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

Abstract

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).

Keywords: Epidemiology; Mechanical ventilation; Mortality; Outcome; Variability.

Conflict of interest statement

The authors declare there is no conflict of interest.

Figures

Fig. 1

Changes over time in tidal volume (blue box plot) and positive end-expiratory pressure (red box plot) set at initiation of mechanical ventilation in patients without criteria of acute respiratory distress syndrome (ARDS) and patients with ARDS. For each box plot, the middle line represents the median, the lower hinge represents the first quartile, the upper hinge represents the third quartile, the whiskers extend to 1.5 times interquartile range, and the outliers are values outside the whiskers’ range

Fig. 2

Regression lines of the evolution of the 28-day mortality by countries (thin lines) and globally (thick line). For simplicity of the graph, only the fifteen countries that participated in the four studies are shown. Overall 28-day mortality decreased over time (thick line). The variability between countries declined (the dispersion is lower in the last year than in the first year). The rate of change in mortality in each country is inversely related to the initial dispersion: countries farthest from the average changed faster in the opposite direction. Countries with initial higher mortality tended to see this decline more rapidly (blue lines), while those with initial lower mortality tended to raise it slowly (red lines)

Fig. 3

Adjusted inter-country variability estimated by mean odds ratio (95% confidence interval) at each study year in all the participating countries (red) and in the 15 countries that took part in all four studies (blue). The Median Odds Ratio (MOR) is defined as the median value of the odds ratio between the area at highest risk of mortality and the area at lowest risk when randomly picking out two areas