OBJECTIVES: Mechanical power (MP) transferred from the ventilator to the lungs has been proposed as a summary variable that may impact mortality in children with acute respiratory distress syndrome (ARDS). To date, no study has shown an association between higher MP and mortality in children with ARDS.

DESIGN: Secondary analysis of a prospective observational study.

SETTING: Single-center, tertiary, academic PICU.

PATIENTS: Five hundred forty-six intubated children with ARDS enrolled between January 2013 and December 2019 receiving pressure-controlled ventilation.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Higher MP was associated with increased mortality (adjusted hazard ratio [HR] 1.34 per 1 sd increase, 95% CI 1.08-1.65; p = 0.007). When assessing the contribution of individual components of MP, only positive end-expiratory pressure (PEEP) was associated with mortality (HR 1.32; p = 0.007), whereas tidal volume, respiratory rate, and driving pressure (ΔP = [peak inspiratory pressure (PIP)-PEEP]) were not. Finally, we tested whether there remained an association when specific terms were removed from the MP equation by calculating MP from static strain (remove ΔP), MP from dynamic strain (remove PEEP), and mechanical energy (remove respiratory rate). MP from static strain (HR 1.44; p < 0.001), MP from dynamic strain (HR 1.25; p = 0.042), and mechanical energy (HR 1.29; p = 0.009) were all associated with mortality. MP was associated with ventilator-free days only when using MP normalized to predicted body weight, but not when using measured weight.

CONCLUSIONS: Higher MP was associated with mortality in pediatric ARDS, and PEEP appears to be the component most consistently driving this association. As higher PEEP is used in sicker patients, the association between MP and mortality may reflect a marker of illness severity rather than MP itself being causal for mortality. However, our results support future trials testing different levels of PEEP in children with ARDS as a potential means to improve outcome.

PRIMARY HYPOTHESIS: We hypothesized that higher alveolar dead space fraction (AVDSf) at pediatric acute respiratory distress syndrome (PARDS) onset would be associated with right ventricular (RV) systolic dysfunction within the first 24 h of PARDS.

STUDY DESIGN AND METHODS: We performed a retrospective single-center cohort study of PARDS patients with clinically obtained echocardiograms within 24 h. Primary exposure was AVDSf at PARDS onset. Primary outcome was RV systolic dysfunction as defined by RV global longitudinal strain (GLS) (>-18%). Secondary outcomes included pulmonary hypertension (PH) and RV systolic dysfunction as defined by other echocardiogram parameters, and measures of oxygenation. Unadjusted and adjusted logistic and linear regression were used to investigate AVDSf associations with outcomes.

RESULTS: Ninety-one patients were included: median age 6.2 years, 46% female, and 65% with moderate or severe PARDS. Median AVDSf was 0.2 (interquartile range [IQR] 0.0-0.3), 33% had RV dysfunction, and 21% had PH. Unadjusted and adjusted logistic regression showed no association between AVDSf and RV systolic dysfunction or PH by any echocardiographic measure, but unadjusted and adjusted linear regression did show an association between AVDSf and PaO /FiO .

CONCLUSION: AVDSf at PARDS onset was not associated with RV systolic dysfunction or PH within 24 h but was associated with PaO /FiO ratio and may be more reflective of pulmonary causes of ventilation-perfusion mismatch. Future investigations should focus on clarifying the clinical utility of AVDSf in relation to existing metrics throughout the course of PARDS.

UNLABELLED: Immunocompromised status, with and without stem cell transplant, confers a worse prognosis in pediatric acute respiratory distress syndrome. An improved understanding of the biochemical profile of immunocompromised children with acute respiratory distress syndrome would inform whether specific pathways are targetable, or merely bystanders, in order to improve outcomes in this high-risk subgroup.

OBJECTIVES: We aimed to identify a biomarker profile of immunocompromised children, with and without stem cell transplant, independent of illness severity.

DESIGN SETTINGS AND PARTICIPANTS: This was a secondary analysis of a prospective cohort study of intubated children with Berlin-defined acute respiratory distress syndrome with existing biomarker measurements conducted in a large academic PICU between 2014 and 2019.

MAIN OUTCOMES AND MEASURES: Biomarker levels were compared between immunocompetent and immunocompromised children, with and without stem cell transplant, both prior to and after adjusting for severity of illness.

RESULTS: In 333 children with acute respiratory distress syndrome, 84 were immunocompromised, of whom 39 had a stem cell transplant. Circulating neutrophil levels were strongly correlated with biomarkers, with 14 of 18 measured proteins differentially expressed in patients with versus without neutropenia. In order to identify biomarker levels independent of severity of illness, acute respiratory distress syndrome etiology, and neutrophil levels, we computed predicted (log-transformed) biomarker levels after adjusting for confounders using linear regression and then compared these severity-adjusted levels between immunocompetent and immunocompromised (with and without stem cell transplant) subjects using analyses of variance and post hoc Bonferroni. After multivariable adjustment, 11 biomarkers were higher in immunocompromised subjects without stem cell transplant, relative to immunocompetent, implicating endotheliopathy (angiopoietin-2), tissue damage (procollagen type III N-terminal peptide), and innate immunity. A single biomarker, C-C motif chemokine ligand 22, was lower in immunocompromised subjects with and without stem cell transplant.

CONCLUSIONS AND RELEVANCE: Immunocompromised children with acute respiratory distress syndrome were characterized by elevations in pro-inflammatory and endothelial damage biomarkers. Our study provides insight into mechanisms underlying the molecular heterogeneity of this population and potentially identifies targetable pathways to mitigate their increased mortality risk.

OBJECTIVES: Emergency transfers (ETs), deterioration events with late recognition requiring ICU interventions within 1 hour of transfer, are associated with adverse outcomes. We leveraged electronic health record (EHR) data to assess the association between ETs and outcomes. We also evaluated the association between intervention timing (urgency) and outcomes.

METHODS: We conducted a propensity-score-matched study of hospitalized children requiring ICU transfer between 2015 and 2019 at a single institution. The primary exposure was ET, automatically classified using Epic Clarity Data stored in our enterprise data warehouse endotracheal tube in lines/drains/airway flowsheet, vasopressor in medication administration record, and/or ≥60 ml/kg intravenous fluids in intake/output flowsheets recorded within 1 hour of transfer. Urgent intervention was defined as interventions within 12 hours of transfer.

RESULTS: Of 2037 index transfers, 129 (6.3%) met ET criteria. In the propensity-score-matched cohort (127 ET, 374 matched controls), ET was associated with higher in-hospital mortality (13% vs 6.1%; odds ratio, 2.47; 95% confidence interval [95% CI], 1.24-4.9, P = .01), longer ICU length of stay (subdistribution hazard ratio of ICU discharge 0.74; 95% CI, 0.61-0.91, P < .01), and longer posttransfer length of stay (SHR of hospital discharge 0.71; 95% CI, 0.56-0.90, P < .01). Increased intervention urgency was associated with increased mortality risk: 4.1% no intervention, 6.4% urgent intervention, and 10% emergent intervention.

CONCLUSIONS: An EHR measure of deterioration with late recognition is associated with increased mortality and length of stay. Mortality risk increased with intervention urgency. Leveraging EHR automation facilitates generalizability, multicenter collaboratives, and metric consistency.

<p><strong>OBJECTIVES: </strong>Emergency transfers (ETs), deterioration events with late recognition requiring ICU interventions within 1 hour of transfer, are associated with adverse outcomes. We leveraged electronic health record (EHR) data to assess the association between ETs and outcomes. We also evaluated the association between intervention timing (urgency) and outcomes.</p>

<p><strong>METHODS: </strong>We conducted a propensity-score-matched study of hospitalized children requiring ICU transfer between 2015 and 2019 at a single institution. The primary exposure was ET, automatically classified using Epic Clarity Data stored in our enterprise data warehouse endotracheal tube in lines/drains/airway flowsheet, vasopressor in medication administration record, and/or ≥60 ml/kg intravenous fluids in intake/output flowsheets recorded within 1 hour of transfer. Urgent intervention was defined as interventions within 12 hours of transfer.</p>

<p><strong>RESULTS: </strong>Of 2037 index transfers, 129 (6.3%) met ET criteria. In the propensity-score-matched cohort (127 ET, 374 matched controls), ET was associated with higher in-hospital mortality (13% vs 6.1%; odds ratio, 2.47; 95% confidence interval [95% CI], 1.24-4.9, P = .01), longer ICU length of stay (subdistribution hazard ratio of ICU discharge 0.74; 95% CI, 0.61-0.91, P &lt; .01), and longer posttransfer length of stay (SHR of hospital discharge 0.71; 95% CI, 0.56-0.90, P &lt; .01). Increased intervention urgency was associated with increased mortality risk: 4.1% no intervention, 6.4% urgent intervention, and 10% emergent intervention.</p>

<p><strong>CONCLUSIONS: </strong>An EHR measure of deterioration with late recognition is associated with increased mortality and length of stay. Mortality risk increased with intervention urgency. Leveraging EHR automation facilitates generalizability, multicenter collaboratives, and metric consistency.</p>

<p><strong>OBJECTIVE: </strong>Heterogeneity has hampered sepsis trials, and sub-phenotyping may assist with enrichment strategies. However, biomarker-based strategies are difficult to operationalize. Four sub-phenotypes defined by distinct temperature trajectories in the first 72 hours have been reported in adult sepsis. Given the distinct epidemiology of pediatric sepsis, the existence and relevance of temperature trajectory-defined sub-phenotypes in children is unknown. We aimed to classify septic children into de novo sub-phenotypes derived from temperature trajectories in the first 72 hours, and compare cytokine, immune function, and immunometabolic markers across subgroups.</p>

<p><strong>METHODS: </strong>This was a secondary analysis of a prospective cohort of 191 critically ill septic children recruited from a single academic pediatric intensive care unit. We performed group-based trajectory modeling using temperatures over the first 72 hours of sepsis to identify latent profiles. We then used mixed effects regression to determine if temperature trajectory-defined sub-phenotypes were associated with cytokine levels, immune function, and mitochondrial respiration.</p>

<p><strong>RESULTS: </strong>We identified four temperature trajectory-defined sub-phenotypes: hypothermic, normothermic, hyperthermic fast-resolvers, and hyperthermic slow-resolvers. Hypothermic patients were less often previously healthy and exhibited lower levels of pro- and anti-inflammatory cytokines and chemokines. Hospital mortality did not differ between hypothermic children (17%) and other sub-phenotypes (3 to 11%; p = 0.26).</p>

<p><strong>CONCLUSIONS: </strong>Critically ill septic children can be categorized into temperature trajectory-defined sub-phenotypes that parallel adult sepsis. Hypothermic children exhibit a blunted cytokine and chemokine profile. Group-based trajectory modeling has utility for identifying subtypes of clinical syndromes by incorporating readily available longitudinal data, rather than relying on inputs from a single timepoint.</p>

<p><strong>OBJECTIVE: </strong>Adolescent e-cigarette use has risen to epidemic levels in the US, revealing a new phenomenon of e-cigarette vaping-associated lung injury (EVALI). It is important to better characterize EVALI in critically ill adolescents as this is a vulnerable and rapidly growing demographic.</p>

<p><strong>METHODS: </strong>This was a retrospective case series of patients ≤21 years old with confirmed or probable EVALI (as defined by the Centers for Disease Control) that resulted in admission to the pediatric intensive care unit (PICU) of a large tertiary academic children's hospital between August 2019 and January 2020.</p>

<p><strong>RESULTS: </strong>There were six eligible patients, with a median age of 17 years. All patients reported tetrahydrocannabinol as well as nicotine e-cigarette use. Half of the patients had a preexisting diagnosis of asthma and four patients had mental health comorbidities. All patients presented with respiratory alkalosis and chest radiography showing diffuse bilateral infiltrates; two patients had pneumomediastinum, subcutaneous air and/or pneumothorax. The lowest documented ratio of oxygen saturation to inspired oxygen (SpO2:FiO2 or S/F ratio) ranged from 146 to 296. Two patients required an arterial line, with the lowest ratio of arterial oxygen to inspired oxygen (PaO2:FiO2 or P/F ratio) of 197 and 165. Two patients tested positive for rhinovirus and respiratory cultures were negative for all patients. Four patients underwent chest computed tomography imaging, which showed diffuse ground-glass opacities. Every patient required noninvasive positive pressure ventilation, with one progressing to invasive ventilation. All patients received broad-spectrum intravenous antibiotics and steroids, though there was considerable variability in dose, frequency, and duration of steroids. The hospital length of stay ranged from 5 to 16 days (median 8.3 days) with PICU length of stay ranging from 4 to 10 days (median 5.5 days). Four patients had pulmonary function testing before discharge, two of which showed decreased diffusing capacity of the lung for carbon monoxide. There were no patient deaths.</p>

<p><strong>CONCLUSIONS: </strong>This single-center case series describes the presentation, course, and treatment of EVALI in a pediatric intensive care unit setting. Our results show nuanced differences in the presentation and management of the critically ill adolescent, and raise many questions about the long term implications on lung health, morbidity, and mortality. Importantly, these cases illustrate the critical care consequences of a public health phenomenon and should spur further research and policy to address the negative health effects of vaping.</p>

<p><strong>OBJECTIVES: </strong>Much of the research related to pediatric acute respiratory distress syndrome has focused on inhospital mortality and interventions affecting this outcome. Limited data exist on survivors' morbidity, hospital disposition, and 1-year survival. The aim of this study was to determine new morbidity rate, discharge disposition, and 1-year mortality for survivors of pediatric acute respiratory distress syndrome.</p>

<p><strong>DESIGN: </strong>Secondary analysis of prospective cohort study.</p>

<p><strong>SETTING: </strong>Quaternary children's hospital.</p>

<p><strong>PATIENTS: </strong>Three-hundred sixteen mechanically ventilated children with pediatric acute respiratory distress syndrome (Berlin and Pediatric Acute Lung Injury Consensus Conference criteria) between July 2011 and December 2014.</p>

<p><strong>INTERVENTIONS: </strong>None.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>We performed secondary analysis of a prospectively recruited cohort of 316 mechanically ventilated children with pediatric acute respiratory distress syndrome between July 2011, and December 2014. Preillness and hospital discharge Functional Status Scale score were determined via chart review, and factors associated with new morbidity, defined as an increase of Functional Status Scale score of 3 or more, were analyzed. Demographic variables, pediatric acute respiratory distress syndrome characteristics, and ventilator management were tested for association with development of new morbidity, discharge disposition, and 1-year mortality. Inhospital mortality of pediatric acute respiratory distress syndrome was 13.3% (42/316). Of 274 survivors to hospital discharge, new morbidity was seen in 63 patients (23%). Discharge to rehabilitation rate was 24.5% (67/274) and associated with development of new morbidity. One- and 3-year mortality of survivors was 5.5% (15 deaths) and 8% (22 deaths) and was associated with baseline Functional Status Scale, immunocompromised status, Pediatric Risk of Mortality III, and organ failures at pediatric acute respiratory distress syndrome onset, but not with pediatric acute respiratory distress syndrome severity.</p>

<p><strong>CONCLUSIONS: </strong>New morbidity was common after pediatric acute respiratory distress syndrome and appears to be intermediate phenotype between survival without morbidity and death, making it a useful metric in future interventional and outcome studies in pediatric acute respiratory distress syndrome.</p>