Pediatric Acute Respiratory Failure Research Articles

Early predictors of unfavorable outcomes in pediatric acute respiratory failure

ObjectiveAcute respiratory failure is a leading cause of critical illness in children. However, patient outcomes and early predictors of unfavorable outcomes are not well understood. This study aimed to describe composite unfavorable outcomes, defined as in-hospital death or discharge with new comorbidities, and to identify early predictors in children with acute respiratory failure in acute care hospitals.DesignRetrospective cohort study using a national inpatient database in Japan.SettingAll acute care hospitals registered in the database.PatientsThis study included children under 20 years of age who were admitted with acute respiratory diseases between July 2010 and March 2022 and received ventilatory support within the first three days of hospitalization.InterventionNone.Measurements and main resultsAmong 29,362 eligible children, the median age was 1.2 (interquartile range, 0.3–3.7) years and 28.8% had underlying conditions. The highest level of ventilatory support within the first three days was invasive ventilation (69.4%), noninvasive ventilation (1.0%), and high-flow nasal cannula (29.7%). Respiratory diagnoses included pneumonia (58.6%), bronchiolitis (29.0%), and asthma (11.1%). Among these children, 669 (2.3%) died and 1994 (6.8%) were discharged with new comorbidities, resulting in 2663 (9.1%) children experiencing unfavorable outcomes. In the logistic regression model, older age, underlying conditions, pneumonia, and low hospital volume were associated with unfavorable outcomes after adjusting for covariates.ConclusionsA significant proportion of pediatric patients with acute respiratory failure experienced unfavorable outcomes, warranting future efforts to improve acute care services for at-risk children. Early predictors identified from national database analyses could inform risk stratification and optimize the provision of acute care services for vulnerable pediatric patients.

Acute Respiratory Failure in Children: A Clinical Update on Diagnosis.

Acute respiratory failure (ARF) is a sudden failure of the respiratory system to ensure adequate gas exchanges. Numerous clinical conditions may cause ARF, including pneumonia, obstructive lung diseases (e.g., asthma), restrictive diseases such as neuromuscular diseases (e.g., spinal muscular atrophy and muscular dystrophy), and albeit rarely, interstitial lung diseases. Children, especially infants, may be more vulnerable to ARF than adults due to anatomical and physiological features of the respiratory system. Assessing respiratory impairment in the pediatric population is particularly challenging as children frequently present difficulties in reporting symptoms and due to compliance and cooperation in diagnostic tests. The evaluation of clinical and anamnestic aspects represents the cornerstone of ARF diagnosis: first level exams (e.g., arterial blood gas analysis) confirm and evaluate the severity of the ARF and second level exams help to uncover the underlying cause. Prompt management is critical, with supplemental oxygen, mechanical ventilation, and the treatment of the underlying problem. The aim of this review is to provide a comprehensive summary of the current state of the art in diagnosing pediatric ARF, with a focus on pathophysiology, novel imaging applications, and new perspectives, such as biomarkers and artificial intelligence.

Epidemiology of Acute Respiratory Failure in US Children: Outcomes and Resource Use.

Acute respiratory failure recalcitrant to conventional management often requires specialized organ-supportive technologies to optimize outcomes. Variation in the availability of these technologies prompted testing of the hypothesis that outcomes and resource use will vary by not only patient characteristics but also hospital characteristics and receipt of organ-supportive technology. Retrospective study of children 0 to 20 years old hospitalized for acute respiratory failure using the 2019 Kids' Inpatient Database. Multivariable regression models identified factors associated with mortality, length of hospitalization, and costs. Of an estimated 75 365 hospitalizations nationally, 97% were to urban teaching hospitals, 57% were of children < 6 years, and 58% were of males. Complex chronic conditions (CCC) existed in 62%, multiorgan dysfunction in 35%, and extreme illness severity in 54%. Mortality was 7%, length of stay 15 days, and hospital costs $77 168. Elevated mortality was associated with cumulative organ dysfunction (odds ratio [OR]:2.31, 95% confidence interval [CI]: 2.22-2.42), CCC (OR: 5.49, 95% CI: 4.73-6.37), transfer, higher illness severity, and cardiopulmonary resuscitation. Lower mortality was associated with extracorporeal membrane oxygenation (OR: 0.36, 95% CI: 0.28-0.47) and new tracheostomy (OR: 0.30, 95% CI: 0.25-0.35). Longer hospitalization was associated with transfer, infancy, CCC, higher illness severity, cumulative organ dysfunction, and urban hospitals. Higher costs accrued with noninfants, cumulative organ dysfunction, private insurance, and urban teaching hospitals. Hospitalizations for pediatric acute respiratory failure incurred substantial mortality and resource consumption. Efforts to reduce mortality and resource consumption should address interhospital transfer, access to organ-supportive technology, and drivers of higher severity-adjusted resource consumption at urban hospitals.

Severity and mortality of acute respiratory failure in pediatrics: A prospective multicenter cohort in Bogotá, Colombia.

Acute respiratory failure (ARF) is the most frequent cause of cardiorespiratory arrest and subsequent death in children worldwide. There have been limited studies regarding ARF in high altitude settings. The aim of this study was to calculate mortality and describe associated factors for severity and mortality in children with ARF. The study was conducted within a prospective multicentric cohort that evaluated the natural history of pediatric ARF. For this analysis three primary outcomes were studied: mortality, invasive mechanical ventilation, and pediatric intensive care unit (PICU) length of stay. Eligible patients were children older than 1 month and younger than 18 years of age with respiratory difficulty at the time of admission. Patients who developed ARF were followed at the time of ARF, 48 h later, at the time of discharge, and at 30 and 60 days after discharge. It was conducted in the pediatric emergency, in-hospital, and critical-care services in three hospitals in Bogotá, Colombia, from April 2020 to June 2021. Out of a total of 685 eligible patients, 296 developed ARF for a calculated incidence of ARF of 43.2%. Of the ARF group, 90patients (30.4%) needed orotracheal intubation, for a mean of 9.57 days of ventilation (interquartile range = 3.00-11.5). Incidence of mortality was 6.1% (n = 18). The associated factors for mortality in ARF were a history of a neurologic comorbidity and a higher fraction of inspired oxygen at ARF diagnosis. For PICU length of stay, the associated factors were age between 2 and 5 years of age, exposure to smokers, and respiratory comorbidity. Finally, for mechanical ventilation, the risk factors were obesity and being unstable at admission. ARF is a common cause of morbidity and mortality in children. Understanding the factors associated with greater mortality and severity of ARF might allow earlier recognition and initiation of prompt treatment strategies.

Admission Functional Status is Associated With Intensivists Perception of Extracorporeal Membrane Oxygenation Candidacy for Pediatric Acute Respiratory Failure.

To determine the association between admission Functional Status Scale (FSS) category and perceived extracorporeal membrane oxygenation (ECMO) candidacy for pediatric acute respiratory failure. Prospective, cross-sectional study. Single-center, quaternary, and ECMO referral academic children's hospital between March 2021 and January 2022. Pediatric intensivists directly caring for patients admitted with acute respiratory failure secondary to shock or respiratory disease. None. Pediatric intensivists were surveyed about current patients within 72 hours of initiation or escalation of invasive mechanical ventilation on whether they would offer ECMO should their patient deteriorate. Baseline functional status was assessed using trichotomized admission FSS: 1) normal/mild dysfunction (6-9), 2) moderate dysfunction (10-15), and 3) severe dysfunction (> 16). Multivariable logistic regression clustered by physician was used to assess the association between admission FSS category with perceived ECMO candidacy. Thirty-seven intensivists participated with 76% (137/180) of survey responses by those with less than 10 years of experience. 81% of patients (146/180) were perceived as ECMO candidates and 19% of patients (34/180) were noncandidates. Noncandidates had worse admission FSS scores than candidates (15.5 vs. 9, p < 0.001). After adjustment for age, admission FSS category of severe dysfunction had lower odds of perceived ECMO candidacy compared with normal to mild dysfunction (odds ratio [OR] 0.18 [95% CI, 0.06-0.56], p < 0.003). Patients with an abnormal communication subscore domain had the lowest odds of being considered a candidate (unadjusted OR 0.44 [95% CI, 0.29-0.68], p < 0.0001). In this prospective, single-center, cross-sectional study, admission FSS category indicating worse baseline functional status impacted pediatric intensivists' perceptions of ECMO candidacy for patients with acute respiratory failure. Abnormal FSS subscores in the neurocognitive domains were the most important considerations. Future studies should better seek to define the decision-making priorities of both parents and medical specialists for the utilization of ECMO in children with acute respiratory failure.

Identification of a pediatric acute hypoxemic respiratory failure signature in peripheral blood leukocytes at 24 hours post-ICU admission with machine learning.

There is no generalizable transcriptomics signature of pediatric acute respiratory distress syndrome. Our goal was to identify a whole blood differential gene expression signature for pediatric acute hypoxemic respiratory failure (AHRF) using transcriptomic microarrays within twenty-four hours of diagnosis. We used publicly available human whole-blood gene expression arrays of a Berlin-defined pediatric acute respiratory distress syndrome (GSE147902) cohort and a sepsis-triggered AHRF (GSE66099) cohort within twenty-four hours of diagnosis and compared those children with a PaO2/FiO2 < 200 to those with a PaO2/FiO2 ≥ 200. We used stability selection, a bootstrapping method of 100 simulations using logistic regression as a classifier, to select differentially expressed genes associated with a PaO2/FiO2 < 200 vs. PaO2/FiO2 ≥ 200. The top-ranked genes that contributed to the AHRF signature were selected in each dataset. Genes common to both of the top 1,500 ranked gene lists were selected for pathway analysis. Pathway and network analysis was performed using the Pathway Network Analysis Visualizer (PANEV) and Reactome was used to perform an over-representation gene network analysis of the top-ranked genes common to both cohorts. Changes in metabolic pathways involved in energy balance, fundamental cellular processes such as protein translation, mitochondrial function, oxidative stress, immune signaling, and inflammation are differentially regulated early in pediatric ARDS and sepsis-induced AHRF compared to both healthy controls and to milder acute hypoxemia. Specifically, fundamental pathways related to the severity of hypoxemia emerged and included (1) ribosomal and eukaryotic initiation of factor 2 (eIF2) regulation of protein translation and (2) the nutrient, oxygen, and energy sensing pathway, mTOR, activated via PI3K/AKT signaling. Cellular energetics and metabolic pathways are important mechanisms to consider to further our understanding of the heterogeneity and underlying pathobiology of moderate and severe pediatric acute respiratory distress syndrome. Our findings are hypothesis generating and support the study of metabolic pathways and cellular energetics to understand heterogeneity and underlying pathobiology of moderate and severe acute hypoxemic respiratory failure in children.

Association of surfactant protein A2 with acute respiratory failure in children.

Interactions among single nucleotide polymorphisms (SNPs) of surfactant protein (SP) are associated with acute respiratory failure (ARF) and its short-term outcome, pulmonary dysfunction at discharge (PDAD) in children. However, genetic association studies using individual SNPs have not been conducted before. We hypothesize that SP genetic variants are associated with pediatric ARF and its short-term complications by themselves. We used available genotype and clinical data in the Floros biobank consisting of 248 children aged ≤24 months with ARF; 86 developed PDAD. A logistic regression analysis was performed for each of the 14 selected SNPs, SP-A1 and SP-A2 genotypes. A p-value less than the Bonferroni correction threshold was considered significant. A likelihood ratio test was done to compare two models (one with demographic data and another with genetic variants). Before Bonferroni correction, female sex is associated with a decreased risk of ARF. Black race and the rs721917 of the SFTPD are associated with increased risk of ARF. After Bonferroni correction, the 1A0 1A1 genotype of SFTPA2 was associated with decreased risk of ARF. The likelihood ratio test showed that the model of the genotype information with demographic data was a better fit to predict ARF risk. None of the SP SNPs and SP-A1, SP-A2 genotypes were associated with PDAD. Our results indicate that SNPs and genotypes of SPs involved in innate immunity and host defense play an important role in ARF and, in the future, may be used as biomarkers.

Pressure-Regulated Volume Control and Pressure-Control Ventilation Modes in Pediatric Acute Respiratory Failure

ObjectiveThe objective of this study is to present our experience using the pressure-regulated volume control and the pressure-control ventilation modes in children.MethodsPatients with acute respiratory failure ventilated with pressure-regulated volume control or pressure-control modes were retrospectively evaluated. The patient’s ventilation parameters (of the first 7 days of ventilation or of the whole ventilation period, if the patient had been ventilated less than 7 days), SpO2, blood gases, and demographic data were collected from the pediatric intensive care unit database. ResultsSixty-one patients (median age 12 [4.8-36.4] months) were enrolled in the study. The pressure-control ventilation mode was used on 40 patients (65.6%) and the pressure-regulated volume-control mode was used on 21 (34.4%) patients. Twenty-eight patients (45.9%) had hypoxemic respiratory failure and 44 (72.1%) had hypercapnic respiratory failure. The median positive end-expiratory pressure was higher in pressure-control ventilation mode (5.4 [4.2-6.3] cmH2O) than the pressure-regulated volume-control mode (4.05 [3.68-4.41] H2O, P < .001). Pressure-control mode was used more frequently in hypoxemic cases but both modes were used equally in hypercapnic cases. Hypoxic respiratory failure (yes/no), odds ratio: 3.9 (95% CI 1.2-12.3, P = .02), Ph (nadir), odds ratio: 0.004 (95% CI 0.000-0.275, P = .01), and base excess, odds ratio: 0.88 (95% CI 0.79-0.98, P = .02) were associated with intensive care mortality.ConclusionsAlthough the pressure-control ventilation mode was preferred more frequently in hypoxemic respiratory failure, there was no significant difference between the 2 respiratory modes in terms of length of pediatric intensive care unit stay, MV duration, and mortality. The pressure-regulated volume-control mode seems to be a safer option for physicians who do not have enough experience in using pressure-control ventilation mode.

School and Work Absences After Critical Care Hospitalization for Pediatric Acute Respiratory Failure

Patients who survive pediatric critical illness and their caregivers commonly experience physical, emotional, and cognitive sequelae. However, the rate and duration of school absence among patients and work absence among their caregivers are unknown. To determine the rates and duration of school absence among children who survived hospitalization with acute respiratory failure and work absence among their caregivers. The Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) cluster randomized trial included 2449 children from 31 sites to protocolized sedation (intervention) vs usual care (control) from June 6, 2009, to December 2, 2013. In total, 1360 children survived hospitalization and were selected for follow-up at 6 months after pediatric intensive care unit (PICU) discharge, which was completed from January 12, 2010, to April 13, 2015. This secondary analysis was conducted from July 1, 2020, to September 30, 2021. PICU hospitalization for acute respiratory failure, including invasive mechanical ventilation. Postdischarge assessments with caregivers of eligible participants at 6 months after PICU discharge, including questions about school and work absence. Risk factors associated with longer absence from school and work were identified. Postdischarge assessments were completed for 960 children who survived treatment for acute respiratory failure, of whom 443 (46.1%) were girls and 517 (53.9%) were boys; 509 of 957 (53.2%) were non-Hispanic White. Median age was 1.8 years (IQR, 0.4-7.9 years). In total, 399 children (41.6%) were enrolled in school, of whom 279 (69.9%) missed school after discharge. Median duration of postdischarge absence was 9.1 days (IQR, 0-27.9 days) among all children enrolled in school and 16.9 days (IQR, 7.9-43.9 days) among the 279 children with postdischarge absence. Among 960 primary caregivers, 506 (52.7%) were employed outside the home, of whom 277 (54.7%) missed work. Median duration of postdischarge work absence was 2 days (IQR, 0-10 days) among all employed primary caregivers, and 8 days (IQR, 4-20 days) among the 277 caregivers who missed work after discharge. The odds of postdischarge school absence and greater duration of absence increased for children 5 years or older (compared with 0-4 years, odds ratios [ORs] for 5-8 years, 3.20 [95% CI, 1.69-6.05] and 2.09 [95% CI, 1.30-3.37], respectively; ORs for 9-12 years, 2.49 [95% CI, 1.17-5.27] and 2.32 [95% CI, 1.30-4.14], respectively; and ORs for 13-18 years, 2.37 [95% CI, 1.20-4.66] and 1.89 [95% CI, 1.11-3.24], respectively) and those with a preexisting comorbidity (ORs, 1.90 [95% CI, 1.10-3.29] and 1.76 [95% CI, 1.14-2.69], respectively). In this secondary analysis of a cluster randomized trial, 2 in 3 children hospitalized for acute respiratory failure missed school after discharge, for a median duration of nearly 2 weeks. In addition, more than half of primary caregivers missed work after discharge. The magnitude of school absenteeism suggests that children may be at increased risk for lower educational achievement, economic hardship, and poor health outcomes in adulthood.

Cluster analysis and profiling of airway fluid metabolites in pediatric acute hypoxemic respiratory failure

Hierarchal clustering of amino acid metabolites may identify a metabolic signature in children with pediatric acute hypoxemic respiratory failure. Seventy-four immunocompetent children, 41 (55.4%) with pediatric acute respiratory distress syndrome (PARDS), who were between 2 days to 18 years of age and within 72 h of intubation for acute hypoxemic respiratory failure, were enrolled. We used hierarchal clustering and partial least squares-discriminant analysis to profile the tracheal aspirate airway fluid using quantitative LC–MS/MS to explore clusters of metabolites that correlated with acute hypoxemia severity and ventilator-free days. Three clusters of children that differed by severity of hypoxemia and ventilator-free days were identified. Quantitative pathway enrichment analysis showed that cysteine and methionine metabolism, selenocompound metabolism, glycine, serine and threonine metabolism, arginine biosynthesis, and valine, leucine, and isoleucine biosynthesis were the top five enriched, impactful pathways. We identified three clusters of amino acid metabolites found in the airway fluid of intubated children important to acute hypoxemia severity that correlated with ventilator-free days < 21 days. Further studies are needed to validate our findings and to test our models.

Driving Pressure Is Associated With Outcome in Pediatric Acute Respiratory Failure.

Driving pressure (ratio of tidal volume over respiratory system compliance) is associated with mortality in acute respiratory distress syndrome. We sought to evaluate if such association could be identified in critically ill children. We studied the association between driving pressure on day 1 of mechanical ventilation and ventilator-free days at day 28 through secondary analyses of prospectively collected physiology data. Medical-surgical university hospital PICU. Children younger than 18 years (stratified by Pediatric Mechanical Ventilation Consensus Conference clinical phenotype definitions) without evidence of spontaneous respiration. Inspiratory hold maneuvers. Data of 222 patients with median age 11 months (2-51 mo) were analyzed. Sixty-five patients (29.3%) met Pediatric Mechanical Ventilation Consensus Conference criteria for restrictive and 78 patients (35.1%) for mixed lung disease, and 10.4% of all patients had acute respiratory distress syndrome. Driving pressure calculated by the ratio of tidal volume over respiratory system compliance for the whole cohort was 16 cm H2O (12-21 cm H2O) and correlated with the static airway pressure gradient (plateau pressure minus positive end-expiratory pressure) (Spearman correlation coefficient = 0.797; p < 0.001). Bland-Altman analysis showed that the dynamic pressure gradient (peak inspiratory pressure minus positive end-expiratory pressure) overestimated driving pressure (levels of agreement -2.295 to 7.268). Rematching the cohort through a double stratification procedure (obtaining subgroups of patients with matched mean levels for one variable but different mean levels for another ranking variable) showed a reduction in ventilator-free days at day 28 with increasing driving pressure in patients ventilated for a direct pulmonary indication. Competing risk regression analysis showed that increasing driving pressure remained independently associated with increased time to extubation (p < 0.001) after adjusting for Pediatric Risk of Mortality III 24-hour score, presence of direct pulmonary indication jury, and oxygenation index. Higher driving pressure was independently associated with increased time to extubation in mechanically ventilated children. Dynamic assessments of driving pressure should be cautiously interpreted.

Implementation of noninvasive neurally adjusted ventilatory assist in pediatric acute respiratory failure: a controlled before-after quality improvement study

BackgroundsPediatric noninvasive neurally adjusted ventilatory assist (NIV-NAVA) has been shown to improve patient-ventilator interaction but no data on clinical outcomes are available. Aim of this study was to compare NIV-NAVA with noninvasive pressure support (NIV-PS) in children with acute hypoxemic respiratory failure (AHRF), in a single-center before-after study. A cohort of thirty-four NIV-PS patients (before group) admitted to our PICU within the 2 years prior NAVA introduction was compared with a cohort of thirty children treated with NIV-NAVA during implementation phase (after group). The primary end-point was intubation rate between groups. Days on mechanical ventilation, number of invasive devices, nosocomial infections, PICU/hospital length of stay (LOS), and physiological parameters at 2 and 24 h after admission were considered.ResultsIntubation rate was lower in the NIV-NAVA group as compared to the NIV-PS group (p = 0.006). Patients treated with NIV-NAVA required fewer invasive devices (p = 0.032) and had lower incidence of ventilator-acquired pneumonia (p = 0.004) and shorter PICU (p = 0.032) and hospital LOS (p = 0.013). At 2 h, NIV-NAVA compared with NIV-PS resulted in higher paO2:FIO2 (p = 0.017), lower paCO2 (p = 0.002), RR (p = 0.026), and HR (p = 0.009).ConclusionsEarly NIV-NAVA vs NIV-PS was associated to lower intubation rate and shorter PICU and hospital LOS. Further studies are needed in order to confirm these preliminary data.

The Inter-Rater Reliability of Pediatric Point-of-Care Lung Ultrasound Interpretation in Children With Acute Respiratory Failure.

Use of point-of-care lung ultrasound (POC-LUS) has increased significantly in pediatrics yet it remains under-studied in the pediatric intensive care unit (PICU). No studies explicitly evaluate the reliability of POC-LUS artifact interpretation among critically ill children with acute respiratory failure (ARF) in the PICU. We thus designed this study to determine the inter-rater reliability of POC-LUS interpretation in pediatric ARF among pediatric intensivists trained in POC-LUS and an expert intensivist. We compared the interpretation of lung sliding, pleural line characteristics, ultrasound artifacts, and POC-LUS diagnoses among pediatric intensivists and an expert intensivist in a cohort of children admitted to the PICU for ARF. Kappa statistics (k) adjusted for maximum attainable agreement (k/kmax ) were used to quantify chance-correct agreement between the pediatric intensivist and expert physician. We enrolled 88 patients, evaluating 3 zones per hemithorax (anterior, lateral, and posterior) for lung sliding, pleural line characteristics, ultrasound artifacts, and diagnosis. There was moderate agreement between the PICU intensivist and expert-derived diagnoses with 56% observed agreement (k/kmax = 0.46, 95% confidence interval [CI] 0.31-0.65). Agreement in identification of lung sliding (k= 0.19, 95% CI -0.17 to 0.56) and pleural line characteristics (k= 0.24, 95% CI 0.08-0.40) was slight and fair, respectively, while agreement in the interpretation of ultrasound artifacts ranged from moderate to substantial. Evidence supporting the evaluation of neonatal and adult patients with POC-LUS should not be extrapolated to critically ill pediatric patients. This study adds to the evidence supporting use of POC-LUS in the PICU by demonstrating moderate agreement between PICU intensivist and expert-derived POC-LUS diagnoses.

Point-of-Care Lung Ultrasound to Diagnose the Etiology of Acute Respiratory Failure at Admission to the PICU.

Determine the sensitivity and specificity of point-of-care lung ultrasound in identifying the etiology of acute respiratory failure at admission to the PICU. Prospective observational study. Tertiary PICU. Children older than 37 weeks gestational age and less than or equal to 18 years old admitted to the PICU with acute respiratory failure from December 2018 to February 2020. Point-of-care lung ultrasound performed within 14 hours of admission to the PICU by physicians blinded to patient history and clinical course. Two physicians, blinded to all clinical information, independently interpreted the point-of-care lung ultrasound and then established a consensus diagnosis (ultrasound diagnosis). The ultrasound diagnosis was compared with an independent, standardized review of the medical record following hospital discharge (final diagnosis). Eighty-eight patients were enrolled in the study. Forty-eight patients had a final diagnosis of bronchiolitis/viral pneumonitis (55%), 29 had pneumonia (33%), 10 had status asthmaticus (11%), and one was excluded because of an inability to differentiate the final diagnosis. Point-of-care lung ultrasound correctly identified the etiology of acute respiratory failure in 56% of patients (49/87; 95% CI, 46-66%). It identified bronchiolitis/viral pneumonitis with 44% sensitivity (95% CI, 0.31-0.58) and 74% specificity (95% CI, 0.59-0.85), pneumonia with 76% sensitivity (95% CI, 0.58-0.88) and 67% specificity (95% CI 0.54-0.78), and status asthmaticus with 60% sensitivity (95% CI, 0.31-0.83) and 88% specificity (95% CI, 0.79-0.94). In contrast to literature demonstrating high utility differentiating the cause of acute respiratory failure in adults, blinded point-of-care lung ultrasound demonstrates moderate sensitivity and specificity in identifying the etiology of pediatric acute respiratory failure at admission to the PICU among children with bronchiolitis, pneumonia, and status asthmaticus.

518: Epidemiology of Resource Use and Outcomes in Pediatric Acute Respiratory Failure

518: Epidemiology of Resource Use and Outcomes in Pediatric Acute Respiratory Failure

High frequency percussive ventilation in pediatric acute respiratory failure.

High frequency percussive ventilation (HFPV) is used in acute respiratory failure, but is poorly described in pediatrics. We aimed to describe the clinical characteristics, ventilator settings, and outcomes of a large pediatric cohort, and to determine predictors of who would benefit from HFPV. Gas exchange 2 h after HFPV initiation predicts success. Single center retrospective cohort study testing association between gas exchange 2 h after HFPV initiation with success, defined a priori. Intubated children on HFPV for ≥2 h from 2012 to 2018. We described indications, ventilator settings, and gas exchange immediately before, 2 h after, and at termination of HFPV. Univariate and multivariate regression tested association of oxygenation and ventilation after HFPV initiation with success. Areas under the receiver operating characteristic (AUROC) curve and adjusted odds ratios (aORs) were computed. We performed 237 courses of HFPV in 193 children (22% non-survivors), of which 162 (68%) were successful. In univariate analysis, pH (AUROC, 0.65) and PCO2 (AUROC, 0.66) 2 h after HFPV predicted success. In multivariate analysis, pH (aOR: 1.67 per 1 SD; 95% confidence interval [CI]: 1.19-2.35), PCO2 (aOR: 0.49 per 1 SD; 95% CI: 0.31-0.79), and oxygenation index (aOR: 0.66 per 1 SD; 95% CI: 0.44-0.97) 2 h after HFPV initiation were associated with success. We describe the largest cohort of HFPV to date, with detailed description of indications and settings. Gas exchange after 2 h of HFPV was independently associated with success.

High-Frequency Jet Ventilation in Pediatric Acute Respiratory Failure.

High-frequency jet ventilation (HFJV) is primarily used in premature neonates; however, its use in pediatric patients with acute respiratory failure has been reported. The objective of this study was to evaluate HFJV use in the pediatric critical care setting. We hypothesized that HFJV would be associated with improvements in oxygenation and ventilation. Medical records of all patients who received HFJV in the pediatric ICU of a quaternary care center between 2014 and 2018 were retrospectively reviewed. Premature infants who had not been discharged home were excluded, as were those in whom HFJV was started while on extracorporeal membrane oxygenation. Data on demographics, pulmonary mechanics, gas exchange, and outcomes were extracted and analyzed using chi-square testing for categorical variables, nonparametric testing for continuous variables, and a linear effects model to evaluate gas exchange over time. A total of 35 subjects (median age = 2.9 months, median weight = 5.2 kg) were included. Prior to HFJV initiation, median (interquartile range) oxygenation index (OI) was 11.3 (7.2-16.9), [Formula: see text] = 133 (91.3-190.0), pH = 7.18 (7.11-7.27), [Formula: see text] = 64 (52-87) mm Hg, and [Formula: see text] = 74 (64-125) mm Hg. For subjects still on HFJV (n = 25), there was no significant change in OI, [Formula: see text], or [Formula: see text] at 4-6 h after initiation, whereas pH increased (P = .001) and [Formula: see text] decreased (P = .001). For those remaining on HFJV for > 72 h (n = 12), the linear effects model revealed no differences over 72 h for OI, [Formula: see text], [Formula: see text], or mean airway pressure, but there was a decrease in [Formula: see text] while pH and [Formula: see text] increased. There were 9 (26%) subjects who did not survive, and nonsurvivors had higher Pediatric Index of Mortality 2 scores (P = .01), were more likely to be immunocompromised (P = .01), were less likely to have a documented infection (P = .02), and had lower airway resistance (P = .02). HFJV was associated with improved ventilation among subjects able to remain on HFJV but had no significant effect on oxygenation.

Diaphragm Atrophy During Pediatric Acute Respiratory Failure Is Associated With Prolonged Noninvasive Ventilation Requirement Following Extubation.

Diaphragm atrophy is evident during invasive ventilation for pediatric acute respiratory failure, but with unknown significance. We hypothesized that diaphragm atrophy in pediatric acute respiratory failure is associated with prolonged noninvasive positive pressure ventilation following extubation. Prospective observational study. Single-center academic PICU. Invasively ventilated children with acute respiratory failure. Diaphragm ultrasound was performed within 36 hours after intubation and repeated within 48 hours preceding extubation. Rapid shallow breathing index at 15 and 30 minutes of a spontaneous breathing trial and negative inspiratory force were collected in a subset of patients concurrently with the ultrasound measurements. Diaphragm thickness at end-expiration was measured to assess for diaphragm atrophy during mechanical ventilation. Percentage change in diaphragm thickness at end-expiration was defined as baseline diaphragm thickness at end-expiration minus final, preextubation diaphragm thickness at end-expiration divided by baseline diaphragm thickness at end-expiration. The primary outcome measure was duration of noninvasive positive pressure ventilation following extubation with prolonged use defined as noninvasive positive pressure ventilation use for greater than 24 hours postextubation. Among 56 children, 47 (median age, 15.5 mo; interquartile range, 6-53 mo) had diaphragm thickness at end-expiration measured within 48 hours prior to extubation. Fourteen (30%) had prolonged noninvasive positive pressure ventilation use with median duration 110 hours (interquartile range, 52-130 hr). The median percentage change of diaphragm thickness at end-expiration from baseline among those with and without prolonged noninvasive positive pressure ventilation use was -20% (interquartile range, -32% to -10%) versus -7% (interquartile range, -21% to 0%) (p = 0.04). Diaphragm atrophy is associated with prolonged postextubation noninvasive positive pressure ventilation in children with acute respiratory failure. Serial bedside diaphragm ultrasound may identify children at risk for prolonged noninvasive positive pressure ventilation use after extubation.

Association of SNP-SNP Interactions of Surfactant Protein Genes with Pediatric Acute Respiratory Failure.

The hallmarks of pediatric acute respiratory failure (ARF) are dysregulated inflammation and surfactant dysfunction. The objective is to study association of surfactant protein (SP) genes’ single nucleotide polymorphisms (SNPs) with ARF and its morbidity: pulmonary dysfunction at discharge (PDAD), employing a single-, two-, and three-SNP interaction model. We enrolled 468 newborn controls and 248 children aged ≤ 24 months with ARF; 86 developed PDAD. Using quantitative genetic principles, we tested the association of SP genes SNPs with ARF and PDAD. We observed a dominant effect of rs4715 of the SFTPC on ARF risk. In a three-SNP model, we found (a) 34 significant interactions among SNPs of SFTPA1, SFTPA2, and SFTPC associated with ARF (p = 0.000000002–0.05); 15 and 19 of those interactions were associated with increased and decreased risk for ARF, respectively; (b) intergenic SNP–SNP interactions of both hydrophobic and hydrophilic SP genes associated with PDAD (p = 0.00002–0.03). The majority of intra- and intergenic interactions associated with ARF involve the SFTPA2 SNPs, whereas most of the intra- and intergenic interactions associated with PDAD are of SFTPA1 SNPs. We also observed a dominant effect of haplotypes GG of SFTPA1 associated with increased and AA of SFTPC associated with decreased ARF risk (p = 0.02). To the best of our knowledge, this is the first study showing an association of complex interactions of SP genes with ARF and PDAD. Our data indicate that SP genes polymorphisms may contribute to ARF pathogenesis and subsequent PDAD and/or may serve as markers for disease susceptibility in healthy children.

Inhaled Nitric Oxide Use in Pediatric Hypoxemic Respiratory Failure.

To characterize contemporary use of inhaled nitric oxide in pediatric acute respiratory failure and to assess relationships between clinical variables and outcomes. We sought to study the relationship of inhaled nitric oxide response to patient characteristics including right ventricular dysfunction and clinician responsiveness to improved oxygenation. We hypothesize that prompt clinician responsiveness to minimize hyperoxia would be associated with improved outcomes. An observational cohort study. Eight sites of the Collaborative Pediatric Critical Care Research Network. One hundred fifty-one patients who received inhaled nitric oxide for a primary respiratory indication. Clinical data were abstracted from the medical record beginning at inhaled nitric oxide initiation and continuing until the earliest of 28 days, ICU discharge, or death. Ventilator-free days, oxygenation index, and Functional Status Scale were calculated. Echocardiographic reports were abstracted assessing for pulmonary hypertension, right ventricular dysfunction, and other cardiovascular parameters. Clinician responsiveness to improved oxygenation was determined. One hundred thirty patients (86%) who received inhaled nitric oxide had improved oxygenation by 24 hours. PICU mortality was 29.8%, while a new morbidity was identified in 19.8% of survivors. Among patients who had echocardiograms, 27.9% had evidence of pulmonary hypertension, 23.1% had right ventricular systolic dysfunction, and 22.1% had an atrial communication. Moderate or severe right ventricular dysfunction was associated with higher mortality. Clinicians responded to an improvement in oxygenation by decreasing FIO2 to less than 0.6 within 24 hours in 71% of patients. Timely clinician responsiveness to improved oxygenation with inhaled nitric oxide was associated with more ventilator-free days but not less cardiac arrests, mortality, or additional morbidity. Clinician responsiveness to improved oxygenation was associated with less ventilator days. Algorithms to standardize ventilator management may improve signal to noise ratios in future trials enabling better assessment of the effect of inhaled nitric oxide on patient outcomes. Additionally, confining studies to more selective patient populations such as those with right ventricular dysfunction may be required.