Sevoflurane in Chronic Obstructive Pulmonary Disease Exacerbation

Study Overview
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Brief Summary
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Prospective, open-label, single-center, study to investigate the effect of sevoflurane sedation compared to a propofol-controlled arm during COPD exacerbation requiring invasive mechanical ventilation in ICU. Primary outcome measure: Evolution of airway resistance before and after sevoflurane in COPD patients, Secondary outcomes measures: Respiratory mechanics (Maximum pressure, PEEPi and PEEPtot, trapped volume), Gas exchange by the help of blood gases, The heterogeneity of alveolar ventilation by electro-impedancemetry, Evolution of pulmonary inflammation, Trophicity and contractility of the diaphragm,

Official Title
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Evaluation of Sevoflurane in Chronic Obstructive Pulmonary Disease Exacerbation in Intensive Care Unit: A Comparative Prospective Study

Conditions
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COPD Exacerbation, Invasive Mechanical Ventilation

Intervention / Treatment
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* Drug: Sevoflurane
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : COPD exacerbation Invasive mechanical ventilation and sedation for a planned duration of at least 24 hours Consent Age ≥ 18 years Affiliation or beneficiary of a social security scheme Exclusion Criteria : Contraindication to the administration of sevoflurane (personal or family history of malignant hyperthermia, allergy or halogenated anesthetic accident, chronic myopathy, halogenated toxic hepatitis, uncontrolled intracranial hypertension, unexplained leukocytosis after anesthesia with a halogenated agent) Contraindication to the administration of propofol (known hypersensitivity to propofol, soy, peanut or any of the excipients of the emulsion, antecedent of Propofol Related Infusion Syndrome) Refusal of consent Guardianship Age < 18 years Pregnant or lactating woman

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sevoflurane group<br> | Drug: Sevoflurane<br>* During the first 30 minutes after randomization, patients will be treated with propofol (same dosage as the propofol group). Once the AnaConDa® system is installed, sevoflurane administration will begin (propofol is stopped).<br>Drug: Propofol<br>* In the control group, sedation will be maintained with the above objective (RASS between -4 and -5, BIS between 40 and 60) until the patient is extubated. In the sevoflurane group, propofol is administrated during the first 30 minutes after the randomization and when the AnaConDa® system is installed propofol is stopped.<br>|
| Active Comparator: Propofol group<br> | Drug: Propofol<br>* In the control group, sedation will be maintained with the above objective (RASS between -4 and -5, BIS between 40 and 60) until the patient is extubated. In the sevoflurane group, propofol is administrated during the first 30 minutes after the randomization and when the AnaConDa® system is installed propofol is stopped.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of airway resistance before and after sevoflurane in COPD patients | Total airway resistance will be measured using the ventilator by setting a 5s inspiratory pause and to measure the sum of (Pmax-P1)/Flow + (P1-Pplat)/Flow. The mechanical ventilation setting will be standardised during the study period and will be similar between the two groups. | Hour 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum pressure |  | Evolution between Hour 0 and Hour 48 | 
| PEEPi |  | Evolution between Hour 0 and Hour 48 | 
| PEEPtot |  | Evolution between Hour 0 and Hour 48 | 
| Trapped volume |  | Evolution between Hour 0 and Hour 48 | 
| Gas exchange by the help of blood gases |  | Evolution between Hour 0 and Hour 48 | 
| Heterogeneity of alveolar ventilation by electro-impedancemetry |  | Evolution between Hour 0 and Hour 48 | 
| Proinflammatory cytokines (IL1, IL6, TNFalpha) and sRAGE measurements in miniBroncho-Alveolar lavages |  | Evolution between Hour 0 and Hour 48 | 
| Thickness of the diaphragm measured by ultrasound |  | Evolution between Hour 0 and Hour 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD exacerbation, Sevoflurane, Airway Resistance