Inhaled Sevoflurane for ARDS Prevention

University Hospital, Clermont-Ferrand80 enrolled

Overview

This study focuses on patients who are at risk of developing a serious, life-threatening respiratory disease called Acute Respiratory Distress Syndrome (ARDS), which severely disrupts the function of their lungs. Preclinical studies have shown that the use of a volatile anesthetic agent such as Sevoflurane could be beneficial in the treatment and prevention of this respiratory condition. By improving gas exchange and attenuating pulmonary inflammation in particular, this agent would make it possible to prevent deterioration or to restore pulmonary function more rapidly. Half of the patients will receive inhaled sedation with sevoflurane and the other half will receive intravenous sedation already routinely used in participating ICUs (typically propofol, dexmedetomidine or a benzodiazepine, i.e. drugs approved for sedation). The aim of this study is to assess whether the use of Sevoflurane could be beneficial in the prevention of ARDS.

MAIN OBJECTIVE To assess the efficacy of inhaled sevoflurane, compared to current intravenous sedation practice, for improving PaO2/FiO2 in ICU patients at high risk for ARDS. HYPOTHESIS The investigators hypothesized that a strategy of inhaled sedation with sevoflurane could be more effective than current intravenous sedation practice at improving pulmonary function during the early days of ICU admission, in patients at risk of ARDS.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Acute Respiratory Distress Syndrome

Interventions

Inhaled sedation with sevofluraneDRUG

In both arms, the management of sedation will be conducted in the broader picture of ICU patient care, as per current standard practice in participating ICUs, and following the current guidelines for Pain, Agitation, Delirium, Immobility, and Sleep Disruption (PADIS) published in 2018 by the Society of Critical Care Medicine. Among many recommendations, this will include the monitoring and titration of both sedation and analgesia using validated scores such as the Richmond Agitation-Sedation Scale (RASS) for sedation. As a result of the current recommendations, the level, dose, and duration of sedation will vary among patients and will be decided by the treating clinicians. The choice of the analgesic drug(s) will be as per the treating clinicians. Other aspects of critical care will adhere to standard care, including the use of the "Checklist for Lung Injury Prevention" (CLIP).

Intravenous sedation (current practice)DRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥ 18 years 2. Admitted to participating ICUs with at least one known risk factor for ARDS and a LIPS equals to, or greater than, 4 (Appendix D)105 3. Patient under invasive mechanical ventilation 4. With expected duration of sedation superior or equal to 4 hours 5. Affiliation to the French Sécurité Sociale Exclusion Criteria: * Patient under judicial protection, guardianship or supervision, as defined by art L1121-8 of the Public Health Code * Patient under psychiatric care as defined by art. L1121-6 of the Public Health Code * Patient deprived of their freedom by judiciary or administrative order * Known pregnancy * Presence of ARDS prior to randomization * Endotracheal ventilation for greater than 24 hours prior to randomization * Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BIPAP used solely for sleep-disordered breathing * Tidal volume of 6 mL/kg predicted body weight (PBW) below 200 mL (i.e. height inferior to 134cm for a man and 139cm for a woman) * Moribund patient, i.e. not expected to survive 24 hours despite intensive care * Previous hypersensitivity or anaphylactic reaction to sevoflurane or to the intravenous sedation agent routinely used in the participating ICU (such as midazolam, propofol, or dexmedetomidine) * Absolute contra-indications to the intravenous sedation agent routinely used in the participating ICU (such as midazolam, propofol, or dexmedetomidine) * Medical history of malignant hyperthermia * Long QT syndrome at risk of arrhythmic events * Medical history of liver disease attributed to previous exposure to a halogenated agent (including sevoflurane) * Suspected or proven intracranial hypertension * Enrollment in another interventional trial with direct impact on oxygenation

Outcomes

Primary Outcomes

PaO2/FiO2 ratio

longitudinal evolution in the PaO2/FiO2 ratio

Time frame: within 5 days from randomization

Secondary Outcomes

Progression to ARDS

Progression to ARDS will be assessed according to the Berlin criteria, including chest radiographs

Time frame: within 5 days from randomization

Rate of pneumonia

Pneumonia will be defined according to the 3 following criteria: * Two chest radiographs showing signs of pneumonia, or one in absence of cardiomyopathy or underlying pulmonary condition. * One item among: body temperature ≥38.3°C without evident cause, leukocytes \<4000/mm3 or ≥12000/mm3 * Two items among: purulent secretions, cough or dyspnea, increased need for oxygen supplementation or ventilatory assistance.

Time frame: Presence of pneumonia will be assessed daily until Day 5, and at Day 28 or ICU discharge, whichever comes first.

Ventilator-free days to day 28

Ventilator free days to day 28 are defined as the number of days from the time of initiating unassisted breathing to day 28 after randomization, assuming survival for at least two consecutive calendar days after initiating unassisted breathing and continued unassisted breathing to day 28. If a patient returns to assisted breathing and subsequently achieves unassisted breathing to day 28, VFDs will be counted from the end of the last period of assisted breathing to day 28. A period of assisted breathing lasting less than 24 hours and for the purpose of a surgical procedure will not count against the VFD calculation. If a patient was receiving assisted breathing at day 27 or dies prior to day 28, VFDs will be zero.