Effect of Sevoflurane and Remimazolam on Arterial Oxygenation During One-lung Ventilation

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare the effect of sevoflurane and remimazolam on arterial oxygenation during one lung ventilation in patients undergoing video-assisted thoracoscopic surgery.

Detailed Description
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One lung ventilation (OLV) is a mechanical ventilation method used during thoracic surgery to collapse the non-ventilated lung and secure the surgical field. During one lung ventilation, the pulmonary artery of the collapsed lung undergoes vasoconstriction in response to hypoxia, which increases the blood flow of the normally ventilated lung as a compensatory physiological response. This is known as hypoxic pulmonary vasoconstriction (HPV). Therefore, by using HPV, arterial blood oxygenation can be maintained and pulmonary shunting can be reduced, preventing hypoxemia during one lung ventilation. The two most commonly used anesthetics in thoracic surgery are sevoflurane, an inhaled anesthetic, and propofol, an intravenous anesthetic. Previous studies have shown that there were no significant differences between two anesthetics on arterial oxygenation during one lung ventilation because sevoflurane administered in clinical concentrations of 1 minimum alveolar concentration (MAC) resulted in similar changes in shunt fraction as did propofol. However, the effect of remimazolam on arterial blood oxygenation and intrapulmonary shunt during one lung ventilation has not been revealed. Therefore, this study is designed to compare the effect of remimazolam and sevoflurane anesthesia on arterial oxygenation during one lung ventilation in patients undergoing video-assisted thoracoscopic surgery.

Official Title
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Effect of Sevoflurane and Remimazolam on Arterial Oxygenation During One-lung Ventilation: a Prospective Randomized Controlled Study

Conditions
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One-Lung Ventilation, Thoracic Surgery, Video-Assisted, Remimazolam

Intervention / Treatment
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* Drug: Remimazolam
* Drug: 1% propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing video-assisted thoracoscopic surgery 19 years of age or older, less than 80 years old The American Society of Anesthesiologists (ASA) classification I-Ⅲ physical status Exclusion Criteria: Patients with known allergy to benzodiazepine, propofol Patients with galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption Patients with hypersensitivity to Dextran40 Patients with end stage renal disease requiring hemodialysis Patients with history of acute angle glaucoma Emergency operation Patients with unstable hemodynamics requiring inotropics Patients with preoperative oxygen supplement Preoperative forced expiratory volume (FEV1) less than 40% of predicted Preoperative ejection fraction less than 50%

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 79 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remimazolam group<br>To induce anesthesia, remimazolam is continuously infused in a dose of 6mg/kg/hr with remifentanil (Ce of 1-4ng/ml) by target-controlled infusion (TCI). Maintenance dose of remimazolam is 1mg/kg/hr, up to 2mg/kg/hr, and remifentanil is titrated to maintain the bispectral index (BIS) between 40 and 60 to achieve appropriate anesthetic depth during general anesthesia. | Drug: Remimazolam<br>* To induce anesthesia, remimazolam is continuously infused in a dose of 6mg/kg/hr with remifentanil (Ce of 1-4ng/ml) by target-controlled infusion (TCI). Maintenance dose of remimazolam is 1mg/kg/hr, up to 2mg/kg/hr, and remifentanil is titrated to maintain the bispectral index (BIS) between 40 and 60 to achieve appropriate anesthetic depth during general anesthesia. Inspired oxygen fraction (FiO2) 1.0 is used during mask ventilation and tracheal intubation. During two lung ventilation (TLV), tidal volumes (8mL/kg predicted body weight), positive end-expiratory pressure (PEEP) 5cmH2O with FiO2 0.3 is applied. At the start of one lung ventilation(OLV), tidal volumes (5mL/kg predicted body weight), PEEP 5cmH2O with FiO2 0.8 is applied. Intraoperative ventilatory frequency is 12 breaths/min, subsequently adjusted to maintain end tidal CO2(ETCO2) ranged between 35-40mmHg.<br>* Other names: Byfavo;|
| Active Comparator: Sevoflurane group<br>To induce anesthesia, 1% propofol 1.5-2.5mg/kg is used with remifentanil (Ce of 1-4ng/ml) by target-controlled infusion (TCI). After patient loses consciousness, anesthesia is maintained through the inhalation of sevoflurane between 1-2 minimum alveolar concentrations (MAC). Remifentanil is titrated to maintain the bispectral index (BIS) between 40 and 60 to achieve appropriate anesthetic depth during general anesthesia. | Drug: 1% propofol<br>* To induce anesthesia, 1% propofol 1.5-2.5mg/kg is used with remifentanil (Ce of 1-4ng/ml) by target-controlled infusion (TCI). After patient loses consciousness, anesthesia is maintained through the inhalation of sevoflurane between 1-2 minimum alveolar concentrations (MAC), and remifentanil is titrated to maintain the bispectral index (BIS) between 40 and 60 to achieve appropriate anesthetic depth during general anesthesia. Inspired oxygen fraction (FiO2) 1.0 is used during mask ventilation and tracheal intubation. During two lung ventilation (TLV), tidal volumes (8mL/kg predicted body weight), positive end-expiratory pressure (PEEP) 5cmH2O with FiO2 0.3 is applied. At the start of one lung ventilation(OLV), tidal volumes (5mL/kg predicted body weight), PEEP 5cmH2O with FiO2 0.8 is applied. Intraoperative ventilatory frequency is 12 breaths/min, subsequently adjusted to maintain end tidal CO2(ETCO2) ranged between 35-40mmHg.<br>* Other names: Fresofol MCT 1%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PaO2 after 30 minutes of OLV (T2) | compare the arterial oxygenation after 30 minutes of one lung ventilation between two groups | arterial blood sampling will be taken over four times: T0 (after 10 minute of TLV in lateral decubitus position), T1 (after 15 minutes of OLV), T2 (after 30 minutes of OLV), T3 (after 60 minutes of OLV) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of PaO2 | Compare the changes of PaO2 between two groups. | During 60 minutes of OLV | 
| Changes of PaCO2 | Compare the changes of PaCO2 between two groups. | During 60 minutes of OLV | 
| Changes of P/F ratio | Compare the changes of PaO2/FiO2 ratio between two groups. | During 60 minutes of OLV | 
| The lowest PaO2 | Compare the lowest PaO2 between two groups. | During 60 minutes of OLV | 
| Changes of ORI | Compare the changes of oxygen reserve index between two groups. | During 60 minutes of OLV | 
| Changes of MAP | Compare the changes of mean arterial pressure between two groups. | During 60 minutes of OLV | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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remimazolam, one-lung ventilation, arterial oxygenation, hypoxic pulmonary vasoconstriction, sevoflurane, thoracic surgery