digoxin and esmolol

A recently conducted observational study of the prehospital treatment of uncontrolled atrial fibrillation brought to light therapeutic inconsistencies by emergency providers in dealing with this dysrhythmia. A review of the literature suggests that digoxin lacks efficacy in controlling ventricular rate in atrial fibrillation and that the slow onset of digoxin makes its use in the emergency setting questionable. Because of their demonstrated ability to rapidly slow ventricular rate, the calcium channel blocker, diltiazem, or the beta-adrenergic blocker, esmolol, should be the preferred agents for treating rapid atrial fibrillation in the emergency department or the paramedic ambulance.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Diltiazem; Emergency Medical Services; Humans; Propanolamines

Safety and efficacy of simultaneous use of intravenous digoxin and esmolol in the control of rapid heart rate in 21 patients with atrial fibrillation or flutter was assessed. The mean age was 67 (range 40 to 90) years. Seven patients had class III congestive heart failure, with left ventricular ejection fraction between 18% and 61%. Baseline mean heart rate was 143 +/- 4. After 0.25 mg or 0.5 mg intravenous digoxin, esmolol was titrated with initial boluses from 2 mg/min to 16 mg/min in 25 minutes. A tolerated dose of esmolol infusion was adjusted for up to 48 hours. Rapid control of heart rate (29% decrease with heart rate 101 +/- 4) occurred at a mean interval of 21 minutes. Minimum heart rate was 87 +/- 4 at 90 minutes of treatment. Conversion to sinus rhythm occurred in five patients (25%), and one patient experienced mild transient congestive heart failure. No symptomatic hypotension or bronchospasm occurred. In conclusion, simultaneous use of digoxin and esmolol is effective in safely and rapidly controlling heart rate in atrial fibrillation or flutter.

Topics: Adrenergic beta-Antagonists; Aged; Atrial Fibrillation; Atrial Flutter; Digoxin; Drug Therapy, Combination; Heart Rate; Humans; Propanolamines; Time Factors

The effects of esmolol, an ultrashort-acting beta blocker, and verapamil were compared in controlling ventricular response in 45 patients with atrial fibrillation or atrial flutter, in a randomized, parallel, open-label study. Patients with either new onset (less than 48 hours, n = 31) or old onset (greater than 48 hours, n = 14) of atrial fibrillation or flutter with rapid ventricular rate were stratified to receive esmolol (n = 21) or verapamil (n = 24). Drug efficacy was measured by ventricular rate reduction and conversion to sinus rhythm. The heart rate declined with esmolol from 139 to 100 beats/min (p less than 0.001) and with verapamil from 142 to 97 beats/min (p less than 0.001). Fifty percent of esmolol-treated patients with new onset of arrhythmias converted to sinus rhythm, whereas only 12% of those who received verapamil converted (p less than 0.03). Mild hypotension was observed in both treatment groups. Esmolol compares favorably with verapamil with respect to both efficacy and safety in acutely decreasing ventricular response during atrial fibrillation or flutter. Moreover, conversion to sinus rhythm is significantly more likely with esmolol.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Atrial Fibrillation; Atrial Flutter; Blood Pressure; Clinical Trials as Topic; Digoxin; Female; Heart Rate; Humans; Male; Middle Aged; Multicenter Studies as Topic; Propanolamines; Random Allocation; Verapamil

The clinical pharmacology and pharmacodynamic data from several clinical trials are summarized. The pharmacokinetic profile of esmolol alone and in the presence of digoxin, morphine and warfarin was studied. Conversely the effect of esmolol on these drugs was monitored. No clinically important effects were observed on vital signs, blood chemistry or hematology. The pharmacokinetic interactions associated with administration of these drug combinations were statistically significant in several cases, but they were not considered to be of clinical importance.

Topics: Adrenergic beta-Antagonists; Clinical Trials as Topic; Digoxin; Drug Interactions; Humans; Infusions, Parenteral; Kinetics; Male; Morphine; Propanolamines; Time Factors; Warfarin

The need for new treatment strategies for cardiac arrhythmias has motivated our continuing development of gene therapeutic options. Previously, we reported a decreased heart rate in an acute model of atrial fibrillation after atrioventricular nodal gene transfer. Here, we expand those observations to persistent atrial fibrillation and severe heart failure.. After 3 weeks of atrial fibrillation, domestic swine received atrioventricular nodal gene transfer with adenoviruses encoding beta-galactosidase (beta-gal), wild-type Galpha(i2) (wtGi), or constitutively active mutant (cGi). Heart rates in awake, alert animals were not altered by beta-gal or wtGi. cGi caused a sustained 15% to 25% decrease in heart rate. The wtGi effect became evident with sedation. A tachycardia-induced cardiomyopathy was present before gene transfer. In the beta-gal group, cardiomyopathy worsened over time. In the wtGi group, the condition improved slightly, and in the cGi group, ejection fraction was near normal at the end of the study. TUNEL staining results corroborated this finding.. cGi overexpression in the porcine atrioventricular node causes physiologically relevant heart rate control in persistent atrial fibrillation. These data advance the development of gene therapy as a potential treatment for common cardiac arrhythmias.

Topics: Acute Disease; Adenoviridae; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrioventricular Node; Cardiac Pacing, Artificial; Digoxin; Diltiazem; Gene Expression Regulation; Genetic Therapy; Genetic Vectors; GTP-Binding Protein alpha Subunit, Gi2; GTP-Binding Protein alpha Subunits, Gi-Go; Heart Failure; Heart Rate; Propanolamines; Proto-Oncogene Proteins; Recombinant Fusion Proteins; Stroke Volume; Sus scrofa; Ultrasonography

Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Calcium Channel Blockers; Digoxin; Diltiazem; Drug Therapy, Combination; Emergency Medicine; Heart Failure; Humans; Propanolamines; Verapamil

An open-label baseline-controlled study was conducted in 11 healthy male subjects to study the possible interaction between the cardioselective, short-acting beta blocker esmolol and digoxin when administered concurrently under steady-state conditions. Steady-state concentration, elimination half-life, and the total body clearance of esmolol were not changed significantly (P greater than .05) by digoxin. Digoxin peak concentration and the time to reach the peak concentration were not affected by esmolol. However, the digoxin AUC during the six-hour esmolol infusion increased from 2.60 +/- 0.59 to 2.88 +/- 0.75 ng.hr/mL (P less than .05). There were no clinically significant changes in the heart rate and blood pressure during this drug interaction study. The PR intervals were similar between digoxin monotherapy and esmolol plus digoxin combined treatment. Although digoxin did not influence the kinetics of esmolol, the small increase seen in digoxin serum concentration during the combination therapy warrants that caution be exercised during concurrent administration of esmolol and digoxin to patients.

Topics: Adolescent; Adrenergic beta-Antagonists; Chromatography, High Pressure Liquid; Digoxin; Drug Interactions; Half-Life; Humans; Male; Propanolamines

Prompt control of heart rate is important for successful treatment of supraventricular tachyarrhythmias early after open heart surgery when sympathetic tone is high and ventricular response rates may be rapid. Esmolol, a new ultrashort-acting (9 minute half-life) beta-receptor blocking agent, was given by continuous intravenous infusion for up to 24 hours in 24 patients (21 with isolated coronary bypass surgery and 3 with valve replacement) 1 to 7 days after surgery. Atrial fibrillation was present in 9 patients, atrial flutter in 2 and sinus tachycardia in 13. Eleven patients had received intravenous digoxin (average dose 0.6 mg, average serum level 1.19 mg/100 ml) before esmolol infusion without adequate control of the supraventricular tachyarrhythmia. After a 1 minute loading infusion of esmolol (500 micrograms/kg per min), maintenance dose, titrated to heart rate and blood pressure response, varied from 25 to 300 micrograms/kg per min. After esmolol administration, at an average dose of 139 +/- 83 micrograms/kg per min, mean heart rate decreased from 130 +/- 15 to 99 +/- 15 beats/min. Within 5 to 18 minutes after initiation of therapy, all patients had achieved a 15% reduction in heart rate at a maintenance dose of 150 micrograms/kg per min or less. A 20% reduction in heart rate was attained in 19 of the 24 patients, and conversion to sinus rhythm occurred during esmolol infusion in 5 of the 11 patients with atrial flutter or fibrillation. Transient asymptomatic hypotension (less than 90/50 mm Hg) was seen in 13 patients, requiring cessation of esmolol therapy in 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic beta-Antagonists; Adult; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Blood Pressure; Cardiac Surgical Procedures; Digoxin; Dose-Response Relationship, Drug; Heart Rate; Humans; Hypotension; Infusions, Parenteral; Middle Aged; Postoperative Complications; Premedication; Propanolamines; Tachycardia