Inhaled Sedation in Acute Respiratory Distress Syndrome
Authors: Matthieu Jabaudon, Jean-Pierre Quenot, Julio Badie, Jules Audard, Samir Jaber, Benjamin Rieu, Caroline Varillon, Antoine Monsel, François Thouy, Julien Lorber, Joël Cousson, Stéphanie Bulyez, Jérémy Bourenne, Ghada Sboui, Claire Lhommet, Virginie Lemiale, Belaïd Bouhemad, Clément 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, Jérémy Vernhes, Vincent Sapin, Lucile Borao, Emmanuel Futier, Bruno Pereira, Jean-Michel Constantin, 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, Maryline Houdre, Sarah Tollot, Catherine Senis, Dominique Descamps, Pierre-Marie Bertrand, Marine Agullo, Mehran Monchi, Arezki Agher, Eric Stoll, Maryse Camus, Joël Cousson, Bruno Mourvillier, Eric Marquis, Amandine Farget, Mélanie Gaillard, Sandy Aerts, Philippe Benoit, François Legay, Catherine Bellot, Nathalie Kerneur, Valéry Bourbonneux, Laurent Pleven, Aude Davy, Amélie Le Gleut, Nathalie Mercier, Bénédicte Hue, Marie-Cécile Herve, Clément Brault, Julien Maizel, Yoann Zerbib, Rayan Braik, Kahina Zid, Sophie Boddaert, Yves-Edouard Herpe, Sigismond Lasocki, Maeva Campfort, Soizic Gergaud, Viviane Cassisa, Anne Sylvie Scholastique, Valérie Daniel, Erwan L'Her, Pierre Bailly, Isabelle Ledu, Hélène Fortin-Prunier, Amandine Tapon, Axelle Cornillet, Patricia Dias, Elsa Menanteau, Jean-Pierre Quenot, Pascal Andreu, Audrey Massard, Solene Villot, Samantha Lima Pinheiro, Jean-Baptiste Roudaut, Belaïd Bouhemad, Nicolas Nowobilski, Vivien Berthoud, Hasni Si-Abdelkader, Samir Jaber, Gérald Chanques, Audrey De Jong, Boris Jung, Albert Prades, Fouad Belafia, Julie Carr, Moussa Cisse, Matthieu Conseil, Jean-Marc Delay, Julien Boudjemaa, Laurent Cachia, Jeanne Boyer, Antoine Roquilly, Karim Asehnoune, Clément Prouteau, Delphine Flattres Du Chaussoy, Cécilia Lebel, Amélie Trichot, Dominique Demeure dit Latte, Yannick Hourmant, Pierre-Joachim Mahe, Laurence Flet, Carole Ichai, Jean-Christophe Orban, Christelle Boczek, Justine Bellegarde, Stéphanie Bulyez, Claire Roger, Laurent Muller, Jean-Yves Lefrant, Sophie Lloret, Audrey Ambert, Mathieu Expert, Caroline Maury, Virginie Viviez, Elodie Jullian, Céline Loiseau, Christian Maillard, Claire Dahyot-Fizelier, Nadia Imzi, Christelle Plumereau, Sabrina Seguin, Isabelle Princet, Arnaud W. Thille, Jean-Pierre Frat, René Robert, Rémy Coudroy, Carole Guignon, Céline Delétage, Nacira Benhamouche, Delphine Chatellier, Damien Marie, Florence Boissier, Anne Veinstein, Thomas Lebouvier, Philippe Seguin, Sophie Caradec, Julien Pottecher, Eric Noll, Pierre Diemunsch, ThienNga Chamaraux-Tran, Habiba Moussa, Stéphane Hecketsweiler, Arnaud Romoli, Alain Meyer, Nadia Dhif, Magdalena Szczot, Alban Pellegrino, Alexandre Debaene, Anne Hutt, Sarah Lang, Claire Lhommet, Roland Amathieu, Thierry Lazard, Gabriel Lejour, Emmanuelle Guillot, Caroline Varillon, Caroline Blazejewski, Sébastien Beague, Maud Vasse, Pauline Boddaert, Maxime Samson, Raphael Krouchi, Cyril Fayolle, Thomas Queruau, François Beze, Solange Tombelle, Fréderique Danicourt, Basile Dectot, Carole Delattre, Valentin Vergriete, Fahima Zidat, Célia Komurkiewicz-Wellems, Virginie Paquez, Arthur Durand, Saad Nseir, Sylvie Brice, Claire Delcourte, Amélie Cerf, Laure Mariller, Benjamin Rieu, Raiko Blondonnet, Thomas Costille, Thierry Gillart, Jean-Baptiste Joffredo, Audrey Johanny, Clémence Louis, Sébastien Perbet, Adrien Carla, Margaux Coudray, Loris Giordanetto, Marc Bégard, Camille Boissy, Thibaud Cammas, Russell Chabanne, Bernard Cosserant, Romain Grobost, Katia Levrier, Pierre-Antoine Pioche, Bertille Paquette, Gauthier Arpajou, Jules Audard, Lucie Aupetitgendre, Sophie Cayot, Renaud Guerin, Benoit Baietto, Laure-Anne Simand, Emmanuel Futier, Jean-Etienne Bazin, Thomas Godet, Marc Garnier, Matthieu Jabaudon, Bruno Pereira, Nathalie Bourguignon, Sylvie Cosserant, Périne Vidal, Guillaume Chauvet, Jérémy Vernhes, Vincent Sapin, Dominique Morand, Camille Theilliere, François Thouy, Bertrand Souweine, Claire Dupuis, Mireille Adda-Pernot, Marine Bereiziat, Frederic Duee, Alexandre Lautrette, Nathanael Eisenmann, Ghislaine Niezgodzki, Rodolphe Hilaire, Régine Chevrier, Sonia Rucart, Julien Lorber, Maud Jonas, Céline Chevalier, Servane Vastral, Julio Badie, Laurent Faivre, Elodie Bouvier, Charlotte Bourgoin, Isabelle Roussez, Pascale Dussert, Fabien Lambiotte, Mohamed Ali Benbali, Hanane Fodil, Justine Lemtiri, Chaouki Bouras, Hedi Dhaouadi, Nabil El Beki, Delphine Bregeaud, Stéphanie Violette, Aziz Berrouba, Gwladys M’Boungou, Eric Gerardin, Romain Blanchon, Elodie Protesti, Alexandre Conia, Pierre Kalfon, Bénédicte Mauchien, Martine Ferrandière, Charlène Piat
Journal: JAMA (2025)

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. 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.