Factors associated with family decision-making after pediatric out-of-hospital cardiac arrest.

AIM: This study aims to identify demographic factors, area-based social determinants of health (SDOH), and clinical features associated with medical decision-making after pediatric out-of-hospital cardiac arrest (OHCA). METHODS: This is a retrospective, exploratory, descriptive analysis of patients < 18 years old admitted to the pediatric intensive care unit (ICU) after OHCA from 2011 to 2022 (n = 217) at an urban tertiary care, free-standing children's hospital. Outcomes of interest included: (1) whether a new advance care plan (ACP) (defined as a written advance directive including do not resuscitate and/or do not intubate) was ordered during hospitalization, and (2) whether the patient was discharged with new medical technology (defined as tracheostomy and/or feeding tube). Logistic regression models identified features associated with these outcomes. RESULTS: Of the 217 patients, 78 patients (36%) had a new ACP placed during their admission. Of the survivors, 26% (27/102) were discharged home with new medical technology. Factors associated with ACP were greater change in Pediatric Cerebral Performance Category (PCPC) score (aOR = 1.49, 95% CI [1.28-1.73], p-value < 0.001) and palliative care consultation (aOR = 2.39, 95% CI [1.16-4.89], p-value 0.018). Factors associated with new medical technology were lower change in PCPC score (aOR = 0.76, 95% C.I. [0.61-0.95], p-value = 0.015) and palliative care consultation (aOR = 7.07, 95% CI [3.01-16.60], p-value < 0.001). There were no associations between area-based SDOH and outcomes. CONCLUSIONS: Understanding factors associated with decision-making related to ACP after OHCA is critical to optimize counseling for families. Multi-institutional studies are warranted to identify whether these findings are generalizable.

Ventilator Weaning and Terminal Extubation: Withdrawal of Life-Sustaining Therapy in Children. Secondary Analysis of the Death One Hour After Terminal Extubation Study.

OBJECTIVE: Terminal extubation (TE) and terminal weaning (TW) during withdrawal of life-sustaining therapies (WLSTs) have been described and defined in adults. The recent Death One Hour After Terminal Extubation study aimed to validate a model developed to predict whether a child would die within 1 hour after discontinuation of mechanical ventilation for WLST. Although TW has not been described in children, pre-extubation weaning has been known to occur before WLST, though to what extent is unknown. In this preplanned secondary analysis, we aim to describe/define TE and pre-extubation weaning (PW) in children and compare characteristics of patients who had ventilatory support decreased before WLST with those who did not. DESIGN: Secondary analysis of multicenter retrospective cohort study. SETTING: Ten PICUs in the United States between 2009 and 2021. PATIENTS: Nine hundred thirteen patients 0-21 years old who died after WLST. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 71.4% ( n = 652) had TE without decrease in ventilatory support in the 6 hours prior. TE without decrease in ventilatory support in the 6 hours prior = 71.4% ( n = 652) of our sample. Clinically relevant decrease in ventilatory support before WLST = 11% ( n = 100), and 17.6% ( n = 161) had likely incidental decrease in ventilatory support before WLST. Relevant ventilator parameters decreased were F io2 and/or ventilator set rates. There were no significant differences in any of the other evaluated patient characteristics between groups (weight, body mass index, unit type, primary diagnostic category, presence of coma, time to death after WLST, analgosedative requirements, postextubation respiratory support modality). CONCLUSIONS: Decreasing ventilatory support before WLST with extubation in children does occur. This practice was not associated with significant differences in palliative analgosedation doses or time to death after extubation.

Effort and work-of-breathing parameters strongly correlate with increased resistance in an animal model.

BACKGROUND: Effort of Breathing (EOB) calculations may be a reliable alternative to Work of Breathing (WOB) calculations in which Respiratory Inductance Plethysmography (RIP) replaces spirometry. We sought to compare EOB and WOB measurements in a nonhuman primate model of increasing extrathoracic inspiratory resistance simulating upper airway obstruction (UAO). METHODS: RIP, spirometry, and esophageal manometry were measured in spontaneously breathing, intubated Rhesus monkeys utilizing 11 calibrated resistors randomly applied for 2-min. EOB was calculated breath-by-breath as Pressure Rate Product (PRP) and Pressure Time Product (PTP). WOB was calculated from the Pressure-Volume curve based on spirometry (WOBSPIR) or RIP flow (WOBRIP). RESULTS: WOB, PRP and PTP showed similar linear increases when exposed to higher levels of resistive loads. When comparing WOBSPIR to WOBRIP, a similar strong correlation was seen for both signals as resistance increased and there were no statistically significant differences. CONCLUSION: EOB and WOB parameters utilizing esophageal manometry and RIP, independent of spirometry, showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates. This allows several potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available. IMPACT: EOB and WOB parameters showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates. There was a strong correlation between spirometry-based WOB versus RIP-based WOB. To date, it has remained untested as to whether EOB is a reliable alternative for WOB and if RIP can replace spirometry in these measurements. Our results enable additional potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available. Where spirometry is not available, there is no need to apply a facemask post extubation to a spontaneously breathing, non-intubated infant to make objective EOB measurements.

Directing CAR NK Cells via the Metabolic Incorporation of CAR Ligands into Malignant Cell Glycans.

The abundance of sialic acid-containing glycans in the glycocalyx of malignant cells enables immune evasion. Here, we leverage the biosynthetic pathways that permit pervasive sialylation to incorporate a chimeric antigen receptor (CAR) ligand into malignant cell glycans, and demonstrate that this increases the susceptibility of malignant cells to the cytolytic activity of CAR-expressing natural killer (NK) cells. Specifically, we applied a C-9-functionalized nonnatural sialic acid [i.e., fluorescein sialic acid (FL-SA)] to modify malignant cell glycans. We confirm the metabolic incorporation of FL-SA into plasma membrane-associated glycans. The preparation of anti-fluorescein CAR NK cells permitted studies demonstrating that treating malignant cells with FL-SA increased susceptibility to CAR NK cell-mediated cytolysis. Furthermore, we observed that the specificity of the anti-fluorescein CAR NK cells is enhanced for fluorescein-labeled cells, and an increased release of cytokines from the CAR NK cells upon incubation with FL-SA-treated cells. The results arising from this study demonstrate that CAR ligands can be metabolically incorporated into malignant cells, and we reason that such strategies could be leveraged to tackle the issue of antigen heterogeneity that limits the clinical efficacy of CAR T/NK cell therapies.

PICU admission and complications following adenotonsillectomies in pediatric patients: A retrospective cohort study.

BACKGROUND: Children with obstructive sleep apnea (OSA) have higher risks of post-operative respiratory complication after adenotonsillectomy. However, there is no clinical standard criteria for pediatric intensive care unit (PICU) admission following adenotonsillectomy. The purpose of this study was to identify perioperative risk factors associated with the need for PICU level care after adenotonsillectomy. METHODS: We performed a retrospective chart review of children with severe OSA (apnea hypopnea index on polysomnography; AHI ≥10) and/or post-operative PICU admission at a tertiary academic center from May 2010 to September 2018. We collected demographics, pre-existing comorbidities, perioperative medications, and post-operative complications. We defined a primary outcome as escalation of airway management while in the PICU or PICU stay >48 h. Airway escalation included the need for an invasive airway, new CPAP application, increased CPAP setting, or increased supplemental oxygen. RESULTS: Analysis included 278 children with severe OSA and/or PICU admission. Median age was 6.6 years old; 181 (65%) were admitted to the PICU, and 60 (21.5%) had the composite outcome of escalation of airway management or prolonged stay. In patients with an escalation of airway management, 28 needed intubation or mechanical ventilation. Multivariable logistic regression showed intraoperative respiratory complications, polysomnography (PSG) peak end-tidal CO2 (EtCO2) reading >60 mmHg, and the presence of neuromuscular disease as significant associated factors for escalation of airway management or prolonged PICU stay (P values < 0.01; odd ratios 3.4, 5.3, and 5.4, respectively). CONCLUSION: For children following adenotonsillectomy, PSG EtCO2 ≥ 60%, preexisting neuromuscular disease, and intraoperative complications (hypoxia, difficult airway, etc.) were independently associated with escalation of airway management or prolonged stay. AHI was not an independent predictor for PICU complication. We concluded factors should be considered for PICU admission in addition to AHI.

High-Flow Nasal Cannula Reduces Effort of Breathing But Not Consistently via Positive End-Expiratory Pressure.

BACKGROUND: High-flow nasal cannula (HFNC) therapy reduces the effort of breathing in patients with bronchiolitis, but the mechanisms are not understood. Theorized mechanisms include dead space washout and positive end-expiratory pressure (PEEP) application. RESEARCH QUESTION: What are the mechanisms of action of HFNC therapy in patients with bronchiolitis? STUDY DESIGN AND METHODS: Prospective, single-center study of children 3 years of age or younger with bronchiolitis from January 2020 through March 2021. Flow was titrated between 0.5 and 2 L/kg/min. Electrical impedance tomography measured end-expiratory lung impedance (EELZ) change as an end-expiratory lung volume (EELV) change surrogate and change in tidal impedance difference (ΔZ) as a tidal volume (VT) surrogate. A subset showed manometry measuring esophageal pressure change (ΔPes; transpulmonary pressure surrogate) and pressure rate product (PRP; effort of breathing metric). We hypothesized that EELV and VT would not change and that effort would reduce via respiratory rate (not ΔPes). Measurements were reported as the difference from 0.5 L/kg/min. RESULTS: We studied 22 patients in total, 10 with esophageal manometry. Median EELZ increased by 0.36 arbitrary unit (AU), 2.42 AU, and 4.8 AU at 1 L/kg/min, 1.5 L/kg/min, and 2 L/kg/min (P = .01, 2 L/kg/min vs 0.5 L/kg/min), which corresponded to a median increase in EELV of 1.8 mL/kg between 0.5 and 2 L/kg/min. Seven patients showed an increase in EELZ of > 5 AU, 12 showed no change in EELZ (± 5 AU), and three showed a decrease in EELZ of > 5 AU. ΔZ (ie, VT) did not change from 0.5 L/kg/min to 2 L/kg/min (median change, 0.29 AU; P = .48). Median PRP decreased by 78 cm H2O/min from 0.5 L/kg/min to 2 L/kg/min (P = .02), with all patients demonstrating a reduction in PRP, with a nonsignificant change in ΔPes (P = .68). INTERPRETATION: Increasing HFNC in children with bronchiolitis reduces the effort of breathing, but no consistent increase occurs in end-expiratory lung volume and no significant change occurs in VT or transpulmonary pressure. This suggests that PEEP application is not the primary mechanism of action of HFNC in children with bronchiolitis.

A New Trick for an Old Dog: L-Epinephrine Delivered Continuously in the Vapor Phase.

Inhaled L-epinephrine is a known treatment of severe croup and postextubation upper airway obstruction. L-epinephrine can be delivered continuously in the vapor phase, but the indications, safety, and efficacy of this novel practice have yet to be evaluated. Theoretical risks are tachycardia, hypertension, and dysrhythmias. The study objective was to describe patient characteristics and vital sign changes related to continuous vaporized L-epinephrine use in critically ill children with the hypothesis that it can be practically and safely administered to children with subglottic edema and lower airway obstruction. DESIGN: Retrospective cohort study. SETTING: PICU and cardiothoracic ICU in a tertiary academic children's hospital. PATIENTS: Patients age 0-21 years treated with continuous vaporized L-epinephrine from 2013 to 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Continuous vaporized L-epinephrine was administered 140 times to 129 subjects via a high-flow nasal oxygen device. The median age was 10.6 months (1.3; interquartile range, 4.8-17.1 mo). The most common indications were lower respiratory tract obstruction (45%), postextubation subglottic edema (31%), and croup (16%). Eighty-eight percent had no escalation of respiratory support within 24 hours of initiation of continuous vaporized L-epinephrine, 5% progressed to require endotracheal intubation, and 3% were reintubated within 24 hours of initiation of continuous vaporized L-epinephrine following an extubation attempt. After starting continuous vaporized L-epinephrine, 85% of subjects had a decrease in heart rate and 80% had a decrease in respiratory rate. Six subjects had an increase in heart rate, and eight had an increase in blood pressure of more than 20% from baseline. These subjects did not receive interventions specific to these vital sign changes, including discontinuation of continuous vaporized L-epinephrine. CONCLUSIONS: Continuous vaporized L-epinephrine was safely administered to critically ill children with most subjects demonstrating a decrease in heart rate, blood pressure, and respiratory rate.

Subglottic Post-Extubation Upper Airway Obstruction Is Associated With Long-Term Airway Morbidity in Children.

OBJECTIVES: Post-extubation upper airway obstruction is the most common cause of extubation failure in children, but there are few data regarding long-term morbidity. We aim to describe the frequency of long-term airway sequelae in intubated children and determine the association with post-extubation upper airway obstruction. DESIGN: Retrospective, post hoc analysis of previously identified prospective cohort of children in the pediatric/cardiothoracic ICU at Children's Hospital Los Angeles from July 2012 to April 2015. A single provider blinded to the upper airway obstruction classification reviewed the electronic medical records of all patients in the parent study, before and after the index extubation (extubation during parent study), to identify pre-index and post-index upper airway disease. Primary outcomes were prevalence of newly diagnosed airway anomalies following index extubation. SETTING: Single center, tertiary, 391-bed children's hospital. PATIENTS: From the parent study, 327 children younger than 18 years (intubated for at least 12 hr) were included if they received subsequent care (regardless of specialty) after the index extubation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: New airway anomalies were identified in 40 of 327 children (12.2%). Patients labeled with subglottic upper airway obstruction at the index extubation were more likely to be diagnosed with new airway anomalies on subsequent follow-up, receive long-term Otolaryngology follow-up, or receive airway surgery (all p ≤ 0.006). In multivariable modeling, upper airway obstruction as the primary reason for initial intubation (odds ratio, 3.71; CI, 1.50-9.19), reintubation during the index ICU admission (odds ratio, 4.44; CI, 1.67-11.80), pre-index airway anomaly (odds ratio, 3.31; CI, 1.36-8.01), and post-extubation subglottic upper airway obstruction (odds ratio, 3.50; CI, 1.46-8.34) remained independently associated with the diagnosis of new airway anomalies. CONCLUSIONS: Post-extubation subglottic upper airway obstruction is associated with a three-fold greater odds of long-term airway morbidity. These patients may represent an at-risk population that should be monitored closely after leaving the ICU.

Declining Procedures in Pediatric Critical Care Medicine Using a National Database.

OBJECTIVES: To investigate the change in rate of invasive procedures (endotracheal intubation, central venous catheters, arterial catheters, and peripheral inserted central venous catheters) performed in PICUs per admission over time. Secondarily, to investigate the change in type of respiratory support over time. DESIGN: Retrospective study of prospectively collected data using the Virtual Pediatric Systems (VPS; LLC, Los Angeles, CA) database. SETTING: North American PICUs. PATIENTS: Patients admitted from January 2009 to December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 902,624 admissions from 161 PICUs included in the analysis. Since 2009, there has been a decrease in rate of endotracheal intubations, central venous catheters placed, and arterial catheters placed and an increase in the rate of peripheral inserted central venous catheter insertion per admission over time after controlling for severity of illness and unit level effects. As compared to 2009, the incident rate ratio for 2017 for endotracheal intubation was 0.90 (95% CI, 0.83-0.98; p = 0.017), for central venous line placement 0.69 (0.63-0.74; p < 0.001), for arterial catheter insertion 0.85 (0.79-0.92; p < 0.001), and for peripheral inserted central venous catheter placement 1.14 (1.03-1.26; p = 0.013). Over this time period, in a subgroup with available data, there was a decrease in the rate of invasive mechanical ventilation and an increase in the rate of noninvasive respiratory support (bilevel positive airway pressure/continuous positive airway pressure and high-flow nasal oxygen) per admission. CONCLUSIONS: Over 9 years across multiple North American PICUs, the rate of endotracheal intubations, central catheter, and arterial catheter insertions per admission has decreased. The use of invasive mechanical ventilation has decreased with an increase in noninvasive respiratory support. These data support efforts to improve exposure to invasive procedures in training and structured systems to evaluate continued competency.

Machine Learning to Predict Cardiac Death Within 1 Hour After Terminal Extubation.

OBJECTIVES: Accurate prediction of time to death after withdrawal of life-sustaining therapies may improve counseling for families and help identify candidates for organ donation after cardiac death. The study objectives were to: 1) train a long short-term memory model to predict cardiac death within 1 hour after terminal extubation, 2) calculate the positive predictive value of the model and the number needed to alert among potential organ donors, and 3) examine associations between time to cardiac death and the patient's characteristics and physiologic variables using Cox regression. DESIGN: Retrospective cohort study. SETTING: PICU and cardiothoracic ICU in a tertiary-care academic children's hospital. PATIENTS: Patients 0-21 years old who died after terminal extubation from 2011 to 2018 (n = 237). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median time to death for the cohort was 0.3 hours after terminal extubation (interquartile range, 0.16-1.6 hr); 70% of patients died within 1 hour. The long short-term memory model had an area under the receiver operating characteristic curve of 0.85 and a positive predictive value of 0.81 at a sensitivity of 94% when predicting death within 1 hour of terminal extubation. About 39% of patients who died within 1 hour met organ procurement and transplantation network criteria for liver and kidney donors. The long short-term memory identified 93% of potential organ donors with a number needed to alert of 1.08, meaning that 13 of 14 prepared operating rooms would have yielded a viable organ. A Cox proportional hazard model identified independent predictors of shorter time to death including low Glasgow Coma Score, high Pao2-to-Fio2 ratio, low-pulse oximetry, and low serum bicarbonate. CONCLUSIONS: Our long short-term memory model accurately predicted whether a child will die within 1 hour of terminal extubation and may improve counseling for families. Our model can identify potential candidates for donation after cardiac death while minimizing unnecessarily prepared operating rooms.

Engaging Parents in Analgesia Selection and Racial/Ethnic Differences in Analgesia Given to Pediatric Patients Undergoing Urologic Surgery.

BACKGROUND: Family-centered care aims to consider family preferences and values in care delivery. Our study examines parent decisions regarding anesthesia type (caudal regional block or local anesthesia) among a diverse sample of children undergoing urologic surgeries. Differences in anesthesia type were examined by known predictors of health disparities, including child race/ethnicity, parental English proficiency, and a proxy for household income. METHODS: A retrospective review of 4739 patients (including 25.4% non-Latino/a White, 8.7% non- Latino/a Asians, 7.3% non-Latino/a Black, 23.1% Latino/a, and 35.4% others) undergoing urologic surgeries from 2016 to 2020 using univariate and logistic regression analyses. RESULTS: 62.1% of Latino/a parents and 60.8% of non-Latino/a Black parents did not agree to a regional block. 65.1% of Spanish-speaking parents with limited English Proficiency did not agree to a regional block. Of parents from households below poverty lines, 61.7% did not agree to a caudal regional block. In regression analysis, Latino/a and non- Latino/a Black youth were less likely to receive caudal regional block than non- Latino/a White patients. CONCLUSIONS: We found disparities in the use of pediatric pain management techniques. Understanding mechanisms underlying Latino/a and non- Latino/a Black parental preferences may help providers reduce these disparities.

Thresholds for oximetry alarms and target range in the NICU: an observational assessment based on likely oxygen tension and maturity.

BACKGROUND: Continuous monitoring of SpO2 in the neonatal ICU is the standard of care. Changes in SpO2 exposure have been shown to markedly impact outcome, but limiting extreme episodes is an arduous task. Much more complicated than setting alarm policy, it is fraught with balancing alarm fatigue and compliance. Information on optimum strategies is limited. METHODS: This is a retrospective observational study intended to describe the relative chance of normoxemia, and risks of hypoxemia and hyperoxemia at relevant SpO2 levels in the neonatal ICU. The data, paired SpO2-PaO2 and post-menstrual age, are from a single tertiary care unit. They reflect all infants receiving supplemental oxygen and mechanical ventilation during a 3-year period. The primary measures were the chance of normoxemia (PaO2 50-80 mmHg), risks of severe hypoxemia (PaO2 ≤ 40 mmHg), and of severe hyperoxemia (PaO2 ≥ 100 mmHg) at relevant SpO2 levels. RESULTS: Neonates were categorized by postmenstrual age: < 33 (n = 155), 33-36 (n = 192) and > 36 (n = 1031) weeks. From these infants, 26,162 SpO2-PaO2 pairs were evaluated. The post-menstrual weeks (median and IQR) of the three groups were: 26 (24-28) n = 2603; 34 (33-35) n = 2501; and 38 (37-39) n = 21,058. The chance of normoxemia (65, 95%-CI 64-67%) was similar across the SpO2 range of 88-95%, and independent of PMA. The increasing risk of severe hypoxemia became marked at a SpO2 of 85% (25, 95%-CI 21-29%), and was independent of PMA. The risk of severe hyperoxemia was dependent on PMA. For infants < 33 weeks it was marked at 98% SpO2 (25, 95%-CI 18-33%), for infants 33-36 weeks at 97% SpO2 (24, 95%-CI 14-25%) and for those > 36 weeks at 96% SpO2 (20, 95%-CI 17-22%). CONCLUSIONS: The risk of hyperoxemia and hypoxemia increases exponentially as SpO2 moves towards extremes. Postmenstrual age influences the threshold at which the risk of hyperoxemia became pronounced, but not the thresholds of hypoxemia or normoxemia. The thresholds at which a marked change in the risk of hyperoxemia and hypoxemia occur can be used to guide the setting of alarm thresholds. Optimal management of neonatal oxygen saturation must take into account concerns of alarm fatigue, staffing levels, and FiO2 titration practices.

Impact of Anesthetic and Ventilation Strategies on Invasive Hemodynamic Measurements in Pediatric Heart Transplant Recipients.

BACKGROUND: Care of pediatric heart transplant recipients relies upon serial invasive hemodynamic evaluation, generally performed under the artificial conditions created by anesthesia and supportive ventilation. OBJECTIVES: This study aimed to evaluate the hemodynamic impacts of different anesthetic and ventilatory strategies. METHODS: We compared retrospectively the cardiac index, right- and left-sided filling pressures, and pulmonary and systemic vascular resistances of all clinically well and rejection-free heart transplant recipients catheterized from 2005 through 2017. Effects of spontaneous versus positive pressure ventilation and of sedation versus general anesthesia were tested with generalized linear mixed models for repeated measures using robust sandwich estimators of the covariance matrices. Least squared means showed adjusted mean outcome values, controlled for appropriate confounders. RESULTS: 720 catheterizations from 101 recipients met inclusion criteria. Adjusted cardiac index was 3.14 L/min/m2 (95% CI 3.01-3.67) among spontaneously breathing and 2.71 L/min/m2 (95% CI 2.56-2.86) among ventilated recipients (p < 0.0001). With spontaneous breathing, left filling pressures were lower (9.9 vs 11.0 mmHg, p = 0.030) and systemic vascular resistances were higher (24.0 vs 20.5 Woods units, p < 0.0001). After isolating sedated from anesthetized spontaneously breathing patients, the observed differences in filling pressures and resistances emerged as a function of sedation versus general anesthesia rather than of spontaneous versus positive pressure ventilation. CONCLUSION: In pediatric heart transplant recipients, positive pressure ventilation reduces cardiac output but does not alter filling pressures or vascular resistances. Moderate sedation yields lower left filling pressures and higher systemic vascular resistances than does general anesthesia. Differences are quantitatively small.

A Phase II randomized controlled trial for lung and diaphragm protective ventilation (Real-time Effort Driven VENTilator management).

Lung Protective Mechanical Ventilation (MV) of critically ill adults and children is lifesaving but it may decrease diaphragm contraction and promote Ventilator Induced Diaphragm Dysfunction (VIDD). An ideal MV strategy would balance lung and diaphragm protection. Building off a Phase I pilot study, we are conducting a Phase II controlled clinical trial that seeks to understand the evolution of VIDD in critically ill children and test whether a novel computer-based approach (Real-time Effort Driven ventilator management (REDvent)) can balance lung and diaphragm protective ventilation to reduce time on MV. REDvent systematically adjusts PEEP, FiO2, inspiratory pressure, tidal volume and rate, and uses real-time measures from esophageal manometry to target normal levels of patient effort of breathing. This trial targets 276 children with pulmonary parenchymal disease. Patients are randomized to REDvent vs. usual care for the acute phase of MV (intubation to first Spontaneous Breathing Trial (SBT)). Patients in either group who fail their first SBT will be randomized to REDvent vs usual care for weaning phase management (interval from first SBT to passing SBT). The primary clinical outcome is length of weaning, with several mechanistic outcomes. Upon completion, this study will provide important information on the pathogenesis and timing of VIDD during MV in children and whether this computerized protocol targeting lung and diaphragm protection can lead to improvement in intermediate clinical outcomes. This will form the basis for a larger, Phase III multi-center study, powered for key clinical outcomes such as 28-day ventilator free days. Clinical Trials Registration: NCT03266016.

Evaluating the Practice of Repositioning Endotracheal Tubes in Neonates and Children Based on Radiographic Location.

OBJECTIVES: Chest radiographs are commonly performed in the ICU setting to confirm the position of the endotracheal tube. The purpose of this study was to evaluate the practice and accuracy of repositioning endotracheal tubes in the pediatric population based on chest radiograph. DESIGN: Retrospective review of patient's medical record and chest radiograph. SETTING: Single-institution, academic children's hospital. PATIENTS: PICU and cardiothoracic ICU patients who had repositioning of their endotracheal tube from September 1, 2016, to September 1, 2017. MEASUREMENTS AND MAIN RESULTS: Chest radiograph before and after endotracheal tube repositioning were examined measuring the distance from the endotracheal tube tip to carina. A total of 183 endotracheal tube repositionings were assessed. Twenty-nine percent of endotracheal tube repositionings resulted in a persistently malpositioned endotracheal tube, requiring another intervention. For intended endotracheal tube repositioning of ± 2.0 cm, the actual change measured compared to intended adjustment was a median of 0.7 cm (interquartile range, 0.35-1.1 cm). For intended ± 1.5 cm, the median difference was 0.4 cm (interquartile range, 0.16-0.90 cm). For intended ± 1.0 cm, the median difference was 0.5 cm (interquartile range, 0.20-0.90 cm). For intended ± 0.5 cm, the median difference was 0.3 cm (interquartile range, 0.2-0.88 cm). When the head was malpositioned the difference from intended endotracheal tube repositioning to actual was median 0.70 cm (interquartile range, 0.40-1.1 cm), this was significantly higher than when the head was in a good position CONCLUSIONS:: When repositioning endotracheal tubes based on chest radiograph, there is a significant difference between intended and actual adjustment with great variability. Avoiding very small repositionings (± 0.5 cm) and standardizing head position prior to daily chest radiograph may reduce these errors.

Body Habitus and Risk of Mortality in Pediatric Sepsis and Septic Shock: A Retrospective Cohort Study.

OBJECTIVE: To investigate the association between body habitus and mortality in critically ill children with sepsis or septic shock. STUDY DESIGN: This was a retrospective cohort study of prospectively collected data of children admitted to US pediatric intensive care units (PICUs) with a primary or secondary diagnosis of sepsis or septic shock. We separated body habitus into underweight, normal weight, overweight, and obese. Outcomes were mortality (primary), treatment with invasive mechanical ventilation (secondary), and time to PICU discharge for survivors (secondary). Multivariable analyses using mixed-effects logistic regression and shared frailty models clustered by unit and adjusted for confounding variables were used to assess the association between body habitus and outcomes. RESULTS: There were 7038 children with sepsis or septic shock. Mortality was 10.1% (n = 714) and 52.9% (n = 3720) required invasive mechanical ventilation. Body habitus was not associated with mortality after controlling for hospital level effects and confounding variables. Children who were overweight and obese had greater odds of invasive mechanical ventilation (overweight OR 1.23 [95% CI 1.05-1.45], P = .011 and obese OR 1.57 [95% CI 1.37-1.80], P < .001) compared with children of normal weight. In survivors treated with invasive mechanical ventilation, children who were obese had a longer time to PICU discharge than children of normal weight (obese hazard ratio for discharge 0.84 [95% CI, 0.77-0.92], P < .0001). CONCLUSIONS: There was no association between body habitus and mortality in critically ill children with sepsis. Children who were overweight and obese were more likely to receive invasive mechanical ventilation and mechanically ventilated survivors who were obsese had a longer time to PICU discharge.

Minimal Change in Cardiac Index With Increasing PEEP in Pediatric Acute Respiratory Distress Syndrome.

Objective: To determine if increasing positive end expiratory pressure (PEEP) leads to a change in cardiac index in children with Pediatric Acute Respiratory Distress Syndrome ranging from mild to severe. Design: Prospective interventional study. Setting: Multidisciplinary Pediatric Intensive Care Unit in a University teaching hospital. Patients: Fifteen intubated children (5 females, 10 males) with a median age of 72 months (IQR 11, 132) and a median weight of 19.3 kg (IQR 7.5, 53.6) with a severity of Pediatric Acute Respiratory Distress Syndrome that ranged from mild to severe with a median lung injury score of 2.3 (IQR 2.0, 2.7). Measurements: Cardiac index (CI) and stroke volume (SV) were measured on baseline ventilator settings and subsequently with a PEEP 4 cmH2O higher than baseline. Change in CI and SV from baseline values was evaluated using Wilcoxon signed rank test. Results: A total of 19 paired measurements obtained. The median baseline PEEP was 8 cmH2O (IQR 8, 10) Range 6-14 cmH2O. There was no significant change in cardiac index or stroke volume with change in PEEP. Baseline median CI 4.4 L/min/m2 (IQR 3.4, 4.8) and PEEP 4 higher median CI of 4.3 L/min/m2 (IQR 3.6, 4.8), p = 0.65. Baseline median SV 26 ml (IQR 13, 44) and at PEEP 4 higher median SV 34 ml (IQR 12, 44) p = 0.63. Conclusion: There is no significant change in cardiac index or stroke volume with increasing PEEP by 4 cmH2O in a population of children with mild to severe PARDS. Clinical Trial Registration: The study is registered on Clinical trails.gov under the Identifier: NCT02354365.

Hypoxemic and hyperoxemic likelihood in pulse oximetry ranges: NICU observational study.

OBJECTIVE: Describe the likelihood of hypoxemia and hyperoxemia across ranges of oxygen saturation (SpO2), during mechanical ventilation with supplemental oxygenation. DESIGN: Retrospective observational study. SETTING: University affiliated tertiary care neonatal intensive care unit. PATIENTS: Two groups of neonates based on postmenstrual age (PMA): <32 weeks (n=104) and >36 weeks (n=709). MAIN MEASURES: Hypoxemia was defined as a PaO2 <40 mm Hg, hyperoxemia as a PaO2 of >99 mm Hg and normoxemia as a PaO2 of 50-80 mm Hg. Twenty-five per cent was defined as marked likelihood of hypoxemia or hyperoxemia. RESULTS: From these infants, 18 034 SpO2-PaO2 pairs were evaluated of which 10% were preterm. The PMA (median and IQR) of the two groups were: 28 weeks (27-30) and 40 weeks (38-41). With SpO2 levels between 90% and 95%, the likelihoods of hypoxemia and hyperoxemia were low and balanced. With increasing levels of SpO2, the likelihood of hyperoxemia increased. It became marked in the preterm group when SpO2 was 99%-100% (95% CI 29% to 41%) and in the term group with SpO2 levels of 96%-98% (95% CI 29% to 32%). The likelihood of hypoxemia increased as SpO2 decreased. It became marked in both with SpO2 levels of 80%-85% (95% CI 20% to 31%, 24% to 28%, respectively). CONCLUSIONS: The likelihood of a PaO2 <40 mm Hg is marked with SpO2 below 86%. The likelihood of a PaO2 >99 mm Hg is marked in term infants with SpO2 above 95% and above 98% in preterm infants. SpO2 levels between 90% and 95% are appropriate targets for term and preterm infants.