Assessment of a Novel Method for Non-invasive Sampling of the Distal Airspace in Acute Respiratory Distress Syndrome Patients Receiving Inhaled Sedation with Sevoflurane: the ANAISS Study Protocol

IntroductionRecently, fluid collected from the heat-and-moisture-exchange filters, which are commonly used in most mechanically ventilated patients under intravenous sedation, has been reported as a potential surrogate for fluid in the distal airspace. Therefore, collection of this fluid represents a promising, non-invasive method for sampling the distal airspace in patients with acute respiratory distress syndrome (ARDS) and for facilitating a mechanistic understanding of this devastating disease. The current study protocol was constructed to assess whether this fluid could be sampled from a dedicated device (Anaesthetic Conserving Device [AnaConDa-S], Sedana Medical, Danderyd, Sweden) used to deliver inhaled sevoflurane for sedation in patients with ARDS. Methods and analysisA total of 30 adult patients within 24 hours of meeting the Berlin criteria for moderate-severe ARDS and receiving inhaled sevoflurane as standard sedation in participating centres will be eligible for inclusion into this investigator-initiated, exploratory, prospective, bicentre study. After at least 12 h of inhaled sedation, a sample of directly aspirated, undiluted pulmonary oedema fluid will be collected concurrently with fluid from the AnaConDa-S device. Levels of proinflammatory cytokines (IL-1{beta}, IL-6, IL-8, TNF- and sTNFr-1) and markers of lung endothelial (Ang-2) and epithelial (sRAGE) injury will be measured in both fluids by Multiplex. The primary endpoint is the correlation between protein markers (IL-1{beta}, IL-6, IL-8, TNF-, sTNFr-1, Ang-2 and sRAGE) measured in the undiluted pulmonary oedema fluid versus the AnaConDa-S fluid. Ethics and disseminationThe study was approved by the appropriate ethics committee (CPP Est I). Informed consent is required. The fluid collection from the AnaConDa-S has potential to foster our understanding of the potential effects of inhaled sedation in clinical ARDS and to open up novel perspectives for prognostic and predictive enrichment in future trials. The results will be published in a peer-reviewed journal. Registration numberNCT03964155.