Inhaled Sedation in Acute Respiratory Distress Syndrome
Matthieu Jabaudon, Jean‐Pierre Quenot, Julio Badié, Jules Audard, Samir Jaber, Benjamin Rieu, Caroline Varillon, Antoine Monsel, François Thouy, Julien Lorber, Joël Cousson, Stéphanie Bulyez, Jérémy Bourenne, G. Sboui, Claire Lhommet, Virginie Lemiale, Bélaïd Bouhemad, C. Brault, Sigismond Lasocki, François 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, J.C. 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 Quémeneur, Sandrine Ndingamondze, Fanny Charbonnier, Franck Verdonk, Souad Fellous, Christophe Quesnel, Anne Daguenel-Nguyen, Virginie Lemiale, Elie Azoulay, Igor Theodose, Michaël Darmon, Isabelle Madeleine, Julien Le Roy, Christophe Vinsonneau, G. Sboui, Sabine Janowski, Maryline Houdre, Sarah Tollot, Catherine Senis, D. Descamps, Pierre-Marie Bertrand, Marine Agullo, Mehran Monchi, Arezki Agher, E Stoll, M. Camus, Joël Cousson, Bruno Mourvillier, Eric Marquis, Amandine Farget, Mélanie Gaillard, Sandy Aerts, P Benoit, François Legay, Catherine Bellot, Nathalie Kerneur, Valéry Bourbonneux, Laurent Pleven, Aude Davy, Amélie Le Gleut, Nathalie Mercier, Bénédicte Hue, M.-L. Hervé
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. Trial Registration: ClinicalTrials.gov Identifier: NCT04235608.