Jabaudon Matthieu, Quenot Jean-Pierre, Badie Julio, Audard Jules, Jaber Samir, Rieu Benjamin, Varillon Caroline, Monsel Antoine, Thouy François, Lorber Julien, Cousson Joël, Bulyez Stéphanie, Bourenne Jérémy, Sboui Ghada, Lhommet Claire, Lemiale Virginie, Bouhemad Belaïd, Brault Clément, Lasocki Sigismond, Legay François, Lebouvier Thomas, Durand Arthur, Pottecher Julien, Conia Alexandre, Brégeaud Delphine, Velly Lionel, Thille Arnaud W, Lambiotte Fabien, L'Her Erwan, Monchi Mehran, Roquilly Antoine, Berrouba Aziz, Verdonk Franck, Chabanne Russell, Godet Thomas, Garnier Marc, Blondonnet Raiko, Vernhes Jérémy, Sapin Vincent, Borao Lucile, Futier Emmanuel, Pereira Bruno, Constantin Jean-Michel
Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France.
iGReD, CNRS, INSERM, Université Clermont Auvergne, Clermont-Ferrand, France.
JAMA. 2025 May 13;333(18):1608-1617. doi: 10.1001/jama.2025.3169.
Whether the use of inhaled or intravenous sedation affects outcomes differentially in mechanically ventilated adults with acute respiratory distress syndrome (ARDS) is unknown.
To determine the efficacy and safety of inhaled sevoflurane compared with intravenous propofol for sedation in patients with ARDS.
DESIGN, SETTING, AND PARTICIPANTS: Phase 3 randomized, open-label, assessor-blinded clinical trial conducted from May 2020 to October 2023 with 90-day follow-up. Adults with early moderate to severe ARDS (defined by a ratio of Pao2 to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure of ≥8 cm H2O) were enrolled in 37 French intensive care units.
Patients were randomized to a strategy of inhaled sedation with sevoflurane (intervention group) or to a strategy of intravenous sedation with propofol (control group) for up to 7 days.
The primary end point was the number of ventilator-free days at 28 days; the key secondary end point was 90-day survival.
Of 687 patients enrolled (mean [SD] age, 65 [12] years; 30% female), 346 were randomized to sevoflurane and 341 to propofol. The median total duration of sedation was 7 days (IQR, 4 to 7) in both groups. The number of ventilator-free days through day 28 was 0.0 days (IQR, 0.0 to 11.9) in the sevoflurane group and 0.0 days (IQR, 0.0 to 18.7) in the propofol group (median difference, -2.1 [95% CI, -3.6 to -0.7]; standardized hazard ratio, 0.76 [95% CI, 0.50 to 0.97]). The 90-day survival rates were 47.1% and 55.7% in the sevoflurane and propofol groups, respectively (hazard ratio, 1.31 [95% CI, 1.05 to 1.62]). Among 4 secondary outcomes, sevoflurane was associated with higher 7-day mortality (19.4% vs 13.5%, respectively; relative risk, 1.44 [95% CI, 1.02 to 2.03]) and fewer intensive care unit-free days through day 28 (median, 0.0 [IQR, 0.0 to 6.0] vs 0.0 [IQR, 0.0 to 15.0]; median difference, -2.5 [95% CI, -3.7 to -1.4]) compared with propofol.
Among patients with moderate to severe ARDS, inhaled sedation with sevoflurane resulted in fewer ventilator-free days at day 28 and lower 90-day survival than sedation with propofol.
ClinicalTrials.gov Identifier: NCT04235608.
对于机械通气的急性呼吸窘迫综合征（ARDS）成年患者，吸入镇静或静脉镇静对预后的影响是否存在差异尚不清楚。
确定与静脉注射丙泊酚相比，吸入七氟醚用于ARDS患者镇静的有效性和安全性。
设计、地点和参与者：2020年5月至2023年10月进行的3期随机、开放标签、评估者盲法临床试验，随访90天。37个法国重症监护病房纳入了早期中度至重度ARDS成年患者（定义为动脉血氧分压与吸入氧分数之比<150 mmHg且呼气末正压≥8 cm H2O）。
患者被随机分配至七氟醚吸入镇静策略（干预组）或丙泊酚静脉镇静策略（对照组），持续7天。
主要终点是28天时无呼吸机天数；关键次要终点是90天生存率。
687名纳入患者（平均[标准差]年龄，65[12]岁；30%为女性）中，346名被随机分配至七氟醚组，341名被随机分配至丙泊酚组。两组镇静总时长中位数均为7天（四分位间距，4至7）。七氟醚组至28天时的无呼吸机天数为0.0天（四分位间距，0.0至11.9），丙泊酚组为0.0天（四分位间距，0.0至18.7）（中位数差异，-2.1[95%置信区间，-3.6至-0.7]；标准化风险比，0.76[95%置信区间，0.50至0.97]）。七氟醚组和丙泊酚组的90天生存率分别为47.1%和55.7%（风险比，1.31[95%置信区间，1.05至1.62]）。在4项次要结局中，与丙泊酚相比，七氟醚与更高的7天死亡率（分别为19.4%和13.5%；相对风险，1.44[95%置信区间，1.02至2.03]）以及至28天时更少的无重症监护病房天数（中位数，0.0[四分位间距，0.0至6.0]对0.0[四分位间距，0.0至15.0]；中位数差异，-2.5[95%置信区间，-3.7至-1.4]）相关。
在中度至重度ARDS患者中，与丙泊酚镇静相比，七氟醚吸入镇静导致28天时无呼吸机天数更少，90天生存率更低。
ClinicalTrials.gov标识符：NCT04235608。
