The Deep Sedation for Ablation Study

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

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation; Sedation; Dexmedetomidine; Propofol; Ablation
• Intervention / Treatment: Drug: Propofol; Drug: Dexmedetomidine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Bern (Kanton)
    • Bern, Bern (Kanton), Switzerland, 3010
      • Department of Cardiology, University Hospital Inselspital Bern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Propofol; Active agent: Propofolum (2,6-Diisopropylphenol). Route of administration: intravenous	Drug: Propofol; 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.
Active Comparator: Dexmedetomidine; Active agent: Dexmedetomidinum ut Dexmedetomidini hydrochloridum. Route of administration: intravenous	Drug: Dexmedetomidine; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Principal Investigator: Helge Servatius, MD, University Hospital Inselspital, Bern

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: October 30, 2018
• First Submitted That Met QC Criteria: February 18, 2019
• First Posted (Actual): February 19, 2019

Study Record Updates

• Last Update Posted (Actual): January 25, 2021
• Last Update Submitted That Met QC Criteria: January 22, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Ablation; Sedation; Propofol; Dexmedetomidine; Anesthesia
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Propofol; Dexmedetomidine
• Other Study ID Numbers: 2018-02128

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No