Clinical trial NCT02697448
Conditions: Atrial Fibrillation
Sponsor: Medical University of South Carolina
Start date: 2016-06-08; Completion date: 2024-02-28
Enrollment: 135 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Comparison of propofol and sevoflurane as a primary anesthetic for cardiac ablation of atrial fibrillation

Detailed description:
A side effect of some volatile anesthetics, such as isoflurane and desflurane, is enhanced automaticity, accounting for secondary atrial pacemakers. Volatile anesthetics also have varying effects on the AV node and His-Pukinje system. These agents also prolong the QT interval and, for this reason, volatile anesthetics as a group have at times been avoided for atrial fibrillation ablation due to the fear that they may affect the efficacy of the ablation and increase recurrence. However, sevoflurane does not have the effects shown for other volatile anesthetics cardiac conduction. At this point there has not been a study comparing propofol, a non volatile anesthetic typically used in these cases, to sevoflurane, a volatile anesthetic, to determine if volatile anesthetics should be avoided during these procedures. This study will challenge the existing belief that sevoflurane increases the length of time to ablate atrial fibrillation and also decreases the efficacy of the ablation.

Arms: arm 1: Participants receiving propofol as anesthetic for cardiac ablation. arm 2: Participants receiving sevoflurane as anesthetic for cardiac ablation.
Interventions: intervention 1: propofol intervention 2: sevoflurane
Intervention descriptions: intervention 1: Participant receives propofol as anesthetic for cardiac ablation. intervention 2: Participant receives sevoflurane as anesthetic for cardiac ablations.

Protocol documents:
Prot_SAP_000.pdf: 
 
Comparison of propofol and sevoflurane as a primary anesthetic for cardiac ablation of atrial 
fibrillation 
 
 
NCT02697448 
 
 
June 28, 2023 


Version 4_6-28-23 
 
 
1 of  7 
 
 
 
 
 
PI Name:  Dr. George Guldan 
 
Study Title: Comparison of propofol and sevoflurane as a primary anesthetic for cardiac ablation of atrial 
fibrillation    
 
  
 
TABLE OF CONTENTS  
 
A. Specific Aims  1                                                                                                                                            
B. Background and Significance 1-2                                                                                                                  
C. Preliminary Study 2                                                                                                                                      
D. Research Design and Methods  2-3                                                                                                             
E. Protection of Human Subjects 3-5                                                                                                                 
F. References  6                                                                                                                                             
 
A. SPECIFIC AIMS___________________________________________________________________________ 
 
The primary aim of this study is to compare two commonly used anesthetic techniques (propofol and sevoflurane) 
during atrial fibrillation ablation cases.  Of greatest interest is to compare the time to awaken the patients after the 
procedure.  Also of interest is the duration of the ablation procedure.  The hypothesis of this investigation is that 
patients who receive propofol will require a longer time to removal of the endotracheal tube after the end of the 
procedure than patients anesthetized with sevoflurane.  
 
B. BACKGROUND AND SIGNIFICANCE_________________________________________________________ 
 
The incidence and prevalence of atrial fibrillation continues to rise in our country. Currently, the incidence is 
predicted to double from 1.2 million cases in 2010 to 2.6 million cases in 2040.  Atrial fibrillation prevalence is 
projected to increase from 5.2 million in 2010 to 12.1 million in 2030. 1 As the rates of atrial fibrillation cases 
increase, treatments such as catheter-based ablation will also increase.   
Ablation procedures require the administration of general anesthesia.  A wide variety of general anesthesia 
techniques have been used since the inception of the ablation procedure, but there are few comparative studies 
of anesthetic techniques.  The lack of evidence comparing two widely used anesthetic techniques means that 
choice of a primary anesthetic is based on personal preference or local custom.  In a recent review of Ablation 
Procedures and Anesthetic implications the authors state: “The literature regarding the best choice for anesthetic 
technique in ablative procedures is still scarce and the decision ultimately depends on the patient’s clinical 
condition, the anesthesiologist’s judgment, and the electrophysiologist’s comfort level.”2  For this reason a study 
comparing two of the commonly employed techniques is warranted. 
Propofol is a sedative hypnotic agent used as an infusion as a general anesthetic at a recommended dose of 
between 100 and 200 mcg/kg/min.  In a continuous infusion, the distribution half-life of propofol is 1 to 3 hours in a 
2-compartment model and 30 to 70 minutes in a 3-compartment model.  The context-sensitive half time for 
infusions of up to 8 hours is 40 minutes. 1 
Propofol produces myocardial depressant effects and decreased systemic vascular resistance; these are both 
dose and concentration dependent.  Propofol has also been found to alter the baroreflex mechanism, which 
causes a smaller increase in heart rate for a given decrease in blood pressure. 
Propofol is commonly used as a general anesthetic agent for many different types of surgical procedures, 
including atrial fibrillation ablations.  Propofol is used as a general anesthetic for cardiac ablation procedures 
because it has no known effects on the cardiac conduction system. 
Medical University of South Carolina 
Protocol 


Version 4_6-28-23 
 
 
2 of  7 
Sevoflurane is a volatile anesthetic, which is administered via inhalation.  A concentration of 2% is typically used 
as a general anesthetic dose of sevoflurane.  Sevoflurane undergoes very little metabolism by the body, rather 
once the vaporizer is turned off and the patient breathes off the gas, the anesthetic effects are gone.  Like other 
inhaled anesthetics, sevoflurane is very rapid acting.  This ability to quickly increase or decrease anesthetic levels 
as necessary aids in efficiency and also increases the margin of error for this drug. 
Sevoflurane, and other volatile anesthetics, are the most commonly used general anesthetic agents in use today, 
both for their confirmed safety profile and also the ease of titrating the drugs.  Sevoflurane is used in some 
centers for ablation procedures. Our institution has also used Sevoflurane for atrial fibrillation ablations in the past 
when there has been a shortage of propofol. 
At our institution a total intravenous anesthetic (TIVA) with propofol is used during atrial fibrillation ablation cases.  
Sevoflurane is used at other centers, such as UCLA.  Due to sevoflurane’s shorter half life and the fact that it is 
not metabolized as much as propofol by the body, patients may have the breathing tube removed in a shorter 
period of time after the procedure is over and also be more awake and alert in the recovery room than if they had 
undergone the procedure using propofol as the primary anesthetic.  Propofol has been shown to have no effect on 
cardiac conduction4 and preliminary evidence shows that sevoflurane may similarly have no effect.3  Because 
shorter wake-up time could reduce hospital costs and improve efficiency, it is important to compare these two 
techniques focusing on time for extubation.   
There have been no head to head comparisons of total intravenous anesthesia (TIVA) versus sevoflurane for 
ablation procedures.  By conducting a randomized blinded study of these two anesthetics, new and important 
knowledge can be generated for this increasingly commonly performed procedure.   
A side effect of other volatile anesthetics, such as isoflurane and desflurane, is enhanced automaticity, accounting 
for secondary atrial pacemakers. 5  Volatile anesthetics also have varying effects on the AV node and His-Pukinje 
system.6  These agents also prolong the QT interval6  and, for this reason, volatile anesthetics as a group have at 
times been avoided for atrial fibrillation ablation.  However, sevoflurane does not seem to have the effects shown 
for other volatile anesthetics on cardiac conduction, based on preliminary evidence.3  Sharpe, et al suggested with 
results from a 15 patient study that Sevoflurane had no effect on the refractoriness of the normal or accessory 
atrioventricular pathway and also no clinically significant effects on sinoatrial node function or intraatrial 
conduction.3  Though the aforementioned study’s population consisted of patients with Wolff-Parkinson-White 
(WPW) syndrome, the concerns with how the anesthetic drugs affect the conduction system are the same with 
WPW as they are for atrial fibrillation cases.  Some institutions, such as UCLA, now use sevoflurane as the 
primary anesthetic for atrial fibrillation ablation cases.   
This study, a partnership between anesthesia and electrophysiology cardiologists, will be the first study to 
compare these two commonly used anesthetic techniques.  The primary end-point of this study is the time interval 
from the end of the procedure to tracheal extubation.  We will also measure the length of procedure, any 
differences in hemodynamics, patient alertness in the immediate postoperative period, as well as the rate of 
postoperative nausea and vomiting to see if there is a difference between the two anesthetics.  At 3 month and 6 
months, medical records will be examined to see if there is any difference in the recurrence of atrial fibrillation.  
Although our study is not powered for this, we will examine for this due to the theoretical risk of recurrence with 
Sevoflurane. 
The significance of this study is that it will be the first study to compare two commonly used anesthetic techniques 
in the setting of atrial fibrillation ablation.  There is currently no comparative evidence available to determine which 
technique is superior in this setting and as a result clinical practice is based on custom and familiarity rather than 
evidence of superiority.   
 
C. PRELIMINARY STUDIES___________________________________________________________________ 
There have not been any blinded randomized studies comparing volatile anesthetics to TIVA for atrial fibrillation 
ablations.  By performing this study, we can demonstrate if one anesthetic is superior to another for time of 
extubation and note any other differences in measured variables including the patient’s satisfaction in the 
immediate post- operative period.   
 
D. RESEARCH DESIGN AND METHODS (including data analysis) __________________________________ 
 


Version 4_6-28-23 
 
 
3 of  7 
Patients with persistent and paroxysmal atrial fibrillation, undergoing their first ablation, will be invited to 
participate in the study during their pre-operative visit if the patient is scheduled for one, but otherwise during their 
pre-operative anesthesia work up in the holding room. Once informed consent is obtained, the participant will be 
randomized via computer-generated randomization into one of two groups.  Group A will receive propofol 100-
150mcg/kg/min; Group B will receive sevoflurane 2% end tidal concentration as their primary, general anesthetic 
for the procedure.  Doses of each drug will be titrated to effect in order to obtain general anesthesia.  The 
electrophysiologist performing the procedure will be blinded as to which drug the patient is receiving.  Data will be 
collected from the patient’s electronic medical record postoperatively.  Our primary endpoint is time from 
procedure end until the time that the endotracheal tube is removed (wake-up time.)  Data will be analyzed using 
an independent 2-sample t-test.   
 
We will also measure and compare duration of the procedure, postoperative nausea and vomiting, hemodynamic 
differences during the case, and patient alertness postoperatively using a short questionnaire to be filled out on 
the morning of POD 1 by a trained study team member.  Following their first clinic visit with their cardiologist and 
for a total of 6 months postoperatively, we will view their medical record to look for recurrence of atrial fibrillation.   
 
 
Analysis plan, sample size and power: 
 
The primary outcomes are procedure duration and time to extubation.  Both outcomes will be analyzed using an 
independent 2-sample t-test.   
Propofol infusion is the most common primary anesthetic at MUSC for patients undergoing cardiac ablation for 
atrial fibrillation.  The primary outcome is time from procedure end to extubation between the two groups that will 
be compared using a two-sample t-test approach.  Sixty-three patients per group (126 total) provides 80% 
detection an effect size of 0.5 between the two groups using a two-sided t-test at significance level α = 0.05. The 
statistical assumptions will be checked graphically and the non-parametric Wilcoxon rank sum test will be used if 
assumptions are violated. 
E. PROTECTION OF HUMAN SUBJECTS________________________________________________________ 
 
1.  RISKS TO THE SUBJECTS  
a.  Human Subjects Involvement and Characteristics  
 
To account for a 6% attrition rate, we plan to enroll 134 participants who are ages 18 and over and have 
paroxysmal atrial fibrillation undergoing their first ablation.  
 
Targeted/Planned Enrollment Table 
 
 
TARGETED/PLANNED ENROLLMENT: Number of Subjects 
Ethnic Category 
Sex/Gender 
Females 
Males 
Total 
Hispanic or Latino 
   3 
    3 
      6 
Not Hispanic or Latino 
   64 
    64 
      134 
Ethnic Category: Total of All Subjects* 
126 
Racial Categories 
 
American Indian/Alaska Native 
0 
0 
0 
Asian 
0 
0 
0 
Native Hawaiian or Other Pacific Islander 
0 
0 
0 
Black or African American 
21 
21 
42 
White 
46 
46 
92 
Racial Categories: Total of All Subjects* 
67 
67 
134 
 
*The “Ethnic Category: Total of All Subjects” must be equal to the”Racial Categories: Total of All Subjects”.  
All eligible participants who volunteer for the study will be enrolled regardless of gender, race, or ethnicity.  It is 
difficult to estimate the proportion of gender or ethnicity representation in the study population as this is 


Version 4_6-28-23 
 
 
4 of  7 
predetermined by the surgical schedule, but every effort will be made to enroll participants from both genders and 
a variety of racial/ethnic backgrounds. The only reason for exclusion based on ethnic category is the inability to 
speak English. Our interpretters’ services are limited in time and availability.  
 
b.  Sources of Materials  
 
Once informed consent is obtained, the participant will be randomized via computer-generated randomization into 
one of two groups.  Group A will receive propofol as their primary, general anesthetic for the procedure and Group 
B will received sevoflurane as their primary, general anesthetic for the procedure.   
 
The following data will be obtained from the participant’s electronic medical record: overall length of procedure, 
time from procedure end to extubation, side effects (nausea, vomiting, hemodynamic differences during the case) 
and patient alertness.   
 
Upon enrollment, subjects will be assigned a randomized numerical identifier for the remainder of the study.  This 
number will be used to label charts and paperwork associated with the subject.  An electronic enrollment log will 
link patient name and MRN with his/her study ID number.  All paper information will be kept in a locked cabinet in 
a locked office.  All electronic data will be kept on MUSC's password protected server. 
 
c.  Potential Risks  
 
The two anesthetics that could be given are both commonly used and investigators are familiar with both. Side 
effects of each drug are typically only seen when the medications are given, or in the immediate postoperative 
period.  However, the risk associated with each medication is as follows: 
Propofol Risks:  
Less Than 5%: 
Slower heart rate 
 
 
Decrease in muscle tone 
                Muscle pain 
Breathing difficulty 
 
 
Temporary loss of feeling/sensation 
 
 
Allergic reaction 
 
 
Increased saliva 
Fainting 
 
 
 
Rash 
Changes in heart rhythm  
 
Cloudy urine 
 
Transient decrease in vision in the immediate postoperative period 
Less Than 20%: 
Burning or stinging at IV site 
Low blood pressure 
Sevoflurane Risks: 
Less Than 5%: 
Low blood pressure 
 
 
 
Slower heart rate 
Tightening of airway 
 
 
 
Holding breath 
Increased in saliva 


Version 4_6-28-23 
 
 
5 of  7 
Less Than 20%: 
Agitation 
 
 
Cough 
 
 
Although both medications may cause patients to stop breathing, this is not a concern in these procedures as 
patients have a breathing tube inserted and are on a ventilator for the duration of the procedure when the drugs 
are being administered. 
 
The risk of decreased efficacy of the ablation procedure is theoretical, however if one medication would cause the 
ablation to be less efficacious, a repeat ablation may be necessary. 
 
There is a risk of loss of confidentiality, as we will be accessing the medical records of patients.  However, all 
paper information will be kept in a locked cabinet in a locked research office and all electronic data will be kept on 
MUSC’s password protected server.  The research team will decrease this risk as much as possible by following 
confidentiality standards. 
 
Randomization risk: Participants will be assigned to a general anesthetic medication by chance. The anesthetic 
that is in turn given, may prove to be less effective or to have more side effects than the other study medication. 
 
2.  ADEQUACY OF PROTECTION AGAINST RISKS  
 
a.  Recruitment and Informed Consent 
 
Inclusion Criteria:  All patients who are 18 years of age or older, have persistent and paradoxical atrial fibrillation, 
and are undergoing their first ablation will be invited to participate in the study during their pre-operative 
anesthesia work up in the holding room.   
 
Exclusion Criteria: Patients will not be eligible for the study if they are unable to speak English or if the patient is 
cognitively incapable of providing their understanding of and consent for the study. 
 
Patients who have contraindications to either study drug, such as an allergy or history of malignant hyperthermia, 
will also be excluded from the study. 
 
Once the patient agrees to enroll in the study he or she will be asked to sign a written informed consent.  An 
anesthesia study team member will obtain the consent. The participant will be given time to read the consent and 
have any questions answered about their procedure and the study. 
 
b.  Protection against Risk 
 
All participants will be monitored during the procedure per MUSC’s policy. 
 
All paper information will be kept in a locked cabinet in a locked office.  All electronic data will be kept on MUSC's 
password protected server. 
 
3.  POTENTIAL BENEFITS OF THE PROPOSED RESEARCH TO THE SUBJECTS AND OTHERS  
 
The participant may or may not benefit from the study procedures. The knowledge gained from this study could 
help future patient’s undergoing this procedure have the best anesthesia treatment.  
 
4.  IMPORTANCE OF THE KNOWLEDGE TO BE GAINED  
 
The study may demonstrate whether one anesthetic provides any benefit over another for this relatively long 
procedure.  If the study shows no difference, or the superiority of sevoflurane, patient outcome and overall cost 
may decrease.  This is the first comparative study of these two techniques and will provide anesthesiologists with 
evidence regarding the choice for one or the other.  
 
5.  SUBJECT SAFETY AND MINIMIZING RISKS (Data and Safety Monitoring Plan) 
 


Version 4_6-28-23 
 
 
6 of  7 
Data and safety monitoring will be performed by the research study committee in the Department of Anesthesia 
and Perioperative Medicine on a annual basis.  The committee is comprised of  an MUSC Professor of 
Anesthesia (Dr. Orin Guidry), an emuritus dean of medicine (Dr. Gerald Reves), Professor Kenneth Catchpole & a 
Research Instructor Kent Armeson.  Any adverse effect on the time of the ablation will also be closely assessed 
during DSMB meetings.  The study will not go on if there has been prolongation of this procedure that is believed 
to be study related. Furthermore, if there are any identified study related complications, participants will be 
switched to receive standard treatment for the duration of the case. Though adverse events are not anticipated, 
any adverse events will be reported to the DSMB committee in real time for evaluation, as well as to MUSC's IRB, 
per protocol.  Of note, these adverse events are no different than what could be seen clinically.  The possibility of 
decreased ablation efficacy via the use of sevoflurane is purely theoretical. 
 
 
 
 
 
 
 
 
F. REFERENCES/LITERATURE CITATIONS_______________________________ 
 
1. Colilla, Susan et al. Estimates of Current and Future Incidence and Prevalence of Atrial Fibrillation in the 
U.S. Adult Population. American Journal of Cardiology, vol 112, Issue 8, 1142-1147 
2. Bhatt HV1, Syros G2, Greco M2, Miller M2, Fischer GW2.  Ablation Therapy for Atrial Fibrillation: 
Implications for the Anesthesiologist.  J Cardiothorac Vasc Anesth. 2015 Oct;29(5):1341-56. doi: 
10.1053/j.jvca.2015.05.197. Epub 2015 May 27 
3. Sharpe MD1, Cuillerier DJ, Lee JK, Basta M, Krahn AD, Klein GJ, Yee R.  Sevoflurane has no effect on 
sinoatrial node function or on normal atrioventricular and accessory pathway conduction in Wolff-
Parkinson-White syndrome during alfentanil/midazolam anesthesia. 
            Anesthesiology. 1999 Jan;90(1):60-5. 
4. Sharpe MD1, Dobkowski WB, Murkin JM, Klein G, Yee R.Propofol has no direct effect on sinoatrial node 
function or on normal atrioventricular and accessory pathway conduction in Wolff-Parkinson-White 
syndrome during alfentanil/midazolam anesthesia. 
  Anesthesiology. 1995 Apr;82(4):888-95 
5. Sharpe, MD, Dobkowski WB, Murkin JM, et al. The electrophysiologic effects of volatile anesthetics and 
sufentanil on the normal atrioventricular conduction system and accessory pathways in Wolff-Parkinson 
White syndrome. Anesthesiology. 1994 Jan;80(1):63-70. 
6. Bosnjak ZJ, Kampine JP. Effects of halothane, enflurane, and isoflurane on the SA node. Anesthesiology 
1978;49:338-60 
7. Lazlo A, Polk S, Atlee JL, Kampine JP, Bosnjak ZJ. Anesthetics and automaticity in latent pacemaker 
fibers: Effects of halothane, enflurane, and isoflurane on automaticity and recovery of automaticity from 
overdrive suppression in Purkinje fibers derived from canine hearts. Anesthesiology 1991;75:98-105 
8. Riley DC, Schmeling WT, Al-Wathiqui MH, et al. Prolongation of the QT interval by volatile anesthetics in 
chronically instrumented dog. Anesth Analg 1988;67:741-9 
 
 
 
G. CONSULTANTS__________________________________________________________________________ 
Where applicable, attach electronic versions of appropriate letters from all individuals confirming their roles in the 
project.  Go to the application under “additional uploads” to attach this information.     
 
H. FACILITES AVAILABLE____________________________________________________________________ 
Describe the facilities available for this project including laboratories, clinical resources, etc. 
 
MUSC’s Research Offices, Library, & the Department of Anesthesia and Perioperative Medicine.  
 
 
I. INVESTIGATOR BROCHURE ____________________________________________________ 


Version 4_6-28-23 
 
 
7 of  7 
If applicable, attach the electronic version of the investigator brochure.  Go to the application under “additional 
uploads” to attach this information.   
 
J. APPENDIX_______________________________________________________________________________ 
Attach any additional information pertinent to the application, such as surveys or questionnaires, diaries or logs, 
etc.  Go to the application under “additional uploads” to attach this information.