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Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

Objectives: Oxygen supplementation is a cornerstone treatment in critically ill children with bronchiolitis in the PICU. However, potential deleterious effects of high-dose oxygen are well-known. In this study, we aim to describe the pulmonary (local) and arterial (systemic) oxygen exposure over the duration of invasive mechanical ventilation (IMV) in children with severe bronchiolitis. Our secondary aim was to estimate potentially avoidable exposure to high-dose oxygen in these patients., Design: Retrospective cohort study., Setting: Single-center, tertiary-care PICU., Patients: Children younger than 2 years old admitted to the PICU for severe bronchiolitis receiving IMV., Interventions: None., Measurements and Main Results: Hourly measurements of Fio2 and peripheral oxygen saturation (Spo2), and arterial blood gas data were collected up to day 10 of IMV. A total of 24,451 hours of IMV were observed in 176 patients (median age of 1.0 mo [interquartile range (IQR), 1.0-2.3 mo]). The pulmonary exposure to oxygen was highest during the first day of IMV (median time-weighted average [TWA]-Fio2 0.46 [IQR, 0.39-0.53]), which significantly decreased over subsequent days. The systemic exposure to oxygen was relatively low, as severe hyperoxemia (TWA-Pao2 > 248 Torr [> 33 kPa]) was not observed. However, overuse of oxygen was common with 52.3% of patients (n = 92) having at least 1 day of possible excessive oxygen exposure and 14.8% (n = 26) with severe exposure. Furthermore, higher oxygen dosages correlated with increasing overuse of oxygen (rrepeated measures, 0.59; 95% CI, 0.54-0.63). Additionally, caregivers were likely to keep Fio2 greater than or equal to 0.50 when Spo2 greater than or equal to 97%., Conclusions: Moderate to high-dose pulmonary oxygen exposure and potential overuse of oxygen were common in this cohort of severe bronchiolitis patients requiring IMV; however, this was not accompanied by a high systemic oxygen burden. Further studies are needed to determine optimal oxygenation targets to prevent overzealous use of oxygen in this vulnerable population., Competing Interests: Dr. Lilien received funding through a PhD scholarship (Academic Medical Center Graduate School, Amsterdam UMC) through which this study and previous work was partly funded and from a KNAW Ter Meulen Grant/KNAW Medical Sciences Fund (Royal Netherlands Academy of Arts & Sciences). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: Swift extubation is important to prevent detrimental effects of invasive mechanical ventilation but carries the risk of extubation failure. Accurate tools to assess extubation readiness are lacking. This study aimed to describe the effect of extubation on diaphragm activity in ventilated infants and children. Our secondary aim was to compare diaphragm activity between failed and successfully extubated patients., Design: Prospective, observational study., Setting: Single-center tertiary neonatal ICU and PICU., Patients: Infants and children receiving invasive mechanical ventilation longer than 24 hours., Interventions: None., Measurements and Main Results: Diaphragm activity was measured with transcutaneous electromyography, from 15 minutes before extubation till 180 minutes thereafter. Peak and tonic activity, inspiratory amplitude, inspiratory area under the curve, and respiratory rate were calculated from the diaphragm activity waveform. One hundred forty-seven infants and children were included (median postnatal age, 1.9; interquartile range, 0.9-6.7 wk). Twenty patients (13.6%) failed extubation within 72 hours. Diaphragm activity increased rapidly after extubation and remained higher throughout the measurement period. Pre extubation, peak (end-inspiratory) diaphragm activity and tonic (end-inspiratory) diaphragm activity were significantly higher in failure, compared with success cases (5.6 vs 7.0 μV; p = 0.04 and 2.8 vs 4.1 μV; p = 0.04, respectively). Receiver operator curve analysis showed the highest area under the curve for tonic (end-inspiratory) diaphragm activity (0.65), with a tonic (end-inspiratory) diaphragm activity greater than 3.4 μV having a combined sensitivity and specificity of 55% and 77%, respectively, to predict extubation outcome. After extubation, diaphragm activity remained higher in patients failing extubation., Conclusions: Diaphragm activity rapidly increased after extubation. Patients failing extubation had a higher level of diaphragm activity, both pre and post extubation. The predictive value of the diaphragm activity variables alone was limited. Future studies are warranted to assess the additional value of electromyography of the diaphragm in combined extubation readiness assessment., Competing Interests: Dr. van Kaam’s institution received funding from Vyaire. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: Viral-lower respiratory tract disease is common in young children worldwide and is associated with high morbidity. Acute respiratory failure due to viral-lower respiratory tract disease necessitates PICU admission for mechanical ventilation. In critically ill patients in PICU settings, early fluid overload is common and associated with adverse outcomes such as prolonged mechanical ventilation and increased mortality. It is unclear, however, if this also applies to young children with viral-lower respiratory tract disease induced acute respiratory failure. In this study, we aimed to investigate the relation of early fluid overload with adverse outcomes in mechanically ventilated children with viral-lower respiratory tract disease in a retrospective dataset., Design: Retrospective cohort study., Setting: Single, tertiary referral PICU., Patients: One hundred thirty-five children (< 2 yr old) with viral-lower respiratory tract disease requiring mechanical ventilation admitted to the PICU of the Academic Medical Center, Amsterdam between 2008 and 2014., Interventions: None., Measurements and Main Results: The cumulative fluid balance on day 3 of mechanical ventilation was compared against duration of mechanical ventilation (primary outcome) and daily mean oxygen saturation index (secondary outcome), using uni- and multivariable linear regression. In 132 children, the mean cumulative fluid balance on day 3 was + 97.9 (49.2) mL/kg. Higher cumulative fluid balance on day 3 was associated with a longer duration of mechanical ventilation in multivariable linear regression (β = 0.166; p = 0.048). No association was found between the fluid status and oxygen saturation index during the period of mechanical ventilation., Conclusions: Early fluid overload is an independent predictor of prolonged mechanical ventilation in young children with viral-lower respiratory tract disease. This study suggests that avoiding early fluid overload is a potential target to reduce duration of mechanical ventilation in these children. Prospective testing in a clinical trial is warranted to support this hypothesis.

Objective: Angiotensin-converting enzyme and its effector peptide angiotensin II have been implicated in the pathogenesis of acute respiratory distress syndrome. Recently, angiotensin-converting enzyme 2 was identified as the counter-regulatory enzyme of angiotensin-converting enzyme that converts angiotensin II into angiotensin-(1-7). The aim of this study was to determine pulmonary angiotensin-converting enzyme and angiotensin-converting enzyme 2 activity in patients with acute respiratory distress syndrome., Design: Prospective observational pilot study., Setting: A PICU of a university hospital., Patients: Fourteen patients admitted, requiring mechanical ventilation for respiratory syncytial virus lower respiratory tract infection., Interventions: None., Measurements and Main Results: Two groups of patients were distinguished at admission: a group fulfilling the criteria for acute respiratory distress syndrome and a non-acute respiratory distress syndrome group. Angiotensin-converting enzyme and angiotensin-converting enzyme 2 activity were measured in bronchoalveolar lavage fluid. Patients with acute respiratory distress syndrome had increased angiotensin-converting enzyme activity and decreased angiotensin-converting enzyme 2 activity (p < 0.001) compared with the control group., Conclusion: It is shown for the first time that in acute respiratory distress syndrome, enhanced angiotensin-converting enzyme activity is paralleled by a reduced angiotensin-converting enzyme 2 activity, similar to that found in an experimental rat model of acute respiratory distress syndrome. The reduced angiotensin-converting enzyme 2 activity may be counteracted by restoring angiotensin-(1-7) level, thereby offering a novel treatment modality for this syndrome.

Objective: To determine biventricular cardiac function in pneumovirus-induced acute lung injury in spontaneously breathing mice., Design: Experimental animal study., Setting: Animal laboratory., Subjects: C57Bl/6 mice., Intervention: Mice were inoculated with the rodent pneumovirus, pneumonia virus of mice., Measurements and Main Results: Pneumonia virus of mice-infected mice were studied for right and left ventricular function variables by high-field strength (7 Tesla) cardiac MRI at specific time points during the course of disease compared with baseline. One day before and at peak disease severity, pneumonia virus of mice-infected mice showed significant right and left ventricular systolic and diastolic volume changes, with a progressive decrease in stroke volume and ejection fraction. No evidence for viral myocarditis or viral presence in heart tissue was found., Conclusions: These findings show adverse pulmonary-cardiac interaction in pneumovirus-induced acute lung injury, unrelated to direct virus-mediated effects on the heart.