Rationale: In acute respiratory distress syndrome (ARDS), the effect of positive end-expiratory pressure (PEEP) may depend on the extent to which multiorgan dysfunction contributes to risk of death, and the precision with which PEEP is titrated to attenuate atelectrauma without exacerbating overdistension. Objectives: To evaluate whether multiorgan dysfunction and lung mechanics modified treatment effect in the EPVent-2 (Esophageal Pressure-guided Ventilation 2) trial, a multicenter trial of esophageal pressure (Pes)-guided PEEP versus empirical high PEEP in moderate to severe ARDS. Methods: This post hoc reanalysis of the EPVent-2 trial evaluated for heterogeneity of treatment effect on mortality by baseline multiorgan dysfunction, determined via Acute Physiology and Chronic Health Evaluation II (APACHE-II). It also evaluated whether PEEP titrated to end-expiratory transpulmonary pressure near 0 cm H2O was associated with survival. Measurements and Main Results: All 200 trial participants were included. Treatment effect on 60-day mortality differed by multiorgan dysfunction severity (P = 0.03 for interaction). Pes-guided PEEP was associated with lower mortality among patients with APACHE-II less than the median value (hazard ratio, 0.43; 95% confidence interval, 0.20-0.92) and may have had the opposite effect in patients with higher APACHE-II (hazard ratio, 1.69; 95% confidence interval, 0.93-3.05). Independent of treatment group or multiorgan dysfunction severity, mortality was lowest when PEEP titration achieved end-expiratory transpulmonary pressure near 0 cm H2O. Conclusions: The effect on survival of Pes-guided PEEP, compared with empirical high PEEP, differed by multiorgan dysfunction severity. Independent of multiorgan dysfunction, PEEP titrated to end-expiratory transpulmonary pressure closer to 0 cm H2O was associated with greater survival than more positive or negative values. These findings warrant prospective testing in a future trial.

中文翻译：

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食管压力引导的呼气末正压对急性呼吸窘迫综合征存活率的影响：EPVent-2 试验的基于风险和机制的再分析。

理由：在急性呼吸窘迫综合征 (ARDS) 中，呼气末正压 (PEEP) 的作用可能取决于多器官功能障碍导致死亡风险的程度，以及滴定 PEEP 以减轻肺不张损伤而不加重肺不张损伤的精确度过度膨胀。目的：评估多器官功能障碍和肺力学是否改变了 EPVent-2（食管压力引导通气 2）试验中的治疗效果，该试验是食管压力 (Pes) 引导 PEEP 与中度至重度 ARDS 经验性高 PEEP 的多中心试验。方法：这项对 EPVent-2 试验的事后再分析通过急性生理学和慢性健康评估 II (APACHE-II) 确定，通过基线多器官功能障碍评估了治疗对死亡率影响的异质性。它还评估了滴定至接近 0 cm H2O 的呼气末跨肺压的 PEEP 是否与生存相关。测量和主要结果：包括所有 200 名试验参与者。治疗对 60 天死亡率的影响因多器官功能障碍的严重程度而异（交互作用 P = 0.03）。在 APACHE-II 低于中值的患者中，Pes 引导的 PEEP 与较低的死亡率相关（风险比，0.43；95% 置信区间，0.20-0.92），并且可能对 APACHE-II 较高的患者产生相反的效果（风险比，1.69；95% 置信区间，0.93-3.05）。独立于治疗组或多器官功能障碍的严重程度，当 PEEP 滴定达到接近 0 cm H2O 的呼气末跨肺压时，死亡率最低。结论：Pes 引导的 PEEP 对生存的影响，与经验性高 PEEP 相比，因多器官功能障碍严重程度而异。独立于多器官功能障碍，PEEP 滴定到接近 0 cm H2O 的呼气末跨肺压与更高的存活率相关，而不是更正或更负的值。这些发现值得在未来的试验中进行前瞻性测试。