NCT04530188

Effects of Sevoflurane on Extravascular Lung Water and Pulmonary Vascular Permeability in Patients With ARDS

Effects of Sevoflurane on Extravascular Lung Water and Pulmonary Vascular Permeability in Patients With Acute Respiratory Distress Syndrome

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 68 (estimated)
• Sponsor: Bicetre Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

The study will investigate the effects of inhaled sedation with sevoflurane using the AnaConDa device on extravascular lung water index (EVLWi) and the pulmonary vascular permeability index (PVPI) in patients with moderate to severe acute respiratory distress syndrome (ARDS). Improvement in oxygenation and decreases in lung inflammatory response has been demonstrated in patients with ARDS compared with intravenous sedation. However, preclinical data showing a decrease in lung edema has not been confirmed. The hypothesis is that inhaled sedation with sevoflurane reduces EVLWi and PVPI in patients with ARDS, assessed with the PiCCO device. Patients will receive either inhaled sedation (interventional group), or a sedation with propofol (control group). Both will be associated with remifentanil. Sedation will be monitored by bispectral index with a targeted value of 30-50. The primary outcome will be daily assessment of EVLWi and PVPI over time in patients sedated with sevoflurane compared to propofol. Secondary outcomes will include value of PVPI and EVLW at 48h after intubation, fluid administration, need in norepinephrine, time between cessation of sedation and trial of weaning sedation, ventilation free days, mortality at day 28, the partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2), plasma and alveolar levels of cytokines (tumor necrosis factor (TNF)-α, interleukine (IL)-1β, IL-6, IL-8). These blood and alveolar samples will be done at baseline, on day 2 and on day 5. A sub-group analysis will be done in Covid-19 related ARDS. Decrease in PVPI and EVLWi with inhaled sevoflurane may be related to the decrease in lung edema in ARDS patients and may ultimately improve patient outcome.

Detailed description

Background: Inhaled sedation with volatile anesthetic agents has been proposed as an efficient and safe alternative to usual intravenous sedation such as propofol or midazolam in the intensive care unit. In acute respiratory distress syndrome (ARDS) models, preclinical studies comparing inhaled sedation to intravenous sedation showed that sedation with sevoflurane improves oxygenation, reduces the lung and systemic inflammatory response, decreases formation of alveolar edema and is associated with a less pronounced increase in extravascular lung water (EVLW, the amount of water contained in the lungs outside the pulmonary vasculature) or pulmonary vascular permeability index (PVPI), the ratio of EVLW over the pulmonary blood volume). Although benefits of inhaled sedation on inflammation and oxygenation have been shown in humans, its direct effect on EVLW or PVPI has never been evaluated in patients with ARDS. It could be important as their levels are factors independently associated with mortality in patients with ARDS. Aim: To evaluate the effect of inhaled sedation with sevoflurane in comparison with sedation with propofol on the degree of PVPI and the amount of EVLW in patients with moderate-to-severe ARDS. Hypothesis: The hypothesis is that inhaled sedation with sevoflurane reduces PVPI and EVLW in patients with ARDS compared to sedation with propofol.

Conditions

• ARDS
• ARDS, Human

Interventions

Type	Name	Description
DRUG	Sevoflurane	Inhaled sedation with sevoflurane using the Anesthesia Conserving Device (AnaConDa-S, Sedana Medical, Danderyd, Sweden)
DRUG	Propofol	Intravenous sedation with propofol, as already used in our ICU

Timeline

• Start date: 2020-11-01
• Primary completion: 2022-05-01
• Completion: 2022-11-01
• First posted: 2020-08-28
• Last updated: 2020-08-28