Use of bretylium tosylate in the management of acute myocardial infarction

doi:10.1016/0002-9149(71)90256-6

The American Journal of Cardiology

Volume 27, Issue 2, February 1971, Pages 177-189

https://doi.org/10.1016/0002-9149(71)90256-6 Get rights and content

Abstract

Sixty-two patients with acute myocardial infarction were treated for 4 days with bretylium tosylate. This agent was effective in suppressing and preventing ventricular fibrillation as well as other irritable arrhythmias and heart block. On admission 37 patients had arrhythmias and 2 complete atrioventricular (A-V) block; 23 had no rhythm disturbances and were treated prophylactically. Of the 37 patients with arrhythmias, 11 had been treated with lidocaine without success. Eight patients had from 1 to 5 episodes of ventricular fibrillation (not suppressed by lidocaine in 7) before treatment with bretylium, but no patient had ventricular fibrillation after bretylium therapy was started. Ventricular arrhythmias were suppressed in from 10 minutes to 12 hours on routine dose therapy; the response indicated a sharp dose-dependent effect for complete suppression. Twenty-two of the 23 patients treated prophylactically had no arrhythmias. One patient had fatal ventricular fibrillation $512$ hours after the first dose was administered and just before the second dose was due; this was the only death due to arrhythmia in the 62 patients. Of the 60 patients without heart block on admission, only 1 had heart block of any degree during treatment. There were 8 deaths in the hospital (12.9 percent), 7 as a result of pump failure. If 2 patients who were in extremis before treatment was started, and who died before an effect could have occurred, are excluded, mortality was under 10 percent. Our previous mortality in the unit was 20 percent. The actions of bretylium in increasing contractile strength, impulse formation and conduction velocity in addition to suppressing rhythm disturbance make it a valuable agent for the management of the major complications of acute myocardial infarction.

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Cited by (37)

Class II antiarrhythmic agents
1988, Pharmacology and Therapeutics
Antifibrillatory drugs: The case for bretylium tosylate
1984, Annals of Emergency Medicine
The preferred treatment for ventricular fibrillation (VF) refractory to maximal electrical defibrillation remains controversial, as evidenced by recent changes in the American Heart Association's treatment algorithm. To date there have been no published studies conclusively proving one mode of therapy to be superior to another. There is, however, an abundance of animal and clinical data suggesting that bretylium tosylate (BT) is the drug of choice in this setting. In animal studies BT has been shown to lower the canine defibrillation threshold, to facilitate conversion of hypothermia-induced ventricular fibrillation, and to effect spontaneous defibrillation. In 15 years of clinical use as a drug of last resort, and more recently as a first-line drug, BT has developed an impressive track record. Most of the clinical reports are uncontrolled and/or retrospective, but they share a central theme: BT is effective in the treatment of VF refractory to standard therapy. Several small studies have reported successful conversion of VF to a stable rhythm with BT after failure of standard electrical and pharmacologic therapy. Recent studies suggest that earlier use of BT may be associated with improved outcome. Finally, as in animal studies, spontaneous defibrillation has been reported. It is important to note that no drug currently used in the treatment of countershock-refractory VF has been proven effective. The use of some of these drugs is based on tradition rather than scientific evidence. The bulk of currently available scientific data indicates that BT is superior to other commonly used antiarrhythmics in the treatment of VF resistant to countershock. There is, therefore, no good rationale for withholding BT until “standard” therapy has proven to be ineffective.
New directions in antiarrhythmic drug therapy
1984, The American Journal of Cardiology
Cardiac arrhythmia causing sudden cardiac death is a serious worldwide public health problem. Antiarrhythmic agents have been available for therapy, but the conventional agents cause a high degree of intolerable side effects. The recent development of many new experimental antiarrhythmic agents has increased our capacity to effectively treat cardiac arrhythmias. Using a multifaceted approach of programmed electrical stimulation studies, drug level determinations, exercise testing and 24-hour ambulatory Holter monitoring, it can reasonably be decided which patient needs therapy and if therapy is going to be effective. Both aspects of the sudden death equation, ectopy frequency (triggering mechanism) and the ability to propagate sustained ventricular tachycardia (substrate), may be examined. Careful follow-up is needed to determine continued drug efficacy and the presence of side effects that may compromise patient compliance with therapy. If side effects intervene that may cause continued therapy to be intolerable, changing the antiarrhythmic agent, as opposed to decreasing the dosage to an ineffective range, may be appropriate. A comprehensive approach to arrhythmia management may begin to reduce the high incidence of sudden death due to fatal arrhythmias.
Electrophysiologic effects of bretylium on canine ventricular muscle during acute ischemia and reperfusion
1983, American Heart Journal
Electrophysiologic effects of bretylium were assessed on a recently developed animal model for analysis of conduction of premature impulses and excitation threshold. Bretylium was administered intravenously 10 mg/kg over 10 minutes followed by 2 mg/min of infusion immediately after coronary ligation. Conduction of the premature impulse was recorded in the epicardial and endocardial sites both in the base-to-apex and apex-to-base directions, in the normal, in the center, and across the border of ischemic myocardium. Compared to the control group of animals, bretylium did not cause any significant change in the conduction characteristics in the ischemic myocardium; however, it delayed the conduction of premature impulses in the normal myocardium. Thus the disparity in conduction times between the normal and the ischemic myocardium was lessened by bretylium. Further, conduction of impulses from normal tissue across the border of ischemia was also delayed. Bretylium also decreased the excitability threshold in the ischemic myocardium, although the normal myocardial excitation threshold was unaffected. These unique effects of bretylium on conduction and excitability in the normal, in the center, and across the border of ischemic myocardium, when a therapeutic dosage of the drug is used, further validate its antiarrhythmic potential and offer an insight into its mechanism of action in the setting of acute myocardial ischemia.
Electrophysiologic testing of bretylium tosylate in sustained ventricular tachycardia
1983, American Heart Journal
We used programmed ventricular stimulation to test intravenous bretylium tosylate in 10 consecutive patients with inducible sustained ventricular tachycardia (usually refractory to type I antiarrhythmic agents). These 10 patients had previously documented sustained ventricular tachycardia and/or ventricular fibrillation complicating stable heart disease. Following control inductions of sustained ventricular tachycardia, bretylium 10 mg/kg was infused over 30 minutes. Thirty minutes after this infusion, sustained ventricular tachycardia could be induced in 9 of the 10 patients (one of these nine patients also had bretylium-potentiated spontaneous ventricular tachycardia). Tachycardia induced in the nine patients after bretylium was similar to control tachycardia with respect to morphology and cycle length (333 ± 16 msec after bretylium versus 330 ± 16 msec during control). However, five of the nine patients tolerated induced tachycardia less well after bretylium (exacerbated hypotension). In one patient, ventricular tachycardia could not be induced after intravenous bretylium.
Antiarrhythmic, antifibrillatory, and hemodynamic actions of bethanidine sulfate: An orally effective analog of bretylium for suppression of ventricular tachyarrhythmias
1982, The American Journal of Cardiology
Bethanidine sulfate is a chemical and pharmacologie analog of bretylium tosylate that has virtually identical antifibrillatory and inotropic actions on the heart. Bretylium is the only drug approved by the Food and Drug Administration specifically for the “prophylaxis and treatment of ventricular fibrillation.” Unlike bretylium, which is poorly absorbed from the gut and limited to parenteral use, oral bethanidine is absorbed rapidly. Bethanidine was given to 23 patients with recurrent multiple drug refractory ventricular tachycardia and fibrillation. Eighteen patients (78%) had complete suppression of spontaneous or electrophysiologically inducible tachyarrhythmias; 3 were improved and 2 had no benefit. In 6 of a 9 patient subgroup studied by programmed electrophysiologic drug testing, bethanidine completely prevented previously inducible ventricular tachyarrhythmias at the maximal stimulus tested (including 4 extrastimuli and burst-pacing at 10 times threshold). Cardiac output measured in 6 patients 1 to 2 hours after bethanidine was increased in 4, unchanged in 2, and decreased in 1. Ten patients on long-term therapy with bethanidine and protriptylene (to prevent orthostatic hypotension) have been free of arrhythmias from 2 to 26 (average 13) months.

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^☆: This work was supported in part by the J. Phillips Foundation, Minneapolis.

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Report on therapyUse of bretylium tosylate in the management of acute myocardial infarction☆

Abstract

Amer J Med

Amer J Cardiol

Amer J Cardiol

Amer J Cardiol

Amer J Cardiol

Life Sci

Amer J Cardiol

Amer J Cardiol

Amer J Cardiol

Lancet

Arrhythmias in acute myocardial infarction

New Eng J Med

The coronary care unit

JAMA

Intensive coronary care

New Eng J Med

Ventricular fibrillation in myocardial infarction (abstr)

Circulation

Lidocaine therapy after acute myocardial infarction

Brit Med J

Bretylium tosylate for suppression of induced ventricular fibrillation

Amer J Cardiol

Effect of bretylium tosylate on ventricular fibrillation threshold

Arch Intern Med (Chicago)

Bretylium tosylate for suppression of ventricular fibrillation after experimental myocardial infarction

Nature (London)

Nota Prelimirrare Sull'impiego del Tosolato di Bretilio Quale Agente Antiaritmico

L'Ospedale Magglore, Rivista Mensile Deg li Instituti Ospitaliere di Milano

Report on therapy
Use of bretylium tosylate in the management of acute myocardial infarction☆