Sabine Janowski研究组取得一项新突破。他们揭示了吸入镇静治疗急性呼吸窘迫综合征。相关论文于2025年3月18日发表在《美国医学会杂志》上。

重要性:在机械通气的急性呼吸窘迫综合征（ARDS）成人患者中，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。

目的:比较吸入七氟醚与静脉注射异丙酚在ARDS患者镇静中的疗效和安全性。

设计、设置和参与者：2020年5月至2023年10月进行的3期随机、开放标签、评估盲临床试验，随访90天。患有早期中度至重度急性呼吸窘迫综合征（以Pao2与吸入氧分数的比值为标准，呼气末正压≥8 cm H2O）的成人纳入了37个法国重症监护病房。

干预措施:患者被随机分为七氟醚吸入镇静组（干预组）和异丙酚静脉镇静组（对照组），时间最长为7天。

主要成果和措施：主要终点为28天无呼吸机天数；关键的次要终点是90天的生存期。

结果:入组687例患者(平均[SD]年龄65岁；30%女性)，346例随机分配到七氟醚组，341例随机分配到异丙酚组。两组患者镇静总持续时间中位数均为7天（IQR, 4 ~ 7）。七氟醚组至第28天无呼吸机天数为0.0天（IQR, 0.0 ~ 11.9），异丙酚组为0.0天（IQR, 0.0 ~ 18.7）(中位差为2.1；标准化风险比0.76)。七氟醚组和异丙酚组90天生存率分别为47.1%和55.7%（风险比为1.31）。在4个次要结局中，七氟醚与较高的7天死亡率相关(分别为19.4%对13.5%；相对风险，1.44)，到第28天无重症监护病房天数更少(中位数，0.0 [IQR， 0.0至6.0]vs 0.0 [IQR， 0.0至15.0]；与异丙酚相比，中位差值为-2.5)。

研究结果表明，在中重度ARDS患者中，与异丙酚镇静相比，七氟醚吸入镇静导致第28天无呼吸机天数更少，90天生存率更低。

附：英文原文

Title: Inhaled Sedation in Acute Respiratory Distress Syndrome: The SESAR Randomized Clinical Trial

Author: Matthieu Jabaudon, Jean-Pierre Quenot, Julio Badie, Jules Audard, Samir Jaber, Benjamin Rieu, Caroline Varillon, Antoine Monsel, Franois Thouy, Julien Lorber, Jol Cousson, Stéphanie Bulyez, Jérémy Bourenne, Ghada Sboui, Claire Lhommet, Virginie Lemiale, Belad Bouhemad, Clément Brault, Sigismond Lasocki, Franois Legay, Thomas Lebouvier, Arthur Durand, Julien Pottecher, Alexandre Conia, Delphine Brégeaud, Lionel Velly, Arnaud W. Thille, Fabien Lambiotte, Erwan L’Her, Mehran Monchi, Antoine Roquilly, Aziz Berrouba, Franck Verdonk, Russell Chabanne, Thomas Godet, Marc Garnier, Raiko Blondonnet, Jérémy Vernhes, Vincent Sapin, Lucile Borao, Emmanuel Futier, Bruno Pereira, Jean-Michel Constantin, SESAR Trial Investigators, Marc Gainnier, Jérémy Bourenne, Béatrice Cresta, Aurélie Larosa, Lionel Velly, Pierre Simeone, Didier Sanchez, Imane Inal, Marine Challier, Valentine Verdier, Bénédicte Deluca-Bosc, Jean-Michel Constantin, Antoine Monsel, Cyril Quemeneur, Sandrine Ndingamondze, Fanny Charbonnier, Franck Verdonk, Souad Fellous, Christophe Quesnel, Anne Daguenel-Nguyen, Virginie Lemiale, Elie Azoulay, Igor Theodose, Michael Darmon, Isabelle Madeleine, Julien Le Roy, Christophe Vinsonneau, Ghada Sboui, Sabine Janowski

Issue&Volume: 2025-03-18

Abstract: Importance  Whether the use of inhaled or intravenous sedation affects outcomes differentially in mechanically ventilated adults with acute respiratory distress syndrome (ARDS) is unknown.

Objective  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.

Interventions  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.

Main Outcomes and Measures  The primary end point was the number of ventilator-free days at 28 days; the key secondary end point was 90-day survival.

Results  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.

Conclusions and Relevance  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.

DOI: 10.1001/jama.2025.3169

Source: https://jamanetwork.com/journals/jama/fullarticle/2831857