Abstract

BACKGROUND: Although low tidal volume is strongly recommended for acute respiratory distress syndrome (ARDS), whether or not the benefit varies according to the severity of ARDS remains unclear. This study aimed to investigate whether or not there is an interaction between low tidal volume and severity of ARDS. METHODS: This was a secondary analysis from a randomized controlled trial. The patients were subgrouped according to whether the PaO₂/FiO₂ (P/F) was > 150 or ≤ 150 mmHg on day 0. The interaction between a tidal volume of 6 mL/kg and the P/F was investigated in hierarchical chi-square analysis and logistic regression models. RESULTS: Eight hundred and thirty-six patients with ARDS were enrolled (345 in the high P/F subgroup [> 150 mmHg] and 491 in the low P/F subgroup [≤ 150 mmHg]). Compared to the traditional tidal volume group, the mortality of patients with low tidal volume was significantly lower in the high P/F subgroup (41/183 (22.4%) vs. 64/162 (39.5%), p = 0.001) but not in the low P/F subgroup (95/256 (37.1%) vs. 96/235 (40.8%), p = 0.414). In the hierarchical chi-square analysis, the test of homogeneity was significant (risk ratio of mortality 0.56 [0.40-0.79] vs. 0.91 [0.73-1.13], p = 0.018). In the multivariable logistic model, the odds ratio of mortality for the interacted item was significant (2.02, 95% confidence interval [CI] 1.06-3.86, p = 0.033). The odds ratio of mortality for low tidal volume was significant in the high P/F subgroup (0.42, 95% CI 0.24-0.72, p = 0.002) but not in the low P/F subgroup (0.89, 95% CI 0.60-1.31, p = 0.554). CONCLUSIONS: The benefits of low tidal volume ventilation remain uncertain in patients with severe ARDS. Further studies are needed to validate this significant interaction.