Sampling in ARDS Patients Under Inhaled Sedation

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Assessment of a Novel Method for Non-invasive Sampling of the Distal Airspace in Acute Respiratory Distress Syndrome Patients Receiving Inhaled Sedation With Sevoflurane)

Conditions
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Acute Distress Respiratory

Intervention / Treatment
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* Biological: Sample


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Analysize correlation between sample from undiluted pulmonary edema andsample from AnaConDa-S® filter from patients presenting ARDS since 24 hours and sedated with inhaled sevoflurane.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with SDRA<br>Patients within 24 hours from meeting the Berlin criteria for moderate or severe ARDS and receiving inhaled sedation with sevoflurane | Biological: Sample<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparaison between levels of protein markers, measured IL-1β, IL-6, IL-8, TNF-α, soluble TNF-receptor 1, angiopoietin-2, and sRAGE, measured in undiluted pulmonary edema fluid and in AnaConDa-S ® fluid | After an exposure duration of at least 12 hours, and when clinically available, a sample of directly-aspirated, undiluted pulmonary edema fluid will be collected (in general, only few ml are collected) concurrently with AnaConDa-S® filter collection. The concordance between levels of markers measured from undiluted alveolar fluid and those measured from AnaConDa-S® fluid will be explored using Lin's concordance coefficient, correlation coefficient (Pearson or Spearman according to the statistical distribution) and Bland-Altman plot. Confidence intervals at 95% will be presented. To complete these analyses, the satisfactory agreement will be confirmed by Passing and Bablok regression in order to highlight non-systematic and non-proportional differences between the two methods (undiluted pulmonary edema fluid and AnaConDa-S® fluid). | Between 12 hours and 24 hours after the begining of Sevoflurane sedation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparisons of levels of protein markers measured in AnaConDa-S® fluid between patients with focal ARDS and those with nonfocal ARDS | The levels of protein markers measured in AnaConDa-S® fluid will be compared between patients with focal ARDS and those with nonfocal ARDS using the unpaired t test or the Mann-Whitney U test when appropriate | Between 12 hours and 24 hours after the begining of Sevoflurane sedation | 
| The correlation between levels of protein markers measured in AnaConDa-S® and the Radiographic Assessment of Lung Edema (RALE) score developed recently by Pr. Lorraine Ware's team at Vanderbilt University. | The relationships between the levels of protein markers measured in AnaConDa-S® and the Radiographic Assessment of Lung Edema (RALE) score will be studied using correlation coefficients. | Between 12 hours and 24 hours after the begining of Sevoflurane sedation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Respiratory Distress Syndrome, Inhaled Sedation with Sevoflurane, Biological collection