Ideal Anesthetic Agent for Cardiac Electrophysiology Study and Catheter Ablation – A Pilot Study

INTRODUCTION

There has been growing interest in cardiac electrophysiology (EP) study and catheter ablation procedures over the years and anesthesiologists are increasingly becoming an integral part of these procedures.^[1-3] EP study and catheter ablation procedure may be painful and of prolonged duration.^[4,5] Movement of the patient during the procedure may reduce catheter stability, cause catheter dislocation, and increase the probability of complications during the delivery of radiofrequency energy. Therefore, anesthesia services are required during catheter ablation of cardiac arrhythmias to provide analgesia, patient comfort, and immobilization while maintaining adequate airway, and ventilation.^[6,7] EP studies conducted for the treatment of supraventricular tachycardia (SVT) create a distinct scenario where it is necessary to induce arrhythmias to accurately diagnose and effectively treat them. The choice of the anesthetic agent is crucial, just as important as the treatment plan, as these agents can impact cardiac electrophysiology and conduction. They have the potential to modify the ability to induce an abnormal rhythm, which could ultimately have adverse effects on the ablation procedure.^[8] When selecting an appropriate anesthetic agent, factors such as the patient’s age, comorbidities, and length of the procedure should be taken into consideration. In addition, the provider’s experience and consultation with the electrophysiologist are also important, in addition to the agent’s potential to induce arrhythmias.

MATERIAL AND METHODS

This prospective and interventional study was conducted in the Cardiac EP Laboratory of our institute. After obtaining Institutional Ethics Committee approval, 30 adult patients with SVT scheduled for elective diagnostic EP study and radiofrequency catheter ablation were enrolled for the study with the aim to identify the ideal anesthetic agent for cardiac EP study and catheter ablation. The primary objective of the study was to compare the effects of anesthetic agents on cardiac electrophysiological parameters and arrhythmia inducibility. The secondary objective was to compare the patient, anesthesiologist, and cardiologist satisfaction scores with respect to the anesthetic agent used. Written informed consent was taken from the patients a day before the day of the procedure. The patients were assigned to one of the following groups according to the anesthetic agent to be used – midazolam (Group M), fentanyl (Group F), propofol (Group P), ketamine (Group K), or sevoflurane (Group S) by using computer-generated random number table with a block size of 15. Patients with liver or kidney dysfunction, severe heart failure (New York Heart Association Class III and Class IV), any psychiatric or neurological disorder, history of adverse reaction to study medications, history of obstructive sleep apnea, or having an anticipated difficult airway were excluded from the study.

A resting 12-lead electrocardiogram, transthoracic echocardiography, and standard laboratory tests were performed before the study as per the institutional protocol. Pre-procedure visit by the anesthesiologist was done a day before and the patients were explained the entire protocol of the study. The patient was assessed for difficult airway and all preoperative investigations were noted. All antiarrhythmic drugs were stopped. No premedication was prescribed to the patients and all patients were kept fasting overnight. Demographic data comprising name, age, gender, height, weight, body mass index, left ventricular ejection fraction, and comorbid conditions (hypertension, structural heart disease, coronary artery disease, diabetes mellitus, hypothyroidism, etc.) were noted. In the EP laboratory, electrocardiography, arterial oxygen saturation (SpO₂), non-invasive blood pressure, end-tidal carbon dioxide, and surface temperature monitoring were initiated. A 20 G peripheral intravenous (IV) access was secured in the upper limb in all patients. The depth of anesthesia was monitored using a bispectral index (BIS) monitor (BIS™ Monitoring System: Covidien, Medtronic) and Richmond Agitation Sedation Scale (RASS). External defibrillation pads were applied before the start of the procedure. Oxygen was supplemented through the face mask. Basic and advanced airway management equipment was kept in readiness for tackling respiratory depression and airway emergencies. Maintenance IV fluid in the form of a balanced salt solution at 2 mL/kg/h was administered throughout the procedure and in the post-procedure period till the time the patient resumed oral intake. Patients were kept warm by maintaining the ambient temperature, using warming blankets and an in-line IV fluid warming system.

RESULTS

The median age of the study population was 39 years (18–66 years) with male to female ratio of 1:1 and ASA physical status I or II. The patients were diagnosed with AV node reentrant tachycardia (AVNRT) (n = 23, 76.7%), paroxysmal SVT (n = 4), orthodromic AV reciprocating tachycardia (n = 2), and Wolff-Parkinson-White (WPW) syndrome (n = 1). The patients were comparable with respect to demographic parameters recorded in all the groups, namely, age, gender, height, weight, body mass index, hemoglobin levels, serum creatinine, and serum electrolytes [Table 1].

EP parameters remained stable with ketamine administration. Sevoflurane and propofol administration was associated with deviation in EP parameters (RR interval, PQ/PR interval, QRS interval, QT interval, cycle length, atrioventricular Wenckebach cycle length [AVWCL], and APERP) more than fentanyl and midazolam. Clinically, arrhythmia could not be induced electrically in one patient in the propofol group but could be induced with isoprenaline [Table 2].

The average duration of the procedure was 51 min. One patient each in the propofol and sevoflurane group suffered hypotension, which was managed by increasing the rate of IV fluid administration. No patient required administration of atropine for symptomatic bradycardia or injection mephentermine for severe hypotension.

Higher RASS scores were observed in the ketamine group at all-time points [Figure 1]. BIS values were found to be comparable at baseline. Thereafter, higher values of BIS were observed in the ketamine group as compared to other groups [Figure 2].

Close

Figure 1:

Comparison of Richmond agitation sedation scores among the groups. *P < 0.05, ^#P < 0.01, ^$P < 0.001.

Export to PPT

Close

Figure 2:

Comparison of Bispectral index values among the groups. *P < 0.05, ^#P < 0.01, ^$P < 0.001.

Export to PPT

The highest patient, anesthesiologist, and cardiologist satisfaction scores were observed in the fentanyl group, while the lowest scores were observed in the ketamine group. Based on the composite average satisfaction scores (average of all three satisfaction scores), overall scores were found to be the highest in the fentanyl group. The order of composite average satisfaction scores can be summarized as group F > group M > group P = group S > group K [Table 3].

DISCUSSION

Drugs such as dexmedetomidine, ketamine, fentanyl, remifentanil, midazolam, and propofol have been used for providing sedation during EP studies and SVT ablations procedures.^[1,9] Induction of arrhythmia during the procedure is crucial for confirming the diagnosis and ensuring the success of the procedure. Hence, diagnosis, ablation, or success becomes limited if the anesthetic used during the procedure inherently has antiarrhythmic properties and by itself hinders the induction of tachycardia.

The most common approach for sedation and pain relief during cardiac procedures is the use of benzodiazepines and narcotics either alone or in combination. The combination of these drugs provides analgesia, sedation, and amnesia. The combination of fentanyl and midazolam may be administered either as a continuous infusion^[10] or intermittently^[11] for a wide range of EP procedures. Selvaraj et al. studied the effects of conscious sedation on tachycardia inducibility and patient comfort during ablation of SVT using intermittent doses of midazolam and fentanyl. They concluded that conscious sedation with intermittent midazolam and fentanyl reduced patient discomfort during the EP study and ablation of SVT without affecting the tachycardia inducibility.^[12]

Midazolam is frequently used for sedation because of its shorter half-life and minimal effects on hemodynamics and the cardiac conduction system at therapeutic doses.^[13-16] Studies have shown that midazolam has no effect on the normal AV node or accessory pathways, sinoatrial (SA) node activity, or the inducibility of re-entrant tachycardias in intermittent doses up to 5 mg.^[17]

Fentanyl is one of the most commonly used opioids for sedation in EP laboratories, its analgesic action being the primary therapeutic effect. IV fentanyl boluses of 10–50 mcg and infusion rates ranging from 0.5 to 2.0 mcg/kg/h showed no significant adverse effects on arrhythmia inducibility. Schaffer et al. demonstrated that fentanyl had no effect on the atrial effective refractory period. They also found no significant difference between fentanyl or desflurane techniques in terms of EP measurements and SVT was inducible with both drugs.^[18]

Propofol has minimal or no direct effect on SA node activity, intra-atrial conduction, accessory pathways, and the atrioventricular conduction systems.^[19-21] Lai et al. examined the feasibility of using propofol anesthesia for radiofrequency catheter ablation of various tachyarrhythmias in 150 patients. They were able to induce tachyarrhythmias, however ectopic atrial tachycardia remained uninducible even with isoprenaline infusion in four out of seven children.^[22] Wutzler et al. compared the effects of propofol/midazolam, ketamine/ midazolam, and midazolam alone on the atrial physiology in 31 patients undergoing an EP study for SVT ablation. They reported that SVT induction rates before and after administration of anesthetic agents did not differ significantly between the groups, nor was there any instance wherein the arrhythmia could not be induced after administration of the anesthetic drug.^[23]

Ketamine as an anesthetic is unique, with sedative, analgesic, and sympathomimetic properties. In clinically relevant concentrations of ketamine, experimental studies have revealed a shortening of action potential duration, with minimal effect on AV node conduction and atrial refractoriness. Significant shortening of atrial conduction time after the administration of ketamine and midazolam, compared to propofol and midazolam, was reported by Wutzler et al.^[23] In their study in the pediatric population, Char et al. observed that the concurrent use of ketamine may mitigate the negative chronotropic effects of dexmedetomidine with an increase in heart rate, decrease in sinus node recovery time, decrease in QT interval, and AVNERP.^[24] At clinically relevant concentrations, ketamine shortens the action potential duration by inhibiting L-type Ca+2 currents.^[25]

Much of the data on general anesthesia for catheter ablations is from pediatric studies because of the need for ensuring immobility in these patients. All modern inhaled anesthetics have been used successfully in children undergoing SVT catheter ablations. When used in combination with alfentanil and midazolam in patients undergoing ablative procedures, sevoflurane was found to have no effect on the electrophysiological properties of the SA node, normal AV conduction system, and accessory pathways in patients with WPW syndrome.^[26] In a study by Pérez et al. on the EP effects of sevoflurane in children with WPW syndrome undergoing radiofrequency ablation, it was found that sevoflurane partially modified the properties of the accessory pathway but did not prevent ablation.^[27] Caldwell et al. noted significant prolongation of APERP under general anesthesia with sevoflurane and cautioned regarding its use in patients with WPW syndrome and coexisting mitochondrial myopathy.^[28]

RASS scores were found to be significantly different among the groups at all time points. Higher mean scores were observed in the ketamine group and lower mean scores were noted in the fentanyl and propofol groups. Similarly, higher BIS values were observed at all-time points in the ketamine group. In our study, two patients in the ketamine group demonstrated restlessness and agitation toward the end of the procedure but could be pacified with the injection of midazolam 1 mg IV. However, one of them subsequently developed apnea, and the airway was managed using basic airway maneuvers-head tilt and chin lift. Sevoflurane also demonstrates emergence delirium which is a complex of perceptual disturbances and psychomotor agitation.^[29-31] One patient in the sevoflurane group demonstrated agitation after 5 min of commencing administration. It was managed by reducing the inspired concentration of the inhalational agent for some time. These episodes may have contributed to dissatisfaction with the use of these drugs.

CONCLUSION

In doses used to provide conscious sedation, fentanyl provided ideal conditions, and midazolam, propofol, sevoflurane, and ketamine provided satisfactory conditions for conducting EP study and catheter ablation for supraventricular tachyarrhythmias. The potential of propofol to impede cardiac conduction needs to be explored further.