Faculty Bibliography

OBJECTIVE:To describe the impact of obesity on disease severity and outcomes of coronavirus disease 2019 (COVID-19) among hospitalized children. METHODS:This retrospective cohort study from the Society of Critical Care Medicine Viral Respiratory Illness Universal Study registry included all children hospitalized with COVID-19 from March 2020 to January 2021. Obesity was defined by Centers for Disease Control and Prevention BMI or World Health Organization weight for length criteria. Critical illness definition was adapted from National Institutes of Health criteria of critical COVID. Multivariate mixed logistic and linear regression was performed to calculate the adjusted odds ratio of critical illness and the adjusted impact of obesity on hospital length of stay. RESULTS:= .38). CONCLUSION:In a large, multicenter cohort, a high proportion of hospitalized children from COVID-19 had obesity as comorbidity. Furthermore, obesity had a significant independent association with critical illness.

Background/UNASSIGNED:Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia. Methods/UNASSIGNED:We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians) <21 years old hospitalized with COVID-19-related illness admitted between 15 March 2020 and 31 December 2020. We compared prevalence of assigned MIS-C labels and clinical features among clusters, followed by recursive feature elimination to identify characteristics of potentially misclassified MIS-C-labeled patients. Findings/UNASSIGNED: = 583; 19% labeled MIS-C) were younger (2·8 ± 2·0 y), PCR positive (86%), with less inflammation. Radiographic findings of pulmonary infiltrates and positive SARS-CoV-2 PCR accurately distinguished cluster 2 MIS-C labeled patients from cluster 1 patients. Interpretation/UNASSIGNED:Using a data driven, unsupervised approach, we identified features that cluster patients into a group with high likelihood of having MIS-C. Other features identified a cluster of patients more likely to have acute severe COVID-19 pulmonary disease, and patients in this cluster labeled by clinicians as MIS-C may be misclassified. These data driven phenotypes may help refine the diagnosis of MIS-C.

Extracorporeal membrane oxygenation (ECMO) is known to alter drug pharmacokinetics (PK). The PK changes can result from drug binding to the oxygenator, alterations in clearance, and drug sequestration but the published literature is outdated. There is limited data regarding the impact of the oxygenator on drug changes in ECMO circuits in comparison to the other components of the ECMO circuit. The purpose of this study was to determine the impact of the Quadrox-i pediatric and adult oxygenators on the PK of peramivir (PRV) in contemporary ECMO circuits. Two of both 1/4-in. and 3/8-in. closed loop ECMO circuits were prepared with a Quadrox-i adult or pediatric oxygenator (Getinge) and two of both sizes without an oxygenator in series. The circuits were primed with 20 mL of 5% albumin, packed red blood cells, heparin, sodium bicarbonate and calcium gluconate. Circuits were run at 1L/minute continuously. PRV was added to the circuit and levels were obtained pre-and postoxygenator at the following time intervals; 5 mins,1, 2, 3, 4, 5, 6, 8,12, and 24 hrs. PRV was also maintained in a glass vial and samples obtained at the same time periods. The results were consistent in both circuit sizes with no significant PRV loss over the 24-hour study period (<15% loss with oxygenator and <3% loss without oxygenator). This preliminary data suggests PRV dosing may not need to be adjusted for concern of drug loss via the oxygenator. Additional single and multiple dose studies are needed to validate these findings

OBJECTIVES/OBJECTIVE:To compare clinical characteristics and outcomes of children admitted to the PICU for severe acute respiratory syndrome coronavirus 2-related illness with or without multisystem inflammatory syndrome in children. The secondary objective was to identify explanatory factors associated with outcome of critical illness defined by a composite index of in-hospital mortality and organ system support requirement. DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Thirty-eight PICUs within the Viral Infection and Respiratory Illness Universal Study registry from March 2020 to January 2021. PATIENTS/METHODS:Children less than 18 years with severe acute respiratory syndrome coronavirus 2-related illness with or without multisystem inflammatory syndrome in children. MEASUREMENTS AND MAIN RESULTS/RESULTS:Of 394 patients, 171 (43.4%) had multisystem inflammatory syndrome in children. Children with multisystem inflammatory syndrome in children were more likely younger (2-12 yr vs adolescents; p < 0.01), Black (35.6% vs 21.9%; p < 0.01), present with fever/abdominal pain than cough/dyspnea (p < 0.01), and less likely to have comorbidities (33.3% vs 61.9%; p < 0.01) compared with those without multisystem inflammatory syndrome in children. Inflammatory marker levels, use of inotropes/vasopressors, corticosteroids, and anticoagulants were higher in multisystem inflammatory syndrome in children patients (p < 0.01). Overall mortality was 3.8% (15/394), with no difference in the two groups. Diagnosis of multisystem inflammatory syndrome in children was associated with longer duration of hospitalization as compared to nonmultisystem inflammatory syndrome in children (7.5 d[interquartile range, 5-11] vs 5.3 d [interquartile range, 3-11 d]; p < 0.01). Critical illness occurred in 164 patients (41.6%) and was more common in patients with multisystem inflammatory syndrome in children compared with those without (55.6% vs 30.9%; p < 0.01). Multivariable analysis failed to show an association between critical illness and age, race, sex, greater than or equal to three signs and symptoms, or greater than or equal to two comorbidities among the multisystem inflammatory syndrome in children cohort. Among nonmultisystem inflammatory syndrome in children patients, the presence of greater than or equal to two comorbidities was associated with greater odds of critical illness (odds ratio 2.95 [95% CI, 1.61-5.40]; p < 0.01). CONCLUSIONS:This study delineates significant clinically relevant differences in presentation, explanatory factors, and outcomes among children admitted to PICU with severe acute respiratory syndrome coronavirus 2-related illness stratified by multisystem inflammatory syndrome in children.

Study: Our Pediatric ECMO Program implemented ECMO Safety Rounds (ESR) as a quality improvement (QI) initiative. Objectives were to ensure implementation of protocols, immediately correct quality/safety deficiencies, and provide real-time education to nurses and perfusionists. Our specific aim was to track compliance with this process-improvement bundle and identify areas to target with QI efforts, with a long-term global aim of reducing quality/safety variances and patient harm over time. XXMethod(s): Our team initiated Pediatric ESR in September 2019. Two process- based QI bundles were developed: (1) Circuit Safety - 35 bundle elements, including maintenance and emergency checks; (2) Patient Safety - 13 bundle elements focused on nursing practices specific to minimizing patient harm. Pediatric ESR consisted of these two bundle assessments performed by designated ESR clinicians at the bedside with the patient's nurse and perfusionist. Credit for bundle compliance was awarded only if all elements were properly met. Noncompliant elements were addressed in real-time. All data was recorded in REDCap database. XXResult(s): 36 Pediatric ESRs were completed (Sept. 2019 - Jan. 2021). Monthly bundle compliance was reported using run charts. Median compliance with both bundles appeared to improve over time, with their most recent centerlines both at 67% compliance (Figure 1). Analysis of individual bundle elements revealed that 19/48 (40%) safety items were deficient at least once during the 36 ESRs (Table 1). Any individual bundle element with greater than 2 noncompliance events prompted our team to target interventions addressing these lapses, including new protocols and education, conducting multidisciplinary reviews, and collaborating with ancillary departments. We conclude that Pediatric ESR provides real-time assessment of compliance, immediate corrective and education measures, and actionable data to drive performance improvement around observed vulnerabilities in ECMO protocols

INTRODUCTION/UNASSIGNED:oxygenator. METHODS/UNASSIGNED:1/4-inch and 3/8-inch, simulated closed-loop ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of MEM/VBR was administered into the circuits and serial pre- and post-oxygenator concentrations were obtained at 5 minutes, 1, 2, 3, 4, 5, 6, 8, 12, and 24-hour time points. MEM/VBR was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation. RESULTS/UNASSIGNED:For the 1/4-inch circuit, there was an approximate mean 55% MEM loss with the oxygenator in series and a mean 33%-40% MEM loss without an oxygenator in series at 24 hours. For the 3/8-inch circuit, there was an approximate mean 70% MEM loss with the oxygenator in series and a mean 30%-38% MEM loss without an oxygenator in series at 24 hours. For both the 1/4-inch circuit and 3/8-inch circuits with and without an oxygenator, there was <10% VBR loss for the duration of the experiment. CONCLUSIONS/UNASSIGNED:This ex-vivo investigation demonstrated substantial MEM loss within an ECMO circuit with an oxygenator in series with both sizes of the Quadrox-i oxygenator at 24 hours and no significant VBR loss. Further evaluations with multiple dose in-vitro and in-vivo investigations are needed before specific MEM/VBR dosing recommendations can be made for clinical application with ECMO.

Importance/UNASSIGNED:Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. Objective/UNASSIGNED:To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Setting, Design, and Participants/UNASSIGNED:Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. Exposures/UNASSIGNED:Severe acute respiratory syndrome coronavirus 2. Main Outcomes and Measures/UNASSIGNED:Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results/UNASSIGNED:Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. Conclusions and Relevance/UNASSIGNED:In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.

Intrapericardial teratomas are rare, predominantly benign tumors that warrant surgical resection in the neonatal period because of their potential detrimental effects on the cardiorespiratory system. Surgical resection can be a challenge when the tumor encases and obscures a coronary artery. Adherence to certain operative principles is necessary to achieve successful outcomes.

Importance/UNASSIGNED:Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. Objective/UNASSIGNED:To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). Setting, Design, and Participants/UNASSIGNED:Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. Exposure/UNASSIGNED:SARS-CoV-2. Main Outcomes and Measures/UNASSIGNED:Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. Results/UNASSIGNED:Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL [212/523 {41%} vs 84/486 {17%}, P < .001]). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days. Conclusions and Relevance/UNASSIGNED:This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.