Sevoflurane PharmacokInetics in ARDS

Acute Respiratory Distress Syndrome Clinical Trial

— SPIDERMAN  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04023305
• Other study ID #: SPIDERMAN Study
• Secondary ID: 2018-003511-21
• Status: Terminated
• Phase: N/A
• Start date: February 23, 2020
• Est. completion date: January 1, 2022

Study information

• Verified date: December 2023
• Source: University Hospital, Clermont-Ferrand
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 37
• Est. completion date: January 1, 2022
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Drug:
• Deep sedation by Sevoflurane on the Morphotype of ARDS in ICU patieNts
Pharmacokinetic of inhaled sevoflurane used for sedation

Locations

Country	Name	City	State
France	Centre Jean Perrin	Clermont-Ferrand
France	CHU	Clermont-Ferrand
France	APHP - University hospital of Saint-Louis	Paris

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Clermont-Ferrand

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma concentrations of sevoflurane	Plasma concentrations of sevoflurane	5 minutes after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit
Primary	Plasma concentrations of sevoflurane	Plasma concentrations of sevoflurane	30 minutes after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit
Primary	Plasma concentrations of sevoflurane	Plasma concentrations of sevoflurane	1 hour after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit
Primary	Plasma concentrations of sevoflurane	Plasma concentrations of sevoflurane	6 hours after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit
Primary	Plasma concentrations of sevoflurane	Plasma concentrations of sevoflurane	24 hours after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit
Primary	Plasma concentrations of sevoflurane	Plasma concentrations of sevoflurane	48 hours after the detection by the monitor of sevoflurane (0.1%) in the breathing circuit
Primary	Plasma concentrations of sevoflurane	Plasma concentrations of sevoflurane	5 minutes after the cessation of sevoflurane administration
Primary	Plasma concentrations of sevoflurane	Plasma concentrations of sevoflurane	30 minutes after the cessation of sevoflurane administration
Primary	Plasma concentrations of sevoflurane	Plasma concentrations of sevoflurane	1 hour after the cessation of sevoflurane administration
Primary	Plasma concentrations of sevoflurane	Plasma concentrations of sevoflurane	4 hours after the cessation of sevoflurane administration
Primary	Plasma concentrations of sevoflurane	Plasma concentrations of sevoflurane	6 hours after the cessation of sevoflurane administration
Secondary	Plasma concentration of hexafluoroisopropanolol	Plasma concentration of hexafluoroisopropanolol	Until sedation can be definitely interrupted or until day 7
Secondary	Fraction of inspired sevoflurane	Fraction of inspired sevoflurane	Until sedation can be definitely interrupted or until day 7
Secondary	Fraction of expired sevoflurane	Fraction of expired sevoflurane	Until sedation can be definitely interrupted or until day 7
Secondary	Dose of sevoflurane	Dose of sevoflurane (mg/l)	Until sedation can be definitely interrupted or until day 7
Secondary	Infusion duration of sevoflurane	Infusion duration of sevoflurane (min)	Until sedation can be definitely interrupted or until day 7
Secondary	Infusion rate of remifentanil	Infusion rate of remifentanil	Until sedation can be definitely interrupted or until day 7
Secondary	Values of a bispectral index	Values of a bispectral index	Until sedation can be definitely interrupted or until day 7