Current in-hospital mortality of the acute respiratory distress syndrome (ARDS) is above 40%. ARDS outcome depends on the lung injury severity within the first 24 hours of ARDS onset. We investigated whether two widely accepted cutoff values of PaO2/FIO2 and positive end-expiratory pressure (PEEP) would identify subsets of patients with ARDS for predicting outcome and guiding therapy.
A 16-month (September 2008 to January 2010) prospective, multicenter, observational study.
Seventeen multidisciplinary ICUs in Spain.
We studied 300 consecutive, mechanically ventilated patients meeting American-European Consensus Conference criteria for ARDS (PaO2/FIO2 ≤ 200 mm Hg) on PEEP greater than or equal to 5 cm H2O, and followed up until hospital discharge.
Based on threshold values for PaO2/FIO2 (150 mm Hg) and PEEP (10 cm H2O) at ARDS onset and at 24 hours, we assigned patients to four categories: group I (PaO2/FIO2 ≥ 150 on PEEP < 10), group II (PaO2/FIO2 ≥ 150 on PEEP ≥ 10), group III (PaO2/FIO2 < 150 on PEEP < 10), and group IV (PaO2/FIO2 < 150 on PEEP ≥ 10). The primary outcome was all-cause in-hospital mortality. Overall hospital mortality was 46.3%. Although at study entry, patients with PaO2/FIO2 less than 150 had a higher mortality than patients with a PaO2/FIO2 greater than or equal to 150 (p = 0.044), there was minimal variability in mortality among the four groups (p = 0.186). However, classification of patients in each group changed markedly after 24 hours of usual care. Group categorization at 24 hours provided a strong association with in-hospital mortality (p < 0.00001): group I had the lowest mortality (23.1%), whereas group IV had the highest mortality (60.3%).
The degree of lung dysfunction established by a PaO2/FIO2 of 150 mm Hg and a PEEP of 10 cm H2O demonstrated that ARDS is not a homogeneous disorder. Rather, it is a series of four subsets that should be considered for enrollment in clinical trials and for guiding therapy. A major contribution of our study is the distinction between survival after 24 hours of care versus survival at the time of ARDS onset.
1CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
2Multidisciplinary Organ Dysfunction Evaluation Research Network, Research Unit, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain.
3Intensive Care Unit, Hospital General de Ciudad Real, Ciudad Real, Spain.
4Intensive Care Unit, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
5Intensive Care Unit, Hospital Universitario Río Hortega, Valladolid, Spain.
6Intensive Care Unit, Hospital General de León, León, Spain.
7Intensive Care Unit, Hospital General Universitario de Albacete, Albacete, Spain.
8Critical Care Center, Corporació Sanitaria Parc Taulí, Sabadell, Spain.
9Intensive Care Unit, Hospital Virgen de la Luz, Cuenca, Spain.
10Intensive Care Unit, Hospital La Mancha Centro, Alcázar de San Juan, Ciudad Real, Spain.
11Intensive Care Unit, Hospital Santa Bárbara, Puertollano, Ciudad Real, Spain.
12Intensive Care Unit, Hospital General Río Carrión, Palencia, Spain.
13Research Unit, Hospital Universitario NS de Candelaria, Santa Cruz de Tenerife, Spain.
14Department of Respiratory Care, Massachusetts General Hospital, Boston, MA.
15Department of Anesthesiology, Harvard University, Boston, MA.
* See also p. 488.
Additional investigators from the Acute Lung Injury: Epidemiology and Natural history Network are listed in Appendix 1.
Drs. Villar and Kacmarek designed the original study. Drs. Ambrós, Parra, Blanco, Domínguez-Berrot, Gutiérrez, Blanch, Añón, Martín, Prieto, Collado enrolled patients and collected the data. Dr. Villar obtained funding for the study. Dr. Villar, Dr. Pérez-Méndez, Ms. Fernández, and Drs. Kacmarek, Ambrós, Parra, Blanco, Domínguez-Berrot, Gutiérrez, Blanch, Añón, Martín, Prieto, and Collado have made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; and approved the final version to be published. Dr. Villar, Ms. Fernández, and Dr. Kacmarek wrote the first draft. Dr. Villar, Ms. Fernández, and Drs. Pérez-Méndez and Kacmarek performed and supervised data management and statistical analysis. Dr. Villar, Ms. Fernández, and Dr. Pérez-Méndez had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Supported, in part, by grants from Instituto de Salud Carlos III, Spain (CB06/06/1088, PI10/0393, PI13/0119), and Asociación Científica Pulmón y Ventilación Mecánica.
Dr. Kacmarek is a consultant for Covidien and has received honorarium from Maquet for lecturing. Dr. Villar has received a research grant from Maquet. Dr. Villar disclosed having received a grant from Maquet for research on mechanical ventilation (Money is not paid to Dr. Villar or to his institution). Dr. Kacmarek consulted and received support for development of educational presentations. The remaining authors have disclosed that they do not have any potential conflicts of interest.
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