Project description:Rationale: Clinicians commonly use short-term physiologic markers to assess the benefit of ventilator adjustments. Improved arterial oxygen tension/pressure (PaO2)/fraction of inspired oxygen (FiO2) after ventilator adjustment in acute respiratory distress syndrome is associated with lower mortality. However, as driving pressure (ΔP) reflects lung stress and strain, changes in ΔP may more accurately reflect benefits or harms of ventilator adjustments compared with changes in oxygenation.Objectives: We aimed to compare the association between mortality and the changes in PaO2/FiO2 and ΔP following protocolized ventilator changes.Methods: We assessed associations between mortality and changes in PaO2/FiO2 (ΔPaO2/FiO2) and ΔP (ΔΔP) after postrandomization positive end-expiratory pressure (PEEP) and tidal volume adjustment in reanalyses of the ALVEOLI (Assessment of Low Tidal Volume and Elevated End-Expiratory Volume to Obviate Lung Injury) and ExPress (Expiratory Pressure) trials. We included subjects with available pre- and postintervention PaO2/FiO2 and ΔP (372 in ALVEOLI and 596 in ExPress). In each separate trial cohort, we performed multivariable Cox regression testing the association between ΔPaO2/FiO2 and ΔΔP with mortality.Results: In ALVEOLI, when analyzed as separate variables, ΔPaO2/FiO2 was associated with mortality only in subjects in whom PEEP increased, whereas ΔΔP was associated with mortality irrespective of direction of PEEP change. When modeled together, improved ΔPaO2/FiO2 was not associated with mortality, whereas ΔΔP remained associated with mortality (adjusted hazard ratio [aHR], 1.50 per 5 cm H2O increase; 95% confidence interval [95% CI], 1.21-1.85). When modeled together in ExPress, ΔΔP (aHR, 1.42; 95% CI, 1.14-1.78) was more strongly associated with mortality than ΔPaO2/FiO2 (aHR, 0.95 per 25 mm Hg increase; 95% CI, 0.90-1.00).Conclusions: Reduced ΔP following protocolized ventilator changes was more strongly and consistently associated with lower mortality than was increased PaO2/FiO2, making ΔΔP more informative about benefit from ventilator adjustments. Our results reinforce the primacy of ΔP, rather than oxygenation, as the key variable associated with outcome.

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:In pediatric acute respiratory distress syndrome, lung injury is mediated by immune activation and severe inflammation. Therefore, we hypothesized that patients with elevated pro- and anti-inflammatory cytokines would have higher mortality rates and that these biomarkers could improve risk stratification of poor outcomes. DESIGN:Multicenter prospective observational study. SETTING:We enrolled patients from five academic PICUs between 2008 and 2015. PATIENTS:Patients were 1 month to 18 years old, used noninvasive or invasive ventilation, and met the American European Consensus Conference definition of acute respiratory distress syndrome. INTERVENTIONS:Eight proinflammatory and anti-inflammatory cytokines were measured on acute respiratory distress syndrome day 1 and correlated with mortality, ICU morbidity as measured by survivor Pediatric Logistic Organ Dysfunction score, and biomarkers of endothelial injury, including angiopoietin-2, von Willebrand Factor, and soluble thrombomodulin. MEASUREMENTS AND MAIN RESULTS:We measured biomarker levels in 194 patients, including 38 acute respiratory distress syndrome nonsurvivors. Interleukin-6, interleukin-8, interleukin-10, interleukin-18, and tumor necrosis factor-R2 were each strongly associated with all-cause mortality, multiple markers of ICU morbidity, and endothelial injury. A multiple logistic regression model incorporating oxygenation index, interleukin-8, and tumor necrosis factor-R2 was superior to a model of oxygenation index alone in predicting the composite outcome of mortality or severe morbidity (area under the receiver operating characteristic, 0.77 [0.70-0.83] vs 0.70 [0.62-0.77]; p = 0.042). CONCLUSIONS:In pediatric acute respiratory distress syndrome, pro- and anti-inflammatory cytokines are strongly associated with mortality, ICU morbidity, and biochemical evidence of endothelial injury. These cytokines significantly improve the ability of the oxygenation index to discriminate risk of mortality or severe morbidity and may allow for identification and enrollment of high-risk subgroups for future studies.

Dataset Information

Comparacion de las caracteristicas clinicas y mortalidad debidas a Sindrome de Distres Respiratorio Agudo debido a COVID-19 versus Influenza A-H!N!pdm09.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets