American Heart Journal November, 1963, Volume 66, Number 5

Editorial

Management of the Stokes-Adams syndrome

Simon Dack, M.D.* New York, N. Y.

I n the past decade we have witnessed major advances in the medical and

surgical control of patients with A-V heart block and Stokes-Adams syndrome. Previ- ously, therapy during the acute attack consisted primarily of intermittent paren- teral injections of epinephrine and atro- pine. Drugs for maintenance therapy included ephedrine, atropine, and Pare- drine. The introduction of sublingual isoproterenol in the early nineteen-fifties was a step forward. lv2 A more significant improvement in therapy of the Stokes- Adams syndrome came in the mid-nine- teen-fifties with the use of dilute solutions of isoproterenol or epinephrine by con- tinuous intravenous infusion.3s4

Simultaneously with the improvement in drug therapy came the pioneer work of Zo115 with external electronic stimulators. He opened a new field of electrical pacing of the heart during ventricular asystole or severe bradycardia. Stimulation by external pacemaker was soon supplemented by intracardiac stimulation through an endocardial catheter electrode placed in the right ventricle.6 Observations in experi- mentally induced heart block in dogs and _ __ _ _ _. .-

num electrodes to the ventricular myo- cardium and stimulate the ventricles by an external electrical pacemaker.’ Finally, in the past 3 years the use of transistors and miniaturization of the pacemaker unit have led to the present technique of sub- cutaneous implantation of the pacemaker and its connecting wires in the chest or abdominal wa11.8pg Although still beset by mechanical difficulties in 2 to 15 per cent of cases, the implantable pacemaker prom- ises to become the device of choice for treating most patients.

At the present time, various methods are available for treating the patient with un- stable heart block during the acute stage of Stokes-Adams syndrome, and for main- taining therapy. The clinician must now decide how long to pursue medical therapy, when to use artificial pacing, and when to recommend surgical implantation of a pacemaker.

Drug therapy of Stokes-Ada’ms syndrome

Isoproterenol and epinephrine. The pa- tient with heart block, slow ventricular rate, and unstable rhythm is subject to

580 Dud? Am, Hcurt J. .Yovember, 1963

situation constitutes a medical emergency that requires immediate resuscitative meas- ures. The patient is given an initial paren- teral injection of epinephrine (0.5 C.C. of 1 :lOOO solution) or isoproterenol (0.2 mg.). If he is seen during the actual episode of svncope or unconsciousness, the mechanical s&ulation of a blow on the precordium or compression of the chest may revive ventricular contraction. If neither is suc- cessful, an intracardiac injection of epi- nephrine or isoproterenol (0.1 mg. in 10 C.C. of water) may produce mechanical, followed by pharmacologic, stimulation of the ventricles. The patient is then attached to an ECG monitor and an exter- nal electrical pacemaker, and a continuous intravenous infusion of isoproterenol or epinephrine is started promptly. The initial concentration is 2 mg. of isopro- terenol or 2 C.C. of 1:lOOO epinephrine per 1,000 C.C. of 5 per cent dextrose in water, and the rate of infusion is regulated to deliver a dose of 4 pig per minute (ap- proximately 2 c.c. of solution per minute). If this concentration does not increase the ventricular rate to 40 to 50 per minute, it should be increased to 4 mg. of isopro- terenol or 4 C.C. of epinephrine per 1,000 C.C. of solution. In severe cases, concentra- tions as high as 5 to 10 mg. of isoproterenol have been required.

Intravenous isoproterenol generally re- sults in stimulation of an idioventricular pacemaker high in the A-V bundle or in one of the bundle branches. Often, two distinct ventricular pacemakers may alter- nate. Continuous monitoring of the rhythm is necessary to detect signs of ventricular irritability (ectopic beats or tachycardia), and the rate of infusion must be slowed accordingly. No attempt should be made to increase the idioventricular rate above 45 to 50 per minute. Patients vary in their sensitivity to isoproterenol : some respond to concentrations as low as 2 mg. per 1,000 c.c., and others require up to 10 mg. per 1,000 C.C. Such intravenous infusions have been maintained for many hours or several davs when necessary, until stabilization

proterenol (0.2 mg.) or epinephrine (0.5 c.c.) may then be continued, supplemented by sublingual isoproterenol (Isuprel) every 1 to 4 hours or oral Proternol (sustained- action isoproterenol) every 4 to 6 hours.

Stokes-Adams syndrome is often pre- cipitated by periods of ventricular tachy- cardia or fibrillation. In the patient with heart block this may be heralded by the appearance of bursts of ventricular ectopic beats. The tachycardia or fibrillation may alternate with periods of ventricular asys- tole. In such a case the use of isoproterenol or epinephrine is preferred to myocardial- depressant agents, such as quinidine and procaine amide. Careful infusion of iso- proterenol or epinephrine, by increasing the idioventricular rate and stabilizing a higher ventricular pacemaker, may success- fully prevent the recurrence of ventricular tachycardia and fibrillation. Quinidine and procaine amide will generally aggravate the myocardial depression responsible for the ventricular arrhythmia. Therefore, even when the mechanism of Stokes- Adams syndrome is proved to be ventricu- lar tachycardia or fibrillation, the preferred method of therapy is the one used for ventricular asystole, except that lower concentrations and more careful titration of intravenous dosage and monitoring of cardiac rhythm are necessary.lO In addi- tion, countershock with the external electri- cal AC defibrillator instead of the external electrical pacemaker is applied during any recurrence of syncope or when there is prolonged ventricular tachycardia or fibril- lation.”

Corticosteroids. In some cases of recurrent ventricular asystole or marked brady- cardia, corticosteroid therapy may ef- fectively increase the ventricular rate, prevent asystole, and stabilize A-V con- duction. Tn acute situations the rapid ad- ministration of a corticosteroid agent may be lifesaving. Its effect becomes manifest within several hours. This applies par- ticularly to -1-V block associated with acute myocardial infarction or myorarditis, ill which case the anti-inflanlmatory action

Munagement of Sjokes-Adams syndrome 581

partial abolition of chronic A-V block or bundle branch block in the absence of clinical signs of infarction or carditis.‘? The latter effect is probably caused by a direct enhancement of A-V conduction, possibly resulting from depletion of intra- cellular potassium in the conduction tissues.

Dosage of the corticosteroid must be relatively high, beginning with 60 to 80 mg. daily of prednisone or an equivalent dosage of methylprednisone (40 to 50 mg.) or triamcinolone (30 to 40 mg.) or dexa- methasone (9 to 12 mg.), and after several days progressively reducing the daily dose to half the initial dose. This dosage should be maintained until the maximum effect has been obtained (resumption of normal sinus rhythm or a stable ventricular rhythm). In acute emergencies, therapy can be instituted by an immediate intra- venous injection of hydrocortisone, 100 to 200 mg., followed by oral dosage as out- lined above. Corticosteroid therapy should be given a trial in all cases when there is no contraindication to its use (gastro- intestinal ulcerations, etc.).

Quinidine and procaine amide. The danger of administering quinidine or pro- caine amide to patients with Stokes- Adams syndrome has been repeatedly emphasized.” These agents are myocardial depressants which further impair A-V conduction. Even when ventricular tachy- cardia or fibrillation is present, these drugs may aggravate or perpetuate ven- tricular irritability by their depressant effects on the myocardium and should not be used routinely. Occasionally, a bene- ficial antiarrhythmic effect is obtained when other measures have failed. The better alternative, as already mentioned, is the cautious intravenous infusion of isoproterenol in weak concentrations, in an attempt to increase the rate of the higher ventricular pacemakers and block the lower ectopic ventricular center responsible for the tachycardia. Potassium salts also have a depressant effect on A-V conduc- tion and should not be used in block, even when it is produced by digitalis toxicity.

Digitalis. This drug, too, must be used with great caution in cases of Stokes- Adams syndrome. By its vagal and direct myocardial actions, it depresses A-V con- , ,. -3. . . . .

block but also ia advanced or complete A-V block, in which case it may affect the idioventricular center below the A-V node, causing further slowing of the ventricular rate and predisposing to ventricular asys- tole and Stokes-Adams attacks. I have observed several patients with partial or complete A-V block who developed in- tractable Stokes-Adams syndrome after they were digitalized with a relatively small dosage because of signs of congestive failure. Digitalis therapy in such cases is safe only after insertion of an intracardiac catheter electrode or implantation of an electrical pacemaker, which ensures con- trol of ventricular rate after digitalis has been administered. Under these circum- stances, digitalis may abolish heart failure by improving ventricular contraction and increasing stroke output.

Maintenance drug therapy

Isoproterenol is the drug of choice for maintenance therapy after parenteral ther- apy has been discontinued.13 The sub- lingual tablet (Isuprel) is absorbed rapidly, and within a few minutes a high peak of action is attained which is dissipated in a relatively short time. It is useful, there- fore, when the patient has premonitory symptoms of standstill or slowing of the rate, such as lightheadedness or transient blackout. For continuous maintenance therapy it should be given at frequent intervals (every 2 to 4 hours) in doses of 5 to 1.5 mg., depending on its effect on ventricular rate and whether or not it produces palpitation or angina.

Oral, sustained-action tablets of iso- proterenol (Proternol), now available for clinical use, are recommended for long- term maintenance therapy in chronic A-V block.14 This drug has been most ef- fective when an unstable cardiac mecha- nism persists after therapy for acute Stokes-Adams syndrome. Its beneficial effect may be manifested by restoration of normal sinus rhythm or lesser degrees of heart block or by maintenance of a faster idioventricular rate. Long-term ex- perience (up to 3 years) has indicated that the incidence of recurrent ventricular asystole and Stokes-Adams attacks can be significantly reduced. Side effects, such

582 Dack Am. Heart I. Sovcmbcr, 1963

tachycardia, are much less frequent than with sublingual administration, since ab- sorption is slower. The peak effect on ven- tricular rate, however, may be maintained for 2 to 4 hours. The usual dosage is one tablet (30 mg.) every 4 to 6 hours around the clock; in some cases, a dosage of 60 w. every 6 hours has been effective.

Interim pacing of heart by bipolar endocardial electrode

Electrical pacing of the heart by a bi- polar catheter electrode inserted into the outflow tract of the right ventricle through a jugular or antebrachial vein represents another major advance in the therapy of Stokes-Adams syndrome.15 It can be ac- complished rapidly and with ease under local anesthesia. Once the bipolar electrode has been properly positioned in the outflow tract of the right ventricle and connected to the electrical pacemaker, a relatively small stimulus (2 to 5 volts) will capture control of ventricular excitation and main- tain a regular ventricular rate (50 to 70 per minute).

The method is applicable for patients with either recurrent ventricular asystole or fibrillation, or with slow ventricular rates. It gives the clinician complete con- trol of ventricular pacing without the discomfort to the patient and the other disadvantages of external electrical stimu- lation. It results in improved cardiac out- put and stable blood pressure and the alleviation of heart failure and coronary insufficiency. For patients who respond poorly to isoproterenol or epinephrine, or who show undue sensitivity to these drugs, prompt insertion of the catheter electrode is indicated. When there is lack of significant response to drug therapy, recurrence of symptoms, instability of ventricular rhythm, or evidence of con- gestive heart failure in the presence of a slow ventricular rate, then drug therapy is supplemented with the endocardial bipolar electrode.

After insertion of the catheter, intra- venous infusion of isoproterenol or epi- nephrine can be discontinued. If heart failure is not abolished after the ventricular rate is increased, digitalis can be given in therapeutic dosage, without fear of de- pressing A-V conduction. Diuretic therapy

can also be administered in the usual manner. At present, this method is used routinely in the preoperative preparation of all our patients who require surgical implantation of a pacemaker.

Indications for surgical implantation of a cardiac pacemaker

Although modern drugs have consider- ably improved the medical management of the patient with A-V block and Stokes- Adams syndrome, the long-term results of therapy and the prognosis are still dis- appointing. The incidence of recurrent Stokes-Adams syndrome and death within the first 6 to 12-month follow-up period remains high. For this reason, we now ad- vise surgical implantation of an electrical pacemaker in all patients in whom there has been a major Stokes-Adams attack or a history of recurrent attacks. It is also recommended for patients with slow ven- tricular rates below 40 per minute, despite adequate drug therapy, particularly when faintness or recurrent blackout occurs because of inadequate cerebral blood flow. Patients with A-V block and congestive heart failure are also candidates for oper- ation, since their low cardiac output can be improved only by increasing the ven- tricular rate. The dangers of digitalis therapy in such patients have been previ- ously emphasized, and intensive dietary and diuretic therapy alone may fail to restore adequate cardiac output.

With improved surgical techniques and preoperative preparation, most patients can tolerate operation successfully, with a relatively low mortality.16 Even patients with previous myocardial infarction and extensive ventricular damage and fibrosis have been operated on successfully. Great caution must be exercised to exclude the patient with recent myocardial infarction, since the operative risk is high, and sudden death may occur. Furthermore, A-V block during acute myocardial infarction is often transitory and will revert to normal rhythm spontaneously or with adequate drug therapy. If the block becomes permanent, then surgery can be considered when the myocardial infarction has healed (generally not before 2 to 3 months). If Stokes-Adams attacks recur during the acute or healing stage of infarction, or if severe brady-

Volume 66 Number 5 Mmagement of Stokes-Adams syndrome 583

cardia or unstable ventricular rhythm persists, interim pacing of the ventricles with the intracardiac bipolar catheter should be maintained until A-V conduction improves spontaneously or until the pa- tient is considered ready for surgical im- plantation of a pacemaker.

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Chardack, W. M., Gage, A. A., and Great- batch, W. A.: Transistorized self-contained implantable pacemaker for the long-term cor- rection of complete heart block, Surgery 48:643, 1960. Zoll, P. M., Frank, H. A., Zarsky, L. R., Linen- thal, A. J., and Belgrade, A. H.: Long-term electric stimulation of the heart for Stokes- Adams disease, Ann. Surg. 1%:330, 1961. Linenthal, A. J., and Zoll, P. M.: Prevention of ventricular tachycardia and fibrillation by intravenous isoproterenol and epinephrine, Circulation 27:5, 1963. Zoll, P. M., Linenthal, A. J., Gibson, W., Paul, M. H., and Norman, L. R.: Termination of ventricular fibrillation in man by externally aoolied countershock. New Eneland 1. Med. Z&27, 1956. ’

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Friedberg, C. K., Kahn, M., Scheuer, J., Bleifer, S., and Dack, S.: Adams-Stokes syn- drome associated with chronic heart block. Treatment with corticosteroids, J.A.M.A. 172:1146, 1960. Robbin, S. R., and Dack, S.: Treatment of Stokes-Adams attacks in heart block, with special reference to parenteral, sublingual and long-acting isoproterenol, Circulation 20:757, 1959. Dack, S., and Robbin, S. R.: Treatment of heart block and Adams-Stokes syndrome with sustained-action isoproterenol, J.A.M.A. 176: 505, 1961. Parsonnet, V., Zucker, I. R., Gilbert, L., and Asa, M. M.: An interim bipolar electrode for interim treatment of complete heart block, Am. J. Cardiol. 10:261, 1962. Chardack, W. M., Gage, A. A., Schimert, G., Thomson. N. B.. and Sanforn. C. E.: Two years’ c&al exierience with the implantable pacemaker for complete heart block, Dis. Chest 43:225, 1963.