative risk, 3.56; 95% CI, 2.06–6.17). Compared to the 188 multiple organ failure patients without these inflammation phenotypes, the 101 multiple organ failure patients with these phenotypes had both increased macrophage activation syndrome (19% vs 3%; relative risk, 7.07; 95% CI, 2.72–18.38) and mortality (24% vs 10%; relative risk, 2.35; 95% CI, 1.35–4.08). CONCLUSIONS: These three inflammation phenotypes were associated with increased macrophage activation syndrome and mortality in pediatric sepsis-induced multiple organ failure. This study provides an impetus and essential baseline data for planning multicenter clinical trials targeting these inflammation phenotypes in children. (Pediatr Crit Care Med 2019; 20:1137–1146)

Objectives To assess the association of diastolic blood pressure cutoffs (≥ 25 mm Hg in infants and ≥ 30 mm Hg in children) during cardiopulmonary resuscitation with return of spontaneous circulation and survival in surgical cardiac versus medical cardiac patients. Secondarily, we assessed whether these diastolic blood pressure targets were feasible to achieve and associated with outcome in physiology unique to congenital heart disease (single ventricle infants, open chest), and influenced outcomes when extracorporeal cardiopulmonary resuscitation was deployed. Design Multicenter, prospective, observational cohort analysis. Setting Tertiary PICU and cardiac ICUs within the Collaborative Pediatric Critical Care Research Network. Patients Patients with invasive arterial catheters during cardiopulmonary resuscitation and surgical cardiac or medical cardiac illness category. Interventions None. Measurements and main results Hemodynamic waveforms during cardiopulmonary resuscitation were analyzed on 113 patients, 88 surgical cardiac and 25 medical cardiac. A similar percent of surgical cardiac (51/88; 58%) and medical cardiac (17/25; 68%) patients reached the diastolic blood pressure targets (p = 0.488). Achievement of diastolic blood pressure target was associated with improved survival to hospital discharge in surgical cardiac patients (p = 0.018), but not medical cardiac patients (p = 0.359). Fifty-three percent (16/30) of patients with single ventricles attained the target diastolic blood pressure. In patients with an open chest at the start of chest compressions, 11 of 20 (55%) attained the target diastolic blood pressure. In the 33 extracorporeal cardiopulmonary resuscitation patients, 16 patients (48%) met the diastolic blood pressure target with no difference between survivors and nonsurvivors (p = 0.296). Conclusions During resuscitation in an ICU, with invasive monitoring in place, diastolic blood pressure targets of greater than or equal to 25 mm Hg in infants and greater than or equal to 30 mm Hg in children can be achieved in patients with both surgical and medical heart disease. Achievement of diastolic blood pressure target was associated with improved survival to hospital discharge in surgical cardiac patients, but not medical cardiac patients. Diastolic blood pressure targets were feasible to achieve in 1) single ventricle patients, 2) open chest physiology, and 3) extracorporeal cardiopulmonary resuscitation patients.