Paradoxical acceleration of ventricular tachycardia after procaine amide therapy

Paradoxical acceleration of ventricular tachycardia after procaine amide therapy

Paradoxical ventricular acceleration tachycardia of after procaine amide therapy Leslie J. Shalan, M.D.* Lionel Walpin, M.D.** Ira L. Rubin, M.D...

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Paradoxical ventricular

acceleration tachycardia

of after

procaine

amide

therapy

Leslie J. Shalan, M.D.* Lionel Walpin, M.D.** Ira L. Rubin, M.D.*** New York, N. Y.

I

t has been over a decade since procaine amide was introduced for the treatment of cardiac arrhythmias. During this time, numerous reports have attested to its effectiveness in the termination of ectopic rhythms, particularly those of ventricular origin. Ventricular tachycardia may represent a medical emergency that requires immediate therapy directed toward abolition of the arrhythmia. As compared to quinidine, procaine amide is the drug of choice in terminating ventricular arrhythmias, since it does not depress myocardial contractility, and has fewer side effects when administered parenteral1y.l We recently treated a patient with ventricular tachycardia by the administration of intravenous procaine amide. Prior to conversion to normal sinus rhythm, there was a significant acceleration of the ventricular rate without any change in the ectopic focus or intraventricular conduction. To our knowledge, such a phenomenon has never been recorded with procaine amide. The mechanism responsible for such a phenomenon, as well as its therawill be discussed. peutic implications, From the Received *Formerlv. tion, **Formerly, ***Attending 2745

387

Case report A 60-year-old white man was well until the afternoon of Feb. 13, 1963, when he experienced the sudden onset of sharp retrosternal pain unrelated to exertion. There was no radiation of the pain. The patient denied dyspnea, diaphoresis, or palpitation. He was seen by a private physician 8 hours prior to admission and was given four (200 mg.) quinidine tablets over two 4-hour periods for a “tachycardia.” Because of persistent chest pain, he came to the emergency room 4 hours after taking the last quinidine tablet. Twelve years previously the patient had had a myocardial infarct. He had no cardiovascular symptoms since that time, except for intermittent claudication, which necessitated a bilateral lumbar sympathectomy in 1957, with considerable improvement. The patient was treated for a duodenal ulcer 1 year before admission. The remainder of the past history was not remarkable, except for an inguinal hernioplasty in 1957, and a ligation and stripping of varicose veins in 1959. He was not taking any cardiac or diuretic drugs prior to the onset of the present illness. Physical examination. He was a well-nourished, well-developed man who lay comfortably in bed. The temperature was lOl”F., the pulse was 170 per minute and regular, the blood pressure was SO/60 mm. Hg, and the respirations were 20 per minute. There was no cyanosis, dyspnea, or orthopnea. The neck veins were flat. Diffuse expiratory wheezes were present over the posterior chest. No r%les were heard. The heart was not enlarged. There was

Medical Service. Montefiore Hospital (Morris&a Affiliation), New York, N. Y. for publication Nov. 26. 1963. Assistant Resident, Medical Division, Mont&ore Hospital. Present address: Chief Resident. Cardiac eGeteranS Administration Hospital, 130 West Kingsbridge Road, Bronx 65, N. Y. Junior Assistant Resident. Medical Division, Mont&ore Hospital. Physician, Montefiore Hospital; Visiting Physician, Morris&a Hospital. Address correspondence Reservoir Ave., New York 68, N. Y.

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Fig. 1. A, Lead II reveals a tachycardia with a ventricular rate of 167 per minute. There are no visible P waves. B, Esophageal lead conlirms the presence of ventricular tachycardia (atrial rate of 88 per minute and ventricular rate of 167 per minute).

Fig. 2. .4, Lead II at beginning of administration of procaine amide (ventricular Lead II at 3 minutes. Patient has received 300 mg. of procaine amide (ventricular C, Seconds later the ECG reveals normal sinus rhythm. Note Q wave of old posterior

variation in the intensity of the first heart sound at the apex. There was no audible murmur, rub, or gallop. The remainder of the examination was within normal limits. Diagnostic studies at the time of admission were as follows: venous pressure of 95 mm. HIO, with a rise to 120 mm. on compression of the right upper quadrant; circulation time (arm to tongue) 17 seconds; hematocrit 47 per cent; white blood cell count 8,200 per cubic millimeter with normal differential; blood urea nitrogen 16 mg. per cent; urinalysis and serum electrolytes normal; SGOT 34 units. A chest x-ray film was normal. The electrocardicgram on admission (Fig. 1,.4 ) revealed a tachycardia with a rate of 167 per minute. There were no visible P waves. Carotid sinus pressure, ocular compression, and stimulation of the gag reflex had no effect on the arrhythmia. Intravenous Neo-Synephrine produced a rise in the systolic pressure to 160 mm. Hg without converting the arrhythmia. Because of hypotension, an intravenous infusion of metaraminol (Aramine) was begun in order to maintain the systolic pressure at 100 mm. Hg. An esophageal lead (Fig. 1,B) confirmed the presence of ventricular tachycardia. During this time, the patient received another 200 mg. of quinidine. During the next 8 hours the patient’s systolic blood pressure remained stable (at 90 to 100 mm. Hg) without vasopressors, and the infusion of metaramillol was replaced with 5 per cent dextrose ill water. Approsima1ciy 1 hctllr later, with monitoring by serial electroc;lrdiogr;tphi,, tracings and blood pressure recordings, procaine amide (Pronestyi) was injected intravenotlsly through the tubing at a rate of 100 mg. (1 cx.) per minute (Fig. 2). After 3 minutes, when the patient had received

rate

of 167 per minute). B, rate of 215 per minute). wall infarction.

a total of 300 mg. of procaine amide, the electrocardiogram (Fie. 2.B) revealed an acceleration c. .of the ventricular rate to 21.5 per minute, without any change in the configuration or duration of the QRS wave. Seconds later the patient’s arrhythmia reverted to normal sinus rhythm (Fig. 2,C). There was no change in blood pressure during the period of conversion. After normal sinus rhythm had been restored, the patient was placed on maintenance oral therapy with procaine amide. His blood pressure remained stable at 110/70 mm. Hg. Serial

electrocardiograms and determinations of transaminase revealed no eGdence of recent myocardinl infarction. The was uneventful, after admission.

remainder of the hospital course and he was discharged 2411 weeks

Discussion The cardiac effects of procaine amide are qualitatively similar to those of quinidine.2 Conduction in cardiac muscle is delayed, although to a different degree, in the atrium, ventricle, and the bundle of His. The effect is most pronounced at the A-V node, which suggests greater sensitivity of this tissue to the drug. The refractory period is prolongetl, the atrium being more affected than the ventricle. In c‘ontrast to the depressantaction of quinidine, (‘Oiltrxtility of the heart is usually not dfected by procaine amide. M~~o~ardi;~l excitability to electrical stimulation is

Acceleration

of venfricular

; this is more inarked irl the veil.. tricle than in the atrium. Since high doses of procaine amide sometimes accelerate the sinus rate in the absence of an arrhythmia, an anticholinergic effect has been postulated. When one considers the pharmacologic actions of procaine amide on the heart, there are several mechanisms whereby acceleration of a ventricular tachycardia may be explained. Although procaine amide may induce a tachycardia in the presence of normal sinus rhythm, it is conceivable that in our case of ventricular tachycardia the ectopic focus received parasympathetic innervation via the vagus nerve. \‘agal fibers have never been conclusively shown to innervate the ventricular musculature. However, Dworkin3 recently described a patient with frequent premature ventricular contractions (who was not taking any cardiac drugs) in whom carotid sinus pressure produced complete abolition of all premature ventricular contractions for the duration of carotid sinus massage. Three minutes after carotid compression the premature ventricular contractions returned at their original frequency. Although compression of the carotid sinus may inhibit sympathetic impulses to the ventricles, the known effects of such a maparasympathetic neuver suggest vagal innervation of the ventricular myocardium. If such be the case, the anticholinergic effect of procaine amide would explain acceleration of an ectopic ventricular focus. Further evidence of vagal innervation of the ventricular myocardium is found in the work of Schwartz and de Sola Pool4 on patients with established atrioventricular dissociation. To summarize their results, the intravenous administration of atropine sulfate (grain l/30) resulted in: (1) a transitory slowing followed by a transitory acceleration of the idioventricular rate; (2) the disappearance of spontaneously developing premature beats of the ventricle; and (3) changes in the site of the idioventricular pacemaker from one of the bundles to the supraventricular portion of the ;i-Jl node. These effects of atropine sulfate strongly suggest that the idioventricuiar pacemaker is under the influence of the vagus nerve. d~prt%Xd

tachycardia

after procaine amide

380

The efficacy of vasopressor drugs ill terminating tachycardias of supraventricular origin, presulnably via the carotid sinus mechanism with increased vagal tone to the heart, is well established. That vagal innervation of the ventricular myocardium may exist is suggested by the report of Greenspan and Shahgoldian,5 who treated 3 patients with ventricular tachycardia by intravenous vasopressor drugs. Restoration of normal rhythm was achieved in all 3 patients. However, in one of their patients with acute myocardial infarction and shock, intravenous metaraminol terminated the ventricular tachycardia despite continued hypotension. This would imply a direct action on the myocardium rather than a secondary effect due to an elevation in the systemic blood pressure. Denney and co-workers6 presented a case of ventricular tachycardia treated with procaine amide in which progressive widening and notching of the QRS wave occurred, followed by a short paroxysm of ventricular acceleration of a prefibrillation type, Normal rhythm was restored upon cessation of procaine amide therapy. They postulated that the mechanism of re-entry excitation was responsible for the acceleration of the ventricular rate. However, in our patient there was no significant widening of the QRS wave nor change in its configuration (QRS = 0.18 to 0.20 sec. at a ventricular rate of 167 per minute, and QRS = 0.20 sec. at a ventricular rate of 21.5 per minute). Finally, a mechanism completely unrelated to the administration of procaine amide may be postulated to account for acceleration of a ventricular tachycardia. It has been amply demonstrated that any disturbance of cardiac rhythm may adversely influence systemic blood pressure, coronary blood flow, and myocardial metabolism.7-9 The severity of the effects in these areas depends on the site of origin, type, rate, and duration of the arrhythmias, and the degree of underlying heart disease. In the presence of ventricular tachycardia, the work of the heart is increased, which results in increased UUtritional requirements. However, the arrhythmia itself causes impaired ventricular filling and output, with a fall in systemic

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and Rubin

blood pressure and coronary perfusion. The resulting myocardial ischemia with impaired myocardial metabolism not only perpetuates, but could conceivably acthe arrhythmia, although the celerate, latter has never been reported. Conclusions

Although it cannot be stated with certainty what mechanisms are responsible for acceleration of a ventricular tachycardia treated with procaine amide, we do not think that this phenomenon represents a toxic manifestation of the drug. The dose given was well within the accepted therapeutic range, and the electrocardiogram showed no change in the duration or configuration of the QRS complex. In the treatment of ventricular tachycardia with procaine amide or quinidine, most authorities recommend continuous treatment until normal rhythm is restored or toxic side effects appear, the latter being most evident as electrocardiographic abnormalities or hypotension. As evidenced by the restoration of normal sinus rhythm in our case, one may judiciously administer procaine amide in the presence of ventricular tachycardia with acceleration of the ventricular rate, provided that careful surveillance of the patient is maintained by continuous recording of the electrocardiograms for widening of the QRS complex, and by frequent determinations of blood pressure. Summary

A case of ventricular tachycardia not associated with clinical myocardial infarction was treated with intravenous procaine amide. Prior to conversion to normal sinus rhythm, a significant acceleration of the ventricular rate, in the absence of any intraventricular conduction defect,

occurred. To our knowledge, such a phenomenon has not been reported previously. Several mechanisms were postulated to explain the pathophysiology of the increased ventricular rate. It was suggested that such an event does not contraindicate further administration of the drug, provided that the patient is closely monitored by the frequent recording of electrocardiograms and determinations of blood pressure. REFERENCES 1. Goodman, L. S., and Gilman, A. 2.: The pharmacological basis of therapeutics, ed. 2, New York, 1956, The Macmillan Co., pp. 724-729. 2. Kayden, H. J., Brodie, B. B., and Steele, J. M.: Procaine amide, A review, Circulation 15:118, Chest 19.57. 3. Dworkin, J.: Abolition of premature ventricular contractions with carotid sinus pressure, Dis. Chest 41:107, 1962. 4. Schwartz, S. P., and de Sola Pool, H.: Transient ventricular fibrillation. III. The effects of bodily rest, atropine sulfate, and exercise on patients with transient ventricular fibrillation during established auriculoventricular dissociation. A study of the influence of the extrinsic nerves on the idioventricular pacemaker of the heart, AM. HEART J. 39:861, 1950. 5. Greenspan, W., and Shahgoldian, Z. L.: The use of vasopressors in cardiac arrhythmias, particularly ventricular tachycardia, Am. J. Cardiol. 7:707, 1961. 6. Denney, J. L., Miller, H., Griffith, G. C., and Nathanson, M. H.: Ventricular acceleration following procaine amide hydrochloride therapy, J.A.M.A. 149:1391, 1952. 7. Corday, E., Williams, J. J., Gold, H., arid de\‘era, L. B.: Hemodynamics of the coronary circulation during cardiac arrhythmias, Mod. Concepts Cardiovas. Dis. 27:493,- 1958. 8. Cordav. E. H.. Williams. I. H.. de Vera. L. B.. and Gold, H.: Effect of systemic blood pressure and vasopressor drugs on coronary blood flow and the electrocardiogram, :lm. J. Cardiol. 3:626, 1959. 9. Corday, E., Gold, H., de Vera, L. B., Williams, J. H., and Fields, J.: Effect of the cardiac arrhythmias on the coronary circrrlation, Ann. Int. Med. 50:53.5, 1959. _I