NCT05259631

Inhalational (Sevoflurane) Versus Intravenous (Propofol) Sedation in Adults With a Moderate Form of ARDS

Inhalational (Sevoflurane) Versus Intravenous (Propofol) Sedation in Adults With a Moderate Form of ARDS: A Multicentral Randomized Pilot Trial

• Status: Suspended
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 310 (estimated)
• Sponsor: Negovsky Reanimatology Research Institute · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The American European Consensus Conference (AECC) 1994 defined acute respiratory distress syndrome (ARDS) as an acute inflammatory syndrome manifesting as diffuse pulmonary edema and respiratory failure that cannot be explained by, but may co-exist with, left-sided heart failure. During the sequel Conference of the European Society of Intensive Care Medicine, in 2012 minor changes were made, and since that so-called Berlin definition of ARDS is used worldwide for the description of this severe disease. Three grades of severity were proposed to distinguish ARDS according to the level of hypoxemia with a mortality of 24% in patients with mild ARDS, rising to 48% in those with severe ones. Systemic inflammation is considered to be the main reason of ARDS. Activated neutrophils interact with the alveolar-capillary membrane causing the increasing permeability with the sequence lung edema's development. Inflammatory exudate inactivates surfactant leading to collapse and consolidation of distal airspaces with progressive loss of the lung's gas exchange surface area. Unfortunately, systemic inflammatory response syndrome (SIRS) simultaneously inhibits the mechanism of active pulmonary vasoconstriction and allows deoxygenated blood to pass through unventilated areas of the lung boosting the right-to-left shunt. Both mechanisms lead to hypoxemia, which is the main and obligatory feature of ARDS. Actually, endothelial dysfunction and transcapillary leakage seem to be one of the main steps in the development of respiratory failure during ARDS. Last decades it was found out that glycocalyx is also participating in this process too. Thus, it became clear that substances preserving endothelium and glycocalyx from SIRS-causing damage may have a beneficial effect in ARDS treatment. It seems to be crucially important so as the majority of drugs failed to demonstrate any positive effects in terms of ARDS treatment. To the moment we have some evidence, which came from experimental studies, that halogenated anesthetics can preserve glycocalyx against ischemia-reperfusion injury. The primary objective for the multicentral INVERSE Trial will be to determine the effects of inhalational (sevoflurane) versus intravenous (propofol) sedation on P/F ratio on the second day, hospital mortality and ICU (intensive care unit), and in-hospital length of stay in adults with a moderate form of ARDS.

Conditions

• Acute Respiratory Distress Syndrome

Interventions

Type	Name	Description
DRUG	Sevoflurane	Patients are to be sedated by sevoflurane inhalation. For this purpose, any certificated devices are suitable - AnaConDa or Mirus evenly. Starting dose of sevoflurane is to be 2 ml/h and may be modified at the discretion of the attending intensivist to achieve and maintain the target level of sedation
DRUG	Propofol	Patients of this group will receive an intravenous infusion of propofol with starting dose of 1 mg/kg/h. The precise dose to maintain the desired level of sedation is left at the discretion of the attending intensivist and may be revised at any time. The upper dose limit for propofol is 4 mg/kg/h. In case of tolerance to propofol infusion, midazolam or antipsychotics (haloperidol) can be added to achieve the desired level of sedation

Timeline

• Start date: 2022-03-14
• Primary completion: 2025-02-25
• Completion: 2026-02-25
• First posted: 2022-02-28
• Last updated: 2023-02-01

Locations

1 site across 1 country: Russia