Background
Atrial fibrillation is the most frequent dysrhythmia managed in the ED, making up 0.5-1.0% of ED visits worldwide. Recent-onset AF (RAF) is typically defined as AF that has been present for < 48 hours.1 As clinicians, we certainly have a higher level of concern when a patient presents to our ED in rapid atrial fibrillation with associated symptoms such as chest pain, hypotension, heart failure or myocardial infarction. Urgent rate control or rhythm correction is ideal in these situations. However, there is quite a bit of variation in the treatment of atrial fibrillation in regards to rate versus rhythm control, choice of drugs, and use of electrical cardioversion depending on region of the world.2 Treatment options include Beta Blockers, Non-dihydropyridine calcium channel blockers, Digoxin, Amiodarone or Synchronized Cardioversion.
This study suggests a target ventricular rate control of 100 beats per minute in the acute setting.3 However, recommendations in the united states suggest a rate control of < 110 bpm for asymptomatic patients and less than 80 bpm for symptomatic patients.4 Beta-blockers or calcium channel blockers are considered first line agents in the United States to achieve this aim.4 Although, these medications should be used with caution in cases of hypotension, heart failure, or depressed left ventricular function. In such instances, some authors advocate the use of amiodarone. Amiodarone blocks multiple ion channels and acts as a noncompetitive beta-adrenergic antagonist. It has a half-life of weeks and large volume of distribution into adipose tissue. It can cause suppression of sinus and AV nodal function within the first few days of oral therapy but the antiarrhythmic effect and QT prolongation can be delayed for days or weeks.4 Even though intravenous amiodarone can be used for rate control in critically ill patients without pre-excitation, it is less effective than non-dihydropyridine calcium channel blockers and requires a longer time to achieve rate control (7 hours for amiodarone versus 3 hours for diltiazem).4 Esmolol, unlike many other beta-blockers, is a fast-acting and short-lasting drug that allows the provider to administer repeated doses at increasing dosages and, if necessary, subsequent administration of second-line antidysrhythmic agents with limited risk of cumulative adverse effects.5
Study Design
Retrospective survey conducted in three different MICUs in France by analyzing patient records between 2002 and 2013. The purpose of this study was to compare the short-term effectiveness of IV esmolol to that of IV amiodarone to treat severe Recent-onset Atrial Fibrillation (RAF) in an emergency setting.
Blinding: All identifying information and outcome data were masked during the matching procedure.
Inclusion Criteria:
- Acute atrial fibrillation (suspected onset delay < 12 h)
- Male or female aged >18y
- Prehospital management by investigating MICU
- Amiodarone or esmolol infusion by MICU
- Clinical presentation including one or more of the following:
- Chest pain (angina pectoris)
- ST shift
- Shock (BP < 90/50)
- Cerebral flow impairment
- Very high HR (>MHR + 30)
Exclusion Criteria:
- Symptom onset > 12 h
- Electric counter-shock by MICU
- Acute pulmonary edema
- Suspected STEMI
- Hemorrhagic shock
- Severe COPD
- Asthma
Sample Size:
- Esmolol group (n = 100)
- Amiodarone group (n = 200), a blind matching procedure two for one was employed: investigators selected 200 patients among 1200 who met the inclusion criteria and had been treated with amiodarone.
Interventions:
IV Amiodarone Protocol
- Standardized infusion for all patients:
- 300 mg IV over 30 min with electric syringe through regular flow (10 mg/min)
- If weight < 40 kg, consider 150 mg during 30 min IV regular flow (5 mg/min)
- If weight > 90 kg, consider 450 mg during 30 min IV regular flow (15 mg/min)
IV Esmolol Protocol
- Goal-guided therapy: every 3 to 5 min inject 0.5 mg/kg IV bolus combined with four-step increasing electric syringe flow: 0.05, 0.10, 0.15, and 0.20 mg/kg/min.
- When desired result is observed (conversion to sinus rhythm or ventricular rate stabilized), stop bolus sequence and maintain electric syringe flow at its level.
- If undesirable side effects appear, cease esmolol administration.
- Maximum dose is 4 times the 0.5 mg/kg IV bolus and 0.20 mg/kg/min electric syringe flow.
Primary outcome criteria:
- Ventricular rate of100 bpm within 40 min after IV treatment initiation
Secondary outcome criteria:
- Rhythm control (conversion to sinus rhythm) from 10 to 120 min after treatment initiation
- Ventricular rate of 90 bpm from 10 to 120 min after treatment initiation
- Rate control = ventricular rate of 100 bpm from 10 to 120 min after treatment initiation
- Ventricular rate of 120 bpm from 10 to 120 min after treatment initiation
Results
- Response at 40 min was not affected by patients with ongoing oral treatment:
- Rate control was 39% for patients with ongoing oral treatment and 38% for patients without ongoing oral treatment (60% and 66%, respectively in the esmolol group, 28% and 24% in the amiodarone group, p > 0.05).
- Gender did not affect treatment effectiveness.
- Successful treatment was decreased the further out the patient was from symptom onset on presentation (p< 0.001).
Effect of Drug Treatment on Heart Rhythm
- Esmolol: 64% rate controlled at 40 minutes (average HR decreased from 154 bpm to 95 bpm)
- Amiodarone: 25% rate controlled at 40 minutes (average HR decreased from 154 bpmto 115 bpm
- 20 min, 40 min, and 60 min response better with esmolol than with amiodarone
- Esmolol superior for rhythm control, rate control and 20% heart rate reduction.
Three patients involved in this study were treated with electrical cardioversion (1 out of 100 in the esmolol group and 2 out of 200 in the amiodarone group) due to persisting very rapid atrial fibrillation with chest pain or clinical shock. All 3 patients converted to sinus rhythm and were symptom free after electrical procedure (one patient in the amiodarone group required two attempts).
Effect of Drug Treatment on Blood Pressure:
- Transient hypotension (MAP < 70 mmHg for < 30 min) was 14% in the esmolol group and 12% in the amiodarone group
- Durable hypotension (MAP < 70 mmHg for > 30 min) was 4% in the esmolol group and 9% in the amiodarone group.
- Among patients with initial mean arterial pressure (MAP) < 70 mmHg, blood pressure improved with amiodarone in 15 out of 24 (63%) cases and with esmolol in 9 out of 11 (82%) cases.
- Although the comparison for blood pressure evolution seems to show slight differences in favor of esmolol, statistical tests were all nonsignificant (p > 0.05).
- This study indicates both drugs have fairly similar hemodynamic effects on this patient population.
Author Conclusions:
- Both drugs showed a significant delay in efficacy.
- When severe symptoms are present, the sooner these medications are initiated, the better.
- This study suggests that Esmolol is superior to amiodarone for short-term effectiveness.
- Authors suggest Esmolol is quick, efficient, and safe, and should be considered a primary intention antidysrhythmic agent for acute RAF.
Limitations:
- This study is not randomized, but a retrospective analysis.
- The two groups were established on the basis of treatment option, which itself depended on the experience and knowledge of the treating physicians.
- It took 11 years to complete the esmolol group with 100 consecutive patients
- Previous severe RAF (with chest pain, ST shift, shock, or very high heart rate) was not registered.
- 30% of the patients were receiving oral antidysrhythmic treatment prior to study enrollment.
- This review was limited to the amiodarone vs. esmolol comparison.
- This study was not designed to explore thromboembolism occurrence, long-term rhythm control, or survival.
Discussion
Amiodarone is not considered a first line agent in these patients in the United States, so the overall objective in this study is unlikely to change clinical practice in this region. However, a few good points come from this study. Beta-blockers and non-dihydropyridine calcium channel blockers are both well-established first line agents for rate control in atrial fibrillation.4 Selection of these agents given as an IV bolus are often times limited by a certain degree of hypotension. Traditional Diltiazem bolus dosing is typically done with a starting dose of 0.25 mg/kg followed by a 0.35 mg/kg bolus, if necessary. This approach is often limited by a blood pressure, leaving the clinician searching for other less established treatment options in these patients.
Low dose Diltiazem at a dose of 0.1 mg/kg has been shown to achieve a similar success rate with less hemodynamic effects.7 Bolus-from-the-bag Diltiazem at a dose of 2.5 mg/min (max 50 min) and hold for hypotension or rate control is also a viable option, although this was really studied in supraventricular tachycaradia.8
Enter Esmolol…
It sure seems like a good candidate medication for patients with relative hypotension with its fast-on, fast-off kinetics and half-life of about 9 minutes. Not to mention, it sure has been getting some good press lately in regard to its use for rate control in septic shock and for its use in refractory ventricular fibrillation.9,10
This study gives a bit more insight into the hemodynamic effects of Esmolol that we can compare to a medication still quite frequently used for patients with atrial fibrillation and relative hypotension and I feel we should consider it more. It would be nice to see a dedicated study involving Esmolol in comparison to Diltiazem for rapid atrial fibrillation in patients with relative hypotension.
References
- Lip GYH, Watson T. Atrial fibrillation (acute onset). BMJ Clin Evid 2008;5:210.
- Rogenstein C, Kelly A-M, Mason S, et al. An international view of how recent-onset atrial fibrillation is treated in the emergency department. Acad Emerg Med 2012;19:1255–60.
- Kolia M, Alexandra B, et al. Esmolol compared with Amiodarone in the treatment of recent-onset atrial fibrillation (RAF): An Emergency Medicine external validity study. The Journal of Emergency Medicine.2019;56(3):308-18
- January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guide- line for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/Amer- ican Heart Association Task Force on practice guidelines and the Hearth Rhythm Society. J Am Coll Cardiol2014;130:2071–104
- Milicevic G, Gavranovic Z, Bakula M. Successful conversion of recent-onset atrial fibrillation by sequential administration of up to three antiarrhythmic drugs. Clin Cardiol2008;31:472–7
- Shen SL, Zhao IC. A comparative study on the efficacy and safety of intravenous esmolol, amiodarone and diltiazem for controlling rapid ventricular rate of patients with atrial fibrillation during anesthesia period. Zhonghua Xin Xue Guan Bing Za Zhi 2010;38:989– 92.
- Lee J, et al. Low-dose diltiazem in atrial fibrillation with rapid ventricular response. Am J Emerg Med. 2011 Oct;29(8):849-854.
- Lim SH, et al. Slow-infusion of calcium channel blockers in the emergency management of supraventricular tachycardia. Resuscitation. 2002 Feb;52(2):167-174.
- Morelli A, et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA. 2013 Oct 23;310(16):1683-1691.
- Driver BE, et al. Use of esmolol after failure of standard cardiopulmonary resuscitation to treat patients with refractory ventricular fibrillation. Resuscitation. 2014 Oct;85(10):1337-1341.
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