Effects of SEvoflurane on Gas Exchange and Inflammation in Patients With ARDS (SEGA Study)
Condition: Acute Respiratory Distress Syndrome
MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Syndrome; Inflammation
Study type: Interventional
Phase: Phase 4

Summary: 
      Numerous trials support the efficacy and safety of volatile anesthetic agents, namely
      inhalation of sevoflurane through dedicated devices, for the sedation of ICU patients.
      Several preclinical studies have shown that sevoflurane inhalation improves gas exchange and
      decreases pulmonary and systemic inflammation in experimental models of acute respiratory
      distress syndrome (ARDS).

      The purpose of our prospective monocentric, randomized, controlled trial is to evaluate the
      effects of an early 48-hour sevoflurane inhalation on gas exchange and inflammation in
      patients with ARDS.
    

Detailed description: 
      BACKGROUND:

      Acute respiratory distress syndrome (ARDS) is characterized by hypoxemic respiratory failure
      that can be lethal in 30 to 60% of patients. Its pathophysiological landmark, diffuse
      alveolar damage, is associated with alveolar inflammation, epithelial injury and alveolar
      fluid clairance impairment.

      Several preclinical studies have shown that early sevoflurane inhalation improves gas
      exchange, reduces alveolar edema and attenuates pulmonary and systemic inflammation in
      experimental models of ARDS.

      To date, no clinical trial has assessed the effects of early sevoflurane inhalation in ARDS
      patients.

      DESIGN NARRATIVE:

      The purpose of this prospective, randomized, controlled study is to evaluate the effects of a
      48-hour sevoflurane inhalation strategy on gas exchange and both systemic and pulmonary
      inflammation in the early phase of ARDS.

      After inclusion, ICU patients with moderate to severe ARDS (according to the Berlin
      definition of ARDS criteria; JAMA 2010) will be randomized into two groups :

        -  a "conventional group", in which intravenous sedation with midazolam will be
           administered

        -  a "sevoflurane group", in which patients will inhale sevoflurane during a 48
           hour-period, through dedicated devices Arterial blood gases will be analyze before
           randomization and at 24, 48, 72, 96, and 120 hours.

      Bronchoalveolar lavages (BAL) and blood samples will be assessed before randomization and at
      48 hours, in order to measure tumor necrosis factor-alpha (TNFα), interleukin (IL)-1β, IL-6,
      IL-8 and sRAGE levels. Duplicate assays will be performed with Multiplex (TNFα/interleukins)
      or ELISA (sRAGE).

      During the 48-hour treatment period, bispectral index (BIS®) values ranging from 40 to 50
      will be targeted and neuromuscular blocking agents (cisatracurium) will be administered in
      both groups. Protective ventilation strategies will be applied, as well as other guidelines
      or recommendations on the management of ICU patients with ARDS.
    

Intervention name(s): sevoflurane; midazolam
Intervention type(s): Drug; Drug
Intervention description(s): Sedation with inhaled sevoflurane; Sedation with intravenous midazolam
Intervention MeSH terms: Midazolam; Sevoflurane
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Acute respiratory distress syndrome (ARDS); Sevoflurane; Mechanical ventilation; Intensive Care Unit (ICU); Prospective study; Lung injury; Gas exchange; Inflammation; Receptor for advanced glycation end-produts (RAGE); sRAGE