Original Investigation February 18, 2019

Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure–Guided Strategy vs an Empirical High PEEP-Fio₂ Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial

Jeremy R. Beitler, Todd Sarge, Valerie M. Banner-Goodspeed, et al; for the EPVent-2 Study Group

JAMA. Published online February 18, 2019. doi:10.1001/jama.2019.0555

Abstract

Importance 背景

Adjusting positive end-expiratory pressure (PEEP) to offset pleural pressure might attenuate lung injury and improve patient outcomes in acute respiratory distress syndrome (ARDS).

调整PEEP对抗胸腔内压能够减轻ARDS患者肺损伤，改善临床预后。

Objective 目的

To determine whether PEEP titration guided by esophageal pressure (P_ES), an estimate of pleural pressure, was more effective than empirical high PEEP–fraction of inspired oxygen (Fio₂) in moderate to severe ARDS.

与经验性高PEEP-Fio₂设置相比，确定食道压(P_ES)（用于估测胸腔内压）指导PEEP滴定对于中重度ARDS患者是否有效。

Design, Setting, and Participants  设计，场景及研究人群

Phase 2 randomized clinical trial conducted at 14 hospitals in North America. Two hundred mechanically ventilated patients aged 16 years and older with moderate to severe ARDS (Pao₂:Fio₂ ≤200 mm Hg) were enrolled between October 31, 2012, and September 14, 2017; long-term follow-up was completed July 30, 2018.

在北美14所医院进行的一项2期随机临床试验。2012年10月31日至2017年9月14日之间，共纳入200名接受机械通气的成年中重度ARDS患者 (Pao₂:Fio₂ ≤200 mm Hg)；长期随访于2018年7月30日终止。

Interventions 干预措施

Participants were randomized to P_ES-guided PEEP (n = 102) or empirical high PEEP-Fio₂ (n = 98). All participants received low tidal volumes.

患者被随机分至P_ES指导PEEP组 (n = 102) 或经验性高PEEP-Fio₂组 (n = 98)。所有患者均接受小潮气量通气。

Main Outcomes and Measures  主要预后指标

The primary outcome was a ranked composite score incorporating death and days free from mechanical ventilation among survivors through day 28. Prespecified secondary outcomes included 28-day mortality, days free from mechanical ventilation among survivors, and need for rescue therapy.

主要预后指标为包括死亡及存活者28天内无机械通气天数的分级复合评分。预先确定的次要预后指标包括28天病死率，存活者无机械通气天数，以及挽救治疗需求。

Results 结果

Two hundred patients were enrolled (mean [SD] age, 56 [16] years; 46% female) and completed 28-day follow-up. The primary composite end point was not significantly different between treatment groups (probability of more favorable outcome with P_ES-guided PEEP: 49.6% [95% CI, 41.7% to 57.5%]; P = .92). At 28 days, 33 of 102 patients (32.4%) assigned to P_ES-guided PEEP and 30 of 98 patients (30.6%) assigned to empirical PEEP-Fio₂ died (risk difference, 1.7% [95% CI, −11.1% to 14.6%]; P = .88). Days free from mechanical ventilation among survivors was not significantly different (median [interquartile range]: 22 [15-24] vs 21 [16.5-24] days; median difference, 0 [95% CI, −1 to 2] days; P = .85). Patients assigned to P_ES-guided PEEP were significantly less likely to receive rescue therapy (4/102 [3.9%] vs 12/98 [12.2%]; risk difference, −8.3% [95% CI, −15.8% to −0.8%]; P = .04). None of the 7 other prespecified secondary clinical end points were significantly different. Adverse events included gross barotrauma, which occurred in 6 patients with P_ES-guided PEEP and 5 patients with empirical PEEP-Fio₂.

研究纳入200名患者（平均 [SD] 年龄，56 [16] 岁；46% 为女性）且完成28天随访。主要复合终点在两组间无显著差异（P_ES指导PEEP组更好预后概率：49.6% [95% CI, 41.7% to 57.5%]; P = .92）。在第28天时，At 28 days, P_ES指导PEEP组102名患者中33名(32.4%)以及经验性PEEP-Fio₂组98名患者中30名(30.6%)死亡（风险差异1.7% [95% CI, −11.1% to 14.6%]; P = .88）。两组存活患者无机械通气天数无显著差异（中位数[四分位区间]: 22 [15-24] vs 21 [16.5-24] 天；中位差异，0 [95% CI, −1 to 2] 天；P = .85）。P_ES指导PEEP组患者更少接受挽救治疗（4/102 [3.9%] vs 12/98 [12.2%]；风险差异 −8.3% [95% CI, −15.8% to −0.8%]; P = .04）。其他7项预先确定的次要临床终点没有显著差异。不良事件包括气压伤， P_ES指导PEEP组及经验性PEEP-Fio₂组分别有6名及5名患者出现。

Conclusions and Relevance 结论与意义

Among patients with moderate to severe ARDS, P_ES-guided PEEP, compared with empirical high PEEP-Fio₂, resulted in no significant difference in death and days free from mechanical ventilation. These findings do not support P_ES-guided PEEP titration in ARDS.

对于中重度ARDS患者，与经验性高PEEP-Fio₂ 相比，P_ES指导PEEP设置不能显著改善死亡及无机械通气天数。这些结果不支持在ARDS患者进行P_ES指导PEEP滴定。