Publications by authors named "Robinder G Khemani"

107 Publications

Value and limitations of real-world data to understand paediatric adherence to positive airway pressure therapy.

Lancet Digit Health 2020 02 23;2(2):e56-e57. Epub 2019 Dec 23.

Children's Hospital Los Angeles, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2589-7500(19)30237-7DOI Listing
February 2020

Frequency and Risk Factors for Reverse Triggering in Pediatric ARDS during Synchronized Intermittent Mandatory Ventilation.

Ann Am Thorac Soc 2020 Dec 16. Epub 2020 Dec 16.

Children's Hospital Los Angeles, Anesthesia and Critical Care Medicine, Los Angeles, California, United States.

Rationale: Reverse triggering (RT) occurs when respiratory effort begins after a mandatory breath is initiated by the ventilator. RT may exacerbate ventilator-induced lung injury and lead to breath stacking.

Objectives: We sought to describe the frequency and risk factors for RT amongst ARDS patients and identify risk factors for breath-stacking.

Methods: Secondary analysis of physiologic data from children on Synchronized Intermittent Mandatory pressure control ventilation enrolled in a single center RCT for ARDS. When children had a spontaneous effort on esophageal manometry, waveforms were recorded and independently analyzed by two investigators to identify RT.

Results: We included 81,990 breaths from 100 patient-days and 36 patients. Overall, 2.46% of breaths were RTs, occurring in 15/36 patients (41.6%). Higher tidal volume and a minimal difference between neural respiratory rate and set ventilator rate were independently associated with RT (p=0.001) in multivariable modeling. Breath stacking occurred in 534 (26.5%) of 2017 RT breaths, and 14 (93.3%) of 15 RT patients. In multivariable modeling, breath stacking was more likely to occur when total airway delta pressure (Peak Inspiratory Pressure-PEEP) at the time patient effort began, Peak Inspiratory Pressure, PEEP, and Delta Pressure were lower, and when patient effort started well after the ventilator initiated breath (higher phase angle) (all p<0.05). Together these parameters were highly predictive of breath stacking (AUC 0.979).

Conclusions: Patients with higher tidal volume and who have a set ventilator rate close to their spontaneous respiratory rate are more likely to have RT, which results in breath stacking over 25% of the time. Clinical trial registered with ClinicalTrials.gov (NCT03266016).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1513/AnnalsATS.202008-1072OCDOI Listing
December 2020

Direction and Magnitude of Change in Plateau From Peak Pressure During Inspiratory Holds Can Identify the Degree of Spontaneous Effort and Elastic Workload in Ventilated Patients.

Crit Care Med 2021 Mar;49(3):517-526

Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Los Angeles, Los Angeles, CA.

Objectives: Inspiratory holds with measures of airway pressure to estimate driving pressure (elastic work) are often limited to patients without respiratory effort. We sought to evaluate if measures of airway pressure during inspiratory holds could be used for patients with spontaneous respiratory effort during mechanical ventilation to estimate the degree of spontaneous effort and elastic work.

Design: We compared the direction and degree of change in airway pressure during inspiratory holds versus esophageal pressure through secondary analysis of physiologic data.

Setting: ICUs at Children's Hospital Los Angeles.

Patients: Children with pediatric acute respiratory distress syndrome with evidence of spontaneous respiration while on pressure control or pressure support ventilation.

Interventions: Inspiratory hold maneuvers.

Measurements And Main Results: From airway pressure, we defined "plateau - peak pressure" as Pmusc, index, which was divided into three categories for analysis (< -1 ["negative"], between -1 and 1 ["neutral"], and > 1 cm H2O ["positive"]). A total of 30 children (age 36.8 mo [16.1-70.3 mo]) from 65 study days, comprising 118 inspiratory holds were included. Pmusc, index was "negative" in 29 cases, was "neutral" in 17 cases, and was "positive" in 72 cases. As Pmusc, index went from negative to neutral to positive, there was larger negative deflection in esophageal pressure -5.0 (-8.2 to 1.9), -5.9 (-7.6 to 4.3), and -10.7 (-18.1 to 7.9) cm H2O (p < 0.0001), respectively. There was a correlation between max negative esophageal pressure and Pmusc, index (r = -0.52), and when Pmusc, index was greater than or equal to 7 cm H2O, the max negative esophageal pressure was greater than 10 cm H2O. There was a stronger correlation between Pmusc, index and markers of elastic work from esophageal pressure (r = 0.84).

Conclusions: The magnitude of plateau minus peak pressure during an inspiratory hold is correlated with the degree of inspiratory effort, particularly for those with high elastic work. It may be useful to identify patients with excessively high effort or high driving pressure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000004746DOI Listing
March 2021

Real-Time Effort Driven Ventilator Management: A Pilot Study.

Pediatr Crit Care Med 2020 11;21(11):933-940

Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA.

Objectives: Mechanical ventilation of patients with acute respiratory distress syndrome should balance lung and diaphragm protective principles, which may be difficult to achieve in routine clinical practice. Through a Phase I clinical trial, we sought to determine whether a computerized decision support-based protocol (real-time effort-driven ventilator management) is feasible to implement, results in improved acceptance for lung and diaphragm protective ventilation, and improves clinical outcomes over historical controls.

Design: Interventional nonblinded pilot study.

Setting: PICU.

Patients: Mechanically ventilated children with acute respiratory distress syndrome.

Interventions: A computerized decision support tool was tested which prioritized lung-protective management of peak inspiratory pressure-positive end-expiratory pressure, positive end-expiratory pressure/FIO2, and ventilatory rate. Esophageal manometry was used to maintain patient effort in a physiologic range. Protocol acceptance was reported, and enrolled patients were matched 4:1 with respect to age, initial oxygenation index, and percentage of immune compromise to historical control patients for outcome analysis.

Measurements And Main Results: Thirty-two patients were included. Acceptance of protocol recommendations was over 75%. One-hundred twenty-eight matched historical controls were used for analysis. Compared with historical controls, patients treated with real-time effort-driven ventilator management received lower peak inspiratory pressure-positive end-expiratory pressure and tidal volume, and higher positive end-expiratory pressure when FIO2 was greater than 0.60. Real-time effort-driven ventilator management was associated with 6 more ventilator-free days, shorter duration until the first spontaneous breathing trial and 3 fewer days on mechanical ventilation among survivors (all p ≤ 0.05) in comparison with historical controls, while maintaining no difference in the rate of reintubation.

Conclusions: A computerized decision support-based protocol prioritizing lung-protective ventilation balanced with reduction of controlled ventilation to maintain physiologic levels of patient effort can be implemented and may be associated with shorter duration of ventilation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PCC.0000000000002556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609612PMC
November 2020

Ventilator Liberation in the Pediatric ICU.

Respir Care 2020 Oct;65(10):1601-1610

Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, California.

Despite the accepted importance of minimizing time on mechanical ventilation, only limited guidance on weaning and extubation is available from the pediatric literature. A significant proportion of patients being evaluated for weaning are actually ready for extubation, suggesting that weaning is often not considered early enough in the course of ventilation. Indications for extubation are often not clear, although a trial of spontaneous breathing on CPAP without pressure support seems an appropriate prerequisite in many cases. Several indexes have been developed to predict weaning and extubation success, but the available literature suggests they offer little or no improvement over clinical judgment. New techniques for assessing readiness for weaning and predicting extubation success are being developed but are far from general acceptance in pediatric practice. While there have been some excellent physiologic, observational, and even randomized controlled trials on aspects of pediatric ventilator liberation, robust research data are lacking. Given the lack of data in many areas, a determined approach that combines systematic review with consensus opinion of international experts could generate high-quality recommendations and terminology definitions to guide clinical practice and highlight important areas for future research in weaning, extubation readiness, and liberation from mechanical ventilation following pediatric respiratory failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4187/respcare.07810DOI Listing
October 2020

The Association Between Ventilatory Ratio and Mortality in Children and Young Adults.

Respir Care 2021 Feb 11;66(2):205-212. Epub 2020 Aug 11.

Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, California.

Background: The ventilatory ratio (VR) is a dead-space marker associated with mortality in mechanically ventilated adults with ARDS. The end-tidal alveolar dead space fraction (AVDSf) has been associated with mortality in children. However, AVDSf requires capnography measurements, whereas VR does not. We sought to examine the prognostic value of VR, in comparison to AVDSf, in children and young adults with acute hypoxemic respiratory failure.

Methods: We conducted a retrospective study of prospectively collected data from 180 mechanically ventilated children and young adults with acute hypoxemic respiratory failure. VR was calculated as (minute ventilation × [Formula: see text])/(age-adjusted predicted minute ventilation × 37.5). AVDSf was calculated as [Formula: see text].

Results: VR and AVDSf had a moderate correlation (rho 0.31, < .001). VR was similar between survivors at 1.22 (interquartile range [IQR] 1.0-1.52) and nonsurvivors at 1.30 (IQR 0.96-1.95) ( = .2). AVDSf was lower in survivors at 0.12 (IQR 0.03-0.23) than nonsurvivors at 0.24 (IQR 0.13-0.33) ( < .001). In logistic regression and competing risk regression analyses, VR was not associated with mortality or rate of extubation at any given time (competing risk death; all > .3). An AVDSf in the highest 2 quartiles, in comparison to the lowest quartile (AVDSf < 0.06), was associated with higher mortality after adjustment for oxygenation index and severity of illness (AVDSf ≥ 0.15-0.26: odds ratio 3.58, 95% CI 1.02-12.64, = .047, and AVDSf ≥ 0.26: odds ratio 3.91 95% CI-1.03-14.83, = .045). At any given time after intubation, a child with an AVDSf ≥ 0.26 was less likely to be extubated than a child with an AVDSf < 0.06, after adjustment for oxygenation index and severity of illness (AVDSf ≥ 0.26: subdistribution hazard ratio 0.55, 95% CI 0.33-0.94, = .03).

Conclusions: VR should not be used for prognostic purposes in children and young adults. AVDSf added prognostic information to the severity of oxygenation defect and overall severity of illness in children and young adults, consistent with previous research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4187/respcare.07937DOI Listing
February 2021

High Breath-by-Breath Variability Is Associated With Extubation Failure in Children.

Crit Care Med 2020 Aug;48(8):1165-1174

1Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA. 2Department of Neonatology, Children's Hospital Los Angeles, Los Angeles, CA. 3Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, CA. 4Department of Biomedical Engineering, University of Southern California, Los Angeles, CA.

Objectives: Extubation failure is multifactorial, and most tools to assess extubation readiness only evaluate snapshots of patient physiology. Understanding variability in respiratory variables may provide additional information to inform extubation readiness assessments.

Design: Secondary analysis of prospectively collected physiologic data of children just prior to extubation during a spontaneous breathing trial. Physiologic data were cleaned to provide 40 consecutive breaths and calculate variability terms, coefficient of variation and autocorrelation, in commonly used respiratory variables (i.e., tidal volume, minute ventilation, and respiratory rate). Other clinical variables included diagnostic and demographic data, median values of respiratory variables during spontaneous breathing trials, and the change in airway pressure during an occlusion maneuver to measure respiratory muscle strength (maximal change in airway pressure generated during airway occlusion [PiMax]). Multivariable models evaluated independent associations with reintubation and prolonged use of noninvasive respiratory support after extubation.

Setting: Acute care, children's hospital.

Patients: Children were included from the pediatric and cardiothoracic ICUs who were greater than 37 weeks gestational age up to and including 18 years who were intubated greater than or equal to 12 hours with planned extubation. We excluded children who had a contraindication to an esophageal catheter or respiratory inductance plethysmography bands.

Interventions: Noninterventional study.

Measurements And Main Results: A total of 371 children were included, 32 of them were reintubated. Many variability terms were associated with reintubation, including coefficient of variation and autocorrelation of the respiratory rate. After controlling for confounding variables such as age and neurologic diagnosis, both coefficient of variation of respiratory rate(p < 0.001) and low PiMax (p = 0.002) retained an independent association with reintubation. Children with either low PiMax or high coefficient of variation of respiratory rate had a nearly three-fold higher risk of extubation failure, and when these children developed postextubation upper airway obstruction, reintubation rates were greater than 30%.

Conclusions: High respiratory variability during spontaneous breathing trials is independently associated with extubation failure in children, with very high rates of extubation failure when these children develop postextubation upper airway obstruction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000004418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755301PMC
August 2020

Design and Rationale for Common Data Elements for Clinical Research in Pediatric Critical Care Medicine.

Pediatr Crit Care Med 2020 11;21(11):e1038-e1041

Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA.

Objectives: Common data elements are a combination of a precisely defined question paired with a specified set of responses. Common data elements contribute to the National Institutes of Health-supported principle of Findable, Accessible, Interoperable, and Reusableness of research data. Routine use of Common data elements and standardized definitions within pediatric critical care research are likely to promote collaboration, improve quality, and consistency of data collection, improve overall efficiency of study or trial setup, and facilitate cross-study comparisons, meta-analysis, and merging of study cohorts. The purpose of this Pediatric Critical Care Medicine Perspective is to establish a road map for the development of multinational, multidisciplinary consensus-based common data elements that could be adapted for use within any pediatric critical care subject area.

Methods: We describe a multistep process for the creation of "core domains" of research (e.g. patient outcomes, health-related conditions, or aspects of health) and the development of common data elements within each core domain. We define a tiered approach to data collection based on relevance of each common data element to future studies and clinical practice within the field of interest. Additionally, we describe the use of the Delphi methods to achieve consensus of these common data element documents using an international, multidisciplinary panel of experts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PCC.0000000000002455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609513PMC
November 2020

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

BMC Pediatr 2020 06 27;20(1):317. Epub 2020 Jun 27.

Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.

Background: Continuous monitoring of SpO in the neonatal ICU is the standard of care. Changes in SpO 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 SpO levels in the neonatal ICU. The data, paired SpO-PaO 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 (PaO 50-80 mmHg), risks of severe hypoxemia (PaO ≤ 40 mmHg), and of severe hyperoxemia (PaO ≥ 100 mmHg) at relevant SpO 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 SpO-PaO 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 SpO range of 88-95%, and independent of PMA. The increasing risk of severe hypoxemia became marked at a SpO 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% SpO (25, 95%-CI 18-33%), for infants 33-36 weeks at 97% SpO (24, 95%-CI 14-25%) and for those > 36 weeks at 96% SpO (20, 95%-CI 17-22%).

Conclusions: The risk of hyperoxemia and hypoxemia increases exponentially as SpO 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 FiO titration practices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12887-020-02225-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320542PMC
June 2020

Lung- and Diaphragm-Protective Ventilation.

Am J Respir Crit Care Med 2020 10;202(7):950-961

Interdepartmental Division of Critical Care Medicine.

Mechanical ventilation can cause acute diaphragm atrophy and injury, and this is associated with poor clinical outcomes. Although the importance and impact of lung-protective ventilation is widely appreciated and well established, the concept of diaphragm-protective ventilation has recently emerged as a potential complementary therapeutic strategy. This Perspective, developed from discussions at a meeting of international experts convened by PLUG (the Pleural Pressure Working Group) of the European Society of Intensive Care Medicine, outlines a conceptual framework for an integrated lung- and diaphragm-protective approach to mechanical ventilation on the basis of growing evidence about mechanisms of injury. We propose targets for diaphragm protection based on respiratory effort and patient-ventilator synchrony. The potential for conflict between diaphragm protection and lung protection under certain conditions is discussed; we emphasize that when conflicts arise, lung protection must be prioritized over diaphragm protection. Monitoring respiratory effort is essential to concomitantly protect both the diaphragm and the lung during mechanical ventilation. To implement lung- and diaphragm-protective ventilation, new approaches to monitoring, to setting the ventilator, and to titrating sedation will be required. Adjunctive interventions, including extracorporeal life support techniques, phrenic nerve stimulation, and clinical decision-support systems, may also play an important role in selected patients in the future. Evaluating the clinical impact of this new paradigm will be challenging, owing to the complexity of the intervention. The concept of lung- and diaphragm-protective ventilation presents a new opportunity to potentially improve clinical outcomes for critically ill patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.202003-0655CPDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710325PMC
October 2020

Research and Quality Improvement Must Evolve With Changing Clinical Practice.

Pediatr Crit Care Med 2020 06;21(6):587-588

Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles; and Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, CA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PCC.0000000000002241DOI Listing
June 2020

Prognostic relevance and inter-observer reliability of chest-imaging in pediatric ARDS: a pediatric acute respiratory distress incidence and epidemiology (PARDIE) study.

Intensive Care Med 2020 Jul 25;46(7):1382-1393. Epub 2020 May 25.

Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Los Angeles, University of Southern California, Los Angeles, CA, USA.

Purpose: Definitions of acute respiratory distress syndrome (ARDS) include radiographic criteria, but there are concerns about reliability and prognostic relevance. This study aimed to evaluate the independent relationship between chest imaging and mortality and examine the inter-rater variability of interpretations of chest radiographs (CXR) in pediatric ARDS (PARDS).

Methods: Prospective, international observational study in children meeting Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria for PARDS, which requires new infiltrate(s) consistent with pulmonary parenchymal disease, without mandating bilateral infiltrates. Mortality analysis focused on the entire cohort, whereas inter-observer variability used a subset of patients with blinded, simultaneous interpretation of CXRs by intensivists and radiologists.

Results: Bilateral infiltrates and four quadrants of alveolar consolidation were associated with mortality on a univariable basis, using CXRs from 708 patients with PARDS. For patients on either invasive (IMV) or non-invasive ventilation (NIV) with PaO/FiO (PF) ratios (or SpO/FiO (SF) ratio equivalent) > 100, neither bilateral infiltrates (OR 1.3 (95% CI 0.68, 2.5), p = 0.43), nor 4 quadrants of alveolar consolidation (OR 1.6 (0.85, 3), p = 0.14) were associated with mortality. For patients with PF ≤ 100, bilateral infiltrates (OR 3.6 (1.4, 9.4), p = 0.01) and four quadrants of consolidation (OR 2.0 (1.14, 3.5), p = 0.02) were associated with higher mortality. A subset of 702 CXRs from 233 patients had simultaneous interpretations. Interobserver agreement for bilateral infiltrates and quadrants was "slight" (kappa 0.31 and 0.33). Subgroup analysis showed agreement did not differ when stratified by PARDS severity but was slightly higher for children with chronic respiratory support (kappa 0.62), NIV at PARDS diagnosis (kappa 0.53), age > 10 years (kappa 0.43) and fluid balance > 40 ml/kg (kappa 0.48).

Conclusion: Bilateral infiltrates and quadrants of alveolar consolidation are associated with mortality only for those with PF ratio ≤ 100, although there is high- inter-rater variability in these chest-x ray parameters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-020-06074-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246298PMC
July 2020

Predicting Mortality in Children With Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.

Crit Care Med 2020 06;48(6):e514-e522

Department of Pediatrics and Public Health Science, Division of Pediatric Critical Care Medicine, Penn State Hershey Children's Hospital, Hershey, PA.

Objectives: Pediatric acute respiratory distress syndrome is heterogeneous, with a paucity of risk stratification tools to assist with trial design. We aimed to develop and validate mortality prediction models for patients with pediatric acute respiratory distress syndrome.

Design: Leveraging additional data collection from a preplanned ancillary study (Version 1) of the multinational Pediatric Acute Respiratory Distress syndrome Incidence and Epidemiology study, we identified predictors of mortality. Separate models were built for the entire Version 1 cohort, for the cohort excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths. Models were externally validated in a cohort of intubated pediatric acute respiratory distress syndrome patients from the Children's Hospital of Philadelphia.

Setting: The derivation cohort represented 100 centers worldwide; the validation cohort was from Children's Hospital of Philadelphia.

Patients: There were 624 and 640 subjects in the derivation and validation cohorts, respectively.

Interventions: None.

Measurements And Main Results: The model for the full cohort included immunocompromised status, Pediatric Logistic Organ Dysfunction 2 score, day 0 vasopressor-inotrope score and fluid balance, and PaO2/FIO2 6 hours after pediatric acute respiratory distress syndrome onset. This model had good discrimination (area under the receiver operating characteristic curve 0.82), calibration, and internal validation. Models excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths also demonstrated good discrimination (all area under the receiver operating characteristic curve ≥ 0.84) and calibration. In the validation cohort, models for intubated pediatric acute respiratory distress syndrome (including and excluding neurologic deaths) had excellent discrimination (both area under the receiver operating characteristic curve ≥ 0.85), but poor calibration. After revision, the model for all intubated subjects remained miscalibrated, whereas the model excluding neurologic deaths showed perfect calibration. Mortality models also stratified ventilator-free days at 28 days in both derivation and validation cohorts.

Conclusions: We describe predictive models for mortality in pediatric acute respiratory distress syndrome using readily available variables from day 0 of pediatric acute respiratory distress syndrome which outperform severity of illness scores and which demonstrate utility for composite outcomes such as ventilator-free days. Models can assist with risk stratification for clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000004345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237024PMC
June 2020

Early Use of Adjunctive Therapies for Pediatric Acute Respiratory Distress Syndrome: A PARDIE Study.

Am J Respir Crit Care Med 2020 06;201(11):1389-1397

Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania.

Few data exist to guide early adjunctive therapy use in pediatric acute respiratory distress syndrome (PARDS). To describe contemporary use of adjunctive therapies for early PARDS as a framework for future investigations. This was a preplanned substudy of a prospective, international, cross-sectional observational study of children with PARDS from 100 centers over 10 study weeks. We investigated six adjunctive therapies for PARDS: continuous neuromuscular blockade, corticosteroids, inhaled nitric oxide (iNO), prone positioning, high-frequency oscillatory ventilation (HFOV), and extracorporeal membrane oxygenation. Almost half (45%) of children with PARDS received at least one therapy. Variability was noted in the median starting oxygenation index of each therapy; corticosteroids started at the lowest oxygenation index (13.0; interquartile range, 7.6-22.0) and HFOV at the highest (25.7; interquartile range, 16.7-37.3). Continuous neuromuscular blockade was the most common, used in 31%, followed by iNO (13%), corticosteroids (10%), prone positioning (10%), HFOV (9%), and extracorporeal membrane oxygenation (3%). Steroids, iNO, and HFOV were associated with comorbidities. Prone positioning and HFOV were more common in middle-income countries and less frequently used in North America. The use of multiple ancillary therapies increased over the first 3 days of PARDS, but there was not an easily identifiable pattern of combination or order of use. The contemporary description of prevalence, combinations of therapies, and oxygenation threshold for which the therapies are applied is important for design of future studies. Region of the world, income, and comorbidities influence adjunctive therapy use and are important variables to include in PARDS investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.201909-1807OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7258654PMC
June 2020

Neurally adjusted ventilatory assist mitigates ventilator-induced diaphragm injury in rabbits.

Respir Res 2019 Dec 23;20(1):293. Epub 2019 Dec 23.

Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA, 90027, United States.

Background: Ventilator-induced diaphragmatic dysfunction is a serious complication associated with higher ICU mortality, prolonged mechanical ventilation, and unsuccessful withdrawal from mechanical ventilation. Although neurally adjusted ventilatory assist (NAVA) could be associated with lower patient-ventilator asynchrony compared with conventional ventilation, its effects on diaphragmatic dysfunction have not yet been well elucidated.

Methods: Twenty Japanese white rabbits were randomly divided into four groups, (1) no ventilation, (2) controlled mechanical ventilation (CMV) with continuous neuromuscular blockade, (3) NAVA, and (4) pressure support ventilation (PSV). Ventilated rabbits had lung injury induced, and mechanical ventilation was continued for 12 h. Respiratory waveforms were continuously recorded, and the asynchronous events measured. Subsequently, the animals were euthanized, and diaphragm and lung tissue were removed, and stained with Hematoxylin-Eosin to evaluate the extent of lung injury. The myofiber cross-sectional area of the diaphragm was evaluated under the adenosine triphosphatase staining, sarcomere disruptions by electron microscopy, apoptotic cell numbers by the TUNEL method, and quantitative analysis of Caspase-3 mRNA expression by real-time polymerase chain reaction.

Results: Physiological index, respiratory parameters, and histologic lung injury were not significantly different among the CMV, NAVA, and PSV. NAVA had lower asynchronous events than PSV (median [interquartile range], NAVA, 1.1 [0-2.2], PSV, 6.8 [3.8-10.0], p = 0.023). No differences were seen in the cross-sectional areas of myofibers between NAVA and PSV, but those of Type 1, 2A, and 2B fibers were lower in CMV compared with NAVA. The area fraction of sarcomere disruptions was lower in NAVA than PSV (NAVA vs PSV; 1.6 [1.5-2.8] vs 3.6 [2.7-4.3], p < 0.001). The proportion of apoptotic cells was lower in NAVA group than in PSV (NAVA vs PSV; 3.5 [2.5-6.4] vs 12.1 [8.9-18.1], p < 0.001). There was a tendency in the decreased expression levels of Caspase-3 mRNA in NAVA groups. Asynchrony Index was a mediator in the relationship between NAVA and sarcomere disruptions.

Conclusions: Preservation of spontaneous breathing using either PSV or NAVA can preserve the cross sectional area of the diaphragm to prevent atrophy. However, NAVA may be superior to PSV in preventing sarcomere injury and apoptosis of myofibrotic cells of the diaphragm, and this effect may be mediated by patient-ventilator asynchrony.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12931-019-1265-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929282PMC
December 2019

The role of computer-based clinical decision support systems to deliver protective mechanical ventilation.

Curr Opin Crit Care 2020 02;26(1):73-81

Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California.

Purpose Of Review: Mechanical ventilation of adults and children with acute respiratory failure necessitates balancing lung and diaphragm protective ventilation. Computerized decision support (CDS) offers advantages in circumstances where complex decisions need to be made to weigh potentially competing risks, depending on the physiologic state of the patient.

Recent Findings: Significant variability in how ventilator protocols are applied still exists and clinical data show that there continues to be wide variability in ventilator management. We have developed a CDS, which we are currently testing in a Phase II randomized controlled trial. The CDS is called Real-time Effort Driven ventilator management (REDvent). We will describe the rationale and methods for development of CDS for lung and diaphragm protective ventilation, using the REDvent CDS as an exemplar.

Summary: Goals for achieving compliance and physiologic objectives can be met when CDS instructions are simple and explicit, provide the clinician with the underlying rule set, permit acceptable reasons for declining and allow for iterative adjustments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCC.0000000000000688DOI Listing
February 2020

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

Contemp Clin Trials 2020 01 16;88:105893. Epub 2019 Nov 16.

Children's Hospital Los Angeles, Department of Anesthesiology and Critical Care, United States of America; University of Southern California, Keck School of Medicine, Department of Pediatrics, United States of America.

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, FiO, 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cct.2019.105893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952541PMC
January 2020

Definition and global epidemiology of pediatric acute respiratory distress syndrome.

Ann Transl Med 2019 Oct;7(19):502

Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.

Acute respiratory distress syndrome (ARDS) has been known to occur in children since early descriptions of the disease, but pediatric specific diagnostic criteria were first established in 2015 with the Pediatric Acute Lung Injury Consensus Conference (PALICC) definition of pediatric ARDS (PARDS). There were substantial changes proposed with the PALICC definition, including simplification of radiographic criteria, use of pulse oximetry based metrics to define PARDS, specific criteria for non-invasive ventilation, and the use of oxygenation index (OI) instead of PaO2/FiO2 ratio for those on invasive ventilation. While these changes could potentially result in major changes in the reported incidence and outcome of PARDS, review of the recent literature since publication of the PALICC definitions highlight that major elements regarding the contemporary epidemiology of PARDS have remained stable over the past 20 years. This highlights that the PARDS definition is likely catching up to changes in clinical practice, and suggests that this new definition should be used moving forward as it is more reflective of current practice than historical definitions. However, it is also clear that PARDS severity alone (as measured by the PALICC) criteria insufficiently characterizes the risk for mortality or other important clinical outcomes amongst PARDS patients, although there appears to be some association between PARDS severity and outcome, particularly when hypoxemia is severe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm.2019.09.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828787PMC
October 2019

Age-Stratified Risk of Critical Illness in Young Children Presenting to the Emergency Department with Suspected Influenza.

J Pediatr 2019 12 24;215:132-138.e2. Epub 2019 Sep 24.

Division of Emergency Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA.

Objective: To investigate the risk of critical illness by age group among young children without a chronic condition presenting to the emergency department (ED) with suspected influenza.

Study Design: Retrospective study of patients aged <2 years presenting to the ED with suspected influenza (defined by diagnostic codes for influenza or influenza-like illness) from 2009 to 2017 in 49 hospitals in the Pediatric Health Information System. Patients with chronic conditions were excluded. The main clinical outcomes were intensive care unit (ICU) admission, ventilatory support, vasopressor administration, and mortality, which were compared independently by age group (<3 months, 3 to <6 months, 6 to <12 months, and 12 to <24 months). To compare outcomes by age, we estimated the prevalence of each outcome by age group after fitting logistic regression models to control for demographic differences between groups.

Results: A total of 55 986 children were studied. Overall admission and ICU admission rates were 20% and 2%, respectively. After adjustment for demographic variables, infants aged <3 months had higher rates of ICU admission (2.7%; 95% CI, 2.0%-3.3%; P < .001 compared with other age groups) and ventilatory support (2.5%; 95% CI, 1.9%-3.2%; P < .001 compared with other age groups); however, there were no differences in vasopressor administration. The overall case fatality rate was low (0.007%) and thus could not be compared across age groups.

Conclusions: Infants aged <3 months with suspected influenza are at greatest risk for critical illness. Although critical illness is uncommon, these findings should be incorporated into acute management decisions, including the need for specified outpatient follow-up or hospitalization, and public health efforts should focus on prevention and disease-modifying interventions in this high-risk population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2019.08.041DOI Listing
December 2019

Risk Factors for Mortality and Pre-ICU Fluid Balance Among Critically Ill Hematopoietic Stem Cell Transplant Patients.

J Intensive Care Med 2020 Nov 11;35(11):1265-1270. Epub 2019 Jun 11.

Department of Anesthesiology and Critical Care Medicine, 5150Children's Hospital Los Angeles, Los Angeles, CA, USA.

Objective: To examine if fluid balance surrounding pediatric intensive care unit (PICU) admission in hematopoietic stem cell transplant (HSCT) patients was associated with mortality, ventilator-free days, and intensive care unit (ICU)-free days. To explore other population-specific factors associated with poor outcome.

Materials And Methods: Retrospective review of HSCT patients admitted to 2 quaternary PICUs, Children's Hospital Los Angeles and University of California San Francisco Benioff Children's Hospital from January 2009 to December 2014.

Results: Of 144 patients, 92 were identified with complete fluid balance data available. No difference in fluid balance between survivors and nonsurvivors in the 24 hours preceding PICU admission ( = .81) or when the first 24 hours of PICU stay were taken into account ( = .48) was identified. There was no difference in ventilator-free or ICU-free days. Comparing Pediatric Index of Mortality (PIM)-2, Pediatric Risk of Mortality (PRISM)-3, and a multivariable model using independent risk factors identified through multivariable analysis, the receiver operating characteristic plot for the multivariable model (area under the curve = 0.844 [95% confidence interval: 0.77-0.92]) was superior to both PIM-2 and PRISM-3 in discriminating mortality.

Conclusions: Fluid balance immediately preceding and early in the course of admission was not associated with mortality in PICU HSCT patients. A subset of variables was identified which better discriminated mortality in this cohort than accepted PICU severity of illness scores.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0885066619855618DOI Listing
November 2020

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

J Pediatr 2019 07 26;210:178-183.e2. Epub 2019 Apr 26.

Department of Anesthesiology Critical Care Medicine, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2019.03.027DOI Listing
July 2019

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

Front Pediatr 2019 29;7. Epub 2019 Jan 29.

Department of Anesthesiology Critical Care Medicine, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, CA, United States.

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. Prospective interventional study. Multidisciplinary Pediatric Intensive Care Unit in a University teaching hospital. 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). Cardiac index (CI) and stroke volume (SV) were measured on baseline ventilator settings and subsequently with a PEEP 4 cmHO higher than baseline. Change in CI and SV from baseline values was evaluated using Wilcoxon signed rank test. A total of 19 paired measurements obtained. The median baseline PEEP was 8 cmHO (IQR 8, 10) Range 6-14 cmHO. There was no significant change in cardiac index or stroke volume with change in PEEP. Baseline median CI 4.4 L/min/m (IQR 3.4, 4.8) and PEEP 4 higher median CI of 4.3 L/min/m (IQR 3.6, 4.8), = 0.65. Baseline median SV 26 ml (IQR 13, 44) and at PEEP 4 higher median SV 34 ml (IQR 12, 44) = 0.63. There is no significant change in cardiac index or stroke volume with increasing PEEP by 4 cmHO in a population of children with mild to severe PARDS. The study is registered on Clinical trails.gov under the Identifier: NCT02354365.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2019.00009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361833PMC
January 2019

The authors reply.

Crit Care Med 2018 12;46(12):e1231

Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA, and Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA; Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, and Southern California Clinical and Translational Science Institute, Biostatistics Core, Los Angeles, CA; Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA, and Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000003448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182096PMC
December 2018

Derivation and Validation of an Objective Effort of Breathing Score in Critically Ill Children.

Pediatr Crit Care Med 2019 01;20(1):e15-e22

Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Los Angeles, Los Angeles, CA.

Objectives: To derive and validate a score that correlates with an objective measurement of a child's effort of breathing.

Design: Secondary analysis of a previously conducted observational study.

Setting: The pediatric and cardiothoracic ICUs of a quaternary-care children's hospital.

Patients: Patients more than 37 weeks gestational age to age 18 years who were undergoing extubation.

Interventions: Effort of breathing was measured in patients following extubation using esophageal manometry to calculate pressure rate product. Simultaneously, members of a multidisciplinary team (nurse, physician, and respiratory therapist) assessed respiratory function using a previously validated tool. Elements of the tool that were significantly associated with pressure rate product in univariate analysis were identified and included in a multivariate model. An Effort of Breathing score was derived from the results of the model using data from half of the subjects (derivation cohort) and then validated using data from the remaining subjects (validation cohort) by calculating the area under the receiver operator characteristic curve for pressure rate product greater than 90th percentile and for the need for reintubation.

Measurements And Main Results: Among 409 subjects, the median age was 5 months, and nearly half were cardiac surgery patients (49.1%). Retractions, stridor, and pulsus paradoxus were included in the Simple Score. Area under the receiver operator characteristic curve for pressure rate product greater than 90th percentile was 0.8359 (95% CI, 0.7996-0.8722) in the derivation cohort and 0.7930 (0.7524-0.8337) in the validation cohort. Area under the receiver operator characteristic curve for reintubation was 0.7280 (0.6807-0.7752) when all scores were analyzed individually and was 0.7548 (0.6644-0.8452) if scores from three clinicians from different disciplines were summated. Results were similar regardless of provider discipline or training.

Conclusions: A scoring system was derived and validated, performed acceptably to predict increased effort of breathing or need for advanced respiratory support and may function best when used by a team.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PCC.0000000000001760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322953PMC
January 2019

Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study.

Lancet Respir Med 2019 02 22;7(2):115-128. Epub 2018 Oct 22.

Penn State Hershey Children's Hospital, Penn State University School of Medicine, Hershey, PA, USA.

Background: Paediatric acute respiratory distress syndrome (PARDS) is associated with high mortality in children, but until recently no paediatric-specific diagnostic criteria existed. The Pediatric Acute Lung Injury Consensus Conference (PALICC) definition was developed to overcome limitations of the Berlin definition, which was designed and validated for adults. We aimed to determine the incidence and outcomes of children who meet the PALICC definition of PARDS.

Methods: In this international, prospective, cross-sectional, observational study, 145 paediatric intensive care units (PICUs) from 27 countries were recruited, and over a continuous 5 day period across 10 weeks all patients were screened for enrolment. Patients were included if they had a new diagnosis of PARDS that met PALICC criteria during the study week. Exclusion criteria included meeting PARDS criteria more than 24 h before screening, cyanotic heart disease, active perinatal lung disease, and preparation or recovery from a cardiac intervention. Data were collected on the PICU characteristics, patient demographics, and elements of PARDS (ie, PARDS risk factors, hypoxaemia severity metrics, type of ventilation), comorbidities, chest imaging, arterial blood gas measurements, and pulse oximetry. The primary outcome was PICU mortality. Secondary outcomes included 90 day mortality, duration of invasive mechanical and non-invasive ventilation, and cause of death.

Findings: Between May 9, 2016, and June 16, 2017, during the 10 study weeks, 23 280 patients were admitted to participating PICUs, of whom 744 (3·2%) were identified as having PARDS. 95% (708 of 744) of patients had complete data for analysis, with 17% (121 of 708; 95% CI 14-20) mortality, whereas only 32% (230 of 708) of patients met Berlin criteria with 27% (61 of 230) mortality. Based on hypoxaemia severity at PARDS diagnosis, mortality was similar among those who were non-invasively ventilated and with mild or moderate PARDS (10-15%), but higher for those with severe PARDS (33% [54 of 165; 95% CI 26-41]). 50% (80 of 160) of non-invasively ventilated patients with PARDS were subsequently intubated, with 25% (20 of 80; 95% CI 16-36) mortality. By use of PALICC PARDS definition, severity of PARDS at 6 h after initial diagnosis (area under the curve [AUC] 0·69, 95% CI 0·62-0·76) discriminates PICU mortality better than severity at PARDS diagnosis (AUC 0·64, 0·58-0·71), and outperforms Berlin severity groups at 6 h (0·64, 0·58-0·70; p=0·01).

Interpretation: The PALICC definition identified more children as having PARDS than the Berlin definition, and PALICC PARDS severity groupings improved the stratification of mortality risk, particularly when applied 6 h after PARDS diagnosis. The PALICC PARDS framework should be considered for use in future epidemiological and therapeutic research among children with PARDS.

Funding: University of Southern California Clinical Translational Science Institute, Sainte Justine Children's Hospital, University of Montreal, Canada, Réseau en Santé Respiratoire du Fonds de Recherche Quebec-Santé, and Children's Hospital Los Angeles, Department of Anesthesiology and Critical Care Medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-2600(18)30344-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045907PMC
February 2019

Accuracy of Transcutaneous Carbon Dioxide Levels in Comparison to Arterial Carbon Dioxide Levels in Critically Ill Children.

Respir Care 2019 Feb 25;64(2):201-208. Epub 2018 Sep 25.

Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, California.

Background: Widespread use of transcutaneous P (P ) monitoring is currently limited by concerns many practitioners have regarding accuracy. We compared the accuracy of P with that of P measurements in critically ill children, and we investigated whether clinical conditions associated with low cardiac output or increased subcutaneous tissue affect this accuracy.

Methods: We performed a single-center prospective study of critically ill children placed on transcutaneous monitoring.

Results: There were 184 children enrolled with paired P and P values. Subjects had a median age of 31.8 mo (interquartile range 3.5-123.3 mo). Most children were mechanically ventilated ( = 161, 87.5%), and many had cardiac disease ( = 76, 41.3%). The median P was 44 mm Hg (interquartile range 39-51 mm Hg). The mean bias between P and P was 0.6 mm Hg with 95% limits of agreement from -13.6 to 14.7 mm Hg. The P and P were within ±5 mm Hg in 126 (68.5%) measurements. In multivariable modeling, cyanotic heart disease (odds ratio 3.5, 95% CI 1.2-10, = .02) and monitor number 2 (odds ratio 3.8 95% CI 1.3-10.5, = .01) remained associated with P ≥ 5 mm Hg higher than P . Serum lactate, fluid balance, renal failure, obesity, vasoactive-inotrope score, and acyanotic heart disease were not associated with high or low P values. In 130 children with a second paired P and P measurement, predicting the second measured P by subtracting the initial observed difference between the P and P from the subsequent measured P decreased the mean bias between observed and predicted P to 0.2 mm Hg and the 95% limits of agreement to -9.4 to 9.7 mm Hg.

Conclusions: P provides an acceptable estimate of P in many critically ill children, including those with clinical conditions that may be associated with low cardiac output or increased subcutaneous tissue, although it does not perform as well in children with cyanotic heart disease. P may be a useful adjunct monitoring method, but it cannot reliably replace P measurement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4187/respcare.06209DOI Listing
February 2019

The Therapeutic Index.

Pediatr Crit Care Med 2018 08;19(8):775-776

Division of Critical Care Medicine, Department of Pediatrics, University of Washington and Seattle Children's Hospital, Seattle, WA Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PCC.0000000000001652DOI Listing
August 2018

Epidemiology of Cause of Death in Pediatric Acute Respiratory Distress Syndrome.

Crit Care Med 2018 11;46(11):1811-1819

Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA.

Objectives: Investigations of acute respiratory distress syndrome in adults suggest hypoxemia is an uncommon cause of death. However, the epidemiology of death in pediatric acute respiratory distress syndrome is not well characterized. We aimed to describe the cause, mode, and timing of death in pediatric acute respiratory distress syndrome nonsurvivors. We hypothesized that most deaths would be due to nonpulmonary factors, rather than hypoxemia.

Design: Retrospective, decedent-only analysis.

Setting: Two large, academic PICUs.

Patients: Nonsurvivors with pediatric acute respiratory distress syndrome.

Interventions: None.

Measurements And Main Results: Of 798 subjects with pediatric acute respiratory distress syndrome, there were 153 nonsurvivors (19% mortality). Median time to death was 6 days (interquartile range, 3-13 d) after pediatric acute respiratory distress syndrome onset. Patients dying less than 7 days after pediatric acute respiratory distress syndrome onset had greater illness severity and worse oxygenation. Patients dying less than 7 days were more likely to die of a neurologic cause, including brain death. Patients dying greater than or equal to 7 days after pediatric acute respiratory distress syndrome onset were more commonly immunocompromised. Multisystem organ failure predominated in deaths greater than or equal to 7 days. Withdrawal of therapy was the most common mode of death at all timepoints, accounting for 66% of all deaths. Organ dysfunction was common at time of death, irrespective of cause of death. Refractory hypoxemia accounted for only a minority of pediatric acute respiratory distress syndrome deaths (20%).

Conclusions: In pediatric acute respiratory distress syndrome, early deaths were due primarily to neurologic failure, whereas later deaths were more commonly due to multisystem organ failure. Deaths from neurologic causes accounted for a substantial portion of nonsurvivors. Refractory hypoxemia accounted for only a minority of deaths. Our study highlights limitations associated with using death as an endpoint in therapeutic pediatric acute respiratory distress syndrome trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000003371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185780PMC
November 2018

Predicting Body Height in a Pediatric Intensive Care Unit Using Ulnar Length.

Front Pediatr 2018 22;6:187. Epub 2018 Jun 22.

Children's Hospital Los Angeles, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, United States.

To determine if ulnar length obtained by the bedside nurse can be used to estimate patient length. To compare our findings to previous predictive equations of height and ulnar length. To evaluate the performance of predictive equations for height and ulnar length on patients with syndromes that affect height. Retrospective observational study of prospectively collected data. Multidisciplinary Pediatric Intensive Care Unit in a university teaching hospital. 1,177 patients, ages 1 month to 23 years. Mean age was 79.7 months (1,3 IQR 19.5, 164.5 months) and 55.4% male. Ulnar length was obtained using digital calipers by bedside nurses in PICU as well as height and weight. The electronic health care record was used to extract patient information. The predictive equation for height for the entire group is: height (cm) = 0.59ulnar length (mm) + 13.1 ( = 0.93). Bland Altman analysis of the derivation formula applied to the testing group did not show any systematic bias. Our study shows that ulnar length measurements can be used to predict height with a simple linear formula in a PICU setting. Not having specific individuals or specific training for ulnar measurement did not seem to alter the accuracy ( = 0.93). The robust nature of the measurement and ease of use may make this an unconventional but reasonable alternative to obtaining height when that cannot be measured directly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2018.00187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023995PMC
June 2018

The Association Between Inhaled Nitric Oxide Treatment and ICU Mortality and 28-Day Ventilator-Free Days in Pediatric Acute Respiratory Distress Syndrome.

Crit Care Med 2018 11;46(11):1803-1810

Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA.

Objectives: To investigate the association between inhaled nitric oxide treatment and ICU mortality and 28-day ventilator-free days in pediatric acute respiratory distress syndrome.

Design: Retrospective cohort study. A propensity score for inhaled nitric oxide treatment was developed and used in the analysis.

Setting: Two quaternary care PICUs.

Patients: Children with pediatric acute respiratory distress syndrome.

Interventions: None.

Measurements And Main Results: There were 499 children enrolled in this study with 143 (28.7%) receiving inhaled nitric oxide treatment. Children treated with inhaled nitric oxide were more likely to have a primary diagnosis of pneumonia (72% vs 54.8%; p < 0.001), had a higher initial oxygenation index (median 16.9 [interquartile range, 10.1-27.3] vs 8.5 [interquartile range, 5.8-12.2]; p < 0.001), and had a higher 72-hour maximal Vasoactive-Inotrope Score (median 15 [interquartile range, 6-25] vs 8 [interquartile range, 0-17.8]; p < 0.001) than those not receiving inhaled nitric oxide. Mortality was higher in the inhaled nitric oxide treatment group (25.2% vs 16.3%; p = 0.02), and children in this group had fewer 28-day ventilator-free days (10 d [interquartile range, 0-18 d] vs 17 d (interquartile range 5.5-22 d]; p < 0.0001). We matched 176 children based on propensity score for inhaled nitric oxide treatment. In the matched cohort, inhaled nitric oxide treatment was not associated with mortality (odds ratio, 1.3 [95% CI, 0.56-3.0]) or 28-day ventilator-free days (incidence rate ratio, 0.91 [95% CI, 0.80-1.04]). These results remained consistent in the entire study cohort when the propensity score for inhaled nitric oxide treatment was used for either inverse probability weighting or stratification in regression modeling with the exception that subjects treated with inhaled nitric oxide were more likely to have 0 ventilator-free days (p ≤ 0.02). In secondary analysis stratified by oxygenation response, inhaled nitric oxide treatment was not associated with mortality or 28-day ventilator-free days in children with a positive oxygenation response (all p > 0.2) CONCLUSIONS:: Treatment with inhaled nitric oxide in pediatric acute respiratory distress syndrome is not associated with improvement in either mortality or ventilator-free days and may be associated with harm. Further prospective trials are required to define the role of inhaled nitric oxide treatment in pediatric acute respiratory distress syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000003312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185752PMC
November 2018