Oscar PeñuelasAlfonso MurielVictor AbrairaFernando Frutos-VivarJordi ManceboKonstantinos RaymondosBin DuArnaud W. ThilleFernando RíosMarco GonzálezLorenzo del-SorboNiall D. FergusonMaria del Carmen MarínBruno Valle PinheiroMarco Antonio SoaresNicolas NinSalvatore M. MaggioreAndrew BerstenPravin AminNahit CakarGee Young SuhFekri AbrougManuel JibajaDimitros MatamisAmine Ali ZeggwaghYuda SutherasanAntonio AnzuetoAndrés EstebanHospital Regional 1° de Octubre ISSSTECHU Fattouma-BourguibaUniversidad Pontificia BolivarianaMedizinische Hochschule Hannover (MHH)Hospital Ramon y CajalCentre Hospitalier Universitaire de PoitiersSamsung Medical Center, Sungkyunkwan UniversityFlinders UniversityMohammed V University in RabatUniversity of Texas Health Science Center at San AntonioFaculty of Medicine, Ramathibodi Hospital, Mahidol UniversityPapageorgiou General HospitalIstanbul Üniversitesi Tıp FakültesiBombay Hospital and Medical Research CentreHospital de La Santa Creu I Sant PauPeking Union Medical College HospitalHospital Nacional Professor Dr. Alejandro PosadasUniversity of G. d'Annunzio Chieti and PescaraHospital Universitario de GetafeUniversidade Federal de Juiz de ForaHospital Universitario de MontevideoHospital de Especialidades Eugenio EspejoInterdepartmental Division of Critical Care MedicineHospital Universitário São José2020-01-272020-01-272020-01-01Intensive Care Medicine. (2020)14321238034246422-s2.0-85077626006https://repository.li.mahidol.ac.th/handle/20.500.14594/49676© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Variations in clinical characteristics and management and in the mortality of mechanically ventilated patients have not been sufficiently evaluated. We hypothesized that mortality shows a variability associated with country after adjustment for clinical characteristics and management. Methods: Analysis of four studies carried out at 6-year intervals over an 18-year period. The studies included 26,024 patients (5183 in 1998, 4968 in 2004, 8108 in 2010, and 7765 in 2016) admitted to 1253 units from 38 countries. The primary outcome was 28-day mortality. We performed analyses using multilevel logistic modeling with mixed-random effects, including country as a random variable. To evaluate the effect of management strategies on mortality, a mediation analysis was performed. Results: Adjusted 28-day mortality decreased significantly over time (first study as reference): 2004: odds ratio 0.82 (95% confidence interval [CI] 0.72–0.93); 2010: 0.63 (95% CI 0.53–0.75); 2016: 0.49 (95% CI 0.39–0.61). A protective ventilatory strategy and the use of continuous sedation mediated a moderate fraction of the effect of time on mortality in patients with moderate hypoxemia and without hypoxemia, respectively. Logistic multilevel modeling showed a significant effect of country on mortality: median odds ratio (MOR) in 1998: 2.02 (95% CI 1.57–2.48); in 2004: 1.76 (95% CI 1.47–2.06); in 2010: 1.55 (95% CI 1.37–1.74), and in 2016: 1.39 (95% CI 1.25–1.54). Conclusions: These findings suggest that country could contribute, independently of confounder variables, to outcome. The magnitude of the effect of country decreased over time. Clinical trials registered with http://www.clinicaltrials.gov (NCT02731898).Mahidol UniversityMedicineArticleSCOPUS10.1007/s00134-019-05867-9