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

University Hospital, Clermont-Ferrand

Status and phase: Completed; Phase 4

Conditions: Acute Respiratory Distress Syndrome

Treatments: Drug: sevoflurane; Drug: midazolam

Study type: Interventional

Funder types: Other

Identifiers

NCT02166853

2013-005389-21

CHU-0195

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

conventional group

Experimental group

Description:

a "conventional group", in which intravenous sedation with midazolam will be administered

Treatment:

Drug: midazolam

sevoflurane group

Experimental group

Description:

a "sevoflurane group", in which patients will inhale sevoflurane during a 48 hour-period, through dedicated devices

Treatment:

Drug: sevoflurane