Novel Echocardiogram Analysis of Cardiac Dysfunction is Associated with Mortality in Pediatric Sepsis.

OBJECTIVES: The objective of our study was to semi-automatically generate echocardiogram indices in pediatric sepsis using novel algorithms and determine which indices were associated with mortality. We hypothesized that strain and diastolic indices would be most associated with mortality. DESIGN: Retrospective cohort study of children with sepsis from 2017-2022. Survivors and non-survivors were compared for echocardiogram indices. Multivariate Cox proportional hazard models were constructed for our primary outcome of in-hospital mortality. Linear regression was performed for secondary outcomes, which included multiple composite 28-day outcomes. RESULTS: Of the 54 patients in the study 9 (17%) died. Multiple echocardiogram indices of both right (RV) and left ventricles (LV) were associated with in-hospital mortality [RV GLS adjusted hazard ratio (aHR): 1.16 (1.03-1.29), p-value 0.011; RV global longitudinal early diastolic strain rate (GLSre) aHR:0.24 (0.07 to 0.75), p-value 0.014; LV GLSre aHR: 0.33 (0.11-0.97), p-value 0.044]. Impairment in GLS was associated with fewer ventilator-free days [RV GLS ß-coefficient: -0.47 (-0.84 to -0.10), p-value 0.013; LV GLS ß-coefficient -0.62 (-1.07 to -0.17), p-value 0.008], organ-support free days [RV GLS ß-coefficient: -0.49 (-0.87 to -0.11), p-value 0.013; LV GLS ß-coefficient: -0.64 (-1.10 to -0.17), p-value 0.008], and days free from ICU [RV GLS ß-coefficient: -0.42 (-0.79 to -0.05), p-value 0.026; LV GLS ß-coefficient:-0.58 (-1.03 to -0.13), p-value 0.012]. Systolic indices were not associated with mortality in this cohort. CONCLUSIONS: Our study demonstrates the feasibility of obtaining echocardiogram indices in a semi-automatic method using our algorithms. We showed that abnormal strain is associated with worse outcomes in a cohort of children with sepsis.

Pre-existing Immunocompromising Conditions and Outcomes of Acute COVID-19 Patients Admitted for Pediatric Intensive Care.

BACKGROUND: We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. METHODS: 55 hospitals in 30 U.S. states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted March 12, 2020-December 30, 2021 to the pediatric intensive care unit (PICU) or high acuity unit for acute COVID-19 were included. RESULTS: Of 1,274 patients, 105 (8.2%) had an ICC including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid organ transplantation, 16 (15.2%) solid tumors and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs. 4.6%, p = 0.005) and hospitalization was longer (p = 0.01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, p = 0.40). In patients with ICC, bacterial co-infection was more common in those with life-threatening COVID-19. CONCLUSIONS: In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities.

Immunocompromised-Associated Pediatric Acute Respiratory Distress Syndrome: Experience From the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Prospective Cohort Study.

OBJECTIVES: To characterize immunocompromised-associated pediatric acute respiratory distress syndrome (I-PARDS) and contrast it to PARDS. DESIGN: This is a secondary analysis of the 2016-2017 PARDS incidence and epidemiology (PARDIE) study, a prospective observational, cross-sectional study of children with PARDS. SETTING: Dataset of 145 PICUs across 27 countries. PATIENTS: During 10 nonconsecutive weeks (from May 2016 to June 2017), data about immunocompromising conditions (ICCs, defined as malignancy, congenital/acquired immunodeficiency, posttransplantation, or diseases requiring immunosuppression) were collected. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 708 subjects, 105 (14.8%) had ICC. Before the development of I-PARDS, those with ICC were more likely to be hospitalized (70% vs. 35%, p < 0.001), have more at-risk for PARDS ( p = 0.046), and spent more hours at-risk (20 [interquartile range, IQR: 8-46] vs. 11 [IQR: 4-33], [ p = 0.002]). Noninvasive ventilation (NIV) use was more common in those with ICC ( p < 0.001). Of those diagnosed with PARDS on NIV ( n = 161), children with ICC were more likely to be subsequently intubated ( n = 28/40 [70%] vs n = 53/121 [44%], p = 0.004). Severe PARDS was more common (32% vs 23%, p < 0.001) in I-PARDS. Oxygenation indices were higher at diagnosis and had less improvement over the first 3 days of PARDS ( p < 0.001). Children with I-PARDS had greater nonpulmonary organ dysfunction. Adjusting for Pediatric Risk of Mortality IV and oxygenation index, children with I-PARDS had a higher severity of illness-adjusted PICU mortality (adjusted hazard ratio: 3.0 [95% CI, 1.9-4.7] p < 0.001) and were less likely to be extubated alive within 28 days (subdistribution hazard ratio: 0.47 [95% CI, 0.31-0.71] p < 0.001). CONCLUSIONS: I-PARDS is a unique subtype of PARDS associated with hospitalization before diagnosis and increased: time at-risk for PARDS, NIV use, hypoxia, nonpulmonary organ dysfunction, and mortality. The opportunity for early detection and intervention seems to exist. Dedicated study in these patients is imperative to determine if targeted interventions will benefit these unique patients with the ultimate goal of improving outcomes.

Interventions Performed in Children With Immunocompromised Conditions in the Pediatric Intensive Care Unit Within 48 Hours of Death.

Background: Understanding interventions preceding death in children with immunocompromised conditions is important to ensure a peaceful and dignified perideath experience. The aim of this study was to describe the number of interventions performed in the pediatric intensive care unit (PICU) within the 48 hours before death in this population. Methods: This was a single-center, retrospective cohort study of all children with an underlying oncologic, hematologic, or immunologic diagnosis admitted to the PICU for at least 72 hours between 2014 and 2021. Medical records were reviewed for interventions within 48 hours preceding death and for palliative care involvement. Interventions were defined as new or escalations in respiratory support, cardiopulmonary resuscitation (CPR), vascular access, drains, and radiographic studies. Associations were evaluated using simple logistic regression. Results: A total of 55 patients were included in this study. The predominant PICU admission diagnoses were respiratory (51%), followed by shock (25%), and neurologic diagnoses (9%). These predominant diagnoses were similar perideath. At PICU admission, only 1 patient had a do-not-resuscitate (DNR) order. Forty-six percent had a DNR order 48 hours preceding death, and 91% had DNR orders in place at time of death. During the 48-hour period preceding death, 80% of children received at least one intervention. Radiographic studies were the most common, used in 78% of children, followed by respiratory (20%), vascular (16%), CPR (13%), and drain placement (7%). Palliative care was involved in 38% of cases and was associated with a decrease in the number of radiologic interventions (p = 0.028) and CPR (p = 0.026). Conclusions: Children in the PICU with underlying immunocompromised conditions frequently receive interventions within the 48-hour period preceding death. Palliative care involvement was associated with fewer radiographic studies and fewer occurrences of CPR. The impact of interventions on the dying experience warrants further investigation.

Critical Care Utilization in Children With Cancer: U.S. Pediatric Health Information System Database Cohort 2012-2021.

OBJECTIVES: To determine changes in pediatric oncology hospitalizations requiring intensive care over the period 2012-2021. DESIGN: Retrospective study of hospital admission. SETTING: Registry data from 36 children's hospitals in the U.S. Pediatric Health Information Systems database. PATIENTS: Children 18 years or younger admitted to any of 36 hospitals with an oncology diagnosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were a total of 55,827 unique patients accounted for 281,221 pediatric oncology hospitalizations over the 10-year period, and 16.6% of hospitalizations included admission to the PICU. Hospitalizations and PICU admissions steadily increased over this decade. Between 2012 and 2016, 15.1% of oncology hospitalizations were admitted to the PICU compared with 18.0% from 2017 to 2021 (difference 2.9% [95% CI, 2.6-3.2%] p ≤ 0.0001). Support with invasive mechanical ventilation also increased over time with 3.7% during 2012-2016 compared with 4.1% from 2017 to 2021 (difference 0.4% [95% CI, 0.2-0.5%] p ≤ 0.0001). Similar results were seen with cardiorespiratory life support using extracorporeal membrane oxygenation (difference 0.05% [95% CI, 0.02-0.07%] p = 0.0002), multiple vasoactive agent use (difference 0.3% [95% CI, 0.2-0.4%] p < 0.0001), central line placement (difference 5.3% [95% CI, 5.1-5.6%], p < 0.001), and arterial line placement (difference 0.4% [95% CI, 0.3-0.4%], p < 0.001). Year-on-year case fatality rate was unchanged over time (1.3%), but admission to the PICU during the second 5 years, compared with the first 5 years, was associated with lower odds of mortality (difference 0.7% [95% CI, 0.3-1.1%]) (odds ratio 0.82 [95% CI, 0.75-0.90%] p < 0.001). CONCLUSIONS: The percentage of pediatric oncology hospitalizations resulting in PICU admission has increased over the past 10 years. Despite the increasing use of PICU admission and markers of acuity, and on comparing 2017-2021 with 2012-2016, there are lower odds of mortality.

Diagnostic yield of bronchoscopy in children with leukemia or post hematopoietic stem cell transplant.

BACKGROUND: The utility of bronchoscopy with bronchoalveolar lavage (BAL) in immunocompromised children is not well understood. We aim to describe the bronchoscopy diagnostic yield and complications and to investigate factors associated with diagnostic yield. METHODS: This is a single-center, retrospective cohort study of 60 children with leukemia or post-hematopoietic stem cell transplant who had a bronchoscopy with BAL between 2017 and 2021. Comparisons were done with regression analysis. RESULTS: Of the 60 bronchoscopies performed, 46 (77%) revealed diagnostic information: 39 (65%) identified a pathogen, 14 (23.3%) found secretions/mucus plugging, and 6 (10%) found pulmonary hemorrhage. BAL results changed antimicrobial therapy in 27 (45%) cases. Bronchoscopies were performed in the intensive care unit (27/60) or operating room (33/60), with the former having a higher diagnostic yield (96% vs. 60%, p = 0.001). Half (50%) of bronchoscopies found a new infectious diagnosis. Respiratory symptoms (n = 58, 97%), supplemental oxygen use (n = 39, 65%), and antibiotic use (n = 56, 93%) before bronchoscopy were all common. The median volume of fluid instilled during bronchoscopy was 1.3 mL/kg (interquatile range [IQR]: 0.7, 2.6). None of these factors were associated with the diagnostic yield. Complications were rare and minor with only one child having self-resolved bleeding and four children, previously in room air requiring a nasal cannula. For the 27 (45%) children on mechanical ventilation when the bronchoscopy was performed, there was no difference in ventilator settings pre- and post-bronchoscopy. CONCLUSION: Bronchoscopies with BAL are useful, safe, and important in the diagnostic management of pulmonary complications in this cohort of children.

Pulmonary microbiome and transcriptome signatures reveal distinct pathobiologic states associated with mortality in two cohorts of pediatric stem cell transplant patients.

Lung injury is a major determinant of survival after pediatric hematopoietic cell transplantation (HCT). A deeper understanding of the relationship between pulmonary microbes, immunity, and the lung epithelium is needed to improve outcomes. In this multicenter study, we collected 278 bronchoalveolar lavage (BAL) samples from 229 patients treated at 32 children's hospitals between 2014-2022. Using paired metatranscriptomes and human gene expression data, we identified 4 patient clusters with varying BAL composition. Among those requiring respiratory support prior to sampling, in-hospital mortality varied from 22-60% depending on the cluster (p=0.007). The most common patient subtype, Cluster 1, showed a moderate quantity and high diversity of commensal microbes with robust metabolic activity, low rates of infection, gene expression indicating alveolar macrophage predominance, and low mortality. The second most common cluster showed a very high burden of airway microbes, gene expression enriched for neutrophil signaling, frequent bacterial infections, and moderate mortality. Cluster 3 showed significant depletion of commensal microbes, a loss of biodiversity, gene expression indicative of fibroproliferative pathways, increased viral and fungal pathogens, and high mortality. Finally, Cluster 4 showed profound microbiome depletion with enrichment of Staphylococci and viruses, gene expression driven by lymphocyte activation and cellular injury, and the highest mortality. BAL clusters were modeled with a random forest classifier and reproduced in a geographically distinct validation cohort of 57 patients from The Netherlands, recapitulating similar cluster-based mortality differences (p=0.022). Degree of antibiotic exposure was strongly associated with depletion of BAL microbes and enrichment of fungi. Potential pathogens were parsed from all detected microbes by analyzing each BAL microbe relative to the overall microbiome composition, which yielded increased sensitivity for numerous previously occult pathogens. These findings support personalized interpretation of the pulmonary microenvironment in pediatric HCT, which may facilitate biology-targeted interventions to improve outcomes.

Development and Implementation of a Quick Response (QR) Code System to Streamline the Process for Fellows' Evaluation in the Pediatric Intensive Care Unit (PICU) and the Neonatal Intensive Care Unit (NICU) at a Large Academic Center.

BACKGROUND/OBJECTIVE: Useful feedback and evaluation are critical to a medical trainee's development. While most academic physicians understand that giving feedback to learners is essential, many do not consider the components of feedback to be truly useful, and there are barriers to implementation. We sought to use a quick reader (QR) system to solicit feedback for trainees in two pediatric subspecialties (pediatric critical care and neonatal-perinatal medicine) at one institution to increase the quality and quantity of feedback received. METHODS: New valuations were modified from the existing evaluations and imported into online systems with QR code capability. Each fellow was given a QR code linking to evaluations and encouraged to solicit feedback and evaluations in a variety of clinical settings and scenarios. Evaluation numbers and quality of evaluations were assessed and compared both pre- and post-intervention. RESULTS: There were increases in the number of evaluations completed for both the pediatric critical care fellows and the neonatal-perinatal medicine fellows. There was no overall change in the quality of written evaluations received. Satisfaction with the evaluation system improved for both faculty and fellows of both training programs. CONCLUSION: In our critical care units, we were successfully able to implement a QR code-driven evaluation for our fellows that improved access for the faculty and offered the ability of the learner to solicit evaluations, without compromising the number or quality of evaluations. What's new: Quick reader (QR) codes can be used by learners to solicit evaluations and feedback from faculty. They can increase the quantity of written evaluations received without affecting their quality.

Risk factors for health impairments in children after hospitalization for acute COVID-19 or MIS-C.

Objective: To identify risk factors for persistent impairments after pediatric hospitalization for acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic. Methods: Across 25 U.S. Overcoming COVID-19 Network hospitals, we conducted a prospective cohort study of patients <21-years-old hospitalized for acute COVID-19 or MIS-C (May 2020 to March 2022) surveyed 2- to 4-months post-admission. Multivariable regression was used to calculate adjusted risk ratios (aRR) and 95% confidence intervals (CI). Results: Of 232 children with acute COVID-19, 71 (30.6%) had persistent symptoms and 50 (21.6%) had activity impairments at follow-up; for MIS-C (n = 241), 56 (23.2%) had persistent symptoms and 58 (24.1%) had activity impairments. In adjusted analyses of patients with acute COVID-19, receipt of mechanical ventilation was associated with persistent symptoms [aRR 1.83 (95% CI: 1.07, 3.13)] whereas obesity [aRR 2.18 (95% CI: 1.05, 4.51)] and greater organ system involvement [aRR 1.35 (95% CI: 1.13, 1.61)] were associated with activity impairment. For patients with MIS-C, having a pre-existing respiratory condition was associated with persistent symptoms [aRR 3.04 (95% CI: 1.70, 5.41)] whereas obesity [aRR 1.86 (95% CI: 1.09, 3.15)] and greater organ system involvement [aRR 1.26 (1.00, 1.58)] were associated with activity impairments. Discussion: Among patients hospitalized, nearly one in three hospitalized with acute COVID-19 and one in four hospitalized with MIS-C had persistent impairments for ≥2 months post-hospitalization. Persistent impairments were associated with more severe illness and underlying health conditions, identifying populations to target for follow-up.

Risk Factors Associated With Development of Multiple-Organ Dysfunction Syndrome After Pediatric Drowning.

OBJECTIVE: This study aimed to describe a single-center experience of pediatric drowning and to investigate risk factors associated with the development of pediatric multiple-organ dysfunction syndrome (MODS) after drowning events. METHODS: A single-center retrospective case-control study was performed at a tertiary children's hospital examining patients aged 1 month to 25 years who were admitted to the pediatric intensive care unit after a drowning event. The study period was June 2016 to June 2021. Patients who developed MODS at day 1 of intensive care admission were compared with those who did not. RESULTS: A total of 48 patients with a median age of 2.3 years were included. Twenty-nine (60%) had MODS at 24 hours. Those with MODS at 24 hours were more likely to require cardiopulmonary resuscitation (CPR), required longer duration of CPR, and had longer submersion times; otherwise, there were no differences in baseline characteristics. Those who developed MODS at 24 hours had longer lengths of stays, longer lengths of mechanical ventilation, and higher mortality. Multiple admission parameters were evaluated based on MODS-free survival at 24 hours. On univariable analysis, patients without MODS-free survival at 24 hours had higher rates of CPR, higher blood glucose on admission, higher illness severity scores, higher lactates, and lower Glasgow Coma Scale scores. A multivariable model was constructed using risk factors at presentation that were significant on univariable analysis; blood glucose greater than 200 mg/dL was associated with decreased odds of MODS-free survival at 24 hours after controlling for CPR administration of greater than 5 minutes and body temperature. CONCLUSIONS: Development of MODS in pediatric drowning is associated with worse patient outcomes. Hyperglycemia was identified as a potentially modifiable risk factor for the development of MODS at 24 hours and could serve as a useful prognostic parameter in this unique patient population.

Predictors of Failure of Noninvasive Ventilation in Critically Ill Children.

Noninvasive ventilation (NIV) is a common modality employed to treat acute respiratory failure. Most data guiding its use is extrapolated from adult studies. We sought to identify clinical predictors associated with failure of NIV, defined as requiring intubation. This single-center retrospective observational study included children admitted to pediatric intensive care unit (PICU) between July 2014 and June 2016 treated with NIV, excluding postextubation. A total of 148 patients was included. Twenty-seven (18%) failed NIV. There was no difference between the two groups with regard to age, gender, comorbidities, or etiology of acute respiratory failure. Those that failed had higher admission pediatric risk of mortality ( p = 0.01) and pediatric logistic organ dysfunction ( p = 0.002) scores and higher fraction of inspired oxygen (FiO 2 ; p = 0.009) at NIV initiation. Failure was associated with lack of improvement in tachypnea. At 6 hours of NIV, the failure group had worsening tachypnea with a median increase in respiratory rate of 8%, while the success group had a median reduction of 18% ( p = 0.06). Multivariable Cox's proportional hazard models revealed FiO 2 at initiation and worsening respiratory rate at 1- and 6-hour significant risks for failure of NIV. Failure was associated with a significantly longer PICU length of stay (success [2.8 days interquartile range (IQR): 1.7, 5.5] vs. failure [10.6 days IQR: 5.6, 13.2], p < 0.001). NIV can be successfully employed to treat acute respiratory failure in pediatric patients. There should be heightened concern for NIV failure in hypoxemic patients whose tachypnea is unresponsive to NIV. A trend toward improvement should be closely monitored.

Infants Admitted to US Intensive Care Units for RSV Infection During the 2022 Seasonal Peak.

Importance: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide. Objective: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission. Design, Setting, and Participants: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection. Exposure: Respiratory syncytial virus. Main Outcomes and Measures: Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity. Results: The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days. Conclusions and Relevance: In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness.

Peri-Intubation Adverse Events in the Critically Ill Child After Hematopoietic Cell Transplant.

OBJECTIVES: Mechanically ventilated children post-hematopoietic cell transplant (HCT) have increased morbidity and mortality compared with other mechanically ventilated critically ill children. Tracheal intubation-associated adverse events (TIAEs) and peri-intubation hypoxemia universally portend worse outcomes. We investigated whether adverse peri-intubation associated events occur at increased frequency in patients with HCT compared with non-HCT oncologic or other PICU patients and therefore might contribute to increased mortality. DESIGN: Retrospective cohort between 2014 and 2019. SETTING: Single-center academic noncardiac PICU. PATIENTS: Critically ill children who underwent tracheal intubation (TI). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from the local airway management quality improvement databases and Virtual Pediatric Systems were merged. These data were supplemented with a retrospective chart review for HCT-related data, including HCT indication, transplant-related comorbidity status, and patient condition at the time of TI procedure. The primary outcome was defined as the composite of hemodynamic TIAE (hypo/hypertension, arrhythmia, cardiac arrest) and/or peri-intubation hypoxemia (oxygen saturation < 80%) events. One thousand nine hundred thirty-one encounters underwent TI, of which 92 (4.8%) were post-HCT, while 319 (16.5%) had history of malignancy without HCT, and 1,520 (78.7%) had neither HCT nor malignancy. Children post-HCT were older more often had respiratory failure as an indication for intubation, use of catecholamine infusions peri-intubation, and use of noninvasive ventilation prior to intubation. Hemodynamic TIAE or peri-intubation hypoxemia were not different across three groups (HCT 16%, non-HCT with malignancy 10%, other 15). After adjusting for age, difficult airway feature, provider type, device, apneic oxygenation use, and indication for intubation, we did not identify an association between HCT status and the adverse TI outcome (odds ratio, 1.32 for HCT status vs other; 95% CI, 0.72-2.41; p = 0.37). CONCLUSIONS: In this single-center study, we did not identify an association between HCT status and hemodynamic TIAE or peri-intubation hypoxemia during TI.

Variation in Early Anakinra Use and Short-Term Outcomes in Multisystem Inflammatory Syndrome in Children.

OBJECTIVE: Evidence regarding effectiveness of interleukin-1 receptor antagonism in multisystem inflammatory syndrome in children (MIS-C) is lacking. We characterized variation in initial treatment with anakinra and evaluated cardiovascular outcomes associated with adding anakinra to standard initial therapy. METHODS: We conducted a retrospective cohort study of MIS-C cases in a US surveillance registry from November 2020 to December 2021. Day 0 was the first calendar day of immunomodulatory treatment. Factors associated with initial anakinra use (days 0-1) were identified. We compared cases in patients ages 2-20 years receiving intravenous immunoglobulin (IVIG) and glucocorticoids versus anakinra plus IVIG and/or glucocorticoids on days 0-1, using inverse probability weighting to balance disease severity. Primary outcomes were vasopressor requirement on day 3 and impaired left ventricular ejection fraction on days 3-4. The secondary outcome was 50% reduction in C-reactive protein on day 3. RESULTS: Among 1,516 MIS-C cases at 44 sites, 193 (13%) patients received anakinra alone or with other immunomodulators as initial treatment (range 0-74% by site). Site accounted for 59% of residual variance in anakinra use. After balancing disease severity, initial treatment with anakinra plus IVIG and/or glucocorticoids (n = 121) versus IVIG plus glucocorticoids (n = 389) was not associated with significant differences in vasopressor requirement (25.6% versus 20.1%, respectively; risk ratio [RR] 1.27 [95% confidence interval (95% CI) 0.88-1.84]), ventricular dysfunction (33.7% versus 25.7%, respectively; RR 1.31 [95% CI 0.98-1.75]), or C-reactive protein reduction. CONCLUSION: We identified substantial variation in initial anakinra use in a real-world population of children with MIS-C, but no average short-term improvement in cardiovascular outcomes associated with early addition of anakinra to IVIG and/or glucocorticoids compared to IVIG and glucocorticoids alone.

Community-Onset Bacterial Coinfection in Children Critically Ill With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Background: Community-onset bacterial coinfection in adults hospitalized with coronavirus disease 2019 (COVID-19) is reportedly uncommon, though empiric antibiotic use has been high. However, data regarding empiric antibiotic use and bacterial coinfection in children with critical illness from COVID-19 are scarce. Methods: We evaluated children and adolescents aged <19 years admitted to a pediatric intensive care or high-acuity unit for COVID-19 between March and December 2020. Based on qualifying microbiology results from the first 3 days of admission, we adjudicated whether patients had community-onset bacterial coinfection. We compared demographic and clinical characteristics of those who did and did not (1) receive antibiotics and (2) have bacterial coinfection early in admission. Using Poisson regression models, we assessed factors associated with these outcomes. Results: Of the 532 patients, 63.3% received empiric antibiotics, but only 7.1% had bacterial coinfection, and only 3.0% had respiratory bacterial coinfection. In multivariable analyses, empiric antibiotics were more likely to be prescribed for immunocompromised patients (adjusted relative risk [aRR], 1.34 [95% confidence interval {CI}, 1.01-1.79]), those requiring any respiratory support except mechanical ventilation (aRR, 1.41 [95% CI, 1.05-1.90]), or those requiring invasive mechanical ventilation (aRR, 1.83 [95% CI, 1.36-2.47]) (compared with no respiratory support). The presence of a pulmonary comorbidity other than asthma (aRR, 2.31 [95% CI, 1.15-4.62]) was associated with bacterial coinfection. Conclusions: Community-onset bacterial coinfection in children with critical COVID-19 is infrequent, but empiric antibiotics are commonly prescribed. These findings inform antimicrobial use and support rapid de-escalation when evaluation shows coinfection is unlikely.

Extracorporeal Membrane Oxygenation Characteristics and Outcomes in Children and Adolescents With COVID-19 or Multisystem Inflammatory Syndrome Admitted to U.S. ICUs.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed. DESIGN: Case series of patients from the Overcoming COVID-19 public health surveillance registry. SETTING: Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021. PATIENTS: Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria for MIS-C or acute COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The final cohort included 2,733 patients with MIS-C ( n = 1,530; 37 [2.4%] requiring ECMO) or acute COVID-19 ( n = 1,203; 71 [5.9%] requiring ECMO). ECMO patients in both groups were older than those without ECMO support (MIS-C median 15.4 vs 9.9 yr; acute COVID-19 median 15.3 vs 13.6 yr). The body mass index percentile was similar in the MIS-C ECMO versus no ECMO groups (89.9 vs 85.8; p = 0.22) but higher in the COVID-19 ECMO versus no ECMO groups (98.3 vs 96.5; p = 0.03). Patients on ECMO with MIS-C versus COVID-19 were supported more often with venoarterial ECMO (92% vs 41%) for primary cardiac indications (87% vs 23%), had ECMO initiated earlier (median 1 vs 5 d from hospitalization), shorter ECMO courses (median 3.9 vs 14 d), shorter hospital length of stay (median 20 vs 52 d), lower in-hospital mortality (27% vs 37%), and less major morbidity at discharge in survivors (new tracheostomy, oxygen or mechanical ventilation need or neurologic deficit; 0% vs 11%, 0% vs 20%, and 8% vs 15%, respectively). Most patients with MIS-C requiring ECMO support (87%) were admitted during the pre-Delta (variant B.1.617.2) period, while most patients with acute COVID-19 requiring ECMO support (70%) were admitted during the Delta variant period. CONCLUSIONS: ECMO support for SARS-CoV-2-related critical illness was uncommon, but type, initiation, and duration of ECMO use in MIS-C and acute COVID-19 were markedly different. Like pre-pandemic pediatric ECMO cohorts, most patients survived to hospital discharge.

Risk Factors for Multisystem Inflammatory Syndrome in Children: A Case-control Investigation.

BACKGROUND: In a 2020 pilot case-control study using medical records, we reported that non-Hispanic Black children were more likely to develop multisystem inflammatory syndrome in children (MIS-C) after adjustment for sociodemographic factors and underlying medical conditions. Using structured interviews, we investigated patient, household, and community factors underlying MIS-C likelihood. METHODS: MIS-C case patients hospitalized in 2021 across 14 US pediatric hospitals were matched by age and site to outpatient controls testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 3 months of the admission date. Caregiver interviews queried race/ethnicity, medical history, and household and potential community exposures 1 month before MIS-C hospitalization (case-patients) or after SARS-CoV-2 infection (controls). We calculated adjusted odds ratios (aOR) using mixed-effects multivariable logistic regression. RESULTS: Among 275 case patients and 496 controls, race/ethnicity, social vulnerability and patient or family history of autoimmune/rheumatologic disease were not associated with MIS-C. In previously healthy children, MIS-C was associated with a history of hospitalization for an infection [aOR: 4.8; 95% confidence interval (CI): 2.1-11.0]. Household crowding (aOR: 1.7; 95% CI: 1.2-2.6), large event attendance (aOR: 1.7; 95% CI: 1.3-2.1), school attendance with limited masking (aOR: 2.6; 95% CI: 1.1-6.6), public transit use (aOR: 1.8; 95% CI: 1.4-2.4) and co-resident testing positive for SARS-CoV-2 (aOR: 2.2; 95% CI: 1.3-3.7) were associated with increased MIS-C likelihood, with risk increasing with the number of these factors. CONCLUSIONS: From caregiver interviews, we clarify household and community exposures associated with MIS-C; however, we did not confirm prior associations between sociodemographic factors and MIS-C.

Multiple Organ Dysfunction and Critically Ill Children With Acute Myeloid Leukemia: Single-Center Retrospective Cohort Study.

OBJECTIVES: To describe the prevalence of multiple organ dysfunction syndrome (MODS) and critical care utilization in children and young adults with acute myeloid leukemia (AML) who have not undergone hematopoietic cell transplantation (HCT). DESIGN: Retrospective cohort study of MODS (defined as dysfunction of two or more organ systems) occurring any day within the first 72 hours of PICU admission. SETTING: Large, quaternary-care children's hospital. PATIENTS: Patients 1 month through 26 years old who were treated for AML from 2011-2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty patients with AML were included. These 80 patients had a total of 409 total non-HCT-related hospital and 71 PICU admissions. The majority 53 of 71 of PICU admissions (75%) were associated with MODS within the first 72 hours. MODS was present in 49 of 71 of PICU admissions (69%) on day 1, 29 of 52 (56%) on day 2, and 25 of 32 (78%) on day 3. The organ systems most often involved were hematologic, respiratory, and cardiovascular. There was an increasing proportion of renal failure (8/71 [11%] on day 1 to 8/32 [25%] on day 3; p = 0.02) and respiratory failure (33/71 [47%] to 24/32 [75%]; p = 0.001) as PICU stay progressed. The presence of MODS on day 1 was associated with a longer PICU length of stay (LOS) (ß = 5.4 [95% CI, 0.7-10.2]; p = 0.024) and over a six-fold increased risk of an LOS over 2 days (odds ratio, 6.08 [95% CI, 1.59-23.23]; p = 0.008). Respiratory failure on admission was associated with higher risk of increased LOS. CONCLUSIONS: AML patients frequently require intensive care. In this cohort, MODS occurred in over half of PICU admissions and was associated with longer PICU LOS. Respiratory failure was associated with the development of MODS and progressive MODS, as well as prolonged LOS.

Early-Onset Ventilator-Associated Pneumonia in Pediatric Severe Traumatic Brain Injury.

BACKGROUND: Early-onset ventilator-associated pneumonia (VAP) is associated with poor outcomes in patients with severe traumatic brain injury (TBI). The primary aim of this study was to describe VAP, including the microbiology of VAP and differences in frequency of VAP when various definitions are applied. The secondary aim was to determine the clinical variables associated with the development of VAP in children with severe TBI. METHODS: This is a retrospective cohort study at a quaternary referral children's hospital with a level I trauma center designation. Inclusion criteria were patients aged 0-18 years admitted to the pediatric intensive care unit between 2015 and 2020 with severe TBI requiring at least 2 days of invasive ventilation. VAP was defined by using Center of Disease Control (CDC) definition or clinical VAP, based on physician diagnosis. We compared general demographics, reviewed trauma and injury data, and outcomes to assess any differences between patients with VAP and non-VAP patients. Associations were tested with regression models. RESULTS: After applying all inclusion and exclusion criteria, 90 patients were included in the analysis. Patients with VAP were older (8.5 vs. 5.6 years, P = 0.03). Patients with VAP were less likely to have suffered from abusive head trauma (P = 0.01). Patients who received continuous neuromuscular blockade or targeted temperature management did not have different frequencies of VAP. CDC-defined VAP was diagnosed in 27% of patients. Number of patients with VAP increased to 41% for physician-diagnosed or clinical VAP. Methicillin-sensitive Staphylococcus aureus was the most common isolate grown, followed by Hemophilus influenza, with most VAP occurring on days 2-5 of intubation. VAP was not associated with mortality but was associated with worse functional status scale in patients who survived to discharge (8 vs. 7.5, P = 0.048). Over a cumulative period of days, nebulized 3% and albuterol were associated with decreased incidence of VAP. CONCLUSIONS: Ventilator-associated pneumonia occurs commonly in children with severe TBI, with rates of 27-41%, depending on CDC-defined VAP or clinical VAP. The discrepancy between clinical VAP and CDC-defined VAP further illustrates the need for a standardized definition for VAP. Although most interventions were not associated with VAP, nebulized 3% saline and albuterol were associated with reduced incidence of VAP; future investigation is needed to determine whether mucolytic agents can decrease the rate of VAP in children with severe TBI.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.