(Circulation. 1995;92:3264-3272.)
© 1995 American Heart Association, Inc.
Articles |
Dose-Ranging Study of Intravenous Amiodarone in Patients With Life-Threatening Ventricular Tachyarrhythmias
Presented in part at the 66th Scientific Sessions of the American Heart Association, Atlanta, Ga, November 8-11, 1993.
Correspondence to Melvin Scheinman, MD, MU East Tower, 4th Floor South, Box 1354, University of California, San Francisco, CA 94143-1354.
Background Oral amiodarone effectively suppresses ventricular arrhythmias; however, full activity may take days or weeks. In patients with frequent, life-threatening ventricular arrhythmias, this delay is not acceptable. Thus, in these patients, the speed and dosing accuracy of an intravenous formulation would be beneficial. The goal of this study was to demonstrate the efficacy of intravenous amiodarone in patients with refractory, recurrent hemodynamically destabilizing ventricular tachycardia or ventricular fibrillation by determining a dose response among three regimens.
Methods and Results A total of 342 patients were enrolled at 46 medical centers in the United States. Patients received one of three randomized, double-blind dose regimens delivering 125, 500, or 1000 mg during the first 24 hours. Supplemental infusions (150 mg) of intravenous amiodarone could be given to treat breakthrough ventricular arrhythmias. The key efficacy end points were the arrhythmia event rate, time to first arrhythmic event, and number of supplemental infusions administered. The event rate decreased with increasing doses: median values were 0.07, 0.04, and 0.02 events per hour for the 125-, 500-, and 1000-mg dose groups, respectively, representing a significant decrease from baseline event rates (P=.043), and approached significance in the overall test for trend (P=.067). There was a significant dose-related increase in the time to first event (trend test P=.025) and a significant dose-related decrease in the number of supplemental boluses per hour (trend test P=.043). Hypotension was the most common (26%) treatment-emergent adverse event during intravenous amiodarone therapy; there was no dose-response relationship. Seventy-eight percent of the patients survived to at least 48 hours.
Conclusions Intravenous amiodarone is effective for the treatment of recurrent, life-threatening ventricular tachyarrhythmias.
Key Words: amiodarone • fibrillation • tachycardia
This article has been cited by other articles:
 |
|
 |
|
  American College of Cardiology Foundation, American Heart Association Task Force on Practice, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interve, Society for Vascular Medicine, Society for Vascular Surgery, L. A. Fleisher, et al. 2009 ACCF/AHA Focused Update on Perioperative Beta Blockade Incorporated Into the ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery J. Am. Coll. Cardiol., November 2, 2009; (2009) j.jacc.2009.07.010v1. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Schmitt, G. Duray, B. J. Gersh, and S. H. Hohnloser Atrial fibrillation in acute myocardial infarction: a systematic review of the incidence, clinical features and prognostic implications Eur. Heart J., May 1, 2009; 30(9): 1038 - 1045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Cushing, M. P. Adams, W. D. Cooper, P. R. Kowey, and R. J. Lipicky Bioequivalence of 2 Intravenous Amiodarone Formulations in Healthy Participants J. Clin. Pharmacol., April 1, 2009; 49(4): 407 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Corbett and J. A. Rebuck Medication-Related Complications in the Trauma Patient J Intensive Care Med, March 1, 2008; 23(2): 91 - 108. [Abstract] [PDF]
|
|
|
|
 |
|
 D R Tomlinson, P Cherian, T R Betts, and Y Bashir Intravenous amiodarone for the pharmacological termination of haemodynamically-tolerated sustained ventricular tachycardia: is bolus dose amiodarone an appropriate first-line treatment? Emerg. Med. J., January 1, 2008; 25(1): 15 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Levy, K. A. Tanaka, and J. M. Bailey Cardiac Surgical Pharmacology Card. Surg. Adult, January 1, 2008; 3(2008): 77 - 110. [Full Text]
|
|
|
|
|
|
M. P. Anstadt and J. E. Lowe Cardiopulmonary Resuscitation Card. Surg. Adult, January 1, 2008; 3(2008): 487 - 506. [Full Text]
|
|
|
|
|
|
L. A. Fleisher, J. A. Beckman, K. A. Brown, H. Calkins, E. L. Chaikof, K. E. Fleischmann, W. K. Freeman, J. B. Froehlich, E. K. Kasper, J. R. Kersten, et al. ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) Developed in Collaboration With the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery J. Am. Coll. Cardiol., October 23, 2007; 50(17): e159 - e242. [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Fleisher, J. A. Beckman, K. A. Brown, H. Calkins, E. L. Chaikof, K. E. Fleischmann, W. K. Freeman, J. B. Froehlich, E. K. Kasper, J. R. Kersten, et al. ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) Circulation, October 23, 2007; 116(17): e418 - e500. [Full Text] [PDF]
|
|
|
|
 |
|
 The International Liaison Committee on Resuscitati The International Liaison Committee on Resuscitation (ILCOR) Consensus on Science With Treatment Recommendations for Pediatric and Neonatal Patients: Pediatric Basic and Advanced Life Support Pediatrics, May 1, 2006; 117(5): e955 - e977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Brigadeau, C. Kouakam, D. Klug, C. Marquie, A. Duhamel, F. Mizon-Gerard, D. Lacroix, and S. Kacet Clinical predictors and prognostic significance of electrical storm in patients with implantable cardioverter defibrillators Eur. Heart J., March 2, 2006; 27(6): 700 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Part 6: Pediatric Basic and Advanced Life Support Circulation, November 29, 2005; 112(22_suppl): III-73 - III-90. [Full Text] [PDF]
|
|
|
|
|
|
W. Whang, C. M. Albert, S. F. Sears Jr, R. Lampert, J. B. Conti, P. J. Wang, J. P. Singh, J. N. Ruskin, J. E. Muller, M. A. Mittleman, et al. Depression as a predictor for appropriate shocks among patients with implantable cardioverter-defibrillators: Results from the Triggers of Ventricular Arrhythmias (TOVA) study J. Am. Coll. Cardiol., April 5, 2005; 45(7): 1090 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Gatzoulis, G. K. Andrikopoulos, T. Apostolopoulos, E. Sotiropoulos, G. Zervopoulos, J. Antoniou, S. Brili, and C. I. Stefanadis Electrical storm is an independent predictor of adverse long-term outcome in the era of implantable defibrillator therapy Europace, January 1, 2005; 7(2): 184 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Yeung-Lai-Wah, A. Qi, E. McNeill, J. G. Abel, S. Tung, K. H. Humphries, and C. R. Kerr New-onset sustained ventricular tachycardia and fibrillation early after cardiac operations Ann. Thorac. Surg., June 1, 2004; 77(6): 2083 - 2088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Committee Members, C. Blomstrom-Lundqvist, M. M. Scheinman, E. M. Aliot, J. S. Alpert, H. Calkins, A. J. Camm, W. B. Campbell, D. E. Haines, K. H. Kuck, et al. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias --executive summary: a report of the American college of cardiology/American heart association task force on practice guidelines and the European society of cardiology committee for practice guidelines (writing committee to develop guidelines for the management of patients with supraventricular arrhythmias) Developed in Collaboration with NASPE-Heart Rhythm Society J. Am. Coll. Cardiol., October 15, 2003; 42(8): 1493 - 1531. [Full Text] [PDF]
|
|
|
|
|
|
C. Blomstrom-Lundqvist, M. M. Scheinman, E. M. Aliot, J. S. Alpert, H. Calkins, A. J. Camm, W. B. Campbell, D. E. Haines, K. H. Kuck, B. B. Lerman, et al. ACC/AHA/ESC Guidelines for the Management of Patients With Supraventricular Arrhythmias*--Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias) Circulation, October 14, 2003; 108(15): 1871 - 1909. [Full Text] [PDF]
|
|
|
|
|
|
Committee Members, C. Blomstrom-Lundqvist, M. M Scheinman, E. M Aliot, J. S Alpert, H. Calkins, A.J. Camm, W.B. Campbell, D. E Haines, K. H Kuck, et al. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias--executive summary: A Report of the American College of Cardiology/American HeartAssociation Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines(Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias)Developed in collaboration with NASPE-Heart Rhythm Society Eur. Heart J., October 2, 2003; 24(20): 1857 - 1897. [Full Text] [PDF]
|
|
|
|
 |
|
 U. N. Srivatsa, R. Ebrahimi, A. El-Bialy, and R. Y. Wachsner Electrical Storm: Case Series and Review of Management Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2003; 8(3): 237 - 246. [Abstract] [PDF]
|
|
|
|
|
|
A. T. Cheung, S. J. Weiss, J. S. Savino, W. J. Levy, J. G. Augoustides, A. Harrington, and T. J. Gardner Acute circulatory actions of intravenous amiodarone loading in cardiac surgical patients Ann. Thorac. Surg., August 1, 2003; 76(2): 535 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Bailey, K. A. Tanaka, and J. H. Levy Cardiac Surgical Pharmacology Card. Surg. Adult, January 1, 2003; 2(2003): 85 - 118. [Full Text]
|
|
|
|
|
|
B. N. Singh Antiarrhythmic Drugs in Cardiac Arrest Resuscitation: Intravenous Amiodarone or Intravenous Lidocaine? Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2002; 7(2): 61 - 64. [PDF]
|
|
|
|
 |
|
 P. Dorian, D. Cass, B. Schwartz, R. Cooper, R. Gelaznikas, and A. Barr Amiodarone as Compared with Lidocaine for Shock-Resistant Ventricular Fibrillation N. Engl. J. Med., March 21, 2002; 346(12): 884 - 890. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Gronefeld and S. H Hohnloser What do implantable cardioverter/defibrillators teach us about the mechanisms of sudden cardiac death? Cardiovasc Res, May 1, 2001; 50(2): 232 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. N. Singh and J. S. M. Sarma Mechanisms of Action of Antiarrhythmic Drugs Relative to the Origin and Perpetuation of Cardiac Arrhythmias Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2001; 6(1): 69 - 87. [PDF]
|
|
|
|
 |
|
 G E Kochiadakis, N E Igoumenidis, M E Marketou, M D Kaleboubas, E N Simantirakis, and P E Vardas Low dose amiodarone and sotalol in the treatment of recurrent, symptomatic atrial fibrillation: a comparative, placebo controlled study Heart, September 1, 2000; 84(3): 251 - 257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nademanee, R. Taylor, W. E. Bailey, D. E. Rieders, and E. M. Kosar Treating Electrical Storm : Sympathetic Blockade Versus Advanced Cardiac Life Support-Guided Therapy Circulation, August 15, 2000; 102(7): 742 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Goldschlager, A. E. Epstein, G. Naccarelli, B. Olshansky, B. Singh, and for the Practice Guidelines Subcommittee, North Am Practical Guidelines for Clinicians Who Treat Patients With Amiodarone Arch Intern Med, June 26, 2000; 160(12): 1741 - 1748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.M. Scheinman Amiodarone after acute myocardial infarcation Eur. Heart J., February 1, 2000; 21(3): 177 - 178. [PDF]
|
|
|
|
|
|
B. N. Singh Initial Antiarrhythmic Drug Therapy During Resuscitation from Sudden Cardiac Death: A Time for a Fundamental Change in Strategy? Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2000; 5(1): 3 - 9. [PDF]
|
|
|
|
|
|
P. Kulakowski, S. Karczmarewicz, G. Karpinski, M. Soszynska, and L. CeremuzYnski Effects of intravenous amiodarone on ventricular refractoriness, intraventricular conduction, and ventricular tachycardia induction Europace, January 1, 2000; 2(3): 207 - 215. [Abstract] [PDF]
|
|
|
|
|
|
M. Greene, D. Newman, M. Geist, M. Paquette, D. Heng, and P. Dorian Is electrical storm in ICD patients the sign of a dying heart?: Outcome of patients with clusters of ventricular tachyarrhythmias Europace, January 1, 2000; 2(3): 263 - 269. [Abstract] [PDF]
|
|
|
|
|
|
P. Dorian and D. Newman Rate dependence of the effect of antiarrhythmic drugs delaying cardiac repolarization: an overview Europace, January 1, 2000; 2(4): 277 - 285. [Abstract] [PDF]
|
|
|
|
|
|
S. J. Connolly Evidence-Based Analysis of Amiodarone Efficacy and Safety Circulation, November 9, 1999; 100(19): 2025 - 2034. [Full Text] [PDF]
|
|
|
|
|
|
P. J. Kudenchuk, L. A. Cobb, M. K. Copass, R. O. Cummins, A. M. Doherty, C. E. Fahrenbruch, A. P. Hallstrom, W. A. Murray, M. Olsufka, and T. Walsh Amiodarone for Resuscitation after Out-of-Hospital Cardiac Arrest Due to Ventricular Fibrillation N. Engl. J. Med., September 16, 1999; 341(12): 871 - 878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Guarnieri, S. Nolan, S. O. Gottlieb, A. Dudek, and D. R. Lowry Intravenous amiodarone for the prevention of atrial fibrillation after open heart surgery: the amiodarone reduction in coronary heart (ARCH) trial J. Am. Coll. Cardiol., August 1, 1999; 34(2): 343 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Coodley Newer Drug Therapy for Congestive Heart Failure Arch Intern Med, June 14, 1999; 159(11): 1177 - 1183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Reiffel Intravenous Amiodarone in the Management of Atrial Fibrillation Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1999; 4(4): 199 - 204. [Abstract] [PDF]
|
|
|
|
|
|
S. C. Credner, T. Klingenheben, O. Mauss, C. Sticherling, and S. H. Hohnloser Electrical storm in patients with transvenous implantable cardioverter-defibrillators: Incidence, management and prognostic implications J. Am. Coll. Cardiol., December 1, 1998; 32(7): 1909 - 1915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. N. Singh Amiodarone and Homogeneity of Ventricular Repolarization and Refractoriness Journal of Cardiovascular Pharmacology and Therapeutics, October 1, 1996; 1(4): 265 - 270. [PDF]
|
|
|
|
|
|
B. S. Stambler, M. A. Wood, K. A. Ellenbogen, K. T. Perry, L. K. Wakefield, and J. T. VanderLugt Efficacy and Safety of Repeated Intravenous Doses of Ibutilide for Rapid Conversion of Atrial Flutter or Fibrillation Circulation, October 1, 1996; 94(7): 1613 - 1621. [Abstract] [Full Text]
|
|
|
|
|
|
G. V. Naccarelli and S. Jalal Intravenous Amiodarone : Another Option in the Acute Management of Sustained Ventricular Tachyarrhythmias Circulation, December 1, 1995; 92(11): 3154 - 3155. [Full Text]
|
|