Esmolol

Multifocal atrial tachycardia (MAT) is a supraventricular tachydysrhythmia precipitated by a number of pharmacologic and physiologic disturbances. Corrections of these disturbances should take precedence in the treatment of MAT.

The following is a report of our experience with esmolol in the treatment of multifocal atrial tachycardia (MAT). We successfully terminated this dysrhythmia in a 79-year-old patient refractory to digoxin and verapamil who had begun to develop angina as a result. Results were achieved at an extremely low dose level, and no apparent untoward effects were experienced, despite his history of severe chronic obstructive airway disease.

CASE REPORT

A 79-year-old man was admitted to the hospital for a radical cystectomy and ileoconduit for transitional cell carcinoma of the bladder. His medical history was significant for chronic obstructive pulmonary disease, non-insulin-dependent diabetes mellitus, peripheral vascular disease, remote inferior wall myocardial infarction, and a 100-pack-year smoking history.

After an uneventful operation, the initial hospital course was complicated by left lower lobe pneumonia on the fourth postoperative day. Respiratory distress ensued ten days later, after the patient aspirated. Telemetry had revealed intermittent atrial fibrillation. Medications included methyl prednisolone, aminophylline infusion, furosemide, digoxin, insulin, and ceftazidime. With stabilization of his respiratory status and termination of the aminophylline infusion, his rhythm returned to baseline, sinus tachycardia. Within the next 24 h, MAT developed with ventricular response rates of 150 to 170 beats per minute (Fig 1). Vital signs included blood pressure of 105/80 mm Hg, apical heart rate of 170, radial pulse of 90, and respiratory rate of 28. The jugular veins were not distended. Breath sounds were diminished bilaterally, but there were no wheezes. Other than tachycardia, findings from the cardiac examination were unremarkable. Laboratory studies included a serum digoxin level of 1.0, potassium of 4.4, magnesium of 2.1, and serum theophylline of 13.9. Arterial blood gas values on 3 L of nasal cannula were pH of 7.54, [Pco.sub.2] of 21, and [Po.sub.2] of 62 MAT was not affected by increments of verapamil totaling 15 mg over 2 hs, and 0.25 mg intravenous digoxin. With the tachycardia remaining refractory, the patient subsequently developed angina.

Intravenous esmolol was administered as a 500 [mu]g/kg loading dose over 1 min. This was followed by a 50 [mu]g/kg/min maintenance infusion. Baseline blood pressure was 104/80 mm Hg with a heart rate of 154. Fifteen minutes after the initiation of the infusion, the rhythm converted to sinus tachycardia, rate of 110 beats per minute, with a blood pressure of 115/80 mm Hg (Fig 2). With the rhythm converting to sinus rhythm, the patient's angina resolved. The maintenance dose of 50 [mu]g/kg/min was continued for the next 18 hs, tapered over 6 hs, and then discontinued. Over the next 24 h, the rhythm remained unchanged. However, respiratory failure ensued, requiring intubation and mechanical ventilation, and it was believed to be secondary to his prior pneumonitis, inability to compensate for metabolic acidosis, and volume retention due to acute renal failure. Despite corrective efforts, the patient died within 24 hs.

DISCUSSION

The electrocardiographic features of MAT include the following: (1) atrial rate of greater than 100 beats per minute; (2) three morphologically distinct P waves in a single ECG lead; and (3) variable R-R, P-P, and P-R intervals.[1-3] Although MAT is usually not a direct cause of death, patients developing this dysrhythmia have in-hospital mortality rates of 29 to 60 percent. These patients frequently are elderly and have advanced cardiopulmonary disease.[1-4]

Hypoxemia, acidemia, hypokalemia, hypomagnesemia, myocardial ischemia, and drugs such as theophylline, beta-adrenergic agonists, and digitalis have been associated with MAT.[5-7] The electrophysiologic mechanism for this dysrhythmia is thought to be related to a hyperadrenergic state that triggers abnormal atrial automatic activity.[5,8,9] MAT is usually self-limiting with corrections of these disturbances, and refractory cases are relatively uncommon.

In critically ill patients, rapid hemodynamic decompensation may result from accelerated heart rates, especially in those with compromised cardiopulmonary reserve.[6] In these patients, pharmacologic intervention to reduce heart rate or convert to sinus rhythm may be beneficial. MAT has been refractory to many modes of therapy, including class 1A and 1B antiarrhythmic agents, digoxin, and direct current cardioversion.[1-3,5-7] Variable success rates have been reported with verapamil and metoprolol.[3-7] Verapamil has resulted in modest reductions in heart rate, with a 23 to 38 percent incidence of conversion to sinus rhythm. Metoprolol has recently been shown to be more effective than verapamil in a recent randomized double-blinded, placebo-controlled study.[6] The [beta]1-receptor selectivity of metoprolol has yielded a favorable side effect profile in the treatment of MAT, even in patients at risk to [beta]-blockade.[5-7] Nevertheless, the potential for bronchospasm does exist at higher dosages. Additionally, the elimination half-life of metoprolol (2 to 6 h) may be of concern should adverse effects occur.[5-7]

Esmolol, an ultra-short-acting intravenous [beta]-blocker, has cardioselectivity similar to metoprolol, and has been reported to be safe and effective in the treatment of supraventricular tachycardias.[9-13] Its characteristics include a distribution half-life of 2 min, elimination half-life of 9 mins, and a duration of action of 5 to 10 min. Multicenter, double-blinded parallel studies have reported esmolol superior to placebos and as effective as propranolol in controlled supraventricular tachycardia.[10,12,14] Esmolol has been used safely and effectively in critically ill patients, and patients at high risk to [beta]-blocker therapy.[14] Hypotension has been the major adverse effect, ranging in incidence from 12 to 44 percent,[9-14] with the majority of these patients appearing asymptomatic. Symptomatic hypotension in these patients resolved either during the infusion or within 30 min after its discontinuation.

Although a number of reports have noted the usefulness of esmolol in the treatment of supraventricular tachycardias, information specifically addressing its dose and therapeutic responses in the treatment of MAT are lacking.

In this report, MAT converted to sinus rhythm within 15 min after the initiation of esmolol infusion. The dosage at which conversion occurred was 50 [mu]g/kg/min. This was below the therapeutic dosage used for supraventricular tachycardias (97 to 115 [mu]g/kg/min).[10-12] Dose response, however, has been reported to range from 50 to 300 [mu]g/kg/min.[10-12] The ease of titration of esmolol allowed for adequate antiarrhythmic effect without significant adverse side effects.

REFERENCES

[1] Phillips J, Spano J, Burch G. Chaotic atrial mechanism. Am Heart J 1969; 78:171-79

[2] Lipson MJ, Naimi S. Multifocal atrial tachycardia (chaotic atrial tachycardia), clinical associations and significance. Circulation 1970; 42:397-407

[3] Shine KI, Kastor JA, Yurchach PM. Multifocal atrial tachycardia, clinical and electrocardiographic features in 32 patients. N Engl J Med 1968; 279:344-49

[4] Hazard PB, Burnett CR. Verapamil in multifocal atrial tachycardia hemodynamic and respiratory changes. Chest 1987; 91:68-70

[5] Hazard PB, Burnett CR. Treatment of multifocal tachycardia with metoprolol. Crit Care Med 1987; 15:20-5

[6] Arsura E, Lefkin AS, Scher DL, Solar M, Tessler S. A randomized double-blind, placebo-controlled study of verapamil and metoprolol in the treatment of multifocal atrial tachycardia. Am J Med 1988; 85:519-24

[7] Arsura E, Solar M, Lefkin AS, Scher DL, Tessler S. Metoprolol in the treatment of multifocal atrial tachycardia. Crit Care Med 1987; 15:591-94

[8] Levine JH, Michael JR, Guarnier T. Treatment of multifocal atrial tachycardia with verapamil. N Engl J Med 1985; 312:21-5

[9] Byrd RC, Sung RJ, Parmley W. Safety and efficacy of esmolol (ASL-8052: an ultra short acting beta-blocking agent) for control of ventricular rate in supraventricular tachycardia. J Am Coll Cardiol 1984; 3:394-99

[10] Abrams J, Allen J, Allin D, Anderson D, Anderson J, Blanski L, et al. Efficacy and safety of esmolol vs propranolol in the treatment of supraventricular tachycardias: a multicenter double-blind clinical trial. Am Heart J 1985; 5:913-22

[11] Anderson S, Blanski L, Byrd RC, Das G, Engler R, Laddu A, et al. Comparison of the efficacy and safety of esmolol, a short-acting beta blocker, with placebo in the treatment of supraventricular tachyarrhythmias. Am Heart J 1986; 111:42-8

[12] Morganroth J, Horowitz L, Anderson J, Turlapaty P, and Esmolol Research Group. Comparative efficacy and tolerance of esmolol to propranolol for control of supraventricular tachyarrhythmia. Am J Cardiol 1985; 56:33F-39F

[13] Esmolol Research Group. Intravenous esmolol for the treatment of supraventricular tachyarrhythmia: results of a multicenter, baseline-controlled safety and efficacy study in 160 patients. Am Heart J 1986; 112:498-505

[14] Gray RJ. Managing critically ill patients with esmolol, an ultrashort acting beta-adrenergic blocker. Chest 1988; 93:398-403

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