The acute respiratory distress syndrome (ARDS) is the most severe and lethal complication of
COVID-19, and healthcare resource utilizations are currently being heavily challenged in most
countries worldwide, with a high risk that some intensive care resources, such as the number
of ventilators to allow management all patients, may be insufficient to face the current
surge in ARDS cases. There is, therefore, an urgent need to evaluate candidate therapies that
may impact clinical outcomes in patients with COVID-19-related ARDS and potentially be
relevant to current public health issues, in accordance with the international efforts by the
World Health Organization (WHO) (Global research on coronavirus disease) and most
international public health organizations. Beyond the current efforts to find specific
antiviral therapies or vaccines, improving supportive care and treatment options for patients
with COVID-19-related ARDS, in accordance with up-to-date guidelines on the management of
critically ill patients with COVID-19 (Surviving Sepsis Campaign: Guidelines on the
Management of Critically Ill Adults with Coronavirus Disease 2019; The Australian and New
Zealand Intensive Care Society (ANZICS) COVID-19 Guidelines; Recommandations d'experts
SRLF-SFAR-SFMU-GFRUP-SPILF sur la prise en charge en réanimation des patients en période
d'épidémie à SARS-CoV2), is of major importance.

Indeed, given the number of intensive care unit (ICU) patients for whom the question of
sedation applies during the current COVID-19 outbreak, any sedation practice that would be
associated with improved clinical outcomes could have significant economic and public health
implications. In this perspective, the rationale supporting inhaled sedation with halogenated
agents (such as isoflurane or sevoflurane) as a way to improve lung function, to decrease the
inflammatory response, and to possibly improve patient outcome is strong.

The authors hypothesized that inhaled sedation, either with isoflurane or sevoflurane, might
be associated with improved clinical outcomes in patients with COVID-19-related ARDS,
compared to intravenous sedation. The authors, therefore, designed the "Inhaled Sedation for
COVID-19-related ARDS" (ISCA) non-interventional, observational, multicenter study of data
collected from the patients' medical records in order to :

1. assess the efficacy of inhaled sedation in improving a composite outcome of mortality
and time off the ventilator at 28 days in patients with COVID-19-related ARDS, in
comparison to a control group receiving intravenous sedation (primary objective),

2. investigate the effects of inhaled sedation, compared to intravenous sedation, on lung
function as assessed by gas exchange and physiologic measures in patients with
COVID-19-related ARDS (secondary objective),

3. report sedation practice patterns in critically ill patients during the COVID-19
pandemics (secondary objective).

This study will be performed in accordance with the Strengthening the Reporting of
Observational studies in Epidemiology (STROBE) statement.