Effects of SEvoflurane on Gas Exchange and Inflammation in Patients With ARDS (SEGA Study) (SEGA)

Effect of Early 48-hour Sevoflurane Inhalation on Gas Exchange and Inflammation in Patients Presenting With Acute Respiratory Distress Syndrome (ARDS) : a Monocentric, Prospective, Randomized Study.

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.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: midazolam; Drug: sevoflurane

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • Chu Clermont-Ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with criteria for moderate to severe ARDS since less than 24 hours (
• Informed consent

Exclusion Criteria:

• Suspected or proven intracranial hypertension
• Midazolam, sevoflurane or cisatracurium allergy
• Medical history of malignant hyperthermia
• Severe liver failure
• Chemotherapy treatment in the last month
• Severe neutropenia (< 0.5 G/l)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: conventional group; a "conventional group", in which intravenous sedation with midazolam will be administered	Drug: midazolam; Sedation with intravenous midazolam
Experimental: sevoflurane group; a "sevoflurane group", in which patients will inhale sevoflurane during a 48 hour-period, through dedicated devices	Drug: sevoflurane; Sedation with inhaled sevoflurane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PaO2/FiO2 ratio	at 48 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
- Plasma and alveolar levels of proinflammatory cytokines : tumor necrosis factor alpha (TNFα, interleukin (IL)-1β, IL-6, IL-8	at 48 hours
Plasma and alveolar levels of sRAGE	at 48 hours
PaO2/FiO2 ratio	at day 1, day 3, day 5
Lowest PaO2/FiO2 during the first 5 days of the study	at 5 days
Mean PaO2/FiO2 ratio during the first 5 days of the study	at 5 days
Pulmonary static compliance, resistance and elastance	at day 1, day 2
Duration of controlled mechanical ventilation	at day 30
Total duration of mechanical ventilation (controlled/assisted)	at day 30
Number of ventilatory-free days	at day 30
Number of organ failure-free days	at day 30
Vasopressor requirements	at 48 hours
Mortality	at day 30

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Investigators: Principal Investigator: Matthieu JABAUDON, University Hospital, Clermont-Ferrand

Publications and helpful links

General Publications

• Jabaudon M, Boucher P, Imhoff E, Chabanne R, Faure JS, Roszyk L, Thibault S, Blondonnet R, Clairefond G, Guerin R, Perbet S, Cayot S, Godet T, Pereira B, Sapin V, Bazin JE, Futier E, Constantin JM. Sevoflurane for Sedation in Acute Respiratory Distress Syndrome. A Randomized Controlled Pilot Study. Am J Respir Crit Care Med. 2017 Mar 15;195(6):792-800. doi: 10.1164/rccm.201604-0686OC.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: June 16, 2014
• First Submitted That Met QC Criteria: June 17, 2014
• First Posted (Estimated): June 18, 2014

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Inflammation; Sevoflurane; Prospective study; Mechanical ventilation; Lung injury; Acute respiratory distress syndrome (ARDS); Gas exchange; Intensive Care Unit (ICU); sRAGE; Receptor for advanced glycation end-produts (RAGE)
• Additional Relevant MeSH Terms: Wounds and Injuries; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Thoracic Injuries; Pathological Conditions, Signs and Symptoms; Respiratory Distress Syndrome; Inflammation; Lung Injury; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Ethers; Hydrocarbons; Hydrocarbons, Halogenated; Benzazepines; Benzodiazepines; Hydrocarbons, Fluorinated; Methyl Ethers; Sevoflurane; Midazolam
• Other Study ID Numbers: CHU-0195; 2013-005389-21