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 

After receiving approval from our Institutional Review Board for Health Sciences Research involving Human Subjects and signed patient consent, we enrolled 15 patients with Wolff-Parkinson-White syndrome who were undergoing elective radiofrequency catheter ablation. None of the patients had histories of renal or hepatic disease. Antiarrhythmic therapy (including calcium channel blockers) were discontinued for a period greater than five half-lives of the agent before the study.

Patients were not premedicated, and a serum sample was taken for biochemical analysis. Anesthesia was induced intravenously with alfentanil (20-50 [micro sign]g/kg) and midazolam (0.15 mg/kg), and tracheal intubation was facilitated with vecuronium (20 mg). Anesthesia was maintained with an alfentanil infusion (0.5 to 2 [micro sign]g [middle dot] kg^-1[middle dot] min^-1) and midazolam (1 or 2 mg every 10-15 min, as required); this anesthetic protocol has been shown not to interfere with the electrophysiologic expression of either the normal atrioventricular conduction system or accessory pathway. [6]Positive pressure ventilation with air and oxygen was used to maintain normocapnia and an arterial oxygen saturation greater than 96%(Nellcor Capnograph/Oximeter, Hayward, CA). Other monitors included a noninvasive blood pressure cuff, a three-lead electrocardiogram, and an esophageal temperature probe.

After induction of anesthesia, a baseline electrophysiologic study was performed using transvenous endocardial electrodes. Right atrial or ventricular extrastimulus testing involved pacing at a standard drive cycle length of 400 ms, followed by an extrastimulus coupled (steps of 20 ms from 400-300 ms and steps of 10 ms less than 300 ms) to every eighth drive beat. This is our standard programmed stimulation protocol and it allows us to calculate the following parameters: right atrial refractory period, atrioventricular node effective refractory period, accessory pathway effective refractory period, and right ventricular effective refractory period. Decremental pacing of the right atrium or ventricle allowed us to determine the shortest cycle length during antegrade and retrograde conduction, which is also called the “Wenckebach cycle length,” with a 1:1 conduction over the normal atrioventricular node and accessory pathway. Sinus node function was measured by right atrial pacing (overdrive suppression) to determine the sinus node recovery time, and corrected sinus node recovery time. Sinoatrial conduction time was measured using a standard extra stimulus protocol. Baseline intervals measured during sinus rhythm included intraatrial conduction time (PA interval), and atrial-His interval. During induced reciprocating tachycardia, conduction times of each component of the reentrant circuit was measured and included cycle length and atrial-His, His-ventricular, and ventriculoatrial intervals. All electrophysiologic measurements were recorded using a standard digitizing tablet at a paper speed of 100 mm/s. A description of the parameters measured can be found elsewhere, [7]and their definitions are listed in Table 1.

After completion of the baseline study, sevoflurane was administered to achieve an end-tidal concentration of 2%(1 minimum alveolar concentration [MAC]). An end-tidal gas monitor (Datex Capnomac Ultima, Helsinki, Finland) was used to ensure the steady state administration of sevoflurane. After this concentration had been achieved, the electrophysiologic study was repeated.

Blood pressure and heart rate were recorded at 3-min intervals throughout the entire study. These variables and the end-tidal carbon dioxide level were averaged for the second electrophysiologic study during sevoflurane administration.

The electrophysiologic parameters of conduction and the physiologic parameters measured before and during sevoflurane administration were compared using the Wilcoxon ranked sum test. The results are expressed as mean values +/− SD. Fisher's exact test was used to determine any difference in the proportion of patients in whom reciprocating tachycardia could be induced before and during sevoflurane administration. P < 0.05 was considered significant.

(Table 2) shows the demographic data. Serum sodium, potassium, chloride, blood urea nitrogen, creatinine, and glucose levels were all within normal limits. Results of the preoperative electrocardiogram were abnormal in 10 patients and showed the presence of an accessory pathway. All patients had clinically relevant episodes of tachycardia.

During sevoflurane administration, the systolic and diastolic blood pressure and end-tidal carbon dioxide levels decreased significantly, but heart rate did not (Table 3); five patients require phenylephrine to treat hypotension during sevoflurane administration.

Comparison of the electrophysiologic parameters in the normal atrioventricular conduction system and accessory pathway performed before and during sevoflurane administration revealed no significant effect during antegrade or retrograde conduction (Table 4). Sustained reciprocating tachycardia could be induced in 8 of 15 patients before and in 6 of these 8 patients during sevoflurane administration, which was not statistically significant. Comparison of the parameters of sustained reciprocating tachycardia measured before and during sevoflurane administration showed no significant change (Table 5).

Comparison of the parameters of sinus node function and intraatrial conduction performed before and during sevoflurane administration showed a significant decrease in sinoatrial conduction time and in the atrial-His interval (Table 6).

All accessory pathways were identified and ablated successfully. No spontaneous tachyarrhythmias occurred during the procedure other than those induced during the electrophysiologic study.

This study showed that the administration of 1.0 MAC sevoflurane, in addition to an underlying alfentanil-midazolam-vecuronium anesthetic, has no effect on the refractoriness of the normal atrioventricular or accessory pathway and no effect on the electrophysiologic characteristics of sustained reciprocating tachycardia. Sevoflurane is therefore a reasonable agent to use when general anesthesia is required for accessory pathway ablation procedures. Furthermore, sevoflurane had no clinically important effect on sinoatrial node function or intraatrial conduction.

During ablation procedures, it is important not to administer any medication that may alter the electrophysiologic expression of the accessory pathway, which may interfere with identifying the location and subsequent successful ablation of the pathway. For example, previously we showed that the refractoriness of the accessory pathway was increased most by enflurane, less so by isoflurane, and least by halothane, and the use of these agents during ablative procedures may confound interpretation of the postablative studies that are performed to confirm that the accessory pathway has been ablated completely. [1]Our data show that 1 MAC sevoflurane in the presence of alfentanil-midazolam anesthesia has no effect on the refractoriness of the normal atrioventricular or accessory pathway during antegrade conduction or during retrograde conduction through the accessory pathway (Table 4). These results concur with animal data that showed that 1 and 2 MAC sevoflurane had no influence on the cardiac conduction system in dogs during pentobarbital anesthesia. [8]Therefore, sevoflurane and other anesthetics, such as sufentanil, [1]alfentanil-midazolam, [6]or propofol, [9]that have been shown not to interfere with the electrophysiologic expression of the accessory pathway are reasonable agents to use for ablation procedures. On the other hand, in patients who require a general anesthetic and are known to have an accessory pathway, enflurane would be the agent of choice for two reasons. First, compared with halothane and isoflurane, enflurane increases the refractoriness of the accessory pathway the most and is therefore more likely to suppress conduction within the accessory pathway. Second, isoflurane and halothane have been shown to increase the coupling interval, which theoretically may induce arrhythmias. Enflurane has no affect on the coupling interval. [1] 

Sustained reciprocating tachycardia is a useful method to identify the reentrant circuit and the site of the accessory pathway. This is done using recording electrodes positioned around the mitral or tricuspid annulus, during rapid atrial or ventricular pacing. It is therefore important that the induction of sustained reciprocating tachycardia is not affected during this process. Reciprocating tachycardia could be induced in only 8 of 15 patients, and a known tachycardia cannot be induced in all patients in the electrophysiology laboratory with the patients awake or during general or neurolept anesthesia. Many factors determine whether a tachyarrhythmia can be induced, particularly the patient's autonomic tone. The presence of anesthetic agents such as alfentanil and midazolam administered during the baseline study also may have determined whether the tachyarrhythmia could be induced. During administration of sevoflurane, reciprocating tachycardia could be induced in only six of these eight patients. In the two patients in whom the tachycardia could not be induced, we suspect that this was not related to sevoflurane administration, because we found that sevoflurane had no effect on the normal atrioventricular conduction system and accessory pathway (Table 4), the measured parameters of reciprocating tachycardia (Table 5), or intraatrial conduction (Table 6). Furthermore, the finding that reciprocating tachycardia cannot be induced in all patients at any given time is consistent with the biologic variability of the electrophysiologic expression of the accessory pathway. We found no electrophysiologic evidence to account for any change in inducibility.

Reports have been published of various heart rate responses during sevoflurane administration in humans that appear to be age related and dose specific. Sevoflurane (0.41 to 1.24 MAC) administered to healthy young volunteers and in young, healthy, unpremedicated patients (as much as 2.7 MAC) elicited no change from baseline heart rates. [10,11]However, an increase in heart rate has been observed in younger age groups. [2-4]In our study, heart rate did not change during sevoflurane administration compared with the baseline alfentanil-midazolam anesthetic (Table 3), despite the finding that sevoflurane significantly decreased blood pressure levels. We suspect that the anticipated increase in heart rate in response to the decrease in blood pressure was attenuated by the underlying alfentanil administration, in combination with sevoflurane. However, sevoflurane did augment the conduction in the atria, as shown by a decrease in the sinoatrial conduction time and atrial-His interval. Although these changes were statistically significant, they are clinically unimportant because the measured values of sinoatrial conduction time and atrial-His interval were still within the normal physiologic range; more importantly, augmented conduction within the atria is not associated with any particular disease. For example, it is not arrhythmogenic. Therefore, we conclude that sevoflurane has no clinically important effect on sinoatrial node function or intraatrial conduction.

There was a significant decrease in systolic and diastolic blood pressure during sevoflurane administration (Table 3), but these changes were clinically unimportant and did not cause any hemodynamic compromise in the patient. Five patients required boluses of phenylephrine during the electrophysiologic study because their hypotension was exacerbated by the induced, rapid cardiac pacing that was part of the electrophysiologic protocol. Phenylephrine may affect the electrophysiologic properties of the heart because of the increase in vagal tone in response to its hypertensive effect. However, in our study heart rate did not change in any patient during sevoflurane administration, indicating a vagolytic effect of the combination of alfentanil-midazolam and sevoflurane. Therefore, it is unlikely that phenylephrine had any significant effect on the measured electrophysiologic parameters. In addition, we did not think a reduction in the end-tidal carbon dioxide level from 35 to 33 mmHg would have affected our results.

This study has two limitations. First, the baseline electrophysiologic parameters were measured during an alfentanil-midazolam anesthetic, rather than while patients were conscious. This was done to reduce, if not completely ameliorate, the potential influence of the autonomic nervous system on the electrophysiologic properties of the heart elicited during the procedure. Therefore, any changes in the parameters measured during sevoflurane administration could be attributed to sevoflurane alone. Conversely, if baseline measurements were performed in the conscious state, any changes in the parameters detected during sevoflurane administration would be difficult to interpret; that is, it would be difficult to determine whether these changes were due to sevoflurane alone or to a combination of sevoflurane and the influence of autonomic tone between the conscious and anesthetized state. Furthermore, previously we documented that alfentanil-midazolam anesthesia has no effects on the electrophysiologic properties of the normal atrioventricular or accessory pathway. [6] 

Second, because of the biologic variability in the expression of the normal atrioventricular and accessory pathways, not all electrophysiologic parameters can be measured in all patients at any given time. For example, during antegrade conduction, we measured the effective refractory period and shortest cycle length of the atrioventricular node only in a few patients, because conduction through the accessory pathway obscures our ability to measure conduction and refractoriness through the atrioventricular node. As a result of the small sample size, the power of the analysis was inadequate to conclude that there was no difference in these parameters during sevoflurane administration (a type 2 error). [12]Despite the small sample size in these parameters (i.e., atrioventricular node effective refractory period, shortest cycle length of the atrioventricular node, atrial-His and His-ventricular intervals, and ventricular atrial interval), there was no considerable discrepancy in these variables measured at baseline and during sevoflurane administration that would be clinically important. Furthermore, there was a tendency for the conduction variables to be reduced, implying augmentation of conduction by sevoflurane. As previously discussed, this is not clinically important.

In conclusion, our study showed that 1 MAC sevoflurane combined with alfentanil and midazolam had no effect on the conduction properties or electrophysiologic expression of the normal atrioventricular conduction system or accessory pathway and no important clinical effects on sinoatrial node activity or intraatrial conduction. We conclude that 1 MAC sevoflurane is a suitable agent to use in patients undergoing accessory pathway ablation who require a general anesthetic.