Clinical relevance of timing of assessment of ICU mortality in patients with moderate-to-severe Acute Respiratory Distress Syndrome

Abstract 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 identify a crossing-point between cumulative survival and death in the intensive care unit (ICU)...

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Main Authors: Jesús Villar, Jesús M. González-Martin, José M. Añón, Carlos Ferrando, Juan A. Soler, Fernando Mosteiro, Juan M. Mora-Ordoñez, Alfonso Ambrós, Lorena Fernández, Raquel Montiel, Anxela Vidal, Tomás Muñoz, Lina Pérez-Méndez, Pedro Rodríguez-Suárez, Cristina Fernández, Rosa L. Fernández, Tamas Szakmany, Karen E. A. Burns, Ewout W. Steyerberg, Arthur S. Slutsky
Format: Article
Language:English
Published: Nature Portfolio 2023-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-28824-5
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author Jesús Villar
Jesús M. González-Martin
José M. Añón
Carlos Ferrando
Juan A. Soler
Fernando Mosteiro
Juan M. Mora-Ordoñez
Alfonso Ambrós
Lorena Fernández
Raquel Montiel
Anxela Vidal
Tomás Muñoz
Lina Pérez-Méndez
Pedro Rodríguez-Suárez
Cristina Fernández
Rosa L. Fernández
Tamas Szakmany
Karen E. A. Burns
Ewout W. Steyerberg
Arthur S. Slutsky
author_facet Jesús Villar
Jesús M. González-Martin
José M. Añón
Carlos Ferrando
Juan A. Soler
Fernando Mosteiro
Juan M. Mora-Ordoñez
Alfonso Ambrós
Lorena Fernández
Raquel Montiel
Anxela Vidal
Tomás Muñoz
Lina Pérez-Méndez
Pedro Rodríguez-Suárez
Cristina Fernández
Rosa L. Fernández
Tamas Szakmany
Karen E. A. Burns
Ewout W. Steyerberg
Arthur S. Slutsky
author_sort Jesús Villar
collection DOAJ
description Abstract 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 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.
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spelling doaj.art-f01ac765e07a4e03b46d4c2f837b676c2023-01-29T12:08:28ZengNature PortfolioScientific Reports2045-23222023-01-0113111010.1038/s41598-023-28824-5Clinical relevance of timing of assessment of ICU mortality in patients with moderate-to-severe Acute Respiratory Distress SyndromeJesús Villar0Jesús M. González-Martin1José M. Añón2Carlos Ferrando3Juan A. Soler4Fernando Mosteiro5Juan M. Mora-Ordoñez6Alfonso Ambrós7Lorena Fernández8Raquel Montiel9Anxela Vidal10Tomás Muñoz11Lina Pérez-Méndez12Pedro Rodríguez-Suárez13Cristina Fernández14Rosa L. Fernández15Tamas Szakmany16Karen E. A. Burns17Ewout W. Steyerberg18Arthur S. Slutsky19CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos IIICIBER de Enfermedades Respiratorias, Instituto de Salud Carlos IIICIBER de Enfermedades Respiratorias, Instituto de Salud Carlos IIICIBER de Enfermedades Respiratorias, Instituto de Salud Carlos IIIIntensive Care Unit, Hospital Universitario Virgen de ArrixacaIntensive Care Unit, Hospital Universitario de A CoruñaIntensive Care Unit, Hospital Universitario Regional Carlos HayaIntensive Care Unit, Hospital General Universitario de Ciudad RealIntensive Care Unit, Hospital Universitario Río HortegaIntensive Care Unit, Hospital Universitario NS de CandelariaIntensive Care Unit, Hospital Universitario Fundación Jiménez DíazIntensive Care Unit, Hospital Universitario de CrucesCIBER de Enfermedades Respiratorias, Instituto de Salud Carlos IIICIBER de Enfermedades Respiratorias, Instituto de Salud Carlos IIIResearch Unit, Hospital Universitario Dr. NegrínCIBER de Enfermedades Respiratorias, Instituto de Salud Carlos IIIDepartment of Intensive Care Medicine and Anesthesia, Bevan University Health BoardLi Ka Shing Knowledge Institute at St. Michael’s HospitalDepartment Biomedical Data Sciences, Leiden University Medical CenterLi Ka Shing Knowledge Institute at St. Michael’s HospitalAbstract 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 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.https://doi.org/10.1038/s41598-023-28824-5
spellingShingle Jesús Villar
Jesús M. González-Martin
José M. Añón
Carlos Ferrando
Juan A. Soler
Fernando Mosteiro
Juan M. Mora-Ordoñez
Alfonso Ambrós
Lorena Fernández
Raquel Montiel
Anxela Vidal
Tomás Muñoz
Lina Pérez-Méndez
Pedro Rodríguez-Suárez
Cristina Fernández
Rosa L. Fernández
Tamas Szakmany
Karen E. A. Burns
Ewout W. Steyerberg
Arthur S. Slutsky
Clinical relevance of timing of assessment of ICU mortality in patients with moderate-to-severe Acute Respiratory Distress Syndrome
Scientific Reports
title Clinical relevance of timing of assessment of ICU mortality in patients with moderate-to-severe Acute Respiratory Distress Syndrome
title_full Clinical relevance of timing of assessment of ICU mortality in patients with moderate-to-severe Acute Respiratory Distress Syndrome
title_fullStr Clinical relevance of timing of assessment of ICU mortality in patients with moderate-to-severe Acute Respiratory Distress Syndrome
title_full_unstemmed Clinical relevance of timing of assessment of ICU mortality in patients with moderate-to-severe Acute Respiratory Distress Syndrome
title_short Clinical relevance of timing of assessment of ICU mortality in patients with moderate-to-severe Acute Respiratory Distress Syndrome
title_sort clinical relevance of timing of assessment of icu mortality in patients with moderate to severe acute respiratory distress syndrome
url https://doi.org/10.1038/s41598-023-28824-5
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