Esketamine-propofol Versus Propofol for Flexible Bronchoscopy

Study Overview
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Brief Summary
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Bronchoscopy is a promising technology for lung and bronchus disease detection and therapy. However, this procedure is associated with a relatively high risk of hypoxemia, coughing, wheezing, and dyspnea. Despite the fact that propofol is the most commonly used agent in procedure sedation, the narrow therapeutic index remains challenging. Esketamine is the s-enantiomer of ketamine with potent analgesic and sedative properties. This study aims to test the hypothesis that adding subanesthetic esketamine to propofol is non-inferior to propofol alone for bronchoscopy on the recovery profile and discharge from the hospital.

Detailed Description
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Bronchoscopy is one of the most common procedures to detect lung and bronchus disease. The procedure is generally uncomfortable and associated with a relatively high risk of hypoxemia, coughing, wheezing, and dyspnea. Therefore, physicians are placing increasing importance on the use of procedure sedation due to the demand for comfortable medical care. Propofol is an effective agent for sedation in bronchoscopy with rapid onset and recovery. However, the safety endpoints of propofol are not cost-effective, including injection pain, hypotension, apnea, airway compromise, and without a reversal agent. Specifically, the depressive effects on the respiratory system are more noteworthy in bronchoscopy, which may lead to hypoxia. These drawbacks may hinder functional recovery and delay the discharge time. Hence, physicians are searching for an optimal sedation regimen for bronchoscopy. Esketamine, the s-enantiomer of ketamine, is an N-methyl-D-aspartic acid receptor antagonist with potent analgesic and sedative properties. Evidence suggested that esketamine could be used as a component of sedative regimen in many settings, such as endoscopy and endoscopic retrograde cholangiopancreatography. Nevertheless, there remains an evidence gap in the efficacy and safety of esketamine used in bronchoscopy. Therefore, we conducted this study to test the hypothesis that low-dose esketamine as an adjuvant to propofol was non-inferior to propofol alone on the recovery profile and discharge from the hospital after ambulatory bronchoscopy.

Official Title
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Discharge Readiness After Propofol With or Without Esketamine for Outpatient Flexible Bronchoscopy: a Randomized, Controlled Study

Conditions
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Postoperative Recovery

Intervention / Treatment
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* Drug: 0.1 mg/kg esketamine
* Drug: 0.2 mg/kg esketamine
* Drug: 0.9% saline
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anesthesiologists (ASA) classification I-III; Scheduled for ambulatory bronchoscopy. Exclusion Criteria: Allergic or contraindications to studying drugs History of obstructive sleep apnea-hypopnea syndrome History of psychiatric illness History of neurological disease Pre-existing memory or cognitive impairment History of seizure disorders Pregnancy Substance abuse or intake of drugs that affect the central nervous system Inability to communicate in Mandarin Chinese. Illiteracy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.1 mg/kg esketamine group<br>Procedure sedation was induced using intravenous 0.1 mg/kg esketamine and propofol 1 mg/kg. Afterward, propofol 0.5 mg/kg was administered to maintain the target sedation level (MOAA/S of less than three). | Drug: 0.1 mg/kg esketamine<br>* Esketamine 0.1 mg/kg was intravenously injected first.<br>* Other names: S-ketamine 0.1 mg/kg;Drug: Propofol<br>* Propofol 1 mg/kg was injected immediately. Afterward, propofol 0.5 mg/kg was administered to maintain the target sedation level (MOAA/S of less than three).<br>* Other names: propofol injection;|
| Experimental: 0.2 mg/kg esketamine group<br>Procedure sedation was induced using intravenous 0.2 mg/kg esketamine and propofol 1 mg/kg. Afterward, propofol 0.5 mg/kg was administered to maintain the target sedation level (MOAA/S of less than three). | Drug: 0.2 mg/kg esketamine<br>* Esketamine 0.2 mg/kg was intravenously injected first.<br>* Other names: S-ketamine 0.2 mg/kg;Drug: Propofol<br>* Propofol 1 mg/kg was injected immediately. Afterward, propofol 0.5 mg/kg was administered to maintain the target sedation level (MOAA/S of less than three).<br>* Other names: propofol injection;|
| Placebo Comparator: Placebo group<br>Procedure sedation was induced using intravenous 0.9% saline and propofol 1 mg/kg. Afterward, propofol 0.5 mg/kg was administered to maintain the target sedation level (MOAA/S of less than three). | Drug: 0.9% saline<br>* 0.9% saline was intravenously injected first.<br>* Other names: Normal saline;Drug: Propofol<br>* Propofol 1 mg/kg was injected immediately. Afterward, propofol 0.5 mg/kg was administered to maintain the target sedation level (MOAA/S of less than three).<br>* Other names: propofol injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportions of patients discharged within 30 min after bronchoscopy | Discharge readiness will be measured using the Modified Post Anesthetic Discharge Scoring System scale (greater than or equal to nine). | Up to 40 minutes postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative quality of recovery | Postoperative quality of recovery will be measured using the Postoperative Quality of Recovery Scale (PostopQRS). The PostopQRS is a digital measurement tool to quantify physiological, emotive, nociceptive, activities of daily living, and cognitive domain of postoperative recovery over time. Recovery in various domains of the PostopQRS is defined by postoperative values equaling or exceeding individual baseline values. | Baseline, up to 72 hours postoperatively | 
| Injection pain | Injection pain was assessed using a numeric rating scale of 0 to 10 (0 equals no pain, and 10 equals the worst pain imaginable). | Immediately after administering the study drugs, on average 2 minutes | 
| Emergency time | Emergency time was defined as the interval from the end of bronchoscopy to the MOAA/S score equal to five. | Immediately after the bronchoscopy completely withdrawn, on average 8 minutes | 
| Incidence of adverse events | Episodes of adverse events such as bradycardia, tachycardia, hypotension, hypertension, hypoxia, nausea, vomiting, nightmare, and blurred vision | Up to 72 h postoperatively | 
| Propofol consumption | Propofol consumption will be recorded during the bronchoscopy procedure. | During the bronchoscopy procedure | 
| Patient willingness to repeat the procedure | Patients will be asked whether they would repeat the identical procedural process (Yes/No/Unsure). | 24 hours postoperatively | 
| Bronchoscopist satisfaction | Bronchoscopist satisfaction will be evaluated using a five-point Likert scale (5=very satisfied, 4=satisfied, 3=neither satisfied nor dissatisfied, 2=dissatisfied, and 1=very dissatisfied). | At completion of bronchoscopy procedure | 
| Patient satisfaction | Bronchoscopist satisfaction will be evaluated using a five-point Likert scale (5=very satisfied, 4=satisfied, 3=neither satisfied nor dissatisfied, 2=dissatisfied, and 1=very dissatisfied). | At completion of bronchoscopy procedure | 
| Patient willingness to recommend screening | Patients will be asked whether they would recommend bronchoscopy screening to a friend or a relative (Yes/No/Unsure). | 24 hours postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bronchoscopy, esketamine, procedure sedation, propofol