The Deep Sedation for Ablation Study

Study Overview
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Brief Summary
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Catheter ablation (CA) is an established therapeutic option for patients with symptomatic atrial fibrillation (AF). During the procedure, patients are usually sedated and analgesized, most commonly by administration of Propofol combined with opioids under the supervision of the electrophysiologist. However, due to the depressive effect of Propofol on the respiratory system, this regimen is not without risk. Dexmedetomidine is a highly selective alpha 2 agonist that demonstrates both analgesic and hypnotic properties with only weak effect on the respiratory system. The pharmacological profile of Dexmedetomidine may be advantageous for sedation during CA of AF. The aim of this randomized trial is to test this hypothesis and explore the safety and efficacy of Dexmedetomidine during CA of AF.

Detailed Description
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Atrial fibrillation (AF) is the most common arrhythmia. In symptomatic patients, electroanatomic mapping aided catheter ablation (CA) is an established therapeutic option. The intervention may last several hours, during which patients are required to lie as still as possible, as inadequate patient movements disturb the electroanatomic map, prolong the intervention and increase its complication risks. Therefore patients are usually sedated and analgesized, most commonly by administration of Propofol combined with opioids under the supervision of the electrophysiologist. Despite its wide use, this regimen is not without risk, as Propofol has a pronounced depressive effect on the respiratory system. Dexmedetomidine is a highly selective alpha 2 agonist that demonstrates both analgesic and hypnotic properties with only weak respiratory depression. By reducing sympathetic activity it also reduces the stress response to an intervention. For these reasons, Dexmedetomidine is commonly used in intensive care units, where it has been shown to be well tolerated. Consequently, its range of application has been increasingly widened and good experience has been made with its use in transfemoral valve replacement procedures or gastroenterological interventions. The pharmacological profile of dexmedetomidine may be also advantageous for sedation during CA of AF. The aim of this randomized trial is to test this hypothesis and explore the safety and efficacy of Dexmedetomidine during CA of AF.

Official Title
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DExmEdetomidine Sedation Versus Propofol SEDATION FOR Catheter ABLATION of Atrial Fibrillation Under a Cardiologist Supervision: A Randomized Controlled Pilot STUDY

Conditions
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Atrial Fibrillation, Ablation, Sedation, Propofol, Dexmedetomidine

Intervention / Treatment
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* Drug: Propofol
* Drug: Dexmedetomidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Informed consent as documented by signature Catheter ablation of atrial fibrillation at the Department of Cardiology, Inselspital Bern Exclusion Criteria: Contraindication to sedation by the electrophysiologist Contraindications to either propofol or dexmedetomidine sedation Contraindication for targeted controlled propofol infusion (BMI > 35) American Society of Anesthesiologists (ASA) classification > III Advanced heart block (second or third degree), if no pacemaker or internal cardioverter defibrillator is implanted Arterial hypotension (mean < 80 mmHg) Severe heart failure (LVEF ≤ 30%) Indication for general anaesthesia Pregnant or breast-feeding women

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Propofol<br>Active agent: Propofolum (2,6-Diisopropylphenol). Route of administration: intravenous | Drug: Propofol<br>* At minimum 5 minutes before start of sedation for atrial fibrillation ablation a bolus of fentanyl (20-50 µg) will be administered. Thereafter, sedation is induced via the continuous infusion of propofol using a target-controlled infusion (TCI) pump. The effect-site propofol concentration will be initially set to 1.5 µg/ml, unless the patient is already sedated by fentanyl. Subsequently, an effect-site propofol concentration of 1 µg/ml will be chosen adjusted stepwise (using steps of 0.3 µg/ml) to reach a target score of 2-3 on the MOAA/S scale. In case of pain fentanyl can be administered bolus-wise (10-30 µg) at the cardiologists discretion.<br>|
| Active Comparator: Dexmedetomidine<br>Active agent: Dexmedetomidinum ut Dexmedetomidini hydrochloridum. Route of administration: intravenous | Drug: Dexmedetomidine<br>* At minimum 5 minutes before start of sedation for atrial fibrillation ablation a bolus of fentanyl (20-50 µg) will be administered. Thereafter, sedation is induced with a loading dose of dexmedetomidine (0.8 µg/kg) over 10 minutes. The maintenance dexmedetomidine dose is adjusted to the appropriate sedation criteria for CA (0.4 µg/kg/h) and for a target score of 2-3 on the MOAA/S scale. In case of pain, additional fentanyl can be administered bolus-wise (10-30 µg) at the cardiologists discretion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined Incidence of Sedation-Emergent Adverse Events (Combined Safety Endpoint) | Number of participants with sustained bradycardia necessitating cardiac pacing Number of participants with Hypercapnia, defined as rise of transcutaneously measured carbon dioxide levels (tcCO2) > 20mmHg Number of participants with Oxygen desaturation (<90%) necessitating assisted ventilation or further airway management in any form (including chin lift, oropharyngeal airway, bag, and mask ventilation or intubation) Number of participants with Hypotension necessitating termination of sedation or vasopressor administration Number of participants with necessity of termination or change of sedation protocol Number of participants with aborted procedure due to sedation issues | within 24 hours after completion of procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Sedation-Emergent Adverse Events (Individual Safety Endpoints) | All single components of the primary endpoint | within 24 hours after completion of procedure | 
| Other complications | Number of complications not related to sedation (cardiac tamponade, stroke/transient ischemic attack, pericardial effusion necessitating therapeutic intervention, bleeding necessitating therapeutic intervention, others) [number of events] | from start until end of ablation procedure | 
| Opiod dose | Opiod dose required for analgesia [ug] | from start until end of ablation procedure | 
| Procedure duration | Total duration of the procedure [minutes] | from start until end of ablation procedure | 
| Fluoroscopy time | Duration of fluoroscopy [minutes] | from start until end of ablation procedure | 
| General sedation efficacy: occurrence and number of shiftings | General sedation efficacy assessed by the occurrence and number of shiftings of the acquired 3D map due to patient movements, necessitating remapping [number of events] | from start until end of ablation procedure | 
| Sedation depth | Depth of sedation assessed by the Modified Observer's Alertness/Sedation (MOAA/S) scale [mean score] | from start until end of ablation procedure | 
| Blood pressure | Mean systolic, diastolic and mean blood pressure during sedation and mean drop of blood pressure (pre-procedural blood pressure minus mean blood pressure during sedation) [mmHg] | from start until end of ablation procedure | 
| Heart rate | Mean heart rate during sedation and mean drop of heart rate (pre-procedural heart rate minus mean heart rate during sedation) [beats per minute] | from start until end of ablation procedure | 
| Refractory period | Effective refractory period of the atria and atrioventricular node [ms] | from start until end of ablation procedure | 
| Wenckebach point | Wenckebach point of the atrioventricular node [ms] | from start until end of ablation procedure | 
| Arrhythmia inducibility | Rate of inducibility of supraventricular arrhythmias during pacing manoeuvres (number of successful/number of attempts) [%] | from start until end of ablation procedure | 
| Patient satisfaction: Patient Satisfaction with Sedation Instrument (PSSI) [score] | Patient satisfaction as assessed by the Patient Satisfaction with Sedation Instrument (PSSI) [score] | within 24 hours after completion of procedure | 
| Cardiologist satisfaction: Clinician Satisfaction with Sedation Instrument (CSSI) [score] | Cardiologist satisfaction as assessed by the Clinician Satisfaction with Sedation Instrument (CSSI) [score] | within 24 hours after completion of procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial Fibrillation, Ablation, Sedation, Anesthesia, Propofol, Dexmedetomidine