Sevoflurane PharmacokInetics in ARDS
- Conditions
- Acute Respiratory Distress Syndrome
- Interventions
- Drug: Deep sedation by Sevoflurane on the Morphotype of ARDS in ICU patieNts
- Registration Number
- NCT04023305
- Lead Sponsor
- University Hospital, Clermont-Ferrand
- Brief Summary
The main objective of this study is to compare the pharmacokinetic models of sevoflurane-induced sedation during ARDS depending on the lung imaging phenotype (focal vs nonfocal phenotypes) The authors hypothesized that sevoflurane used for inhaled sedation could have distinct pharmacokinetic profiles depending on lung imaging phenotypes (focal vs nonfocal) during ARDS in ICU patients.
- Detailed Description
Adult patients admitted to the ICU within 12 hours of moderate-severe ARDS onset and under sedation with sevoflurane will be enrolled in the study with inclusion criteria. They will be enrolled, depending on their morphotype (focal or nonfocal), as routinely assessed in participating centers using CT-scan, chest x-ray and/or lung ultrasound.
These patients will receive inhaled sevoflurane as a standard practice of sedation that is routinely used in participating ICUs. After inclusion, the mechanical ventilation protocol must be initiated within two hours (if not already being used). In both groups, deep sedation followed by neuromuscular blockade must be initiated within four hours of inclusion.
Adult patients admitted to the ICU within 12 hours of moderate-severe ARDS onset and under sedation with sevoflurane will be enrolled in the study with inclusion criteria. They will be enrolled, depending on their morphotype (focal or nonfocal), as routinely assessed in participating centers using CT-scan, chest x-ray and/or lung ultrasound.
These patients will receive inhaled sevoflurane as a standard practice of sedation that is routinely used in participating ICUs. After inclusion, the mechanical ventilation protocol must be initiated within two hours (if not already being used). In both groups, deep sedation followed by neuromuscular blockade must be initiated within four hours of inclusion.
Blood sample will be collected at different times after the onset of sevoflurane administration and after its cessation.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 37
- Age ≥18 years
- Presence for ≤ 12 hours of all of the following conditions, within one week of a clinical insult or new or worsening respiratory symptoms :
a PaO2/FiO2 < 200 mmHg with positive end-expiratory pressure (PEEP) ≥ 8 cmH2O (or, if arterial blood gas not available : SpO2/FiO2 ratio that is equivalent to a PaO2/FiO2 < 200 mmHg with PEEP ≥8 cmH2O, and a confirmatory SpO2/FiO2 ratio between 1-6 hours after the initial SpO2/FiO2 ratio determination) b Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules c Respiratory failure not fully explained by cardiac failure or fluid overload; need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present
- Lack of informed consent
- Continuous sedation with inhaled sevoflurane at enrollment
- Currently receiving ECMO therapy
- Chronic respiratory failure defined as PaCO2 > 60 mmHg in the outpatient setting
- Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BIPAP used solely for sleep-disordered breathing
- Body mass index > 40 kg/m2
- Chronic liver disease defined as a Child-Pugh score of 12-15
- Expected duration of mechanical ventilation < 48 hours
- Tidal volume of 6 mL/kg predicted body weight (PBW) below 200 mL
- Decision to withhold life-sustaining treatment; except in those patients committed to full support except cardiopulmonary resuscitation
- Moribund patient, i.e. not expected to survive 24 hours despite intensive care
- Burns > 70% total body surface
- Previous hypersensitivity or anaphylactic reaction to sevoflurane
- Medical history of malignant hyperthermia
- Suspected or proven intracranial hypertension
- Know pregnancy - Pregnancy testing will be systematically performed to rule out pregnancy in female patients of reproductive age
- Enrollment in another interventional ARDS trial with direct impact on sedation and PEEP
- Endotracheal ventilation for greater than 120 hours (5 days)
- PaO2/FiO2 (if available) > 200 mmHg after meeting inclusion criteria and before start of the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Nonfocal ARDS Deep sedation by Sevoflurane on the Morphotype of ARDS in ICU patieNts ARDS patient with nonfocal lung imaging phenotype Focal ARDS Deep sedation by Sevoflurane on the Morphotype of ARDS in ICU patieNts ARDS patient with focal lung imaging phenotype
- Primary Outcome Measures
Name Time Method Plasma concentrations of sevoflurane 6 hours after the cessation of sevoflurane administration Plasma concentrations of sevoflurane
- Secondary Outcome Measures
Name Time Method Fraction of inspired sevoflurane Until sedation can be definitely interrupted or until day 7 Fraction of inspired sevoflurane
Fraction of expired sevoflurane Until sedation can be definitely interrupted or until day 7 Fraction of expired sevoflurane
Plasma concentration of hexafluoroisopropanolol Until sedation can be definitely interrupted or until day 7 Plasma concentration of hexafluoroisopropanolol
Dose of sevoflurane Until sedation can be definitely interrupted or until day 7 Dose of sevoflurane (mg/l)
Infusion duration of sevoflurane Until sedation can be definitely interrupted or until day 7 Infusion duration of sevoflurane (min)
Infusion rate of remifentanil Until sedation can be definitely interrupted or until day 7 Infusion rate of remifentanil
Values of a bispectral index Until sedation can be definitely interrupted or until day 7 Values of a bispectral index
Trial Locations
- Locations (3)
APHP - University hospital of Saint-Louis
🇫🇷Paris, France
CHU
🇫🇷Clermont-Ferrand, France
Centre Jean Perrin
🇫🇷Clermont-Ferrand, France