Does Inhaled Sevoflurane Sedation Affect ARDS Outcomes?

TOPLINE:

Inhaled sedation with sevoflurane in patients with moderate to severe acute respiratory distress syndrome (ARDS) resulted in fewer ventilator-free days at 28 days and lower 90-day survival than intravenous propofol sedation.

METHODOLOGY:

• Researchers conducted a randomized clinical trial (May 2020 to October 2023) across 37 intensive care units in France and compared the efficacy and safety between sevoflurane and propofol sedation in 687 patients with moderate to severe ARDS.
• They enrolled adults who were undergoing invasive mechanical ventilation and met the Berlin definition criteria for < 24 hours, with a ratio of PaO2 to the fraction of inspired oxygen < 150 mm Hg and positive end–expiratory pressure ≥ 8 cm H2O.
• The study protocol involved the use of initial deep sedation with subsequent neuromuscular blockade, before transitioning to lighter sedation.
• Patients were randomly assigned to receive either inhaled sevoflurane (n = 346; mean age, 64.9 years; 32.1% women) or IV propofol (n = 341; mean age, 64.4 years; 27% women) for sedation for up to 7 days.
• The primary endpoint was the number of ventilator-free days at 28 days, with the ventilator-free days considered zero if a patient died before day 28; secondary endpoints included 90-day survival and safety assessments.

TAKEAWAY:

• At 28 days, the median difference in the number of ventilator-free days was −2.1 (95% CI, −3.6 to −0.7) between the two groups.
• The 90-day survival rate was lower in the sevoflurane group than in the propofol group (47.1% vs 55.7%).
• Fewer patients in the sevoflurane group were free from acute kidney injury by day 7 than those in the propofol group (between-group difference, −0.11; 95% CI, −0.18 to −0.04).
• Nephrogenic diabetes insipidus occurred in five patients in the sevoflurane group but did not occur in the propofol group.

IN PRACTICE:

“The findings of the current study contrast with evidence suggesting benefits of volatile anesthetics, such as sevoflurane or isoflurane, in patients without ARDS. They also challenge proposed oxygenation benefits in ARDS, suggested by smaller and preclinical studies,” the researchers wrote.

“Our findings may have important clinical implications because inhaled sedation has garnered growing attention in ICU patients with ARDS or those at risk for the syndrome. However, this trial does not inform whether outcomes would have differed with shorter durations of sevoflurane or with the use of other volatile anesthetics such as isoflurane,” they added.

“The investigators demonstrated that prolonged sevoflurane sedation resulted in worse outcomes as compared with propofol alone in patients with ARDS. These findings do not support the routine use of sevoflurane for sedation in critically ill patients with moderate to severe ARDS,” according to the authors of an editorial accompanying the journal article.

SOURCE:

This study was led by Matthieu Jabaudon, MD, PhD, of the Department of Perioperative Medicine, at the CHU Clermont-Ferrand in Clermont-Ferrand, France. It was published online on March 18, 2025, in JAMA.

LIMITATIONS:

This study could not be double-blinded due to the nature of the intervention. Data on volumes of fluid administered, expired fractions of sevoflurane, dosing of corticosteroid, and opioid analgesia were not recorded. COVID-19 pneumonia being the predominant cause of ARDS may have limited the generalizability across causes or subphenotypes of ARDS.

DISCLOSURES:

This study was funded by grants from the French Ministry of Health, the European Society of Anaesthesiology and Intensive Care, and Sedana Medical. Few authors reported receiving personal fees from pharmaceutical, healthcare, and medical device companies unrelated to this work. One author reported receiving grants and funding for trial and being a co-founder and shareholder of Oxynov Inc and Ivanae Medical.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.