Efficacy of Cardioselective Beta-Adrenergic Blockade with Intravenously Administered Metoprolol in the Treatment of Supraventricular Tachyarrhythmias Ezra
A. Amsterdam,
MD, James
Kulcyski,
MD,
and
Michael
G. Ridgeway,
MD
The efficacy of intravenously administered metoprolol, a cardioselective beta-adrenergic blocking agent, was evaluated in the treatment of supraventricular tachyarrhythmias in 16 patients. The arrhythmias that were treated were atrial fibrillation (11 patients), atrial flutter (2 patients), supraventricular tachycardia (2 patients), and multifocal atrial tachycardia (1 patient). Mean dose of metoprolol was 9.5 mg (range: 2-15 mg) administered in one or two separate infusions of up to 7.5 mg each over a cumulative maximum interval of 25 minutes. In the 13 responders (81%), mean ventricular rate decreased from 134 ± 6 to 106 ± 7 beats/mm 10 minutes after metoprolol administration and was controlled for 40 to 320 minutes without further therapy. Minimum ventricular rate (98 ± 6 beats/mm) was reached 48 minutes after initiation of metoprolol. Metoprolol reduced ventricular rate by >15% (decrease of 26-60 beats/mm) in 11(69%) of 16 patients, including 9(82%) oil I patients with atrial fibrillation. In two other patients, one with atrial fibrillation and one with supraventricular tachycardia, ventricular rate was reduced by >12%. Hypotension, occurring in five patients, was the most frequent side effect but was transient and readily managed. Cardioselective beta-adrenergic blockade by metoprolol was rapidly effective in controlling ventricular rate in a majority of patients with supraventricular tachyarrhythmias and may be of particular use in selected patients with chronic obstructive pulmonary disease in whom intravenous beta-adrenergic blockade is indicated. Hypotension is an important potential side effect.
T
he efficacy of beta-adrenergic blocking agents has been demonstrated in the treatment of a variety of cardiac arrhythmias.15 Most clinical experience with this class of compounds pertains to propranolol’12 and esmolol,5 a recently developed ultrashort-acting beta blocker. Both propranolol and esmolol are nonselective beta blockers, limiting or contraindicating their use in a variety of conditions.1’6 Beta-blockers with relative cardioselectivity have broadened the indications and increased the applicability of this form of therapy. Initial reports in a limited number of patients have demonstrated effiFrom the Division of Cardiovascular Medicine, Department of internal Medicine, University of California School of Medicine, Davis, California. Address for reprints: Ezra A. Amsterdam, MD, Division of Cardiovascular Medicine, University of California, Davis, 4301 X Street, Room 2050,
Sacramento,
CA 95817.
714
#{149} J Ciin Pharmacol
1991;31:714-718
cacy of metoprolol, a beta-i adrenergic blocker, in the treatment of supraventricular tachyarrhythmias.7#{176} However, there has been only one evaluation of intravenously administered metoprolol in patients with sustained supraventricular arrhythmias.1#{176}The purpose of this investigation was to further evaluate the use and safety of intravenous metoprolol (Ciba-Geigy, Summit, NJ) in the treatment of cardiac arrhythmias of supraventricular origin related to diverse etiologies. Materials
The
and
Methods
study group comprised 16 hospitalized patients men, 4 women) of mean age 60 years (range: 2786 yr). The arrhythmias consisted of atrial fibrillation (11 patients), atrial flutter (2 patients), supraventricular tachycardia (2 patients), and multifocal (12
METOPBOLOL
IN SUPRAVENTRICULAB
atrial tachycardia (I patient). Diagnoses included coronary artery disease (3 patients), chronic obstructive pulmonary disease (3 patients), lymphoma (I patient), rheumatic heart disease (1 patient), post-abdominal aortic aneurysmectomy (I patient), hypertensive heart disease (I patient) and no detectable organic disease (6 patients). Five patients were already on treatment with other antiarrhythmic agents (quinidine, 3 patients; digitalis, 2 patients) at the time of metoprolol administration. Written, informed consent, which was approved by our Institutional Human Subjects Review Committee, was obtained before entering each patient into the study.
ARRHYTHMIAS
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Electrocardiographic
Data
The mean ventricular rate before metoprolol therapy for the entire group of patients was 140 beats/ mm (range: 100-186 beats/mm). Persistence of tachyarrhythmia was documented after 5 minutes of bedrest by 12-lead electrocardiogram and 1-minute rhythm strip (lead II), following which the rhythm was monitored an additional 10 minutes after venipuncture before initiating metoprolol infusion. The patients were monitored at bedside with frequent electrocardiographic rhythm strips (5-10 minutes for the first hour and every 30-60 minutes thereafter) of one-half to 1 minute duration. Response of cardiac rhythm and rate to metoprolol was analyzed over an interval of 320 minutes drug administration. Data are expressed as mean ± standard error of the mean. Metoprolol
Administration
Metoprolol infusion rate was I mg/mm until satisfactory response (decrease of ventricular rate to 15% (decrease of 26-60 beats/mm) in 11 (69%) patients. In another two patients, reduction of ventricular rate was >12%. Mean metoprolol dose in the 13 responders was 10.2 mg (range: 3-15 mg), and in the three nonresponders was 6.6 mg (range: 2-12 mg). In two of three nonresponders, lack of efficacy was related to adverse reactions to metoprolol, which limited dose of the drug to 40 and 80% of the average effective dose in the responders. Eight responders required part or all of the second metoprolol infusion to achieve therapeutic effect. In the responsive group, there was no consistent relationship between dose of metoprolol and magnitude of ventricular rate reduction (Figure 2). No patient converted to normal sinus rhythm after metoprolol therapy alone within the 320-minute monitoring period. In one patient, angina associated with tachycardia was alleviated by controlling ventricular rate with metoprolol. A therapeutic effect on ventricular rate was achieved in 10 of 11 patients with atrial fibrillation, both patients with supraventricular tachycardia, the single patient with multifocal atrial tachycardia, but
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neither patient with atrial flutter. Of the three nonresponsive patients, one patient was in the group (n = 5) which had received prior antiarrhythmic therapy; whereas, the other two were in the group (n = II) which was not on any other antiarrhythmic agent. Side
Effects
Metoprolol was associated with nine adverse reactions in seven patients (Table I). Five patients experienced hypotension (defined as a decrease in systolic blood pressure to