Inter-country variability over time in the mortality of mechanically ventilated patients

Peñuelas, Oscar; Muriel, Alfonso; Abraira, Victor; Frutos-Vivar, Fernando; Mancebo, Jordi; Raymondos, Konstantinos; Du, Bin; Thille, Arnaud W.; Ríos, Fernando; González, Marco; del-Sorbo, Lorenzo; Ferguson, Niall D.; del Carmen Marín, Maria; Pinheiro, Bruno Valle; Soares, Marco Antonio; Nin, Nicolas; Maggiore, Salvatore M.; Bersten, Andrew; Amin, Pravin; Cakar, Nahit; Suh, Gee Young; Abroug, Fekri; Jibaja, Manuel; Matamis, Dimitros; Zeggwagh, Amine Ali; Sutherasan, Yuda; Anzueto, Antonio; Esteban, Andrés

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). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05867-9) contains supplementary material, which is available to authorized users.