Cognitive, Functional, and Quality of Life Outcomes 6 Months After Mechanical Ventilation for Bronchiolitis: A Secondary Analysis of Data From the Randomized Evaluation of Sedation Titration for Respiratory Failure Trial ( RESTORE ).

OBJECTIVES: To describe rates and associated risk factors for functional decline 6 months after critical bronchiolitis in a large, multicenter dataset. DESIGN: Nonprespecified secondary analysis of existing 6-month follow-up data of patients in the Randomized Evaluation of Sedation Titration for Respiratory Failure trial ( RESTORE , NCT00814099). SETTING: Patients recruited to RESTORE in any of 31 PICUs in the United States, 2009-2013. PATIENTS: Mechanically ventilated PICU patients under 2 years at admission with a primary diagnosis of bronchiolitis. INTERVENTIONS: There were no interventions in this secondary analysis; in the RESTORE trial, PICUs were randomized to protocolized sedation versus usual care. MEASUREMENTS AND MAIN RESULTS: "Functional decline," defined as worsened Pediatric Overall Performance Category and/or Pediatric Cerebral Performance Category (PCPC) scores at 6 months post-PICU discharge as compared with preillness baseline. Quality of life was assessed using Infant Toddler Quality of Life Questionnaire (ITQOL; children < 2 yr old at follow-up) or Pediatric Quality of Life Inventory (PedsQL) at 6 months post-PICU discharge. In a cohort of 232 bronchiolitis patients, 28 (12%) had functional decline 6 months postdischarge, which was associated with unfavorable quality of life in several ITQOL and PedsQL domains. Among 209 patients with normal baseline functional status, 19 (9%) had functional decline. In a multivariable model including all subjects, decline was associated with greater odds of worse baseline PCPC score and longer PICU length of stay (LOS). In patients with normal baseline status, decline was also associated with greater odds of longer PICU LOS. CONCLUSIONS: In a random sampling of RESTORE subjects, 12% of bronchiolitis patients had functional decline at 6 months. Given the high volume of mechanically ventilated patients with bronchiolitis, this observation suggests many young children may be at risk of new morbidities after PICU admission, including functional and/or cognitive morbidity and reduced quality of life.

Wide Institutional Variability in the Treatment of Pediatric Critical Asthma: A Multicenter Retrospective Study.

OBJECTIVES: Children with status asthmaticus refractory to first-line therapies of systemic corticosteroids and inhaled beta-agonists often receive additional treatments. Because there are no national guidelines on the use of asthma therapies in the PICU, we sought to evaluate institutional variability in the use of adjunctive asthma treatments and associations with length of stay (LOS) and PICU use. DESIGN: Multicenter retrospective cohort study. SETTING: Administrative data from the Pediatric Health Information Systems (PHIS) database. PATIENTS: All inpatients 2-18 years old were admitted to a PHIS hospital between 2013 and 2021 with a diagnostic code for asthma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: This study included 213,506 inpatient encounters for asthma, of which 29,026 patient encounters included care in a PICU from 39 institutions. Among these PICU encounters, large variability was seen across institutions in both the number of adjunctive asthma therapies used per encounter (min: 0.6, median: 1.7, max: 2.5, p < 0.01) and types of adjunctive asthma therapies (aminophylline, ipratropium, magnesium, epinephrine, and terbutaline) used. The center-level median hospital LOS ranged from 1 (interquartile range [IQR]: 1, 3) to 4 (3, 6) days. Among all the 213,506 inpatient encounters for asthma, the range of asthma admissions that resulted in PICU admission varied between centers from 5.2% to 47.3%. The average number of adjunctive therapies used per institution was not significantly associated with hospital LOS ( p = 0.81) nor the percentage of encounters with PICU admission ( p = 0.47). CONCLUSIONS: Use of adjunctive therapies for status asthmaticus varies widely among large children's hospitals and was not associated with hospital LOS or the percentage of encounters with PICU admission. Wide variance presents an opportunity for standardizing care with evidence-based guidelines to optimize outcomes and decrease adverse treatment effects and hospital costs.

Prevalence of Bacterial Codetection and Outcomes for Infants Intubated for Respiratory Infections.

OBJECTIVES: To determine the prevalence of respiratory bacterial codetection in children younger than 2 years intubated for acute lower respiratory tract infection (LRTI), primarily viral bronchiolitis, and identify the association of codetection with mechanical ventilation duration. DESIGN: Prospective observational study evaluating the prevalence of bacterial codetection (moderate/heavy growth of pathogenic bacterial plus moderate/many polymorphonuclear neutrophils) and the impact of codetection on invasive mechanical ventilation (IMV) duration. SETTING: PICUs in 12 high and low/middle-income countries. PATIENTS: Children younger than 2 years old requiring intubation and ICU admission for LRTI and who had a lower respiratory tract culture obtained at the time of intubation between December 1, 2019, and November 30, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 472 analyzed patients (median age 4.5 mo), 55% had a positive respiratory culture and 29% ( n = 138) had codetection. 90% received early antibiotics starting at a median of 0.36 hours after respiratory culture. Median (interquartile range) IMV duration was 151 hours (88, 226), and there were 28 deaths (5.3%). Codetection was more common with younger age, a positive respiratory syncytial virus test, and an admission diagnosis of bronchiolitis; it was less common with an admission diagnosis of pneumonia, with admission to a low-/middle-income site, and in those receiving vasopressors. When adjusted for confounders, codetection was not associated with longer IMV duration (adjusted relative risk 0.854 [95% CI 0.684-1.065]). We could not exclude the possibility that codetection might be associated with a 30-hour shorter IMV duration compared with no codetection, although the CI includes the null value. CONCLUSIONS: Bacterial codetection was present in almost a third of children younger than 2 years requiring intubation and ICU admission for LRTI, but this was not associated with prolonged IMV. Further large studies are needed to evaluate if codetection is associated with shorter IMV duration.

Suicide and Self-Harm in Adolescents During the COVID-19 Pandemic: A U.S. Virtual Pediatric Systems, LLC, Database Study of PICU Admissions, 2016-2021.

OBJECTIVES: To characterize the epidemiology of suicide and self-harm among adolescents admitted to PICUs during the first 2 years of the COVID-19 pandemic in the United States. DESIGN: Descriptive analysis of a large, multicenter, quality-controlled database (Virtual Pediatric Systems [VPS]), and of a national public health dataset (U.S. Centers for Disease Control and Prevention web-based Wide-ranging ONline Data for Epidemiology Research [CDC WONDER]). SETTING: The 69 PICUs participating in the VPS database that contributed data for the entire the study period, January 1, 2016, to December 31, 2021. PATIENTS: Adolescents older than 12 years to younger than 18 years old admitted to a participating PICU during the study period with a diagnosis involving self-harm or a suicide attempt (VPS sample), or adolescent suicide deaths over the same period (CDC WONDER sample). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 10,239 suicide deaths and 7,692 PICU admissions for self-harm, including 5,414 admissions in the pre-pandemic period (Q1-2016 to Q1-2020) and 2,278 in the pandemic period (Q2-2020 to Q4-2021). Compared with the pre-pandemic period, there was no increase in the median (interquartile range) number of suicide deaths per quarter (429 [399-453] vs. 416 [390-482]) or PICU admissions for self-harm per quarter (315 [289-353] vs. 310 [286-387]) during the pandemic period, respectively. There was an increase in the ratio of self-harm PICU admissions to all-cause PICU admissions per quarter during the pandemic (1.98 [1.43-2.12]) compared with the pre-pandemic period per quarter (1.59 [1.46-1.74]). We also observed a significant decrease in all-cause PICU admissions per quarter early in the pandemic compared with the pre-pandemic period (16,026 [13,721-16,297] vs. 19,607 [18,371-20,581]). CONCLUSIONS: The number of suicide deaths and PICU admissions per quarter for self-harm remained relatively constant during the pandemic, while the number of all-cause PICU admissions per quarter decreased compared with the pre-pandemic period. The resultant higher ratio of self-harm admissions to all-cause PICU admissions may have contributed to the perception that more adolescents required critical care for mental health-related conditions early in the pandemic.

The use of machine learning and artificial intelligence within pediatric critical care.

The field of pediatric critical care has been hampered in the era of precision medicine by our inability to accurately define and subclassify disease phenotypes. This has been caused by heterogeneity across age groups that further challenges the ability to perform randomized controlled trials in pediatrics. One approach to overcome these inherent challenges include the use of machine learning algorithms that can assist in generating more meaningful interpretations from clinical data. This review summarizes machine learning and artificial intelligence techniques that are currently in use for clinical data modeling with relevance to pediatric critical care. Focus has been placed on the differences between techniques and the role of each in the clinical arena. The various forms of clinical decision support that utilize machine learning are also described. We review the applications and limitations of machine learning techniques to empower clinicians to make informed decisions at the bedside. IMPACT: Critical care units generate large amounts of under-utilized data that can be processed through artificial intelligence. This review summarizes the machine learning and artificial intelligence techniques currently being used to process clinical data. The review highlights the applications and limitations of these techniques within a clinical context to aid providers in making more informed decisions at the bedside.

Scoping Review: Neurocognitive Outcome Assessments After Critical Illness in Children.

OBJECTIVES: To map the literature regarding assessment of neurocognitive outcomes in PICU survivors. Secondary objectives were to identify literature gaps and to provide data for development of a Core Outcome Measures Set in the domain. METHODS: Planned, a priori analysis was performed of data from an over-all scoping review of Post-Intensive Care Syndrome-pediatrics (PICS-p) functional outcomes. English-language databases and registries from 1970 to 2017 were searched by a medical librarian to identify manuscripts reporting on Post Intensive Care Syndrome-pediatrics (PICS-p). Further, detailed data extraction for neurocognitive outcomes was performed focusing on study characteristics, instruments used, and populations. RESULTS: 114 instruments evaluated neurocognitive function in 183 manuscripts. 83% of manuscripts were published after 2000. Median of 3 (IQR 2-5) neurocognitive instruments per manuscript were reported. Wechsler Scales (45%), clinical neurologic evaluations (21%), Pediatric Cerebral Performance Category (20%), Bayley Scales of Infant Development (16%), and Vineland Adaptive Behavior Scales (11%) were the most commonly used instruments. Median sample size was 65 (IQR 32-129) subjects. Most (63%) assessments were conducted in-person and parents/guardians (40%) provided the information. Patients with congenital heart disease and traumatic brain injury were most commonly evaluated (31% and 24% of manuscripts, respectively). Adolescents were the most commonly studied age group (34%). Baseline function was infrequently assessed (11% of manuscripts); most studies assessed patients at only one time point after PICU discharge. Within studies, neurocognitive assessments were often combined with others - especially social (18%) and physical (8%). CONCLUSIONS: 183 manuscripts studied the neurocognitive domain of PICS-p. Studies were quantitative and tended to focus on populations with anticipated cognitive impairment. Considerable variability exists among the chosen 114 instruments used; however, 4 instruments were frequently chosen with focus on intelligence, cerebral functioning, and developmental and adaptive behavior. The literature is marked by lack of agreement on methodologies but reflects the burgeoning interest in studying PICS-p neurocognitive outcomes.

Association of Interventions With Outcomes in Children At-Risk for Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.

OBJECTIVES: Describe the frequency with which transfusion and medications that modulate lung injury are administered to children meeting at-risk for pediatric acute respiratory distress syndrome (ARF-PARDS) criteria and evaluate for associations of transfusion, fluid balance, nutrition, and medications with unfavorable clinical outcomes. DESIGN: Secondary analysis of the Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study, a prospective point prevalence study. All enrolled ARF-PARDS patients were included unless they developed subsequent pediatric acute respiratory distress syndrome (PARDS) within 24 hours of PICU admission or PICU length of stay was less than 24 hours. Univariate and multivariable analyses were used to identify associations between therapies given during the first 2 calendar days after ARF-PARDS diagnosis and subsequent PARDS diagnosis (primary outcome), 28-day PICU-free days (PFDs), and 28-day ventilator-free days (VFDs). SETTING: Thirty-seven international PICUs. PATIENTS: Two hundred sixty-seven children meeting Pediatric Acute Lung Injury Consensus Conference ARF-PARDS criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the first 2 days after meeting ARF-PARDS criteria, 55% of subjects received beta-agonists, 42% received corticosteroids, 28% received diuretics, and 9% were transfused. Subsequent PARDS (15%) was associated with platelet transfusion (n = 11; adjusted odds ratio: 4.75 [95% CI 1.03-21.92]) and diuretics (n = 74; 2.55 [1.19-5.46]) in multivariable analyses that adjusted for comorbidities, PARDS risk factor, initial oxygen saturation by pulse oximetry:Fio2 ratio, and initial type of ventilation. Beta-agonists were associated with lower adjusted odds of subsequent PARDS (0.43 [0.19-0.98]). Platelets and diuretics were also associated with fewer PFDs and fewer VFDs in the multivariable models, and TPN was associated with fewer PFDs. Corticosteroids, net fluid balance, and volume of enteral feeding were not associated with the primary or secondary outcomes. CONCLUSIONS: There is an independent association between platelet transfusion, diuretic administration, and unfavorable outcomes in children at risk for PARDS, although this may be related to treatment bias and unmeasured confounders. Nevertheless, prospective evaluation of the role of these management strategies on outcomes in children with ARF-PARDS is needed.

Definition, Incidence, and Epidemiology of Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: In 2015, the Pediatric Acute Lung Injury Consensus Conference (PALICC) provided the first pediatric-specific definitions for acute respiratory distress syndrome (pediatric acute respiratory distress syndrome [PARDS]). These definitions have since been operationalized in cohort and interventional PARDS studies. As substantial data have accrued since 2015, we have an opportunity to assess the construct validity and utility of the initial PALICC definitions. Therefore, the Second PALICC (PALICC-2) brought together multiple PARDS experts and aimed to identify and summarize relevant evidence related to the definition and epidemiology of PARDS and create modifications to the definition of PARDS. DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: We included studies of subjects with PARDS, or at risk for PARDS, excluding studies pertaining primarily to adults except as specified for identifying age-specific cutoffs. DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. A total of 97 studies were identified for full-text extraction addressing distinct aspects of the PARDS definition, including age, timing, imaging, oxygenation, modes of respiratory support, and specific coexisting conditions. Data were assessed in a Patient/Intervention/Comparator/Outcome format when possible, and formally summarized for effect size, risk, benefit, feasibility of implementation, and equity. A total of 17 consensus-based definition statements were made that update the definition of PARDS, as well as the related diagnoses of "Possible PARDS" and "At-Risk for PARDS." These statements are presented alongside a summary of the relevant epidemiology. CONCLUSIONS: We present updated, data-informed consensus statements on the definition for PARDS and the related diagnoses of "Possible PARDS" and "At-Risk for PARDS."

Noninvasive Ventilation for Pediatric Acute Respiratory Distress Syndrome: Experience From the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Prospective Cohort Study.

OBJECTIVES: The worldwide practice and impact of noninvasive ventilation (NIV) in pediatric acute respiratory distress syndrome (PARDS) is unknown. We sought to describe NIV use and associated clinical outcomes in PARDS. DESIGN: Planned ancillary study to the 2016/2017 prospective Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study. SETTING: One hundred five international PICUs. PATIENTS: Patients with newly diagnosed PARDS admitted during 10 study weeks. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children were categorized by their respiratory support at PARDS diagnosis into NIV or invasive mechanical ventilation (IMV) groups. Of 708 subjects with PARDS, 160 patients (23%) received NIV at PARDS diagnosis (NIV group). NIV failure rate (defined as tracheal intubation or death) was 84 of 160 patients (53%). Higher nonrespiratory pediatric logistic organ dysfunction (PELOD-2) score, Pa o2 /F io2 was less than 100 at PARDS diagnosis, immunosuppression, and male sex were independently associated with NIV failure. NIV failure was 100% among patients with nonrespiratory PELOD-2 score greater than 2, Pa o2 /F io2 less than 100, and immunosuppression all present. Among patients with Pa o2 /F io2 greater than 100, children in the NIV group had shorter total duration of NIV and IMV, than the IMV at initial diagnosis group. We failed to identify associations between NIV use and PICU survival in a multivariable Cox regression analysis (hazard ratio 1.04 [95% CI, 0.61-1.80]) or mortality in a propensity score matched analysis ( p = 0.369). CONCLUSIONS: Use of NIV at PARDS diagnosis was associated with shorter exposure to IMV in children with mild to moderate hypoxemia. Even though risk of NIV failure was high in some children, we failed to identify greater hazard of mortality in these patients.

DDX58 Is Associated With Susceptibility to Severe Influenza Virus Infection in Children and Adolescents.

BACKGROUND: Seasonal influenza virus infection causes a range of disease severity, including lower respiratory tract infection with respiratory failure. We evaluated the association of common variants in interferon (IFN) regulatory genes with susceptibility to critical influenza infection in children. METHODS: We performed targeted sequencing of 69 influenza-associated candidate genes in 348 children from 24 US centers admitted to the intensive care unit with influenza infection and lacking risk factors for severe influenza infection (PICFlu cohort, 59.4% male). As controls, whole genome sequencing from 675 children with asthma (CAMP cohort, 62.5% male) was compared. We assessed functional relevance using PICFlu whole blood gene expression levels for the gene and calculated IFN gene signature score. RESULTS: Common variants in DDX58, encoding the retinoic acid-inducible gene I (RIG-I) receptor, demonstrated association above or around the Bonferroni-corrected threshold (synonymous variant rs3205166; intronic variant rs4487862). The intronic single-nucleotide polymorphism rs4487862 minor allele was associated with decreased DDX58 expression and IFN signature (P < .05 and P = .0009, respectively) which provided evidence supporting the genetic variants' impact on RIG-I and IFN immunity. CONCLUSIONS: We provide evidence associating common gene variants in DDX58 with susceptibility to severe influenza infection in children. RIG-I may be essential for preventing life-threatening influenza-associated disease.

Vaccine Effectiveness Against Life-Threatening Influenza Illness in US Children.

BACKGROUND: Predominance of 2 antigenically drifted influenza viruses during the 2019-2020 season offered an opportunity to assess vaccine effectiveness against life-threatening pediatric influenza disease from vaccine-mismatched viruses in the United States. METHODS: We enrolled children aged <18 years admitted to the intensive care unit with acute respiratory infection across 17 hospitals. Respiratory specimens were tested using reverse-transcription polymerase chain reaction for influenza viruses and sequenced. Using a test-negative design, we estimated vaccine effectiveness comparing odds of vaccination in test-positive case patients vs test-negative controls, stratifying by age, virus type, and severity. Life-threating influenza included death or invasive mechanical ventilation, vasopressors, cardiopulmonary resuscitation, dialysis, or extracorporeal membrane oxygenation. RESULTS: We enrolled 159 critically ill influenza case-patients (70% ≤8 years; 51% A/H1N1pdm09 and 25% B-Victoria viruses) and 132 controls (69% were aged ≤8 years). Among 56 sequenced A/H1N1pdm09 viruses, 29 (52%) were vaccine-mismatched (A/H1N1pdm09/5A+156K) and 23 (41%) were vaccine-matched (A/H1N1pdm09/5A+187A,189E). Among sequenced B-lineage viruses, majority (30 of 31) were vaccine-mismatched. Effectiveness against critical influenza was 63% (95% confidence interval [CI], 38% to 78%) and similar by age. Effectiveness was 75% (95% CI, 49% to 88%) against life-threatening influenza vs 57% (95% CI, 24% to 76%) against non-life-threating influenza. Effectiveness was 78% (95% CI, 41% to 92%) against matched A(H1N1)pdm09 viruses, 47% (95% CI, -21% to 77%) against mismatched A(H1N1)pdm09 viruses, and 75% (95% CI, 37% to 90%) against mismatched B-Victoria viruses. CONCLUSIONS: During a season when vaccine-mismatched influenza viruses predominated, vaccination was associated with a reduced risk of critical and life-threatening influenza illness in children.

Epidemiology and Outcomes of Critically Ill Children at Risk for Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.

OBJECTIVES: Interventional trials aimed at pediatric acute respiratory distress syndrome prevention require accurate identification of high-risk patients. In this study, we aimed to characterize the frequency and outcomes of children meeting "at risk for pediatric acute respiratory distress syndrome" criteria as defined by the Pediatric Acute Lung Injury Consensus Conference. DESIGN: Planned substudy of the prospective multicenter, international Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study conducted during 10 nonconsecutive weeks (May 2016-June 2017). SETTING: Thirty-seven international PICUs. PATIENTS: Three-hundred ten critically ill children meeting Pediatric Acute Lung Injury Consensus Conference "at-risk for pediatric acute respiratory distress syndrome" criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated the frequency of children at risk for pediatric acute respiratory distress syndrome and rate of subsequent pediatric acute respiratory distress syndrome diagnosis and used multivariable logistic regression to identify factors associated with subsequent pediatric acute respiratory distress syndrome. Frequency of at risk for pediatric acute respiratory distress syndrome was 3.8% (95% CI, 3.4-5.2%) among the 8,122 critically ill children who were screened and 5.8% (95% CI, 5.2-6.4%) among the 5,334 screened children on positive pressure ventilation or high-flow oxygen. Among the 310 at-risk children, median age was 2.1 years (interquartile range, 0.5-7.3 yr). Sixty-six children (21.3%) were subsequently diagnosed with pediatric acute respiratory distress syndrome, a median of 22.6 hours (interquartile range, 9.8-41.0 hr) later. Subsequent pediatric acute respiratory distress syndrome was associated with increased mortality (21.2% vs 3.3%; p < 0.001) and longer durations of invasive ventilation and PICU care. Subsequent pediatric acute respiratory distress syndrome rate did not differ by respiratory support modality at the time of meeting at risk criteria but was independently associated with lower initial saturation:Fio2 ratio, progressive tachycardia, and early diuretic administration. CONCLUSIONS: The Pediatric Acute Lung Injury Consensus Conference "at-risk for pediatric acute respiratory distress syndrome" criteria identify critically ill children at high risk of pediatric acute respiratory distress syndrome and poor outcomes. Interventional trials aimed at pediatric acute respiratory distress syndrome prevention should target patients early in their illness course and include patients on high-flow oxygen and positive pressure ventilation.

Hospital Charges Associated With Critical Bronchiolitis From 2009 to 2019.

OBJECTIVES: To evaluate the contribution of PICU care to increasing hospital charges for patients with bronchiolitis over a 10-year study period. DESIGN: In this retrospective multicenter study, changes in annual hospital charges (adjusted for inflation) were analyzed using linear regression for subjects admitted to the PICU with invasive mechanical ventilation (PICU + IMV) and without IMV (PICU - IMV), and for children not requiring PICU care. SETTING: Free-standing children's hospitals contributing to the Pediatric Health Information System (PHIS) database. SUBJECTS: Children less than 2 years with bronchiolitis discharged from a PHIS hospital between July 2009 and June 2019. Subjects were categorized as high risk if they were born prematurely or had a chronic complex condition. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PICU patients were 26.5% of the 283,006 included subjects but accrued 66% of the total $14.83 billion in charges. Annual charges increased from $1.01 billion in 2009-2010 to $2.07 billion in 2018-2019, and PICU patients accounted for 83% of this increase. PICU + IMV patients were 22% of all PICU patients and accrued 64% of all PICU charges, but PICU - IMV patients without a high-risk condition had the highest relative increase in annual charges, increasing from $76.7 million in 2009-2010 to $377.9 million in 2018-2019 (374% increase, ptrend < 0.001). CONCLUSIONS: In a multicenter cohort study of children hospitalized with bronchiolitis, PICU patients, especially low-risk children without the need for IMV, were the highest driver of increased hospital charges over a 10-year study period.

Trends in Time to Extubation for Pediatric Postoperative Cardiac Patients and Its Correlation With Changes in Clinical Outcomes: A Virtual PICU Database Study.

OBJECTIVES: Mechanical ventilation is often used in children after cardiac surgery but can impair hemodynamics and cause lung injury. Early extubation may improve ICU length of stay and survival. We aimed to describe trends in early extubation rates and evaluate if centers that more commonly practice early extubation have better severity-adjusted outcomes. DESIGN: Retrospective analysis was performed of admissions in the Virtual Pediatric Systems (VPS, LLC) database from 2009 to 2018. Early extubation was defined as patients extubated in the operating room or within 6 hours of PICU admission. SETTING: PICUs participating in the VPS database. PATIENTS: Children in the VPS database who underwent cardiac surgery. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Among 69,739 subjects, 20% were neonates, 47% underwent early extubation, 5.3% failed extubation, and 2.5% died. Overall, early extubation rates did not change over the study period. Centers were placed in one of four groups based on their early extubation rate in lower complexity surgeries. Centers that most commonly used early extubation had more ICU-free time among all patients in univariable analysis (lowest early extubation group, 23.8 d [interquartile range, 18.2-25.9 d]; highest early extubation group, 24.7 d [20.0-26.2 d]; p < 0.001). After adjusting for center volume, sex, age, surgical complexity, and preoperative ICU admission, increasing center-level early extubation rates were not associated with more ICU-free days. Higher center-level early extubation rate was not associated with mortality in univariable or multivariable analysis but was associated with decreased extubation failure rate (lowest early extubation group, 6.4%; highest early extubation group, 3.6%; p < 0.001). CONCLUSIONS: In this large, multicenter database study, early extubation rates in postoperative cardiac patients did not significantly change between 2009 and 2018. Centers that performed early extubation more frequently did not have shorter ICU stays or difference in mortality rates but did have lower reintubation rates.

Commentary on High-Flow Nasal Cannula and Continuous Positive Airway Pressure Practices After the First-Line Support for Assistance in Breathing in Children Trials.

Continuous positive airway pressure (CPAP) and heated humidified high-flow nasal cannula (HFNC) are commonly used to treat children admitted to the PICU who require more respiratory support than simple oxygen therapy. Much has been published on these two treatment modalities over the past decade, both in Pediatric Critical Care Medicine (PCCM ) and elsewhere. The majority of these studies are observational analyses of clinical, administrative, or quality improvement datasets and, therefore, are only able to establish associations between exposure to treatment and outcomes, not causation. None of the initial randomized clinical trials comparing HFNC and CPAP were definitive due to their relatively small sample sizes with insufficient power for meaningful clinical outcomes (e.g., escalation to bilevel noninvasive ventilation or intubation, duration of PICU-level respiratory support, mortality) and often yielded ambiguous findings or conflicting results. The recent publication of the First-Line Support for Assistance in Breathing in Children (FIRST-ABC) trials represented a major step toward understanding the role of CPAP and HFNC use in critically ill children. These large, pragmatic, randomized clinical trials examined the efficacy of CPAP and HFNC either for "step up" (i.e., escalation in respiratory support) during acute respiratory deterioration or for "step down" (i.e., postextubation need for respiratory support) management. This narrative review examines the body of evidence on HFNC published in PCCM , contextualizes the findings of randomized clinical trials of CPAP and HFNC up to and including the FIRST-ABC trials, provides guidance to PICU clinicians on how to implement the literature in current practice, and discusses remaining knowledge gaps and future research priorities.

Derivation and Validation of the Critical Bronchiolitis Score for the PICU.

OBJECTIVES: To derive and internally validate a bronchiolitis-specific illness severity score (the Critical Bronchiolitis Score) that out-performs mortality-based illness severity scores (e.g., Pediatric Risk of Mortality) in measuring expected duration of respiratory support and PICU length of stay for critically ill children with bronchiolitis. DESIGN: Retrospective database study using the Virtual Pediatric Systems (VPS, LLC; Los Angeles, CA) database. SETTING: One-hundred twenty-eight North-American PICUs. PATIENTS: Fourteen-thousand four-hundred seven children less than 2 years old admitted to a contributing PICU with primary diagnosis of bronchiolitis and use of ICU-level respiratory support (defined as high-flow nasal cannula, noninvasive ventilation, invasive mechanical ventilation, or negative pressure ventilation) at 12 hours after PICU admission. INTERVENTIONS: Patient-level variables available at 12 hours from PICU admission, duration of ICU-level respiratory support, and PICU length of stay data were extracted for analysis. After randomly dividing the cohort into derivation and validation groups, patient-level variables that were significantly associated with the study outcomes were selected in a stepwise backward fashion for inclusion in the final score. Score performance in the validation cohort was assessed using root mean squared error and mean absolute error, and performance was compared with that of existing PICU illness severity scores. MEASUREMENTS AND MAIN RESULTS: Twelve commonly available patient-level variables were included in the Critical Bronchiolitis Score. Outcomes calculated with the score were similar to actual outcomes in the validation cohort. The Critical Bronchiolitis Score demonstrated a statistically significantly stronger association with duration of ICU-level respiratory support and PICU length of stay than mortality-based scores as measured by root mean squared error and mean absolute error. CONCLUSIONS: The Critical Bronchiolitis Score performed better than PICU mortality-based scores in measuring expected duration of ICU-level respiratory support and ICU length of stay. This score may have utility to enrich interventional trials and adjust for illness severity in observational studies in this very common PICU condition.

School Closures in the United States and Severe Respiratory Illnesses in Children: A Normalized Nationwide Sample.

OBJECTIVES: To determine the association between nationwide school closures and prevalence of common admission diagnoses in the pediatric critical care unit. DESIGN: Retrospective cohort study. SETTING: National database evaluation using the Virtual Pediatric Systems LLC database. PATIENTS: All patients admitted to the PICU in 81 contributing hospitals in the United States. MEASUREMENTS AND MAIN RESULTS: Diagnosis categories were determined for all 110,418 patients admitted during the 20-week study period in each year (2018, 2019, and 2020). Admission data were normalized relative to statewide school closure dates for each patient using geographic data. The "before school closure" epoch was defined as 8 weeks prior to school closure, and the "after school closure" epoch was defined as 12 weeks following school closure. For each diagnosis, admission ratios for each study day were calculated by dividing 2020 admissions by 2018-2019 admissions. The 10 most common diagnosis categories were examined. Significant changes in admission ratios were identified for bronchiolitis, pneumonia, and asthma. These changes occurred at 2, 8, and 35 days following school closure, respectively. PICU admissions decreased by 82% for bronchiolitis, 76% for pneumonia, and 76% for asthma. Nonrespiratory diseases such as diabetic ketoacidosis, status epilepticus, traumatic injury, and poisoning/ingestion did not show significant changes following school closure. CONCLUSIONS: School closures are associated with a dramatic reduction in the prevalence of severe respiratory disease requiring PICU admission. School closure may be an effective tool to mitigate future pandemics but should be balanced with potential academic, economic, mental health, and social consequences.

Characteristics and Outcomes of Critically Ill Children With Multisystem Inflammatory Syndrome.

OBJECTIVES: To characterize the prevalence of pediatric critical illness from multisystem inflammatory syndrome in children (MIS-C) and to assess the influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain on outcomes. DESIGN: Retrospective cohort study. SETTING: Database evaluation using the Virtual Pediatric Systems Database. PATIENTS: All children with MIS-C admitted to the PICU in 115 contributing hospitals between January 1, 2020, and June 30, 2021. MEASUREMENTS AND MAIN RESULTS: Of the 145,580 children admitted to the PICU during the study period, 1,338 children (0.9%) were admitted with MIS-C with the largest numbers of children admitted in quarter 1 (Q1) of 2021 ( n = 626). The original SARS-CoV-2 viral strain and the D614G Strain were the predominant strains through 2020, with Alpha B.1.1.7 predominating in Q1 and quarter 2 (Q2) of 2021. Overall, the median PICU length of stay (LOS) was 2.7 days (25-75% interquartile range [IQR], 1.6-4.7 d) with a median hospital LOS of 6.6 days (25-75% IQR, 4.7-9.3 d); 15.2% received mechanical ventilation with a median duration of mechanical ventilation of 3.1 days (25-75% IQR, 1.9-5.8 d), and there were 11 hospital deaths. During the study period, there was a significant decrease in the median PICU and hospital LOS and a decrease in the frequency of mechanical ventilation, with the most significant decrease occurring between quarter 3 and quarter 4 (Q4) of 2020. Children admitted to a PICU from the general care floor or from another ICU/step-down unit had longer PICU LOS than those admitted directly from an emergency department. CONCLUSIONS: Overall mortality from MIS-C was low, but the disease burden was high. There was a peak in MIS-C cases during Q1 of 2021, following a shift in viral strains in Q1 of 2021. However, an improvement in MIS-C outcomes starting in Q4 of 2020 suggests that viral strain was not the driving factor for outcomes in this population.

Adherence to Lung-Protective Ventilation Principles in Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.

OBJECTIVES: To describe mechanical ventilation management and factors associated with nonadherence to lung-protective ventilation principles in pediatric acute respiratory distress syndrome. DESIGN: A planned ancillary study to a prospective international observational study. Mechanical ventilation management (every 6 hr measurements) during pediatric acute respiratory distress syndrome days 0-3 was described and compared with Pediatric Acute Lung Injury Consensus Conference tidal volume recommendations (< 7 mL/kg in children with impaired respiratory system compliance, < 9 mL/kg in all other children) and the Acute Respiratory Distress Syndrome Network lower positive end-expiratory pressure/higher Fio2 grid recommendations. SETTING: Seventy-one international PICUs. PATIENTS: Children with pediatric acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Analyses included 422 children. On pediatric acute respiratory distress syndrome day 0, median tidal volume was 7.6 mL/kg (interquartile range, 6.3-8.9 mL/kg) and did not differ by pediatric acute respiratory distress syndrome severity. Plateau pressure was not recorded in 97% of measurements. Using delta pressure (peak inspiratory pressure - positive end-expiratory pressure), median tidal volume increased over quartiles of median delta pressure (p = 0.007). Median delta pressure was greater than or equal to 18 cm H2O for all pediatric acute respiratory distress syndrome severity levels. In severe pediatric acute respiratory distress syndrome, tidal volume was greater than or equal to 7 mL/kg 62% of the time, and positive end-expiratory pressure was lower than recommended by the positive end-expiratory pressure/Fio2 grid 70% of the time. In multivariable analysis, tidal volume nonadherence was more common with severe pediatric acute respiratory distress syndrome, fewer PICU admissions/yr, non-European PICUs, higher delta pressure, corticosteroid use, and pressure control mode. Adherence was associated with underweight stature and cuffed endotracheal tubes. In multivariable analysis, positive end-expiratory pressure/Fio2 grid nonadherence was more common with higher pediatric acute respiratory distress syndrome severity, ventilator decisions made primarily by the attending physician, pre-ICU cardiopulmonary resuscitation, underweight stature, and age less than 2 years. Adherence was associated with respiratory therapist involvement in ventilator management and longer time from pediatric acute respiratory distress syndrome diagnosis. Higher nonadherence to tidal volume and positive end-expiratory pressure recommendations were independently associated with higher mortality and longer duration of ventilation after adjustment for confounding variables. In stratified analyses, these associations were primarily influenced by children with severe pediatric acute respiratory distress syndrome. CONCLUSIONS: Nonadherence to lung-protective ventilation principles is common in pediatric acute respiratory distress syndrome and may impact outcome. Modifiable factors exist that may improve adherence.

Use of Negative Pressure Ventilation in Pediatric Critical Care: Experience in 56 PICUs in the Virtual Pediatric Systems Database (2009-2019).

OBJECTIVES: Negative pressure ventilation may be more physiologic than positive pressure ventilation, but data describing negative pressure ventilation use in the PICU are limited. We aimed to describe the epidemiology and outcomes of PICU patients receiving negative pressure ventilation. DESIGN: Descriptive analysis of a large, quality-controlled multicenter database. SETTING: Fifty-six PICUs in the Virtual Pediatric Systems database who reported use of negative pressure ventilation. PATIENTS: Children admitted to a participating PICU between 2009 and 2019 who received negative pressure ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 788 subjects, 71% were less than 2 years old, and 45% had underlying health conditions. Two concurrent aspiration events were the only adverse events reported. After excluding one over-represented center, the 3 years with the most negative pressure ventilation usage were 2017-2019 (all > 25 cases/yr and ≥ 13 centers reporting usage). Among those 187 children, the most common primary diagnoses were bronchiolitis and cardiac disease (both 15.5%), 24.1% required endotracheal intubation after negative pressure ventilation, and 9.1% died. CONCLUSIONS: Negative pressure ventilation is being used in many PICUs, most commonly for pulmonary infections or cardiac disease, in children with high rates of subsequent intubation and mortality and with few documented adverse events. Use at individual centers is rare but increasing, suggesting need for prospective collaboration to better evaluate the role of negative pressure ventilation in the PICU.