Cardiac Arrhythmias

The first use of PHT in cardiac disorders was reported by Leonard in 1958. Since it was the pioneer paper in this field, it will be summarized in some detail. It brings into focus three important points which develop throughout the literature: 1) PHT is an effective antiarrhythmic, prompt in its action; 2) PHT has a high margin of safety; 3) In the acute stage, substantial amounts of PHT may be required, adjusted to the severity of the condition.

Leonard, Archives of Internal Medicine (1958), 221 demonstrated the beneficial effect of PHT in controlling ventricular hyperirritability complicating myocardial infarction in a patient. The patient was gravely ill with cardiographic findings of typical ventricular tachycardia. In spite of the previous history of complete heart block, it was felt that intravenous procainamide, if carefully controlled, was the treatment of choice. The patient was receiving Arterenol to maintain his blood pressure at 110/70. Procainamide was given intravenously. During a period of approximately two hours, 2300 mg of procainamide was given, in spite of several episodes of marked hypotension, but finally discontinued because of disturbing widening of the QRS complex without reversion to a normal sinus mechanism. The patient’s condition remained critical, and it was considered advisable to investigate the therapeutic potential of intravenous PHT. PHT was administered slowly intravenously in a dose of 250 mg. A cardiogram recorded approximately two minutes later revealed a normal sinus mechanism coupled with premature auricular contractions. In twenty minutes ventricular tachycardia had recurred. An immediate additional dose of 250 mg of PHT was given and within moments a normal sinus mechanism appeared. Four hours later ventricular tachycardia returned and was again successfully reverted to a normal sinus rhythm with 250 mg of intravenous PHT. Because the duration of effectiveness of PHT was unknown, a constant, slow intravenous infusion of 250 mg of PHT was started. The normal sinus mechanism was maintained in this fashion for successive periods of six and four hours. At these intervals ventricular tachycardia returned, but was promptly reverted with additional intravenous doses of 250 mg of PHT. At this time it was considered advisable to supplement the intravenous therapy with 3 grains of PHT and 500 mg of procainamide every four hours orally. Eighteen hours after its initiation the intravenous PHT was discontinued. An electrocardiogram at this time showed posterior myocardial infarction with a normal sinus mechanism. On the following day procainamide was discontinued, and the patient was maintained with 3 grains of PFU orally every six hours. There was no recurrence of signs of ventricular irritability. The patient made an uneventful recovery. The author suggests that PHT may represent a drug with a wide margin of safety that is effective in controlling serious ventricular hyperirritability.

221. Leonard, W. A., Jr., The use of diphenylhydantoin (Dilantin) sodium in the treatment of ventricular tachycardia, A.M.A. Arch. Intern. Med., 101: 714-717, 1958.

Bernstein, Gold, Lang, Pappelbaum, Bazika and Corday, Journal of the American Medical Association (1965),18 used oral PHT in the treatment and prevention of recurring cardiac arrhythmias in a group of sixty patients, who had been refractory to or intolerant of conventional medication. In thirty-seven patients with premature ventricular contractions, twenty-six returned to normal sinus rhythm, and seven had a decrease in the number of ectopic beats. In thirteen patients who had atrial tachycardia, ten had excellent response and two had moderate improvement. Six patients with paroxysmal atrial fibrillation had excellent response. Two patients with premature atrial contractions and one with premature nodal beats had excellent response. One patient with recurrent atrial flutter did not respond. Some side effects were observed. None were serious and all disappeared upon withdrawal of the medicine. The patients had been evaluated for periods up to nineteen months, the time the study was reported.

18. Bernstein, H., Gold, H., Lang, T. W., Pappelbaum, S., Bazika, V., and Corday, E., Sodium diphenylhydantoin in the treatment of recurrent cardiac arrhythmias, JAMA, 191: 695-697, 1965.

Conn, New England Journal of Medicine (1965), 61 found that PHT, administered intravenously to twenty-four patients with a variety of cardiac arrhythmias, was particularly effective in supraventricular and ventricular arrhythmias resulting from digitalis excess. It was also of benefit in controlling paroxysmal atrial and ventricular arrhythmias. In three cases of atrial fibrillation and two with atrial flutter no therapeutic effect was noted. Toxicity consisted of transient bradycardia and hypotension in one patient and short-term atrioventricular block with bradycardia in another. The author stated that PHT appears to be a significant addition to the drug therapy of cardiac arrhythmias.

61. Conn, R. D., Diphenylhydantoin sodium in cardiac arrhythmias, New Eng. J. Med., 272: 277-282, 1965.

Lugo and Sanabria, Acta Medica Venezolana (1966), 517 reported the effectiveness of oral PHT, 100 mg q.i.d., in eleven patients with chronic Chagasic cardiac disease, with multifocal ventricular extrasystoles. In eight cases response was excellent with conversion to normal sinus rhythm which continued up to the eight months the patients were followed. In two cases there was excellent response, but the drug had to be discontinued because of skin rash. In one case with ventricular extrasystoles and atrial fibrillation, the extrasystoles were controlled.

517. Lugo, V. and Sanabria, A., Treaunent of extrasystole in chronic Chagasic cardiopathy with diphenylhydantoin, Acta Medica Venezolana, 148-151, Mar.-Apr., 1966.

Karliner, Diseases of the Chest (1967),187 described fifty-four patients who received intravenous PHT on fifty-seven occasions for abnormal cardiac rhythm. Nineteen of twenty-three who had digitalis-induced arrhythmias responded with abolition or marked suppression of a ventricular ectopic focus, or with conversion of supraventricular arrhythmias to a regular sinus mechanism. Of twenty-eight patients whose arrhythmias were unrelated to digitalis, seven responded favorably. As a result of this study the author confirmed the usefulness of PHT in a variety of cardiac arrhythmias, especially those which appear to be related to digitalis excess. Rapidity of action and relative paucity of side effects make PHT an effective antiarrhythmic agent.

187. Karliner, J. S., Intravenous diphenylhydantoin sodium (Dilantin) in cardiac arrhythmias, Dis. Chest, 51: 256-269, 1967.

Mercer and Osborne, Annals of Internal Medicine (1967), 248 reported on their six years’ experience in the treatment, with PHT, of 774 cases of cardiac arrhythmias. The authors state that intravenous PHT is highly efficacious in the treatment of ventricular arrhythmias associated with anesthesia, cardioversion, cardiac catheterization, and cardiac surgery. On the basis of their experience they consider PHT to be superior to quinidine and procainamide in these arrhythmias. PHT also had a good effect against digitalis-induced ventricular arrhythmias and an even better effect against digitalis-induced atrial tachycardia. The authors reviewed the literature, including their own series, on the oral use of PHT. There were reported successes in twenty out of twenty-four cases of supraventricular arrhythmias, twenty-six out of thirty-eight cases of ventricular arrhythmias and five out of eight cases of unclassified paroxysmal tachycardia.

248. Mercer, E. N. and Osborne, J. A., The current status of diphenylhydantoin in heart disease, Ann. Intern. Med., 67: 1084-1107, 1967.

Bashour, Edmonson, Gupta and Prati, Diseases of the Chest (1968),418 reported on twelve patients who were treated with PHT, all of whom had clinical evidence of digitalis toxicity. Most patients had more than one type of arrhythmia. During intravenous administration of PHT, continuous electrocardiographic monitoring was usually performed, and after conversion to sinus rhythm or subsidence of the arrhythmia, monitoring of the cardiac rhythm was continued for a period of ten minutes. In five of the cases, atrial fibrillation was present with other arrhythmias. Two of these arrhythmias were of recent origin and were restored to normal sinus rhythm by PHT. Three cases of chronic atrial fibrillation did not respond to treatment. Four of the patients were uremic. The successful termination of their cardiac arrhythmias, especially ventricular tachycardia, with PHT, was of special interest. In uremic patients with arrhythmias the usual therapeutic measures are both less effective and more hazardous.

418. Bashour, F. A., Edmondson, R. E., Gupta, D. N., and Prati, R., Treatment of digitalis toxicity by diphenylhydantoin (Dilantin), Dis. Chest, 53: 263-270, 1968.

Eddy and Singh, British Medical Journal (1969), 987 treated thirty-seven patients with cardiac arrhythmias with intravenous PHT. Twenty-one had acute myocardial infarctions and sixteen had other conditions. There was a favorable response in eighteen of the twenty-one cases of myocardial infarction and in six of the other sixteen cases.

987. Eddy, J. D. and Singh, S. P., Treatment of cardiac arrhythmias with phenytoin, Brit. Mod. J., 4: 270-273, 1969.

Gattenlohner and Schneider, Munchener Medizinische Wochenschrift (1969), 1052 reported fifteen patients in whom they studied cardiac hemodynamics. PHT, in doses of 125 and 250 mg, did not alter or interfere with cardiac output or stroke volume. In the eight patients with digitalis-induced arrhythmias, they noted return to normal sinus rhythm. They conclude that PHT is not only effective but may be lifesaving in digitalis-induced arrhythmias. (See also Ref. 2230.)

1052. Gattenlohner, W. and Schneider, K. W., The effect of diphenylhydantoin on hemodynamics, Munchen Med. Wschr., 11: 2561-2566, 1969.

Helfant, Steuffert, Patton, Stein and Damato, American Heart Journal (1969), 720 report on the use of intravenous PHT in a variety of cardiac arrhythmias. In a controlled study, eight of eleven patients treated with PHT prior to cyclopropane anesthesia did not develop arrhythmias; whereas, in the control group, eight of nine patients did develop arrhythmias. In another phase of the study, PHT restored sinus rhythm in all eight patients who developed arrhythmias during the administration of various anesthetics. In a second group with ventricular arrhythmias, unresponsive to procainamide, PHT abolished or decreased the ectopia in ten of twelve patients. In a third group of twelve patients given prophylactic PHT prior to DC counter-shock, none developed arrhythmias. In patients on digitalis, twenty-one of twenty-four with ventricular arrhythmias, and six of eleven with supraventricular arrhythmias responded to PHT. The authors confirmed PHT’s effectiveness and safety in the prevention and treatment of cardiac arrhythmias.

720. Helfant, R. H., Seuffert, G. W., Patton, R. D., Stein, E., and Damato, A. N., The clinical use of diphenylhydantoin (Dilantin) in the treatment and prevention of cardiac arrhythmias, Amer. Heart J., 77: 315-323, 1969.

Lesbre, Cathala, Salvador, Florid, Lescure and Meriel, Archives des Maladies du Coeur et des Vaisseaux (1969),1264 investigated the antiarrhythmic value of PHT in a variety of arrhythmic disturbances with the following results:
 
Patients 
Successes
Atrial tachysystole 
3
2
Atrial extrasystole 
3
3
Ventricular extrasystoles
17
16
Bouts of tachycardia  
3
3
First-degree block
8
5
Second-degree block
6
5

In another study, they compared forty patients with atrial fibrillation given PHT before cardioversion with a similar group of forty patients given a beta-blocking agent. The results with PHT were better.

1264. Lesbre, J. P., Cathala, B., Salvador, M., Florio, R. Lescure, F., and Meriel, P., Diphenylhydantoin and digitalis toxicity, Arch. Mal. Coeur., 62: 412-437, 1969.

Gautam, British Heart Journal (1969), 721 reports on the use of intravenous PHT in treating serious cardiac arrhythmias following open heart surgery in fourteen patients. PHT was rapidly and highly effective in abolishing supraventricular and ventricular arrhythmias in thirteen of these patients. Higher doses were required for the more serious arrhythmias. The author states that the rapidity of its action and the relative paucity of side effects make PHT an effective antiarrhythmic agent.

 721. Gautam, H. P., Phenytoin in post-operative cardiac arrhythmias, Brit. Heart J., 31: 641-644, 1969.

Bielak and Pokora, Polski Tygodnik Lekarsky (1970),2331 report their experience in 106 patients with either oral or intravenous PHT for various arrhythmias caused by infarction, digitalis toxicity, valvular heart lesions, chronic cardiopulmonary disease and myocarditis as follows:

 
Patients
Successes
Ventricular extrasystoles
73
63
Ventricular tachycardia
4
2
Supraventricular extrasystole
12
9
Paroxysmal atrial flutter
1
1
Paroxysmal atrial fibrillation
6
4

Paroxysmal supraventricular tachycardia

10
5
TOTAL
106
84

The authors also evaluated the prophylactic use of PHT, 300 mg/day. No arrhythmias were recorded in sixty-three of 125 patients with acute myocardial infarction. Twenty-two patients with ectopic ventricular beats were successfully treated with PHT. In twelve of these patients, ectopic beats, returned when PHT was discontinued. In a group of ten patients with recurring atrial arrhythmias, five had no recurrences.

2331. Bielak, J., Pokora, J., The effect of hydantoinal on cardiac arrhythmias, Pol. Tyg. Lek., 25: 967-9, 1970.

Hansen, Medizinische Klinik (1970),2569 reported the use of PHT in 150 patients who developed arrhythmias during digitalis treatment. One hundred and three of 115 with ventricular arrhythmias responded favorably. Seventy-nine of these converted to normal sinus rhythm. In twenty-four patients who had atrial fibrillation and extrasystoles, the ventricular extrasystoles disappeared, but the fibrillation was not affected. Seven patients with supraventricular extrasystoles were successfully treated with PHT. Eight of nine patients with paroxysmal atrial fibrillation and five of seven patients with supraventricular tachycardia were also controlled. In seven of twelve patients with partial second-degree heart block of Wenckebach type, conduction irregularity was reversed by PHT.

2569. Hansen, H. W., The treatment of digitalis induced cardiac arrhythmia with diphenylhydantoin, Med. Klin., 65: 101-4, 1970.

Chiche, Benaim and Chesnais, Annales de Cardiologie et D’Angeiologie (1971),2390 reported that thirteen of twenty-six patients with atrial arrhythmias, other than atrial fibrillation and flutter, responded to intravenous PHT. In eight patients with atrial flutter or fibrillation, PHT slowed the ventricular response without change in the atrial arrhythmia. Fourteen out of seventeen patients with ventricular arrhythmias responded to PHT. Seven patients undergoing DC cardioversion were pretreated with PHT and there were no arrhythmias. In the group treated with oral PHT, seven of thirteen patients with atrial arrhythmias and nine of fifteen with ventricular arrhythmias were successfully treated.

2390. Chiche, P., Benaim, R., Chesnais, F., Phenytoin: Clinical pharmacology. Use in various arrhythmias in 86 cases, Ann. Cardiol. Angeiol., 2: 231-42, 1971.

Hansen and Wagener, Deutsche Medizinische Wochenschrift (1971),1121 in a controlled study of 200 patients with PHT and 300 patients without PHT, evaluated the effect of PHT when added to cardiac glycoside administration. By combining PHT and glycosides, the incidence of arrhythmias was reduced from 21 % in the non-PHT group to 2.5 % in the PHT-treated group. The authors state that this clinical experience indicates that PHT administration reduces the toxic effect of glycosides in man without affecting their inotropic benefits. Thus, the use of PHT improves the chance of effective treatment in heart failure.

1121. Hansen, H. W. and Wagener, H. H., Diphenylhydantoin in the treatment of heart failure, Deutsch. Med. Wschr., 96: 1866-1873, 1971.

Kemp, Journal of the American Geriatrics Society (1972),1214 studied the effect of PHT on ventricular ectopic rhythms. These arrhythmias were not caused by digitalis. PHT was given to five patients and five patients were given placebo. For the first three weeks the dosage of PHT was 100 mg q.i.d. During the rest of the three-month study the dosage was reduced to 100 mg t.i.d. The numbers of premature ventricular contractions during a five minute continuous ECG monitoring period were recorded before therapy, after three weeks of therapy, and after three months of therapy. At the end of the three-month period, premature ventricular contractions were abolished in two of the PHT patients and almost eliminated (165 to 1, 100 to 2, and 80 to 3) in three patients. On the other hand, in the control group, contractions increased in two patients, and were moderately decreased in three.

1214. Kemp, G. L., Treatment of ventricular ectopic rhythms with diphenylhydantoin, J. Amer. Geriat. Soc., 20: 265-267, 1972.

O’Reilly and MacDonald, British Heart Journal (1973),1390 reported on the successful use of PHT in treating two cases of ventricular arrhythmia induced by hypokalemia. (Hypokalemia results in below normal potassium in nerve and muscle cells. Relevant to the above paper is the fact that PHT has been demonstrated to have a regulatory effect on low potassium in cells. See “downhill movement” of ions, Refs. 157, 387, 728, 731, 1012, 1025, 1225, 1379, 1418, 1642, 1662, 2224, 2374, 2458.) The authors emphasize the usefulness of PHT in the management of the notoriously resistant and malignant arrhythmias associated with hypokalemia, where the usual antiarrhythmic agents are at best ineffective and may even be dangerous.

1390. O’Reilly, M. V. and MacDonald, R. T., Efficacy of phenytoin in the management of ventricular arrhythmias induced by hypokalaemia, Brit. Heart J., 35: 631-634, 1973.
157. Helfant, R. H., Ricciutti, M. A., Scherlag, B. J., and Damato, A. N., Effect of diphenylhydantoin sodium (Dilantin) an myocardial A-V potassium difference, Amer. J. Physiol., 214: 880-884, 1968.
387. Woodbury, D. M., Effect of diphenylhydantoin on electrolytes and radiosodium turnover in brain and other tissues of normal, hyponatremic and postictal rats, J. Pharm. Exp. Ther., 115: 74-95, 1955.
728. Crane, P. and Swanson, P. D., Diphenylhydantoin and the cations and phosphates of electrically stimulated brain slices, Neurology, 20: 1119-1123, 1970.
731. Escueta, A. V. and Appel, S. H., The effects of electrically induced seizures on potassium transport within isolated nerve terminals, Neurology, 20: 392, 1970.
1012. Escueta, A. V. and Appel, S. H., Brain synapses-an in vitro model for the study of seizures, Arch. Intern. Med., 129: 333-344, 1972.
1025. Fertziger, A. P., Liuzzi, S. E., and Dunham, P. B., Diphenylhydantoin (Dilantin): stimulation of potassium influx in lobster axons, Brain Res., 33: 592-596, 1971.
1225. Koch, A., Higgins, R., Sande, M., Tierney, J., and Tulin, R., Enhancement of renal Na+ transport by Dilantin, Physiologist, 5: 168, 1962.
1379. Nasello, A. G., Montini, E. E., and Astrada, C. A., Effect of veratrine, tetraethylammonium and diphenylhydantoin on potassium release by rat hippocampus, Pharmacology, 7: 89-95, 1972.
1418. Pincus, J. H., Diphenylhydantoin and ion flux in lobster nerve, Arch. Neurol., 26: 4-10, 1972.
1642. Van Rees, H., Woodbury, D. M. and Noach, E. L., Effects of ouabain and diphenylhydantoin on electrolyte and water shifts during intestinal absorption in the rat, Arch. Int. Pharmacodyn., 182: 437, 1969.
1662. Watson, E. L. and Woodbury, D. M., Effect of diphenylhydantoin on active sodium transport in frog skin, J. Pharmacol. Exp. Ther., 180: 767-776, 1972.
2224. Loh, C.K., Effects of diphenylhydantoin (DPH) on potassium exchange kinetics and transynembrane potentials in amphibian atrium, Fed. Proc., 33: 445, 1974.
2374. Caldwell, K. K., Harris, R. A., Effects of anesthetic and anticonvulsant drugs on calcium dependent efflux of potassium from human erythrocytes, Eur. J. Pharmacol., 107(2): 119-25, 1985.
2458. Doemer, D., Partridge, L. D., Effects of convulsant and anticonvulsant drugs on potassium inactivation, Soc. Neurosci. Abstracts, 9 PT 1: 396,1983.

Rumack, Wolfe and Gilfrich, British Heart Journal (1974),1488 detailed the successful treatment with PHT of a patient who attempted suicide with a massive digoxin overdose. (In addition to the digoxin, seventeen 400 mg tablets of meprobamate had also been ingested.) Serum digoxin levels reached 35 ng/ml. Pronounced hyperkalemia was noted fourteen hours after ingestion. The patient responded to seven doses of 25 mg intravenous PHT over a period of thirty-six hours. The patient had complete heart block and PHT improved this to a first-degree block. The authors note that low doses of PHT were effective in this case and they suggest that it should be used early in the treatment of acute digoxin overdose.

1488. Rumack, B. H., Wolfe, R. R. and Gilfrich, H., Phenytoin (diphenythydantoin) treatment of massive digoxin overdose, Brit. Heart J., 36: 405-408, 1974.

Rotmensch, Graff, Ayzenberg, Amir and Laniado, Israel Journal of Medical Sciences (1977),2058 reported on three cases of suicide attempt with massive digoxin overdoses. Intravenous PHT was dramatically effective in controlling digitalis arrhythmias in these three patients. The authors suggest PHT’s early use in the treatment of this type emergency.

2058. Rotmensch, H. H., Graff, E., Ayzenberg, O., Amir, C. and Laniado, S., Self-poisoning with digitalis glycosides-successful treatment of three cases, Israel J. Med. Sci., 13: 1109-13, 1977.

Adamska-Dyniewska, Polskie Archiwum Medycyny Wewnetrznej(Warszawa) (1969), 3158 reported that phenytoin (100 and 300 mg orally) was given together with cardiac glycosides (deslanoside 0.4 mg and ouabaine, 0.25 mg intravenously) to 49 patients with chronic cardiac failure. Phenytoin leveled the digitalis-induced elongation of atrioventricular conduction, reduced the negative chronotropic action of ouabaine but did not impair the digitalis-induced dynamics of the complete ventricular contraction, as measured by the Q-IIA index. According to the author, combined administration of the average clinical doses of cardiac glycosides together with PHT in patients with chronic cardiac failure may be applied in such clinical conditions in that the chrono- and dromotropic action of digitalis must be counteracted but without any interference with its favorable effect on the heart muscle contractability (bradycardia due to digitalis or atrioventricular dissociation degree I and II).

3158. Adamska-Dyniewska, H., Effect of combined treatment with hydantoinal and cardiac glycosides on the dynamics of left ventricular contraction, Pol. Arch Med. Wewn., 43(1):985-9, 1969.

See also: Myocardial Infarction

Coltorti, Ivey, Bardy and Greene, Gionale Italiano di Cardiologia (1986), 3159 present a case report of a 71-year-old patient, who had undergone electrophysiological surgery for recurrent ventricular fibrillation. Postoperatively, the patient had atrial fibrillation with ventricular rates between 130 and 150/min that were suppressed with digoxin and quinidine. Subsequently, an accelerated junctional rhythm and atrial flutter, at the rate of 300/min, occurred. Intravenous procainamide (500 mg) resulted in conversion of atrial flutter to sinus rhythm and diminished the ventricular rate from 190 to 180/min. Digitalis toxicity was excluded as causal, based on the low serum level of the drug and on the recurrence of the junctional tachycardia during five days after digitalis withdrawal. Phenytoin (1000 mg intravenously) was effective in controlling the junctional rhythm on the sixth day of its occurrence. Oral phenytoin (300 mg/day) daily was initiated to prevent recurrent tachycardia. It was discontinued six weeks following surgery. Postoperative electrophysiological evaluation did not reveal any inducible ventricular arrhythmias. The patient has remained arrhythmia free on no antiarrhythmic medication over a follow-up period of twelve months.

3159. Coltorti, F., Ivey, T.D., Bardy, G.H., Greene, H.L., Double tachycardia following surgery for recurrent ventricular arrhythmias, G. Ital. Cardiol., 16: 522-526, 1986.

See also: Myocardial Infarction

Epstein, Plumb, Henthorn and Waldo, Pace (1987), 3160 reported on PHT treatment of inducible ventricular tachycardia as assessed by serial electrophysiologic studies (EPS). 64 patients, 53 males and 11 females, with inducible ventricular tachycardia, cardiac arrest or a ventricular tachyarrhythmia were administered PHT treatment. 38 subjects were treated intravenously with 1000 mg of PHT and 31 subjects were treated orally to achieve a serum level of 15-20 mcg/ml. Data from the study indicated the usefulness of PHT as an effective antiarrhythmic agent for the treatment of ventricular tachyarrhythmais as judged by patientsí response to electrophysiologic testing - when PHT is maintained at effective serum levels established during electrophysiologic testing, the incidence of subsequent arrhythmic events may be reduced.

3160. Epstein, A.E., Plumb, V.J., Henthorn, R.W., Waldo, A.L., Phenytoin in the treatment of inducible ventricular tachycardia: results of Electrophysiologic testing and long-term follow-up, Pace, 10(5): 1049-57, 1987.

See also: Myocardial Infarction

Vaksmann, Fournier, Davignon, Ducharme, Houyel and Fouron, American Journal of Cardiology (1990), 3161 a study from the division of Pediatric Cardiology, Sainte-Justine Hospital, and the University of Montreal, Montreal, Quebec, Canada reports that among 24 patients operated on for tetralogy of Fallot who were followed for 1 to 28 years. Forty-one patients demonstrated significant ventricular arrhythmias. The occurrence of ventricular arrhythmias correlated with the duration of the cardiopulmonary bypass surgery. Nine patients with significant ventricular arrhythmias were treated with PHT. Treatment was successful in 7 of the 9 patients.

3161. Vaksmann, G., Fournier, A., Davignon, A., Ducharme, G., Houyel, L., and Fouron, J.C., Frequency and prognosis of arrhythmias after operative "correction ì of tetralogy of fallot, Am. J. Cardiol., 66: 346-49, 1990.

See also: Myocardial Infarction

Smithdeal, Personal Communication (1992), 3162 conducted a study to evaluate the effectiveness of prophylactic phenytoin for prevention of cardiac arrhythmias associated with phenol face peels. Twenty consecutive patients who were to undergo a phenol-based chemical peel of the face were pretreated with phenytoin, 100 mg for 3 days preoperatively in an attempt to prevent cardiac arrhythmias from the cardiotoxic effects of phenol. Nineteen of the twenty patients exhibited no cardiac arrhythmias during their procedure. One patient exhibited one small run of PVC's readily corrected by a single bolus of 50 mg lidocaine intravenously. The average time of application of the phenol solution was 30 minutes. Phenytoin used prophylactically, appears to raise the cardiac threshold of excitability, thereby protecting against the cardiotoxic effects of phenol. There were no untoward effects attributable to phenytoin either preoperatively, intraoperatively, or post-operatively in any of these 20 patients.

3162. Smithdeal, C.D., Prevention of cardiac arrhythmias during chemical face peeling (phenol peel arrhythmias), Personal Communication, 1992.

See also: Under Basic Mechanisms, Anti-Tox

Suarez-Kurtz, Meneges, Lorga and Moraes, International Journal of Cardiology (1992), 3163 investigated the effects of phenytoin on the ventricular tachyarrhythmias of 11 patients with chronic chagasic myocarditis. Physical examination, laboratory tests and 24- to 48-hour ambulatory electrocardiogram (Holter) recordings were performed before, during (7 - 14 days) and after treatment with oral phenytoin (4 - 6 mg/kg/day in three divided doses). Significant (> 90%) reduction of couplets, bigeminy and runs of ventricular tachycardia were observed in 50 - 67% of the patients, whereas the frequency of isolated PVCs was significantly (> 70%) reduced in only 2 patients (18%). Proarrhythmic activity was not observed and adverse side effects were of mild intensity and usually transient, except in one patient, who developed pruritus and skin rash in the presence of toxic phenytoin serum levels (27 mcg/ml). The authors report that their results suggest that phenytoin may be useful for the control of repetitive forms of ventricular tachyarrhythmias in selected patients with chronic chagasic myocarditis.

3163. Suarez-Kurtz, G., Meneges Lorga, A., and Moraes, F.D., Effects of phenytoin on the ventricular tachyarrhythmias of chronic chagasí disease, Int. J. Cardiol., 36: 81-86, 1992.

See also: Myocardial Infarction

Da Paola, Gondin, Hara and Mendonca, Sao Paulo Medical Journal (1995), 3164 report on the clinical use of various 1A, 1B, and 1C antiarrhythmic agents in the treatment of patients with chronic chagasic cardiomyopathy and ventricular arrhythmias. Phenytoin was effective in controlling the ventricular arrhythmias in 2 of 11 patients. Propafenone was effective and tolerated in 41-66% of patients; mexiletine in 32-69% (with 19% side effects; and the beta blockers, 39-56%. The authors emphasize that this is only their clinical experience and a not a controlled study.

3164. De Paola, A.A., Gondin, A.A., Hara, V., and Mendonca, A., Medical treatment of cardiac arrhythmias in Chagasí heart disease, Sao Paulo Med. J., 113(2): 858-61, 1995.

See Also Refs:

3165. Jackson, L.K., Sustained and nonsustained ventricular tachycardia: genesis, significance, and management, Cardiovasc. Clin., 16(3): 83-100, 1986.

3166. Cain, M.E., Management of ventricular arrhythmias occurring in patients after myocardial infarction, Angiology, 39(3/2): 307-20, 1988.

3167. Vaksmann, G., Fournier, A., Van Doesburg, N.H., Kratz, C., Fouron, J.C., and Davingnon, A., Incidence and prognosis of Arrhythmias in post-operative tetralogy of fallot: long-term follow-up study, Circulation, 78(PT2): II-595, 1988.

3168. Kudenchuk, P.J., Kron, J., Walancie, C.G., Cutler, J.E., Griffith, K.K., and Mcanulty, J.H., Day-today reproducibility of antiarrhythmic tacharrhythmias drug trials using programmed extrastimulus techniques for ventricular tachyarrhythmias associated with coronary artery disease, Am. J. Cardiol., 66(7): 725-30, 1990.

3169. Kudenchuk, P.J., Halperin, B., Kron, J., Walance, C.G., Griffith, K.K., and Mcnulty, J.H., Serial electropharmacologic studies in patients with ischemic heart disease and sustained ventricular tachyarrhythmias: When is drug testing sufficient?, Am. J. Cardiol., 72(18):1400-5, 1993.

3170. Fisher, J.D., Krikler, D., and Hallidie-Smith, K.A., Familial polymorphic ventricular arrhythmias, J. Am. Coll. Cardiol., 34(7):2015-2022, 1999.

Cardiac Arrhythmias in Children

Garson, Kugler, Gillette, Simonelli and McNamara, The American Journal of Cardiology (1980),1847 reported the use of PHT in treating six young patients with chronic postoperative ventricular arrhythmias and abnormal hemodynamics following surgery for congenital cardiac defects. Arrhythmias varied from ten or more premature ventricular complexes per hour to bigeminy and ventricular tachycardia. PHT alone controlled the arrhythmias in five patients. In the sixth, a combination of PHT and disopyramide was effective.

1847. Garson, A., Kugler, J. D., Gillette, P. C., Simonelli, A. and McNamara, D. G., Control of late postoperative ventricular arrhythmias with phenytoin in young patients, Am. J. Cardiol., 46(2): 290-4, 1980.

Garson and Gillette, Pacing and Clinical Electrophysiology (1981), 2528 studied the effects of PHT in fifty-one young patients with chronic arrhythmias consisting of multiform premature ventricular contractions (PVCs), couplets and ventricular tachycardia. The patients were divided into three groups according to hemodynamics. PHT was the initial drug used, followed by the addition or substitution of other drugs if effective response was not obtained. Five patients were not responsive to any treatment. PHT alone corrected the arrhythmias in thirty-nine patients: twenty-two with severe, and sixteen with moderate hemodynamic abnormalities, and one with normal hemodynamics.  The authors observed that PHT was most effective in patients with the most abnormal hemodynamics, and say that PHT is the drug of choice for children with ventricular dysrhythmias.

2528. Garson, A., Gillette, P. C., Treatment of chronic ventricular dysrhythmias in the young, Pace, 4: 658-69, 1981.

Rocchini, Chun and Dick, American Journal of Cardiology (1981),2251 reviewing their records on treatment and follow-up of children with ventricular tachycardias of various etiologies, report that PHT abolished arrhythmias in four patients with ventricular tachycardia following tetralogy of Fallot repair. A combination of PHT and propanolol effectively controlled symptoms and abolished ventricular tachycardias in two patients with prolonged Q-T interval.

2251. Rocchini, A. P., Chun, P. O., and Dick, M., Ventricular tachycardia in children, Am. J. Cardiol., 47: 1091-7, 1981.

Kavey, Blackman and Sondheimer, American Heart Journal (1982), 2654 reported the effects of oral PUF in nineteen patients, seen consecutively, who developed ventricular premature complexes (VPCS) late after surgery for congenital heart disease. Arrhythmias included ventricular tachycardia, couplets and frequent multiform or uniform VPCS, documented by twenty-four-hour ambulatory ECG. Sixteen had undergone previous repair of the tetralogy of Fallot and three had had aortic valve surgery. Nine of these children had been unresponsive to previous treatment. PHT decreased ventricular dysrhythmias in all nineteen patients. The arrhythmias were completely suppressed in fifteen, and in four they were reduced to uniform VPCs. The authors state that the high rate of success in treating these patients, who are at particular risk for sudden death, and the relative lack of side effects suggest that PHT is the drug of choice for this patient group.

2654. Kavey, R. E., Blackman, M. S., Sondheimer, H. M., Phenytoin therapy for ventricular arrhythmias occurring late after surgery for congenital heart disease, Am. Heart J., 104: 794-8, 1982.

Maxwell, Martin and Yaster, Anesthesiology (1994), 3171 present case reports of two newborns who developed cardiac dysrhythmias while receiving epidural bupivacaine either by continuous infusion or by repeated bolus dosing. In both cases, the dysrhythmias were successfully treated with intravenous phenytoin after other therapies, including bretylium, had been unsuccessful.

3171. Maxwell, L.G., Martin, L.D., Yaster, M., Bupivacaine-induced cardiac toxicity in neonates: successful treatment with intravenous phenytoin, Anesthesiology, 80(3): 682-6, 1994.

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