Pediatric Critical Care and COVID-19

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, disproportionally affects adults (children 60 centers in nearly 20 countries from the Americas and Europe. In this report, we provide preliminary insights into our first 17 patients. Methods The Critical Coronavirus and Kids Epidemiology is a cohort study of children <19 years old with severe or critical COVID-19. The study period runs from April through December 2020. For this report, we included patients enrolled through April 23. We defined critical COVID-19 as a positive severe acute respiratory syndrome coronavirus 2 test result and requiring ICU therapies (high-flow nasal cannula [HFNC], noninvasive ventilation [NIV], invasive mechanical ventilation [IMV], vasoactive support, continuous renal replacement therapy). Severe COVID-19 included those receiving mask or nasal oxygen exceeding the pediatric acute respiratory distress syndrome (ARDS) “at risk” threshold.8 Deidentified data were collected by using a modification of the International Severe Acute Respiratory and Emerging Infection Consortium form (https://isaric.tghn.org/COVID-19-CRF/). Local ethics approval was obtained with a waiver of need for consent. Results We enrolled 17 children from 10 PICUs in Chile, Colombia, Italy, Spain, and the United States. Detailed data are in the Supplemental Information. Most patients were male (65%), young (median 4 years; range 0.08–18 years), and without known COVID-19 exposure (14 of 17). Comorbidities (Table 1, Supplemental Table 3) were common (71%) but variable. Symptoms were heterogenous, with fever and cough being most frequent (Table 1, Supplemental Table 3). Most with gastrointestinal (GI) symptoms (4 of 6) were also diagnosed with myocarditis (Supplemental Table 4). All these were from Europe and without previous cardiovascular disease

A Network Meta-analysis of Dexamethasone for Preventing Post-Extubation Upper Airway Obstruction in Children

RATIONALE: Peri-extubation corticosteroids are commonly used in children to prevent upper airway obstruction (UAO). However, the best timing and dose combination of corticosteroids is unknown. OBJECTIVES: To compare effectiveness of different corticosteroid regimens in preventing UAO and reintubation. METHODS: MEDLINE, CINAHL and Embase search identified randomized trials in children using corticosteroids to prevent UAO. All studies used dexamethasone. The studies were categorized based on timing of initiation of dexamethasone (early use: >12 hours prior to extubation) and the dose (high dose: (>/= 0.5mg/kg/dose). We performed Bayesian network meta-analysis (NMA) with studies grouped into four regimens- High dose, Early use (HE); Low dose, Early use (LE); High dose, Late use (HL) and Low dose, Late use (LL). RESULTS: 8 trials (n=903) were included in the analysis. For preventing UAO, (odds ratio, 95% credible interval), HE (0.13; 0.04, 0.36), HL (0.39; 0.19, 0.74) and LE (0.15; 0.04, 0.58) regimens appear to be more effective compared to no dexamethasone (low certainty). HE and LE had the highest probability of being the top ranked regimens for preventing UAO [surface under the cumulative ranking (SUCRA) 0.901 and 0.808 respectively]. For preventing reintubation, the effect estimate was imprecise for all four dexamethasone regimens compared to no dexamethasone (very low certainty). HE and LE were the top ranked regimens (SUCRA 0.803 and 0.720 respectively) for preventing reintubation. Sensitivity analysis showed that regimens which started >12 hours prior to extubation were likely more effective than regimens started >6 hours prior to extubation. CONCLUSIONS: Peri-extubation dexamethasone can prevent post-extubation UAO in children but effectiveness is highly dependent on timing and dosing regimen. Early initiation (ideally >12 hours prior to extubation) appears to be more important than the dose of dexamethasone. Ultimately the specific steroid strategy should be personalized considering the potential for adverse events associated with dexamethasone and the individual risk of UAO and reintubation.Eunice Kennedy Shriver National Institute of Child Health & Human Development. Grant number: R13HD10213

Executive Summary:International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Document

Rationale: Pediatric-specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients’ readiness for extubation. Methods: Twenty-six international experts comprised a multiprofessional panel to establish pediatrics-specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. A systematic review was conducted for questions that did not meet an a priori threshold of &gt;80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence and drafted and voted on the recommendations. Measurements and Main Results: Three questions related to systematic screening using an extubation readiness testing bundle and a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of &gt;80% agreement. For the remaining eight questions, five systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials, measures of respiratory muscle strength, assessment of risk of postextubation upper airway obstruction and its prevention, use of postextubation noninvasive respiratory support, and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. Conclusions: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.</p

Executive Summary: International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A PALISI Network Document

RATIONALE: Pediatric specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients' readiness for extubation. METHODS: Twenty-six international experts comprised a multi-professional panel to establish pediatric specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. Systematic review was conducted for questions which did not meet an a-priori threshold of ≥80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence, drafted, and voted on the recommendations. MEASUREMENTS AND MAIN RESULTS: Three questions related to systematic screening, using an extubation readiness testing bundle and use of a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of ≥80% agreement. For the remaining 8 questions, 5 systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials; measures of respiratory muscle strength; assessment of risk of post-extubation upper airway obstruction and its prevention; use of post-extubation non-invasive respiratory support; and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. CONCLUSION: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.The project was funded by Eunice Kennedy Shriver National Institute of Child Health (NICHD) and Human Development National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) (R13HD102137), in addition to funds from department of pediatrics at Indiana University School of Medicine, Indianapolis, Indiana

Operational Definitions related to Pediatric Ventilator Liberation

BACKGROUND: Common, operational definitions are crucial to assess interventions and outcomes related to pediatric mechanical ventilation. These definitions can reduce unnecessary variability amongst research and quality improvement efforts, to ensure findings are generalizable and can be pooled to establish best practices. RESEARCH QUESTION: Can we establish operational definitions for key elements related to pediatric ventilator liberation using a combination of detailed literature review and consensus-based approaches? STUDY DESIGN AND METHODS: A panel of 26 international experts in pediatric ventilator liberation, two methodologists and two librarians conducted systematic reviews on eight topic areas related to pediatric ventilator liberation. Through a series of virtual meetings, we established draft definitions which were voted upon using an anonymous web-based process. Definitions were revised by incorporating extracted data gathered during the systematic review and discussed in another consensus meeting. A second round of voting was conducted to confirm the final definitions. RESULTS: In eight topic areas identified by the experts, 16 preliminary definitions were established. Based on initial discussion and the first round of voting, modifications were suggested for 11 of the 16 definitions. There was significant variability in how these items were defined in the literature reviewed. The final round of voting achieved ≥80% agreement for all 16 definitions in the following areas: what constitutes respiratory support (invasive mechanical ventilation and non-invasive respiratory support), liberation and failed attempts to liberate from invasive mechanical ventilation, liberation from respiratory support, duration of non-invasive respiratory support, total duration of invasive mechanical ventilation, spontaneous breathing trials, extubation readiness testing, 28-ventilator free days, and planned vs rescue use of post-extubation non-invasive respiratory support. INTERPRETATION: We propose these consensus-based definitions for elements of pediatric ventilator liberation, informed by evidence, be used for future quality improvement initiatives and research studies to improve generalizability, and facilitate comparison.The project was funded by Eunice Kennedy Shriver National Institute of Child Health (NICHD) and Human Development National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) (R13HD102137), in addition to funds from the Department of Pediatrics at Indiana University School of Medicine, Indianapolis, Indiana

Global respiratory syncytial virus–related infant community deaths

Background Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. Methods The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. Results We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8−3.3) was lower than in-hospital (2.4 months; IQR: 1.5−4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). Conclusions We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines

Does equipoise exist for masking children for COVID-19?

Clinical equipoise is characterized by genuine uncertainty within the medical community about the effectiveness of a medical intervention. Its existence is often deemed necessary for clinical trials and signals a need for higher quality evidence, most often with randomized controlled trials, before the intervention can be considered effective. A leading official of the United States Centers for Disease Control and Prevention Director, when testifying before Congress in February of 2023, indicated there was no need for randomized controlled trials of masking because, owing to overwhelming evidence of benefit, there was no longer equipoise about masking children for COVID-19. We disagree with this statement and outline the reasons why in this piece. We review the concept of clinical equipoise specifically using the example of child masking. We list reasons equipoise still exists for masking children, including a lack of consensus among experts, contradictory medical evidence and recent and ongoing randomized efforts. Finally, we differentiate between clinical equipoise and ethical appropriateness. Despite ongoing equipoise about masking children, we outline why, owing to lack of evidence of net benefit, recommending this intervention does not currently appear to be medically ethical

Does equipoise exist for masking children for COVID-19?

Clinical equipoise is characterized by genuine uncertainty within the medical community about the effectiveness of a medical intervention. Its existence is often deemed necessary for clinical trials and signals a need for higher quality evidence, most often with randomized controlled trials, before the intervention can be considered effective. A leading official of the United States' Centers for Disease Control and Prevention Director, when testifying before Congress in February of 2023, indicated there was no need for randomized controlled trials of masking because, owing to overwhelming evidence of benefit, there was no longer equipoise about masking children for COVID-19. We disagree with this statement and outline the reasons why in this piece. We review the concept of clinical equipoise specifically using the example of child masking. We list reasons equipoise still exists for masking children, including a lack of consensus among experts, contradictory medical evidence and recent and ongoing randomized efforts. Finally, we differentiate between clinical equipoise and ethical appropriateness. Despite ongoing equipoise about masking children, we outline why, owing to lack of evidence of net benefit, recommending this intervention does not currently appear to be medically ethical