- Email: [email protected]
Effects of enflurane on inducibility of ventricular tachycardia
Effects of Enflurane on lnducibility Ventricular Tachycardia
of
Christine Hief, MD, Martin Borggrefe, MD, Xu Chen, MD, Antonio Martinez-Rubio, MD, Thomas Hachenberg, MD, Peter Lawin, MD, and Gilnter Breithardt, MD
The effects of enflurane on cardiac electrophysiologic parameters and on inducibility of ventriwlar tachycardia (VT) by programmed stimulation were studied in 12 patients (11 men, 1 woman, mean age f standard deviation 55 f 8 years) with drug refractory sustained monomorphic VT who underwent transcatheter ablation with highenergy direct-current shocks. One catheter ablation procedure was performed in 10 patients, whereas 2 ablation sessions were necessary in 2 patients. Programmed ventricular stimulation was performed on 2 separate days (mean interval 19). There were 2 baseline studies, 1 several days before (“baseline study I”) and the second at the beginning of the ablation procedure (“baseline study II”) while the patient was awake and nonsedated. The third programmed stlmulation study was done 15 to 30 minutes after administration of anesthesia with enflurane, oxygen and nitrous oxide (“enflurane study”). Rate of sinus rhythm, QRS duration, PQ interval and ventricular effective refractory period were unaltered, whereas QTc interval increased significantly after initiation of anesthesia. Before and after induction of general anesthesla, clinical VT was inducible in all patients. However, in 1 patient, induction of VT was only possible by pacing in the left ventricle after enflurane administration. Based on these data, it is concluded that general anesthesia with enflurane, oxygen and nitrous oxide has no marked influence on inducibility of clinical VTs. Therefore, this type of anesthesia may be useful for nonpharmacologic, ablative procedures requiring general anesthesia. (Am J Cardiol 1991;6&60%613)
From the Department of Cardiology and Angiology, and the Department of Anesthesiology,Hospital of the Westfilische Wilhelms-University of Miinster, Miinster, Germany. Manuscript receivedOctober 24, 1990;revisedmanuscript receivedand acceptedApril 29, 1991. Address for reprints: Martin Borggrefe, MD, Westf$lischeWilhelms-Universitlt, Medizinische Klinik und Poliklinik, Innere Medizin C, Albert-Schweitzer-Strasse33, D-4400 Miinster, Germany.
any anestheticagentshave effectson cardiac electrophysiologic parameters owing to either direct action on the myocardium or to their indirect influence on the sympathetic nervous system, which is of critical importance in the regulation of heart rate, myocardial function and peripheral vascular resistance.These effects do not play a role in clinical electrophysiologicstudies of awake and nonsedatedpatients.l-4 However, intraoperative mapping of supraventricular and ventricular tachycardias (VTs) is performed under general anesthesia. Studies in patients undergoing surgical treatment of recurrent sustained VT or ventricular fibrillation, or both, have shown that, in addition to other factors, general anesthesia may decreasethe inducibility of ventricular tachyarrhythmias.5-12Recent experimental studies have investigated the inducibility of VT after administration of anesthetic drugs.13-18However, there are no systematic studies available on humans. Therefore, we evaluated the effects of general anesthesiawith enflurane, oxygen and nitrous oxide using high-energy direct-current shocksin 12 patients with recurrent monomorphic sustained VT undergoing catheter ablation procedures.
M
METHODS In 12 patients (Table I) (11 men and 1 woman, mean age f standard deviation 55 f 8 years, range 48 to 71) with recurrent monomorphic sustained VT, a total of 14 catheter ablation procedureswere performed (1 procedurein 10 patients, 2 proceduresin 2 patients). Nine patients had coronary artery diseasewith a history of previous myocardial infarction; 6 of thesehad had an inferior wall infarction and 3 had had an anterior wall infarction. Of the remaining 3 patients, 1 had arrhythmogenic right ventricular disease, 1 presented with dilated cardiomyopathy and 1 had aortic valvular heart disease.The mean ejection fraction in patients with coronary artery diseaseand dilated cardiomyopathy was 36 f 9%. Two patients with coronary artery diseasehad undergone previous cardiac surgery and 1 of these had failed to respondto map-guided antitachycardia surgery. All patients had a history of recurrent sustained monomorphic VT refractory to class I or III antiarrhythmic drugs. In all 12 patients, at least several episodesof sustained VT had been recorded by 12-lead INDUCIBILITY OF VENTRICULAR TACHYCARDIA
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TABLE I Clinical Characteristics of 12 Patients with DrugResistant Ventricular Tachycardia Who Underwent DirectCurrent Catheter Ablation Pt. No. 1
2 3 4 5 6 7 8 9 10 11 12
Age (yr) & Sex
Diagnosis
EF (%)
Arrhythmia
60M 55 M 67 M 50 M 62 M 46 M 71 M 52 M 48M 48 F 54 M 49 M
CAD VHD CAD CAD CAD DC CAD CAD ARVD CAD CAD CAD
35 65 35 36 65 37 33 64 22 36 28
IncessantVT CRVT CRVT CRVT Incessant VT CRVT CRVT CRVT CRVT CRVT CRVT CRVT
ARVD = arrhythmogenic right ventricular disease; CAD = coronary artery disease: CRVT = chronic recurrent VT; DC = dilated cardiomyopathy: EF = ejection fraction; VHD = valvular heart disease; VT = ventricular tachycardia. 1
,
electrocardiogram on which the diagnosis of “clinical VT” was based.The median number of episodesof sustained VT before catheter ablation was 10 (range 1 to 40). Eight patients had 1 VT morphology, 2 patients had 2, 1 patient had 5 and 1 patient had 6. Previous antiarrhythmic drug therapy was unsuccessfulin all patients. Seven patients (58%) had unsuccessful longterm therapy involving amiodarone alone or in combination with class I antiarrhythmic agents. At the time of catheter ablation, 4 patients had no antiarrhythmic therapy, whereas the remaining 8 patients were receiving drug therapy. Sevenpatients were treated with amiodarone, 2 with classI antiarrhythmic drugs and 1 with sotalol. These drugs were administered to further slow VT to allow a detailed mapping or, in the caseof amiodarone, becauseof its long elimination half-life. Programmed ventricular stimulation was performed at the right ventricular apex using bipolar electrode catheters.’ Single and double premature stimuli were applied during sinus rhythm and during pacedventricular drives at cycle lengths of 500, 430, 370 and 330 ms until sustained VT was induced. If VT was not inducible with this protocol, triple premature stimuli were used at a basic drive of 500 ms. All patients had inducible VT at the right ventricular apex. Stimulation at the right ventricular outflow tract was not part of the protocol. The end point of stimulation was either the induction of sustainedVT or the completion of the entire pacing protocol. Endocardial catheter mapping was performed after intravenous administration of heparin. Quadripolar electrode catheters were used (USC1 6Fr or USC1 Josephson).A bipolar electrode catheter was placed in the right ventricular apex (Cordis 5Fr). The techniques of catheter mapping and catheter ablations have been describedpreviously.r8 During the first step of the mapping procedure, electrograms during induced VT were 610
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 68
recorded at multiple sites at the left or, when indicated, the right ventricle using biplane fluoroscopy. Then, a more detailed mapping was performed at an area that was identified as showing the earliest presystolic activation. Induction and maintenance of anesthesiawere performed according to a well-established protocol. After administration of thiopental (3 to 5 mg/kg) or etomidate (0.15 to 0.3 mg/kg), the patients were relaxed and intubated. Anesthesiawas maintained with enflurane at an end-expired concentration of 0.5 to 1.0 minimum alveolar anesthetic concentration in an oxygen (30%)nitrous oxide (70%) mixture. Patients were ventilated at a rate of 10 to 16 ventilations per minute, with a tidal volume of 12 to 15 ml/kg. Respiration was controlled to maintain partial pressure of carbon dioxide and pH within normal limits. Arterial blood pressure was continuously monitored. Sustained VT was defined as monomorphic VT lasting >30 secondsor requiring termination before this time because of hemodynamic compromise. Clinical VT was defined as VT identical in morphology to documented spontaneousVT. Differences in heart rate f20 beats/min were accepted as still representing clinical VT if no differencesin morphology occurred. Inducibility of VT was considered to be unchanged if VT was initiated at the same basic drive cycle length as that during the control study. Inducibility was consideredto be changed if VT was elicited at a basic drive different from the control rate. Differences in the mode of induction were classified as “one step more difficult” for VT induced at a rate 20 beats/min higher than the control rate and as “one step easier” for VT induced at a rate 20 beats/min lower than the control rate. Programmed ventricular stimulation was performed on 2 separate days with a mean interval of 19 days (range 2 to 62) between studies. Thus, there were 2 baseline studies; the first while the patient was awake and nonsedatedseveraldays before the ablation procedure (“baseline study I”) and the secondat the beginning of the ablation procedure (“baseline study II”). Fifteen to 30 minutes after initiation of general anesthesia, the third programmed stimulation study (“enflurane study”) was performed before the first shock was delivered. The same stimulation protocol was used for each of the 3 studies. In patients in whom a second ablation procedure was attempted, the results of baseline study I were compared with baseline study II and the enflurane study. The following parameterswere analyzed:electrocardiographic data (PQ interval, QRS duration, QTc interval and cycle length of sinus rhythm); mode of VT induction; morphology; cycle length; and mode of termination of VT. All measurementswere obtained be-
SEPTEMBER 1, 1991
fore the beginning of programmed ventricular stimulation in awake, nonsedatedpatients or 15 to 30 minutes after induction of general anesthesia,or both. Statistical analysis: Data were compared with Student’s paired t test. A p value <0.0.5 was considered significant. All data are expressedas mean f standard deviation. RESULTS The inducibility of VT was unchanged in 11 of 12 (92%) patients and was one step more difficult in 1 (Figure 1). Baseline study I was not performed in 2 patients with incessant VT. VT was elicited with the same number of premature stimuli in 8 patients. In the remaining 4 patients, the number of extrastimuli required for induction of arrhythmia changed; the basic drive cycle length was the same in 3, but changed in 1 from 500 to 430 ms (Figure 2). During the 2 baseline studies, the cycle length of induced VT (376 f 61 to 367 f 72 ms, p = not significant [NS]) and the effective refractory period of the right ventricular apex at a paced cycle length of 500 ms were not different (254 f 26 to 255 f 19, p = NS). The morphologies of VT were identical in 10 patients but different in 2. These 2 patients had several different clinical VT morphologies. During baseline study I, VT was terminated by rapid ventricular pacing in 11 patients and by direct-current shock in 1, whereasno VT required termination by external cardioversion during baseline study II. During general anesthesia,VT was inducible in 13 of 14 studies (93%) by programmed ventricular stimulation at the right ventricle. In 1 study, the induction of VT was only possible by pacing the left ventricle. The mode of induction of VT was unchanged in 12 of 13 studies (92%) (Figure 1). In the remaining study, VT
TABLE II Electrophysiologic Findings Before (baseline study II) and During (enflurane study) General Anesthesia
QRS(ms) PQ (ms) QTc (ms) SR (beatsimin) ERP-V(ms) VT-CL (ms)
Baseline Study II
Enflurane Study
113 f 21 188k20 456 * 51 80 + 18 255 +- 19 367 f 72
113 189 482 83 269 389
zk 22 f 20 + 57 zt 22 2 34 + 67
NS NS p co.05
NS NS NS
ERP-V = effective refractory period of right ventricle: NS = not significant; sinus rhythm: VT-CL = cycle length of ventricular tachycardia.
SR =
was induced by 2 premature stimuli during sinus rhythm in baseline study II, but after general anesthesia; the same VT was reproduced by pacing at 500 ms and application of 1 premature stimulus. The number of extrastimuli necessaryto induce VT was identical in 10 of 13 (77%) studies (Figure 2). In 3 studies,VT was induced by 2 premature stimuli during baselinestudy II and by only 1 premature stimulus after induction of general anesthesia.The basic drive cycle length to induce VT was the samein 2 patients and changed in 1. The morphologies of VT were similar during 12 ablation procedures and different in 2 patients having 5 and 6 morphologiesof clinical tachycardia, respectively, before catheter ablation. The cycle length of VT was longer after induction of anesthesia, but this difference was not statistically significant (367 f 72 and 389 f 67 ms, p = NS). Rapid ventricular pacing terminated VT in 11 patients before and in 10 after induction of anesthesia,whereasin the remaining 2 patients VT terminated spontaneously after 30 seconds(during anesthesia).There were no cardioversions necessaryto terminate VT during baseline study II, but after general anesthesia,VT had to be terminated with external direct-current shock in 2 patients because of hemodynamic compromise.
430 ms
L Baseline-study
I
Baseline-study
II
Enflurane-study
FIGURE 1. Induction mods of ventricular tachycardia by programmed v-c&r stimulation during 2 conscious studies (Baseline-study I and Baseline-study II) and during general anesthesla (Enfturane-study) dependent on paced basic drive cytie lengths. SR = sinus rhythm.
I Baseline-study
I
Baseline-study
II
Enflurone-study
FIGURE 2. Induction mode of vantricular tachycardii by programmed ventkular siimulatian during two conscious studies Paseline-study I and Baseline-study II) and during general anesthesia (Enfturane-study) aepemlent on number of premature stimuli. S = stimulus. INDUCIBILITY OF VENTRICULAR TACHYCARDIA
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Effects on electrophysiologic
parameters
(Table II):
The effects of general anesthesiawere assessedby comparing measurementsduring baseline study II and the enflurane study. The rate of sinus rhythm, PQ interval and QRS duration were not changed. QTc interval increased significantly from 456 f 51 to 482 f 57 ms (p
15916
this study, there was no prolongation in atrioventricular conduction during anesthesiausing enflurane in an endexpired concentration of 0.5 to 1.0 minimum alveolar anestheticconcentration. However, this doesnot reflect the refractory period of the atrioventricular node, but suggeststhat enflurane may also be used during catheter ablation of supraventricular tachycardia with directcurrent high-energy shocks. Halothane slows intramyocardial conduction.2 Therefore, inhalational narcotic drugs would be expected to change the modality of VT induction and to increase VT-cycle lengths. Halothane has also been shown to suppress induction of tachyarrhythmias by programmed stimulation in experimental studies.14J7J8 VT was inducible in only 5014and 65%18of dogs. In this study, anesthesiacaused no marked change in inducibility of VT. VT was inducible by programmed stimulation at the right ventricle in 13 of 14 (93%) ablation proceduresand in 1 patient by pacing in the left ventricle. Denniss et al’s stated that their inability to induce ventricular tachyarrhythmias with halothane was due to an increasein the ventricular effective refractory period, which prevented the use of short extrastimulus coupling intervals. There was no significant increase in the effective refractory period after induction of anesthesia. Nevertheless,we did not need a shorter extrastimulus coupling interval to induce VT during anesthesia. There was also no marked difference in the mode of VT induction. The basic drive rhythm was unchanged in 92% of studies and the number of extrastimuli was unchanged in 77%. In contrast to experimental studiesin chronically instrumented dogs narcotized with halothane,14the rate of induced VT did not change significantly as a consequence of anesthesia. This may reflect an unaltered ventricular conduction time. There were no changesin morphology of induced VT in 10 of 12 (83%) patients, whereasthe 2 remaining patients had 5 and 6 clinical morphologies of VT, respectively. Ventricular fibrillation was not induced in any patient. Basedon thesedata, we conclude that general anesthesia with enflurane, oxygen and nitrous oxide has no marked influence on inducibility of clinical VT. Therefore, this anestheticdrug regimen can be used especially during map-guided antitachycardia surgery and transcatheter ablation procedures,where inducibility of VT is a prerequisite.
Previous studies have reported that VT remains inducible in 80 to 90% of patients during map-guided surgery. As well as other factors, anesthesiamay influence the inducibility of VT. Bitar et all3 reported on 2 patients with life-threatening VT unresponsiveto antiarrhythmic therapy who were successfullytreated with general anesthesia using intravenous lorazepam and morphine sulfate. Hunt and Rossi compared the effects of 3 anesthetic agents on induction of VT in infarcted dogs. Halothane and pentobarbital suppressed the inducibility of VT in 40 to 50% of the dogs. In contrast, a neuroleptic combination of fentanyl-droperido1 plus nitrous oxide caused no significant change in the inducibility or character of VT. There are no detailed studies on the inducibility of VT during inhalational anesthesiain humans. Nevertheless, experimental studies have shown that the inducibility of atria1 tachycardia and VT decreasedwith programmed stimulation in dogs narcotized with halothane,14J7*18 In this study, the effects of general anesthesia, using enflurane, oxygen and nitrous oxide, on cardiac electrophysiologic parameters and on inducibility of VT were studied. Using enflurane, an inhalational anestheticdrug that has a negative effect on myocardial contractility, depresses peripheral vascular resistance,but doesnot sensitizethe myocardium to catecholamines in contrast with halothane. Except for QT interval, the electrophysiologic parameters did not differ after anesthesia.However, QTc increased significantly when evaluated before and during anesthesia,as previously reported.21 REFERENCES Halothane and enflurane cause similar dose-depen- 1. Atlee JL, Brownlee SW, Burstrom RE. Conscious state comparison of inhalational anesthetics on specialized atrioventricular conduction times in dogs. Anesdent prolongations of atrioventricular nodal conduction thesiology 1986;64:703-710. time and refractoriness in anesthetized dogs.1,14,20 In 2. Turner LA, Zuperku EJ, Purtock RV, Kampine JP. In viva changes in canine 612
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ventricular cardiac conduction during halothane anesthesia. An&h Analg 1980;59:327-334. 3. Morrow DH, Haley JV, Logic JR. Anesthesiaand digitalis. VII. The effect of pentobarbital,halothaneand methoxyflurane on the AV conductionand inotropic responsesto ouabain. Anesth Analog 197251:430-438. 4. DeSilva RA, Verrier RL, Lown B. The effects of psychologicalstressandvagal stimulation with morphine on vulnerability to ventricular fibrillation in the consciousdog. Am Heart J 1978;95:197-203. 5. Moran JM, Kehoe RF, Leob JM, Lichtenthal PR, SandersJH, Michaelis LL. Extendedendocardial resectionfor the treatment of ventricular tachycardia and ventricular fibrillation. Ann Thorac Surg 1982;34:538-550. 6. Kron IL, Lerman BB, DiMarco JP. Extended subendocardialresection. A surgical approachto ventricular tachyarrhythmias that cannot be mappedintraoperatively. J Thorac Cardiovasc Surg 1985;90:586-591. 7. Miller J, Kienzle M, Harken A, JosephsonM. Subendocardialresectionfor ventricular tachycardia: predictors of surgical success.Circulation 1984;70: 624-631. 8. Guiraudon G, Fontaine G, Frank R, Cabral C, GrosgozentY. Apport de la ventriculomie circulaere d’exclusion:dansle traitment de la tachycardieventriculake recidivante apres infarctus du myocarde. Arch Ma/ Coeur 198275: 1013-1020. 9. Moran J, Kehoe R, Loeb J, FredricksonJ, Zheutlin T, SandersJ, Michaelis L. The role of papillary muscleresectionand mitral valve replacementin the control of refractory ventricular arrhythmia. Circulation 1983;68:11-154. LO. Horowitz LN, Harken AH, Kastor JA, JosephsonME. Ventricular resection guided by epicardial or endocardialmappingfor treatment of recurrent ventricular tachycardia. N Engl J Med 1980;302:589-593. 11. Mason JW, Stinson EB, Winkle RA, Griftin JC, Oyer PE, RossDL, Derby G. Surgery for ventricular tachycardia: efficacy of left ventricular aneurysm
resectioncomparedwith operation guided by electrical activation mapping.Circulation 1982;65:1148-1155.
12. Krafcheck J, Lawrie GM, Margo SA, Pa C, Wyndham CRC. Surgical ablation of ventricular tachycardia:improvedresultswith a map-directedregional approach. Circulation 1986;73:1239-1247. 13. Bitar J, Lakier J, Goldstein S. General anesthesiafor intractable ventricular tachycardia. Am J Cnrdiol 1989;62:1318. 14. Hunt GH, Ross DL. Comparison of effects of three anesthetic agents on induction of ventricular tachycardia in a canine model of myocardial infarction. Circularion 1988;78:221-226. 15. Katz RL, Bigger JT. Cardiac arrhythmias during anesthesiaand operation, Anesthesiology 1970;33:193-213. 16. Rcdrigo MRC, Moles TM, Lee PK. Comparisonof the incidenceand nature of cardiac arrhythmias occurring during isofluraneor halothaneanesthesia.Studies during dental surgery. Br J Anaesth 1986;58:394-400. 17. Hart AP, Royster RL, JohnstonWE, Howard G. Halothane suppressesatria1 dysrhythmiasinducedby programmedstimulation in dogs(abstr). Anesthesiology 1986;65:A31. 18. DennissAR, Richards DA, Taylor AT, Uther JB. Antiarrhythmic effect of halothane anesthesiain the dog (abstr). Circulation 1986;74(supplII):ll-254. 19. Borggrefe M, Breithardt G, PodczeckA, Rohner D, Budde T, MartinezRubio A. Catheter ablation of ventricular tachycardia using defibrillator pulses: electrophysiologicalfinding and long-term results. Ear Heart J 1989;10:1-11. 20. Atlee JL, Rusy BF. Atrioventricular conduction times and atrioventricular nodal conductivity during enflurane anesthesiain dogs.Anesthesiology 1977;47: 498-503. 21. Riley DC, SchmelingWT, Al-Wathiqui MH, Kampine JP, Warmer DC. Prolongationof the QT interval by volatile anaestheticsin chronically instrumented dog. Anesth Analog 1988;67:741-749.
INDUCIBILITY OF VENTRICULAR TACHYCARDIA
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of
Christine Hief, MD, Martin Borggrefe, MD, Xu Chen, MD, Antonio Martinez-Rubio, MD, Thomas Hachenberg, MD, Peter Lawin, MD, and Gilnter Breithardt, MD
The effects of enflurane on cardiac electrophysiologic parameters and on inducibility of ventriwlar tachycardia (VT) by programmed stimulation were studied in 12 patients (11 men, 1 woman, mean age f standard deviation 55 f 8 years) with drug refractory sustained monomorphic VT who underwent transcatheter ablation with highenergy direct-current shocks. One catheter ablation procedure was performed in 10 patients, whereas 2 ablation sessions were necessary in 2 patients. Programmed ventricular stimulation was performed on 2 separate days (mean interval 19). There were 2 baseline studies, 1 several days before (“baseline study I”) and the second at the beginning of the ablation procedure (“baseline study II”) while the patient was awake and nonsedated. The third programmed stlmulation study was done 15 to 30 minutes after administration of anesthesia with enflurane, oxygen and nitrous oxide (“enflurane study”). Rate of sinus rhythm, QRS duration, PQ interval and ventricular effective refractory period were unaltered, whereas QTc interval increased significantly after initiation of anesthesia. Before and after induction of general anesthesla, clinical VT was inducible in all patients. However, in 1 patient, induction of VT was only possible by pacing in the left ventricle after enflurane administration. Based on these data, it is concluded that general anesthesia with enflurane, oxygen and nitrous oxide has no marked influence on inducibility of clinical VTs. Therefore, this type of anesthesia may be useful for nonpharmacologic, ablative procedures requiring general anesthesia. (Am J Cardiol 1991;6&60%613)
From the Department of Cardiology and Angiology, and the Department of Anesthesiology,Hospital of the Westfilische Wilhelms-University of Miinster, Miinster, Germany. Manuscript receivedOctober 24, 1990;revisedmanuscript receivedand acceptedApril 29, 1991. Address for reprints: Martin Borggrefe, MD, Westf$lischeWilhelms-Universitlt, Medizinische Klinik und Poliklinik, Innere Medizin C, Albert-Schweitzer-Strasse33, D-4400 Miinster, Germany.
any anestheticagentshave effectson cardiac electrophysiologic parameters owing to either direct action on the myocardium or to their indirect influence on the sympathetic nervous system, which is of critical importance in the regulation of heart rate, myocardial function and peripheral vascular resistance.These effects do not play a role in clinical electrophysiologicstudies of awake and nonsedatedpatients.l-4 However, intraoperative mapping of supraventricular and ventricular tachycardias (VTs) is performed under general anesthesia. Studies in patients undergoing surgical treatment of recurrent sustained VT or ventricular fibrillation, or both, have shown that, in addition to other factors, general anesthesia may decreasethe inducibility of ventricular tachyarrhythmias.5-12Recent experimental studies have investigated the inducibility of VT after administration of anesthetic drugs.13-18However, there are no systematic studies available on humans. Therefore, we evaluated the effects of general anesthesiawith enflurane, oxygen and nitrous oxide using high-energy direct-current shocksin 12 patients with recurrent monomorphic sustained VT undergoing catheter ablation procedures.
M
METHODS In 12 patients (Table I) (11 men and 1 woman, mean age f standard deviation 55 f 8 years, range 48 to 71) with recurrent monomorphic sustained VT, a total of 14 catheter ablation procedureswere performed (1 procedurein 10 patients, 2 proceduresin 2 patients). Nine patients had coronary artery diseasewith a history of previous myocardial infarction; 6 of thesehad had an inferior wall infarction and 3 had had an anterior wall infarction. Of the remaining 3 patients, 1 had arrhythmogenic right ventricular disease, 1 presented with dilated cardiomyopathy and 1 had aortic valvular heart disease.The mean ejection fraction in patients with coronary artery diseaseand dilated cardiomyopathy was 36 f 9%. Two patients with coronary artery diseasehad undergone previous cardiac surgery and 1 of these had failed to respondto map-guided antitachycardia surgery. All patients had a history of recurrent sustained monomorphic VT refractory to class I or III antiarrhythmic drugs. In all 12 patients, at least several episodesof sustained VT had been recorded by 12-lead INDUCIBILITY OF VENTRICULAR TACHYCARDIA
609
TABLE I Clinical Characteristics of 12 Patients with DrugResistant Ventricular Tachycardia Who Underwent DirectCurrent Catheter Ablation Pt. No. 1
2 3 4 5 6 7 8 9 10 11 12
Age (yr) & Sex
Diagnosis
EF (%)
Arrhythmia
60M 55 M 67 M 50 M 62 M 46 M 71 M 52 M 48M 48 F 54 M 49 M
CAD VHD CAD CAD CAD DC CAD CAD ARVD CAD CAD CAD
35 65 35 36 65 37 33 64 22 36 28
IncessantVT CRVT CRVT CRVT Incessant VT CRVT CRVT CRVT CRVT CRVT CRVT CRVT
ARVD = arrhythmogenic right ventricular disease; CAD = coronary artery disease: CRVT = chronic recurrent VT; DC = dilated cardiomyopathy: EF = ejection fraction; VHD = valvular heart disease; VT = ventricular tachycardia. 1
,
electrocardiogram on which the diagnosis of “clinical VT” was based.The median number of episodesof sustained VT before catheter ablation was 10 (range 1 to 40). Eight patients had 1 VT morphology, 2 patients had 2, 1 patient had 5 and 1 patient had 6. Previous antiarrhythmic drug therapy was unsuccessfulin all patients. Seven patients (58%) had unsuccessful longterm therapy involving amiodarone alone or in combination with class I antiarrhythmic agents. At the time of catheter ablation, 4 patients had no antiarrhythmic therapy, whereas the remaining 8 patients were receiving drug therapy. Sevenpatients were treated with amiodarone, 2 with classI antiarrhythmic drugs and 1 with sotalol. These drugs were administered to further slow VT to allow a detailed mapping or, in the caseof amiodarone, becauseof its long elimination half-life. Programmed ventricular stimulation was performed at the right ventricular apex using bipolar electrode catheters.’ Single and double premature stimuli were applied during sinus rhythm and during pacedventricular drives at cycle lengths of 500, 430, 370 and 330 ms until sustained VT was induced. If VT was not inducible with this protocol, triple premature stimuli were used at a basic drive of 500 ms. All patients had inducible VT at the right ventricular apex. Stimulation at the right ventricular outflow tract was not part of the protocol. The end point of stimulation was either the induction of sustainedVT or the completion of the entire pacing protocol. Endocardial catheter mapping was performed after intravenous administration of heparin. Quadripolar electrode catheters were used (USC1 6Fr or USC1 Josephson).A bipolar electrode catheter was placed in the right ventricular apex (Cordis 5Fr). The techniques of catheter mapping and catheter ablations have been describedpreviously.r8 During the first step of the mapping procedure, electrograms during induced VT were 610
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 68
recorded at multiple sites at the left or, when indicated, the right ventricle using biplane fluoroscopy. Then, a more detailed mapping was performed at an area that was identified as showing the earliest presystolic activation. Induction and maintenance of anesthesiawere performed according to a well-established protocol. After administration of thiopental (3 to 5 mg/kg) or etomidate (0.15 to 0.3 mg/kg), the patients were relaxed and intubated. Anesthesiawas maintained with enflurane at an end-expired concentration of 0.5 to 1.0 minimum alveolar anesthetic concentration in an oxygen (30%)nitrous oxide (70%) mixture. Patients were ventilated at a rate of 10 to 16 ventilations per minute, with a tidal volume of 12 to 15 ml/kg. Respiration was controlled to maintain partial pressure of carbon dioxide and pH within normal limits. Arterial blood pressure was continuously monitored. Sustained VT was defined as monomorphic VT lasting >30 secondsor requiring termination before this time because of hemodynamic compromise. Clinical VT was defined as VT identical in morphology to documented spontaneousVT. Differences in heart rate f20 beats/min were accepted as still representing clinical VT if no differencesin morphology occurred. Inducibility of VT was considered to be unchanged if VT was initiated at the same basic drive cycle length as that during the control study. Inducibility was consideredto be changed if VT was elicited at a basic drive different from the control rate. Differences in the mode of induction were classified as “one step more difficult” for VT induced at a rate 20 beats/min higher than the control rate and as “one step easier” for VT induced at a rate 20 beats/min lower than the control rate. Programmed ventricular stimulation was performed on 2 separate days with a mean interval of 19 days (range 2 to 62) between studies. Thus, there were 2 baseline studies; the first while the patient was awake and nonsedatedseveraldays before the ablation procedure (“baseline study I”) and the secondat the beginning of the ablation procedure (“baseline study II”). Fifteen to 30 minutes after initiation of general anesthesia, the third programmed stimulation study (“enflurane study”) was performed before the first shock was delivered. The same stimulation protocol was used for each of the 3 studies. In patients in whom a second ablation procedure was attempted, the results of baseline study I were compared with baseline study II and the enflurane study. The following parameterswere analyzed:electrocardiographic data (PQ interval, QRS duration, QTc interval and cycle length of sinus rhythm); mode of VT induction; morphology; cycle length; and mode of termination of VT. All measurementswere obtained be-
SEPTEMBER 1, 1991
fore the beginning of programmed ventricular stimulation in awake, nonsedatedpatients or 15 to 30 minutes after induction of general anesthesia,or both. Statistical analysis: Data were compared with Student’s paired t test. A p value <0.0.5 was considered significant. All data are expressedas mean f standard deviation. RESULTS The inducibility of VT was unchanged in 11 of 12 (92%) patients and was one step more difficult in 1 (Figure 1). Baseline study I was not performed in 2 patients with incessant VT. VT was elicited with the same number of premature stimuli in 8 patients. In the remaining 4 patients, the number of extrastimuli required for induction of arrhythmia changed; the basic drive cycle length was the same in 3, but changed in 1 from 500 to 430 ms (Figure 2). During the 2 baseline studies, the cycle length of induced VT (376 f 61 to 367 f 72 ms, p = not significant [NS]) and the effective refractory period of the right ventricular apex at a paced cycle length of 500 ms were not different (254 f 26 to 255 f 19, p = NS). The morphologies of VT were identical in 10 patients but different in 2. These 2 patients had several different clinical VT morphologies. During baseline study I, VT was terminated by rapid ventricular pacing in 11 patients and by direct-current shock in 1, whereasno VT required termination by external cardioversion during baseline study II. During general anesthesia,VT was inducible in 13 of 14 studies (93%) by programmed ventricular stimulation at the right ventricle. In 1 study, the induction of VT was only possible by pacing the left ventricle. The mode of induction of VT was unchanged in 12 of 13 studies (92%) (Figure 1). In the remaining study, VT
TABLE II Electrophysiologic Findings Before (baseline study II) and During (enflurane study) General Anesthesia
QRS(ms) PQ (ms) QTc (ms) SR (beatsimin) ERP-V(ms) VT-CL (ms)
Baseline Study II
Enflurane Study
113 f 21 188k20 456 * 51 80 + 18 255 +- 19 367 f 72
113 189 482 83 269 389
zk 22 f 20 + 57 zt 22 2 34 + 67
NS NS p co.05
NS NS NS
ERP-V = effective refractory period of right ventricle: NS = not significant; sinus rhythm: VT-CL = cycle length of ventricular tachycardia.
SR =
was induced by 2 premature stimuli during sinus rhythm in baseline study II, but after general anesthesia; the same VT was reproduced by pacing at 500 ms and application of 1 premature stimulus. The number of extrastimuli necessaryto induce VT was identical in 10 of 13 (77%) studies (Figure 2). In 3 studies,VT was induced by 2 premature stimuli during baselinestudy II and by only 1 premature stimulus after induction of general anesthesia.The basic drive cycle length to induce VT was the samein 2 patients and changed in 1. The morphologies of VT were similar during 12 ablation procedures and different in 2 patients having 5 and 6 morphologiesof clinical tachycardia, respectively, before catheter ablation. The cycle length of VT was longer after induction of anesthesia, but this difference was not statistically significant (367 f 72 and 389 f 67 ms, p = NS). Rapid ventricular pacing terminated VT in 11 patients before and in 10 after induction of anesthesia,whereasin the remaining 2 patients VT terminated spontaneously after 30 seconds(during anesthesia).There were no cardioversions necessaryto terminate VT during baseline study II, but after general anesthesia,VT had to be terminated with external direct-current shock in 2 patients because of hemodynamic compromise.
430 ms
L Baseline-study
I
Baseline-study
II
Enflurane-study
FIGURE 1. Induction mods of ventricular tachycardia by programmed v-c&r stimulation during 2 conscious studies (Baseline-study I and Baseline-study II) and during general anesthesla (Enfturane-study) dependent on paced basic drive cytie lengths. SR = sinus rhythm.
I Baseline-study
I
Baseline-study
II
Enflurone-study
FIGURE 2. Induction mode of vantricular tachycardii by programmed ventkular siimulatian during two conscious studies Paseline-study I and Baseline-study II) and during general anesthesia (Enfturane-study) aepemlent on number of premature stimuli. S = stimulus. INDUCIBILITY OF VENTRICULAR TACHYCARDIA
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Effects on electrophysiologic
parameters
(Table II):
The effects of general anesthesiawere assessedby comparing measurementsduring baseline study II and the enflurane study. The rate of sinus rhythm, PQ interval and QRS duration were not changed. QTc interval increased significantly from 456 f 51 to 482 f 57 ms (p
15916
this study, there was no prolongation in atrioventricular conduction during anesthesiausing enflurane in an endexpired concentration of 0.5 to 1.0 minimum alveolar anestheticconcentration. However, this doesnot reflect the refractory period of the atrioventricular node, but suggeststhat enflurane may also be used during catheter ablation of supraventricular tachycardia with directcurrent high-energy shocks. Halothane slows intramyocardial conduction.2 Therefore, inhalational narcotic drugs would be expected to change the modality of VT induction and to increase VT-cycle lengths. Halothane has also been shown to suppress induction of tachyarrhythmias by programmed stimulation in experimental studies.14J7J8 VT was inducible in only 5014and 65%18of dogs. In this study, anesthesiacaused no marked change in inducibility of VT. VT was inducible by programmed stimulation at the right ventricle in 13 of 14 (93%) ablation proceduresand in 1 patient by pacing in the left ventricle. Denniss et al’s stated that their inability to induce ventricular tachyarrhythmias with halothane was due to an increasein the ventricular effective refractory period, which prevented the use of short extrastimulus coupling intervals. There was no significant increase in the effective refractory period after induction of anesthesia. Nevertheless,we did not need a shorter extrastimulus coupling interval to induce VT during anesthesia. There was also no marked difference in the mode of VT induction. The basic drive rhythm was unchanged in 92% of studies and the number of extrastimuli was unchanged in 77%. In contrast to experimental studiesin chronically instrumented dogs narcotized with halothane,14the rate of induced VT did not change significantly as a consequence of anesthesia. This may reflect an unaltered ventricular conduction time. There were no changesin morphology of induced VT in 10 of 12 (83%) patients, whereasthe 2 remaining patients had 5 and 6 clinical morphologies of VT, respectively. Ventricular fibrillation was not induced in any patient. Basedon thesedata, we conclude that general anesthesia with enflurane, oxygen and nitrous oxide has no marked influence on inducibility of clinical VT. Therefore, this anestheticdrug regimen can be used especially during map-guided antitachycardia surgery and transcatheter ablation procedures,where inducibility of VT is a prerequisite.
Previous studies have reported that VT remains inducible in 80 to 90% of patients during map-guided surgery. As well as other factors, anesthesiamay influence the inducibility of VT. Bitar et all3 reported on 2 patients with life-threatening VT unresponsiveto antiarrhythmic therapy who were successfullytreated with general anesthesia using intravenous lorazepam and morphine sulfate. Hunt and Rossi compared the effects of 3 anesthetic agents on induction of VT in infarcted dogs. Halothane and pentobarbital suppressed the inducibility of VT in 40 to 50% of the dogs. In contrast, a neuroleptic combination of fentanyl-droperido1 plus nitrous oxide caused no significant change in the inducibility or character of VT. There are no detailed studies on the inducibility of VT during inhalational anesthesiain humans. Nevertheless, experimental studies have shown that the inducibility of atria1 tachycardia and VT decreasedwith programmed stimulation in dogs narcotized with halothane,14J7*18 In this study, the effects of general anesthesia, using enflurane, oxygen and nitrous oxide, on cardiac electrophysiologic parameters and on inducibility of VT were studied. Using enflurane, an inhalational anestheticdrug that has a negative effect on myocardial contractility, depresses peripheral vascular resistance,but doesnot sensitizethe myocardium to catecholamines in contrast with halothane. Except for QT interval, the electrophysiologic parameters did not differ after anesthesia.However, QTc increased significantly when evaluated before and during anesthesia,as previously reported.21 REFERENCES Halothane and enflurane cause similar dose-depen- 1. Atlee JL, Brownlee SW, Burstrom RE. Conscious state comparison of inhalational anesthetics on specialized atrioventricular conduction times in dogs. Anesdent prolongations of atrioventricular nodal conduction thesiology 1986;64:703-710. time and refractoriness in anesthetized dogs.1,14,20 In 2. Turner LA, Zuperku EJ, Purtock RV, Kampine JP. In viva changes in canine 612
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12. Krafcheck J, Lawrie GM, Margo SA, Pa C, Wyndham CRC. Surgical ablation of ventricular tachycardia:improvedresultswith a map-directedregional approach. Circulation 1986;73:1239-1247. 13. Bitar J, Lakier J, Goldstein S. General anesthesiafor intractable ventricular tachycardia. Am J Cnrdiol 1989;62:1318. 14. Hunt GH, Ross DL. Comparison of effects of three anesthetic agents on induction of ventricular tachycardia in a canine model of myocardial infarction. Circularion 1988;78:221-226. 15. Katz RL, Bigger JT. Cardiac arrhythmias during anesthesiaand operation, Anesthesiology 1970;33:193-213. 16. Rcdrigo MRC, Moles TM, Lee PK. Comparisonof the incidenceand nature of cardiac arrhythmias occurring during isofluraneor halothaneanesthesia.Studies during dental surgery. Br J Anaesth 1986;58:394-400. 17. Hart AP, Royster RL, JohnstonWE, Howard G. Halothane suppressesatria1 dysrhythmiasinducedby programmedstimulation in dogs(abstr). Anesthesiology 1986;65:A31. 18. DennissAR, Richards DA, Taylor AT, Uther JB. Antiarrhythmic effect of halothane anesthesiain the dog (abstr). Circulation 1986;74(supplII):ll-254. 19. Borggrefe M, Breithardt G, PodczeckA, Rohner D, Budde T, MartinezRubio A. Catheter ablation of ventricular tachycardia using defibrillator pulses: electrophysiologicalfinding and long-term results. Ear Heart J 1989;10:1-11. 20. Atlee JL, Rusy BF. Atrioventricular conduction times and atrioventricular nodal conductivity during enflurane anesthesiain dogs.Anesthesiology 1977;47: 498-503. 21. Riley DC, SchmelingWT, Al-Wathiqui MH, Kampine JP, Warmer DC. Prolongationof the QT interval by volatile anaestheticsin chronically instrumented dog. Anesth Analog 1988;67:741-749.
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