Conscious Sedation Versus General Anesthesia for Pulsed Field Ablation in Paroxysmal Atrial Fibrillation

Pulsed field ablation is an emerging catheter ablation technology for the treatment of atrial fibrillation. Delivery of pulsed field energy may cause chest discomfort, coughing, involuntary movement, and phrenic nerve stimulation. General anesthesia is therefore commonly used to improve participant tolerance and facilitate catheter stability during the procedure. However, general anesthesia requires dedicated anesthesia personnel and resources and may prolong preprocedural preparation and postprocedural recovery.

Local anesthesia combined with conscious sedation may provide a simpler alternative for pulsed field ablation. This strategy may reduce the need for anesthesia resources while maintaining participant safety and procedural effectiveness. However, high-quality evidence directly comparing local anesthesia with conscious sedation and general anesthesia during pulsed field ablation remains limited.

This study is a prospective, multicenter, randomized, controlled, noninferiority trial designed to compare the efficacy and safety of the two anesthesia strategies in participants with paroxysmal atrial fibrillation. A total of 390 eligible participants will be randomly assigned in a 1:1 ratio to either local anesthesia with conscious sedation or general anesthesia. The randomization sequence will be generated by an independent statistician using computer-based block randomization.

Participants assigned to the local anesthesia with conscious sedation group will receive protocol-specified antitussive pretreatment, local anesthesia, analgesia, and conscious sedation. Additional sedative or analgesic medication may be administered according to vital signs, pain, coughing, agitation, and clinical tolerance. Participants who experience persistent severe coughing or agitation, respiratory depression or refractory hypoxemia, uncorrectable hemodynamic instability, or an inability to tolerate the assigned strategy may be converted to general anesthesia. Participants who are converted to general anesthesia will remain in their originally assigned group for the primary intention-to-treat analysis.

Participants assigned to the general anesthesia group will receive general anesthesia administered and managed by an anesthesiologist according to the clinical practice of the participating center.

All participants will undergo bilateral pulmonary vein isolation using the VARIPULSE pulsed field ablation catheter under CARTO 3 electroanatomic mapping guidance. Additional ablation of the left atrial posterior wall, superior vena cava, or other atrial substrate may be performed when clinically indicated. Activated clotting time will be maintained at 350 seconds or longer during left atrial ablation.

Participants will be followed at 1, 2, 3, 6, and 12 months after ablation. Wearable electrocardiographic monitoring will be performed for at least 7 days at each scheduled follow-up. The first 8 weeks after ablation will be considered the blanking period.

The primary outcome is recurrence of an electrocardiographically documented atrial tachyarrhythmia, defined as atrial fibrillation, atrial flutter, or atrial tachycardia lasting at least 30 seconds after the 8-week blanking period through 12 months after ablation. The primary analysis will evaluate whether local anesthesia with conscious sedation is noninferior to general anesthesia, using a prespecified absolute noninferiority margin of 13 percentage points.

Secondary outcomes include successful completion of the planned ablation procedure with support from the assigned anesthesia strategy, conversion from conscious sedation to general anesthesia, anesthesia-related adverse events, ablation-related complications, acute pulmonary vein isolation success, procedure and recovery times, fluoroscopy time, participant-reported pain and anxiety, overall procedural experience, and direct anesthesia- or sedation-related medical costs.

• Local Anesthesia With Conscious Sedation (Procedure): Protocol-specified antitussive pretreatment is followed by local anesthesia, analgesia, and conscious sedation. Before femoral venous puncture, intravenous tropisetron hydrochloride 5 mg, dexamethasone 5 mg, lidocaine 100 mg over 10 minutes, fentanyl 50 micrograms, midazolam 2 mg, and atropine 1 mg are given. After transseptal puncture, fentanyl 50-100 micrograms is given intravenously, followed by 0.04 micrograms/kg/min infusion. Additional midazolam or fentanyl may be given according to vital signs and clinical tolerance. Conversion to general anesthesia is permitted for persistent severe coughing, pain, anxiety, or agitation interfering with catheter positioning or energy delivery; persistent respiratory depression or refractory hypoxemia; uncorrectable hemodynamic instability; or inability or unwillingness to tolerate the assigned strategy.
• General Anesthesia (Procedure): General anesthesia will be induced, maintained, and monitored by an anesthesiologist according to routine clinical practice at each participating center. Airway management, anesthetic medications, ventilation parameters, hemodynamic management, and post-anesthesia recovery will be documented.
• VARIPULSE Pulsed Field Ablation System (Device): All participants will undergo bilateral pulmonary vein isolation using the VARIPULSE pulsed field ablation catheter under CARTO 3 electroanatomic mapping guidance. Additional ablation of the left atrial posterior wall, superior vena cava, or other atrial substrate may be performed when clinically indicated. Bidirectional pulmonary vein isolation will be evaluated at the end of the procedure. Activated clotting time will be maintained at 350 seconds or longer during left atrial ablation.
• Compound methoxyphenamine capsules (Drug): Oral antitussive pretreatment with compound methoxyphenamine capsules (Asmeton) during the 24 hours before the procedure, as specified in the protocol.
• Salbutamol (Drug): Nebulized pretreatment in combination with budesonide and lidocaine within 90 minutes before the procedure, as specified in the protocol for the local anesthesia with conscious sedation arm.
• Budesonide (Drug): Nebulized pretreatment in combination with salbutamol and lidocaine within 90 minutes before the procedure, as specified in the protocol for the local anesthesia with conscious sedation arm.
• Lidocaine (Drug): Administered by nebulization with salbutamol and budesonide within 90 minutes before the procedure, and intravenously before femoral venous puncture, as specified in the protocol for the local anesthesia with conscious sedation arm.
• Fentanyl (Drug): For the local anesthesia with conscious sedation arm: intravenous fentanyl 50 micrograms before femoral venous puncture, followed by 50 to 100 micrograms after transseptal puncture and a continuous intravenous infusion at 0.04 micrograms/kg/min. Additional doses may be administered according to vital signs, pain, and clinical tolerance, as specified in the protocol.
• Midazolam (Drug): For the local anesthesia with conscious sedation arm: intravenous midazolam 2 mg before femoral venous puncture. Additional doses may be given according to vital signs and clinical response, as specified in the protocol.
• Tropisetron hydrochloride (Drug): Intravenous tropisetron hydrochloride 5 mg before femoral venous puncture as part of the protocol-specified premedication regimen for the local anesthesia with conscious sedation arm.
• Dexamethasone (Drug): Intravenous dexamethasone 5 mg before femoral venous puncture as part of the protocol-specified premedication regimen for the local anesthesia with conscious sedation arm.
• Atropine (Drug): Intravenous atropine 1 mg before femoral venous puncture as part of the protocol-specified premedication regimen for the local anesthesia with conscious sedation arm.

Primary outcomes

• Percentage of Participants With Recurrence of Atrial Tachyarrhythmia After the Blanking Period [From the end of the 8-week post-ablation blanking period through 12 months after the index ablation procedure]: Recurrence is defined as at least one episode of atrial fibrillation, atrial flutter, or atrial tachycardia lasting 30 seconds or longer and documented by electrocardiographic monitoring after the 8-week post-ablation blanking period. Rhythm monitoring will be performed using a wearable electrocardiographic device for at least 7 days at each scheduled follow-up. The outcome will be reported as the percentage of participants with recurrence.

Secondary outcomes

• Percentage of Participants With Successful Procedural Support by the Assigned Anesthesia Strategy [During the index ablation procedure]: Successful procedural support is defined as completion of the planned ablation strategy without an anesthesia-related event causing interruption, premature termination, or inability to complete the intended ablation strategy. For participants assigned to local anesthesia with conscious sedation, success requires: (1) no interruption of ablation on three or more occasions because of severe coughing, pain, or agitation; (2) no single interruption lasting more than 5 minutes because of severe coughing, pain, or agitation; and (3) no conversion to general anesthesia because of intolerance of the assigned anesthesia strategy. For participants assigned to general anesthesia, success requires no premature termination of the procedure because of hemodynamic instability, a severe allergic reaction, or another anesthesia-related event.
• Percentage of Participants With Airway Mechanical Injury [From initiation of anesthesia or sedation through discharge from the index hospitalization, an expected average of 2 days.]: The percentage of participants experiencing at least one airway mechanical injury, including sore throat, mucosal bleeding, or hoarseness, following the assigned anesthesia or sedation strategy. Individual components will also be recorded separately.
• Percentage of Participants Requiring Conversion From Conscious Sedation to General Anesthesia [During the index ablation procedure]: The percentage of participants assigned to local anesthesia with conscious sedation who require conversion to general anesthesia because of persistent severe coughing, pain, anxiety, or agitation interfering with catheter positioning or energy delivery; persistent respiratory depression or refractory hypoxemia; uncorrectable hemodynamic instability; or inability or unwillingness to tolerate the assigned anesthesia strategy.
• Percentage of Participants With Intraoperative Agitation [During the index ablation procedure]: The percentage of participants with intraoperative agitation documented by the procedural team during the index ablation procedure.
• Duration of Procedural Area Occupancy [During the index procedure]: The elapsed time in minutes from the participant's entry into the procedural area, recorded by the first entry scan, to the participant's exit from the procedural area, recorded by the corresponding exit scan.
• Duration of Catheter Laboratory Occupancy [During the index procedure]: The elapsed time in minutes from the participant's entry into the catheter laboratory, recorded by the second entry scan, to the participant's exit from the catheter laboratory, recorded by the corresponding exit scan.
• Percentage of Participants With Acute Pulmonary Vein Isolation Success [At the end of the index ablation procedure]: The percentage of participants in whom bidirectional electrical isolation of all targeted pulmonary veins is confirmed at the end of the index ablation procedure.
• Pain Visual Analog Scale Score [Immediately after the index ablation procedure]: Pain will be assessed using a 0-to-100 visual analog scale, where 0 indicates no pain and 100 indicates the worst imaginable pain. Higher scores indicate greater pain.
• Anxiety Visual Analog Scale Score [Immediately after the index ablation procedure]: Anxiety will be assessed using a 0-to-100 visual analog scale, where 0 indicates no anxiety and 100 indicates the worst imaginable anxiety. Higher scores indicate greater anxiety.
• Overall Procedural Experience Visual Analog Scale Score [Immediately after the index ablation procedure]: Overall procedural experience will be assessed using a 0-to-100 visual analog scale, where 0 indicates the worst possible procedural experience and 100 indicates the best possible procedural experience. Higher scores indicate a better procedural experience.
• Direct Anesthesia- or Sedation-Related Supplies and Medication Cost [During the index procedure and associated procedural preparation and recovery]: The total itemized cost in Chinese yuan of supplies and medications directly related to the assigned anesthesia or sedation strategy. Items may include laryngeal masks, anesthesia breathing circuits, anesthesia masks, respiratory filters, intravenous anesthetics, muscle relaxants, reversal agents, local anesthetics, nasal oxygen-delivery supplies, fentanyl, midazolam, dexmedetomidine, and lidocaine, as applicable.
• Anesthesia- or Sedation-Related Monitoring and Service Cost [During the index procedure and associated procedural preparation and recovery]: The total cost in Chinese yuan of anesthesia- or sedation-related monitoring and professional services, including respiratory function monitoring under general anesthesia and local anesthesia or sedation procedure fees, as applicable.
• Ancillary and Rescue Care Cost [During the index hospitalization, through discharge (expected an average of 2 days after initiation of anesthesia or sedation).]: The total cost in Chinese yuan of ancillary and rescue care associated with the assigned anesthesia or sedation strategy, including oxygen therapy, intravenous access, pressure-monitoring catheters, oxygen sensors, supportive treatment, emergency treatment, and antiemetic medications.
• Percentage of Participants With Anesthesia-Related Adverse Events [From initiation of anesthesia or sedation through 30 days after the index ablation procedure]: The percentage of participants experiencing at least one prespecified anesthesia-related adverse event, including sore throat, mucosal bleeding, hoarseness, bradycardia, intraoperative hypotension, hypoxemia, postoperative cognitive dysfunction, or severe vomiting. Each component event will also be recorded and reported separately.
• Percentage of Participants With Ablation-Related Complications [From the index ablation procedure through 12 months after the procedure]: The percentage of participants experiencing at least one prespecified ablation-related complication, including cardiac tamponade, pericardial effusion, coronary artery spasm, phrenic nerve injury, kidney injury, hemolysis, or vascular access complications. Each component event will also be recorded and reported separately.

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

1. Diagnosis of paroxysmal atrial fibrillation.
2. Age 18 to 80 years.
3. Scheduled and willing to undergo pulsed field ablation.
4. American Society of Anesthesiologists physical status class I to III.
5. Able to understand the study procedures and provide written informed consent.

Exclusion Criteria:

1. Contraindication to catheter ablation, including intracardiac or atrial thrombus.
2. Previous catheter ablation for atrial fibrillation or left atrial premature contractions.
3. Known allergy to iodinated contrast media.
4. Concurrent participation in another clinical trial involving a drug or medical device.
5. Pregnancy, breastfeeding, or planned pregnancy in the near future.
6. Active infection.
7. Unwilling to participate or unable to comply with the study procedures and scheduled follow-up.

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• Ligang Ding, Study chair, Chinese Academy of Medical Sciences & Peking Union Medical College Fuwai Hospital