Sevoflurane PharmacokInetics in ARDS (SPIDERMAN)

Sevoflurane pharmacokInetics During Inhaled Sedation Relies on the Morphotype of ARDS in ICU Patients

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.

Study Overview

• Status: Terminated
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Deep sedation by Sevoflurane on the Morphotype of 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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France
    • Centre Jean Perrin
  • Clermont-Ferrand, France
    • CHU
  • Paris, France, 75010
    • APHP - University hospital of Saint-Louis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nonfocal ARDS; ARDS patient with nonfocal lung imaging phenotype	Drug: Deep sedation by Sevoflurane on the Morphotype of ARDS in ICU patieNts; Pharmacokinetic of inhaled sevoflurane used for sedation
Experimental: Focal ARDS; ARDS patient with focal lung imaging phenotype	Drug: Deep sedation by Sevoflurane on the Morphotype of ARDS in ICU patieNts; Pharmacokinetic of inhaled sevoflurane used for sedation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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
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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Investigators: Principal Investigator: Raiko Blondonnet, MD, MSc, University Hospital, Clermont-Ferrand

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2020
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): January 1, 2022

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: July 16, 2019
• First Posted (Actual): July 17, 2019

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Sevoflurane; Mechanical ventilation; Nonfocal Acute respiratory distress syndrome; Focal Acute respiratory distress syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Anesthetics, Inhalation; Sevoflurane
• Other Study ID Numbers: SPIDERMAN Study; 2018-003511-21 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No