Logistical issues

The main objective of this study is to compare the protein composition of simultaneously collected undiluted pulmonary edema fluid and AnaConDa-S ® fluid from patients with ARDS.

In a previous pilot randomized controlled trial, in patients with moderate-severe acute respiratory distress syndrome (ARDS), the use of inhaled sevoflurane improved oxygenation and decreased levels of a marker of lung epithelial injury (soluble receptor for advanced glycation end-products, sRAGE) and of some inflammatory markers (interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α), compared to intravenous midazolam. These results reinforce those from previously published preclinical studies as they suggest a protective effect of sevoflurane from alveolar/systemic inflammation and from reduced epithelial injury and/or improved alveolar fluid clearance, as assessed by plasma soluble receptor for advanced glycation end-products (sRAGE). The results from available studies support the safe use of sevoflurane inhalation through dedicated device is well tolerated, with no major adverse effect, e.g. on renal function or respiratory mechanics, in critically ill patients admitted to the intensive care unit (ICU), including those with ARDS.

Because the investigators group frequently uses sevoflurane in patients with ARDS and are interested in developing further research on the effects of inhaled sedation in ARDS, the current study has been designed to verify whether the same concept could be applied to the filter the investigators use to vaporize sevoflurane in their ICUs.

Patients with moderate-to-severe ARDS (within 24 hours of onset) and already receiving inhaled sevoflurane for sedation as a current practice in participating centers will be enrolled in this observational study.

After an exposure duration of at least 12 hours, a sample of directly-aspirated, undiluted pulmonary edema fluid will be collected concurrently with AnaConDa-S®filter collection. This sample will be the only specific intervention of this study.

Patient data prospectively collected from the medical record will include demographics, ARDS risk factor, chest x-ray, ventilator settings at the time of AnaConDa-S ® filter collection, hospital and ICU length of stay and hospital mortality. Murray's lung injury score and the Acute Physiology and Chronic Health Evaluation (APACHE) II score will be calculated from data already available in the medical record.

AnaConDa-S ® filters will transported to the laboratory on ice and centrifuged at 2,000 x g for 10 minutes to collect condensed fluid that will be subsequently aliquoted and stored at -80°C for further analysis. Undiluted pulmonary edema fluid will be centrifuged at 2,000 x g for 10 minutes. Supernatants will be aliquoted and stored at - 80°C. Levels of IL-1β, IL-6, IL-8, TNF-α, soluble TNF-receptor 1, angiopoietin-2, and sRAGE will be measured in duplicate in both types of fluid with Multiplex.

Inclusion Criteria:

• All adult patients within 24 hours from meeting the Berlin criteria for moderate or severe ARDS and receiving inhaled sedation with sevoflurane will be eligible for inclusion into the study.

Exclusion Criteria:

• Patients <18 years
• Lack of deferred informed consent

The investigators and personals in charge of measuring protein markers in this study will be unaware of the fluid type (either AnaConDa-S® fluid,or undiluted pulmonary edema fluid or plasma). In addition, the study statistician will also be blinded during statistical analyses.