Inhalational (Sevoflurane) Versus Intravenous (Propofol) Sedation in Adults With a Moderate Form of ARDS
Status:
Not yet recruiting
Trial end date:
2026-02-25
Target enrollment:
Participant gender:
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.