sevoflurane pharmacokinetics in ards

Conditions: Acute Respiratory Distress Syndrome

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.

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.

Eligibility criteria:
inclusion criteria: * 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 exclusion criteria: * 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

Keywords: nonfocal acute respiratory distress syndrome focal acute respiratory distress syndrome sevoflurane pharmacokinetics mechanical ventilation