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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-003511-21 | EudraCT Number |
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Recruitment difficulties
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nonfocal ARDS | Experimental | ARDS patient with nonfocal lung imaging phenotype |
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| Focal ARDS | Experimental | ARDS patient with focal lung imaging phenotype |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Deep sedation by Sevoflurane on the Morphotype of ARDS in ICU patieNts | Drug | Pharmacokinetic of inhaled sevoflurane used for sedation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma concentrations of sevoflurane | Plasma concentrations of sevoflurane | 5 minutes after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit |
| Plasma concentrations of sevoflurane | Plasma concentrations of sevoflurane | 30 minutes after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit |
| Plasma concentrations of sevoflurane | Plasma concentrations of sevoflurane | 1 hour after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit |
| Plasma concentrations of sevoflurane | Plasma concentrations of sevoflurane | 6 hours after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit |
| Plasma concentrations of sevoflurane | Plasma concentrations of sevoflurane | 24 hours after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit |
| Plasma concentrations of sevoflurane | Plasma concentrations of sevoflurane | 48 hours after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit |
| Plasma concentrations of sevoflurane | Plasma concentrations of sevoflurane | 5 minutes after the cessation of sevoflurane administration |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma concentration of hexafluoroisopropanolol | Plasma concentration of hexafluoroisopropanolol | Until sedation can be definitely interrupted or until day 7 |
| Fraction of inspired sevoflurane | Fraction of inspired sevoflurane |
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Inclusion Criteria:
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
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Raiko Blondonnet, MD, MSc | University Hospital, Clermont-Ferrand | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Jean Perrin | Clermont-Ferrand | France | ||||
| CHU |
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| ID | Term |
|---|---|
| D012128 | Respiratory Distress Syndrome |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
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Inhaled sedation with sevoflurane, will be vaporized via the miniaturized Anesthesia Conserving Device (AnaConDa-S®, Sedana Medical, Uppsala, Sweden).
Sevoflurane infusion rate will be adapted from manufacturer's instructions in order to reach a target of expired sevoflurane fraction (FEsevo) of 0.8-1.1.
Mechanical ventilation will be protocolized in both arms, based on recent results of a RCT from our group, in which 90-day survival was improved in patients with nonfocal ARDS when an individualized ventilation strategy was applied, compared to the ARDSNet strategy (PEEP set according to FiO2). We will recommend sites wait at least 12 hours before proning, as in the PROSEVA study.
In both groups, patients will receive cisatracurium besylate for neuromuscular blockade, and deep sedation will be protocolized to Richmond Agitation-Sedation Scale (RASS) of -4 to -5 (Ramsay of 5-6, or Riker of 1-2) before starting, and during, the cisatracurium besylate infusion.
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It is an open label trial because the patients are included from a group depending to the morphotype of ARDS. However, all subsequent evaluations will be conducted by clinical research staff according to the attributed group
| Plasma concentrations of sevoflurane | Plasma concentrations of sevoflurane | 30 minutes after the cessation of sevoflurane administration |
| Plasma concentrations of sevoflurane | Plasma concentrations of sevoflurane | 1 hour after the cessation of sevoflurane administration |
| Plasma concentrations of sevoflurane | Plasma concentrations of sevoflurane | 4 hours after the cessation of sevoflurane administration |
| Plasma concentrations of sevoflurane | Plasma concentrations of sevoflurane | 6 hours after the cessation of sevoflurane administration |
| Until sedation can be definitely interrupted or until day 7 |
| Fraction of expired sevoflurane | Fraction of expired sevoflurane | Until sedation can be definitely interrupted or until day 7 |
| Dose of sevoflurane | Dose of sevoflurane (mg/l) | Until sedation can be definitely interrupted or until day 7 |
| Infusion duration of sevoflurane | Infusion duration of sevoflurane (min) | Until sedation can be definitely interrupted or until day 7 |
| Infusion rate of remifentanil | Infusion rate of remifentanil | Until sedation can be definitely interrupted or until day 7 |
| Values of a bispectral index | Values of a bispectral index | Until sedation can be definitely interrupted or until day 7 |
| Clermont-Ferrand |
| France |
| APHP - University hospital of Saint-Louis | Paris | 75010 | France |