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Risk Stratification Using Oxygenation in the First 24 Hours of Pediatric Acute Respiratory Distress Syndrome.

ABSTRACT: OBJECTIVE:Oxygenation measured 24 hours after acute respiratory distress syndrome onset more accurately stratifies risk, relative to oxygenation at onset, in both children and adults. However, waiting 24 hours is problematic, especially for interventions that are more efficacious early in the disease course. We aimed to delineate whether oxygenation measured at timepoints earlier than 24 hours would retain predictive validity in pediatric acute respiratory distress syndrome. DESIGN:Observational cohort study. SETTING:Two large, academic PICUs. PATIENTS:Invasively ventilated children with acute respiratory distress syndrome. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:PaO2/FIO2 and oxygenation index (mean airway pressure × FIO2 × 100)/PaO2) were measured at acute respiratory distress syndrome onset, at 6, 12, 18, and 24 hours after in 459 children at the Children's Hospital of Philadelphia. Neither PaO2/FIO2 nor oxygenation index at acute respiratory distress syndrome onset discriminated outcome. Between 6 and 24 hours, both PaO2/FIO2 (area under receiver operating curve for mortality between 0.57 and 0.62; p = 0.049-0.002) and oxygenation index (area under receiver operating curve, 0.60-0.62; p = 0.006-0.001) showed good discrimination and calibration across multiple outcomes, including mortality, ventilator-free days at 28 days, ventilator days in survivors, and probability of extubation, given competing risk of death. The utility of oxygenation at 12 hours was confirmed in an independent cohort from the Children's Hospital of Los Angeles. CONCLUSION:Oxygenation measured between 6 and 12 hours of acute respiratory distress syndrome onset accurately stratified outcomes in children. Our results have critical implications for the design of trials, especially for interventions with greater impact in early acute respiratory distress syndrome.

SUBMITTER: Yehya N

PROVIDER: S-EPMC5851808 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Risk Stratification Using Oxygenation in the First 24 Hours of Pediatric Acute Respiratory Distress Syndrome.

Yehya Nadir N Thomas Neal J NJ Khemani Robinder G RG

Critical care medicine 20180401 4

<h4>Objective</h4>Oxygenation measured 24 hours after acute respiratory distress syndrome onset more accurately stratifies risk, relative to oxygenation at onset, in both children and adults. However, waiting 24 hours is problematic, especially for interventions that are more efficacious early in the disease course. We aimed to delineate whether oxygenation measured at timepoints earlier than 24 hours would retain predictive validity in pediatric acute respiratory distress syndrome.<h4>Design</h ...[more]

PMID: 29293150

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Project description:ObjectivesChildren with an immunocompromised condition and requiring invasive mechanical ventilation have high risk of death. Such patients are commonly transitioned to rescue modes of nonconventional ventilation, including airway pressure release ventilation and high-frequency oscillatory ventilation, for acute respiratory distress syndrome refractory to conventional ventilation. Our aim was to describe our experience with airway pressure release ventilation and high-frequency oscillatory ventilation in children with an immunocompromised condition and acute respiratory distress syndrome refractory to conventional ventilation and to identify factors associated with survival.DesignRetrospective cohort study.SettingTertiary care, university-affiliated PICU.PatientsSixty pediatric patients with an immunocompromised condition and acute respiratory distress syndrome refractory to conventional ventilation transitioned to either airway pressure release ventilation or high-frequency oscillatory ventilation.InterventionsNone.Measurements and main resultsDemographic data, ventilator settings, arterial blood gases, oxygenation index, and PaO(2)/FIO(2) were recorded before transition to either mode of nonconventional ventilation and at predetermined intervals after transition for up to 5 days. Mortality in the entire cohort was 63% and did not differ between patients transitioned to airway pressure release ventilation and high-frequency oscillatory ventilation. For both airway pressure release ventilation and high-frequency oscillatory ventilation, improvements in oxygenation index and PaO(2)/FIO(2) at 24 hours expressed as a fraction of pretransition values (oxygenation index(24)/oxygenation index(pre) and PaO(2)/FIO(224)/PaO(2)/FIO(2pre)) reliably discriminated nonsurvivors from survivors, with receiver operating characteristic areas under the curves between 0.89 and 0.95 (p for all curves < 0.001). Sensitivity-specificity analysis suggested that less than 15% reduction in oxygenation index (90% sensitive, 75% specific) or less than 90% increase in PaO(2)/FIO(2) (80% sensitive, 94% specific) 24 hours after transition to airway pressure release ventilation were the optimal cutoffs to identify nonsurvivors. The comparable values 24 hours after transition to high-frequency oscillatory ventilation were less than 5% reduction in oxygenation index (100% sensitive, 83% specific) or less than 80% increase in PaO(2)/FIO(2) (91% sensitive, 89% specific) to identify nonsurvivors.ConclusionsIn this single-center retrospective study of pediatric patients with an immunocompromised condition and acute respiratory distress syndrome failing conventional ventilation transitioned to either airway pressure release ventilation or high-frequency oscillatory ventilation, improved oxygenation at 24 hours expressed as PaO(2)/FIO(224)/PaO(2)/FIO(2pre) or oxygenation index(24)/oxygenation indexpre reliably discriminates nonsurvivors from survivors. These findings should be prospectively verified.

Project description:ObjectivesPediatric 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.DesignLeveraging 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.SettingThe derivation cohort represented 100 centers worldwide; the validation cohort was from Children's Hospital of Philadelphia.PatientsThere were 624 and 640 subjects in the derivation and validation cohorts, respectively.InterventionsNone.Measurements and main resultsThe 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.ConclusionsWe 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.

Project description:OBJECTIVES:The original Pediatric Sepsis Biomarker Risk Model and revised (Pediatric Sepsis Biomarker Risk Model-II) biomarker-based risk prediction models have demonstrated utility for estimating baseline 28-day mortality risk in pediatric sepsis. Given the paucity of prediction tools in pediatric acute respiratory distress syndrome, and given the overlapping pathophysiology between sepsis and acute respiratory distress syndrome, we tested the utility of Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II for mortality prediction in a cohort of pediatric acute respiratory distress syndrome, with an a priori plan to revise the model if these existing models performed poorly. DESIGN:Prospective observational cohort study. SETTING:University affiliated PICU. PATIENTS:Mechanically ventilated children with acute respiratory distress syndrome. INTERVENTIONS:Blood collection within 24 hours of acute respiratory distress syndrome onset and biomarker measurements. MEASUREMENTS AND MAIN RESULTS:In 152 children with acute respiratory distress syndrome, Pediatric Sepsis Biomarker Risk Model performed poorly and Pediatric Sepsis Biomarker Risk Model-II performed modestly (areas under receiver operating characteristic curve of 0.61 and 0.76, respectively). Therefore, we randomly selected 80% of the cohort (n = 122) to rederive a risk prediction model for pediatric acute respiratory distress syndrome. We used classification and regression tree methodology, considering the Pediatric Sepsis Biomarker Risk Model biomarkers in addition to variables relevant to acute respiratory distress syndrome. The final model was comprised of three biomarkers and age, and more accurately estimated baseline mortality risk (area under receiver operating characteristic curve 0.85, p < 0.001 and p = 0.053 compared with Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II, respectively). The model was tested in the remaining 20% of subjects (n = 30) and demonstrated similar test characteristics. CONCLUSIONS:A validated, biomarker-based risk stratification tool designed for pediatric sepsis was adapted for use in pediatric acute respiratory distress syndrome. The newly derived Pediatric Acute Respiratory Distress Syndrome Biomarker Risk Model demonstrates good test characteristics internally and requires external validation in a larger cohort. Tools such as Pediatric Acute Respiratory Distress Syndrome Biomarker Risk Model have the potential to provide improved risk stratification and prognostic enrichment for future trials in pediatric acute respiratory distress syndrome.

Dataset Information

Risk Stratification Using Oxygenation in the First 24 Hours of Pediatric Acute Respiratory Distress Syndrome.

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Risk Stratification Using Oxygenation in the First 24 Hours of Pediatric Acute Respiratory Distress Syndrome.

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