Jesús Villar1,2, Domingo Martínez3, Fernando Mosteiro4, Alfonso Ambrós5, José M Añón1,6, Carlos Ferrando1,7, Juan A Soler3, Raquel Montiel8, Anxela Vidal9, Luís A Conesa-Cayuela3, Jesús Blanco1,10, Regina Arrojo4, Rosario Solano11, Lucía Capilla12, Rafael Del Campo5, Belén Civantos6, María Mar Fernández13, César Aldecoa14, Laura Parra15, Andrea Gutiérrez7, Chanel Martínez-Jiménez16, Jesús M González-Martín17, Rosa L Fernández1,2, Robert M Kacmarek18,19. 1. CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain. 2. Research Unit, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain. 3. Intensive Care Unit, Hospital Universitario Virgen de Arrixaca, Murcia, Spain. 4. Intensive Care Unit, Hospital Universitario de La Coruña, La Coruña, Spain. 5. Intensive Care Unit, Hospital General de Ciudad Real, Ciudad Real, Spain. 6. Intensive Care Unit, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain. 7. Department of Anesthesiology, Hospital Clínico Universitario de Valencia, Valencia, Spain. 8. Intensive Care Unit, Hospital Universitario NS de Candelaria, Santa Cruz de Tenerife, Spain. 9. Intensive Care Unit, Hospital Fundación Jiménez Díaz, Madrid, Spain. 10. Intensive Care Unit, Hospital Universitario Río Hortega, Valladolid, Spain. 11. Intensive Care Unit, Hospital Virgen de la Luz, Cuenca, Spain. 12. Intensive Care Unit, Hospital Universitario Morales Meseguer, Murcia, Spain. 13. Intensive Care Unit, Hospital Universitario Mutua de Terrasa, Terrasa, Barcelona, Spain. 14. Department of Anesthesiology, Hospital Universitario Río Hortega, Valladolid, Spain. 15. Intensive Care Unit, Hospital Clínico Universitario de Valladolid, Valladolid, Spain. 16. Intensive Care Unit, Hospital del Bierzo, Ponferrada, León, Spain. 17. Department of Biostatistics, Research Unit, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain. 18. Department of Respiratory Care, Massachusetts General Hospital, Boston, MA. 19. Department of Anesthesia, Harvard University, Boston, MA.
Abstract
OBJECTIVES: Overall mortality in patients with acute respiratory distress syndrome is a composite endpoint because it includes death from multiple causes. In most acute respiratory distress syndrome trials, it is unknown whether reported deaths are due to acute respiratory distress syndrome or the underlying disease, unrelated to the specific intervention tested. We investigated the causes of death after contracting acute respiratory distress syndrome in a large cohort. DESIGN: A secondary analysis from three prospective, multicenter, observational studies. SETTING: A network of multidisciplinary ICUs. PATIENTS: We studied 778 patients with moderate-to-severe acute respiratory distress syndrome treated with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We examined death in the ICU from individual causes. Overall ICU mortality was 38.8% (95% CI, 35.4-42.3). Causes of acute respiratory distress syndrome modified the risk of death. Twenty-three percent of deaths occurred from refractory hypoxemia due to nonresolving acute respiratory distress syndrome. Most patients died from causes unrelated to acute respiratory distress syndrome: 48.7% of nonsurvivors died from multisystem organ failure, and cancer or brain injury was involved in 37.1% of deaths. When quantifying the true burden of acute respiratory distress syndrome outcome, we identified 506 patients (65.0%) with one or more exclusion criteria for enrollment into current interventional trials. Overall ICU mortality of the "trial cohort" (21.3%) was markedly lower than the parent cohort (relative risk, 0.55; 95% CI, 0.43-0.70; p < 0.000001). CONCLUSIONS: Most deaths in acute respiratory distress syndrome patients are not directly related to lung damage but to extrapulmonary multisystem organ failure. It would be challenging to prove that specific lung-directed therapies have an effect on overall survival.
OBJECTIVES: Overall mortality in patients with acute respiratory distress syndrome is a composite endpoint because it includes death from multiple causes. In most acute respiratory distress syndrome trials, it is unknown whether reported deaths are due to acute respiratory distress syndrome or the underlying disease, unrelated to the specific intervention tested. We investigated the causes of death after contracting acute respiratory distress syndrome in a large cohort. DESIGN: A secondary analysis from three prospective, multicenter, observational studies. SETTING: A network of multidisciplinary ICUs. PATIENTS: We studied 778 patients with moderate-to-severe acute respiratory distress syndrome treated with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We examined death in the ICU from individual causes. Overall ICU mortality was 38.8% (95% CI, 35.4-42.3). Causes of acute respiratory distress syndrome modified the risk of death. Twenty-three percent of deaths occurred from refractory hypoxemia due to nonresolving acute respiratory distress syndrome. Most patients died from causes unrelated to acute respiratory distress syndrome: 48.7% of nonsurvivors died from multisystem organ failure, and cancer or brain injury was involved in 37.1% of deaths. When quantifying the true burden of acute respiratory distress syndrome outcome, we identified 506 patients (65.0%) with one or more exclusion criteria for enrollment into current interventional trials. Overall ICU mortality of the "trial cohort" (21.3%) was markedly lower than the parent cohort (relative risk, 0.55; 95% CI, 0.43-0.70; p < 0.000001). CONCLUSIONS: Most deaths in acute respiratory distress syndromepatients are not directly related to lung damage but to extrapulmonary multisystem organ failure. It would be challenging to prove that specific lung-directed therapies have an effect on overall survival.
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