Mortality is a frequently reported outcome in clinical studies of acute respiratory distress syndrome (ARDS). However, timing of mortality assessment has not been well characterized. We aimed to... Show moreMortality is a frequently reported outcome in clinical studies of acute respiratory distress syndrome (ARDS). However, timing of mortality assessment has not been well characterized. We aimed to identify a crossing-point between cumulative survival and death in the intensive care unit (ICU) of patients with moderate-to-severe ARDS, beyond which the number of survivors would exceed the number of deaths. We hypothesized that this intersection would occur earlier in a successful clinical trial vs. observational studies of moderate/severe ARDS and predict treatment response. We conducted an ancillary study of 1580 patients with moderate-to-severe ARDS managed with lung-protective ventilation to assess the relevance and timing of measuring ICU mortality rates at different time-points during ICU stay. First, we analyzed 1303 patients from four multicenter, observational cohorts enrolling consecutive patients with moderate/severe ARDS. We assessed cumulative ICU survival from the time of moderate/severe ARDS diagnosis to ventilatory support discontinuation within 7-days, 28-days, 60-days, and at ICU discharge. Then, we compared these findings to those of a successful randomized trial of 277 moderate/severe ARDS patients. In the observational cohorts, ICU mortality (487/1303, 37.4%) and 28-day mortality (425/1102, 38.6%) were similar (p = 0.549). Cumulative proportion of ICU survivors and non-survivors crossed at day-7; after day-7, the number of ICU survivors was progressively higher compared to non-survivors. Measures of oxygenation, lung mechanics, and severity scores were different between survivors and non-survivors at each point-in-time (p < 0.001). In the trial cohort, the cumulative proportion of survivors and non-survivors in the treatment group crossed before day-3 after diagnosis of moderate/severe ARDS. In clinical ARDS studies, 28-day mortality closely approximates and may be used as a surrogate for ICU mortality. For patients with moderate-to-severe ARDS, ICU mortality assessment within the first week of a trial might be an early predictor of treatment response. Show less
Introduction: In patients with acute respiratory distress syndrome (ARDS), the PaO2/FiO(2) ratio at the time of ARDS diagnosis is weakly associated with mortality. We hypothesized that setting a... Show moreIntroduction: In patients with acute respiratory distress syndrome (ARDS), the PaO2/FiO(2) ratio at the time of ARDS diagnosis is weakly associated with mortality. We hypothesized that setting a PaO2/FiO(2) threshold in 150 mm Hg at 24 h from moderate/severe ARDS diagnosis would improve predictions of death in the intensive care unit (ICU). Methods: We conducted an ancillary study in 1303 patients with moderate to severe ARDS managed with lung-protective ventilation enrolled consecutively in four prospective multicenter cohorts in a network of ICUs. The first three cohorts were pooled (n = 1000) as a testing cohort; the fourth cohort (n = 303) served as a confirmatory cohort. Based on the thresholds for PaO2/FiO(2) (150 mm Hg) and positive end-expiratory pressure (PEEP) (10 cm H2O), the patients were classified into four possible subsets at baseline and at 24 h using a standardized PEEP-FiO(2) approach: (I) PaO2/FiO(2) >= 150 at PEEP < 10, (II) PaO2/FiO(2) > 150 at PEEP >= 10, (III) PaO2/FiO(2) < 150 at PEEP < 10, and (IV) PaO2/FiO(2) < 150 at PEEP >= 10. Primary outcome was death in the ICU. Results: ICU mortalities were similar in the testing and confirmatory cohorts (375/1000, 37.5% vs. 112/303, 37.0%, respectively). At baseline, most patients from the testing cohort (n = 792/1000, 79.2%) had a PaO2/FiO(2) < 150, with similar mortality among the four subsets (p = 0.23). When assessed at 24 h, ICU mortality increased with an advance in the subset: 17.9%, 22.8%, 40.0%, and 49.3% (p < 0.0001). The findings were replicated in the confirmatory cohort (p < 0.0001). However, independent of the PEEP levels, patients with PaO2/FiO(2) < 150 at 24 h followed a distinct 30-day ICU survival compared with patients with PaO2/FiO(2) >= 150 (hazard ratio 2.8, 95% CI 2.2-3.5, p < 0.0001). Conclusions: Subsets based on PaO2/FiO(2) thresholds of 150 mm Hg assessed after 24 h of moderate/severe ARDS diagnosis are clinically relevant for establishing prognosis, and are helpful for selecting adjunctive therapies for hypoxemia and for enrolling patients into therapeutic trials. Show less
OBJECTIVES: To develop a scoring model for stratifying patients with acute respiratory distress syndrome into risk categories (Stratification for identification of Prognostic categories In the... Show moreOBJECTIVES: To develop a scoring model for stratifying patients with acute respiratory distress syndrome into risk categories (Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score) for early prediction of death in the ICU, independent of the underlying disease and cause of death. DESIGN: A development and validation study using clinical data from four prospective, multicenter, observational cohorts. SETTING: A network of multidisciplinary ICUs. PATIENTS: One-thousand three-hundred one patients with moderate-to-severe acute respiratory distress syndrome managed with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study followed Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines for prediction models. We performed logistic regression analysis, bootstrapping, and internal-external validation of prediction models with variables collected within 24 hours of acute respiratory distress syndrome diagnosis in 1,000 patients for model development. Primary outcome was ICU death. The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score was based on patient's age, number of extrapulmonary organ failures, values of end-inspiratory plateau pressure, and ratio of Pao(2) to Fio(2) assessed at 24 hours of acute respiratory distress syndrome diagnosis. The pooled area under the receiver operating characteristic curve across internal-external validations was 0.860 (95% CI, 0.831-0.890). External validation in a new cohort of 301 acute respiratory distress syndrome patients confirmed the accuracy and robustness of the scoring model (area under the receiver operating characteristic curve = 0.870; 95% CI, 0.829-0.911). The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score stratified patients in three distinct prognostic classes and achieved better prediction of ICU death than ratio of Pao(2) to Fio(2) at acute respiratory distress syndrome onset or at 24 hours, Acute Physiology and Chronic Health Evaluation II score, or Sequential Organ Failure Assessment scale. CONCLUSIONS: The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score represents a novel strategy for early stratification of acute respiratory distress syndrome patients into prognostic categories and for selecting patients for therapeutic trials. Show less
