Background: The effects of plateau pressure during the initial days of mechanical ventilation on outcomes for patients with acute respiratory distress syndrome have not been fully examined. We conducted meta-regression analysis of plateau pressure during the first 7 days using randomized control trials to investigate the optimal upper limits of plateau pressure on different days of mechanical ventilation. Methods: Randomized controlled trials comparing two mechanical ventilation strategies with lower and higher plateau pressures in patients with acute respiratory distress syndrome were included. Metaregression analysis was performed to determine the association of plateau pressure with mortality on days 1, 3, and 7 of mechanical ventilation. Results: After evaluation of 2,975 citations from a comprehensive search across electronic databases, 14 studies were included in the final qualitative analysis. A total of 4,984 patients were included in the quantitative analysis. As a result of the pairwise comparison, overall short-term mortality was significantly higher for patients with plateau pressures over 32 cm H2O during the first 3 days after intensive care unit (ICU) admission (day 1: relative risk (RR), 0.77; 95% confidence interval (CI), 0.66-0.89; I2 = 0%; day 3: RR, 0.76; 95% CI, 0.64-0.90; I2 = 0%), but not on day 7 (RR, 0.82; 95% CI, 0.65-1.04; I2 = 16%). Plateau pressures below 27 cm H2O and 30 cm H2O were not associated with an absolute risk reduction of shortterm mortality. According to univariable meta-regression analysis, mortality was significantly associated with plateau pressure on day 1 (β = 0.01 (95% CI, 0.002-0.024), P = 0.02). On days 3 and 7, however, no significant difference was detected. When the cutoffs were set at 27, 30 and 32 cm H2O on day 1, which showed a significant difference, plateau pressure tended to be associated with increased mortality at pressures above the cut-off values, and there were no significant differences at pressures below the cut-off values, regardless of the cutoff used. Conclusions: This study suggests that the optimal cut-off value for plateau pressure may be 27 cm H2O especially during the initial period of mechanical ventilation, although this association may not continue during the latter period of mechanical ventilation.
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