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Administration of amiodarone during resuscitation of ventricular arrhythmias

Authors: Heather D. Eppert, PharmD, BCPS, and Kara B. Goddard, BS, Maryville and Knoxville, TN Amiodaroneisanantiarrhythmicdrugindicatedin administrationofamiodaroneisasanintravenousbolus the treatment of ventricular arrhythmias. Early dose. In the typical medical setting, the preferred standard studies evaluating amiodarone for the management of practice is to prepare an infusion of amiodarone diluted of ventricular arrhythmias demonstrated the efficacy of amio- in 5% dextrose in water placed in a polyolefin bag, admi- darone in patients who were refractory to treatment with nistered through an in-line filter via a central vein or large multiple antiarrhythmic drugs.1-13 More recently, 2 major peripheral vein.However, in the setting of cardiac emer- trials, published in 1999 and 2002, described the efficacy gency, administration by prolonged infusion is not desir- of amiodarone as a primary treatment modality in the treat- able. The vast differences in the recommendations for ment of ventricular arrhythmias compared with another administration of amiodarone in this setting have raised antiarrhythmic drug, lidocaine, and placebo.14,15 As a significant questions in the medical community.
result of this literature, the American Heart AssociationAdvanced Cardiac Life Support (ACLS) guidelines recom- Amiodarone: A Complex Antiarrhythmic Drug mend amiodarone as the antiarrhythmic of choice in theresuscitation of patients with ventricular arrhythmias.
Amiodarone is a Vaughn Williams class III antiarrhythmic The use of amiodarone for the emergent treatment of drug. It has a complex mechanism of action, with mecha- ventricular arrhythmias, including ventricular tachycardia nistic properties that include action at α- and β-adrenergic and ventricular fibrillation, has steadily increased in recent receptors, as well as action on the potassium, sodium, and years. This increased use is a result of emerging literature calcium channels in the In general, the beneficial relating to the efficacy of amiodarone, combined with the effects of amiodarone are due to its ability to prolong the updated ACLS treatment guidelines available from the cardiac action potential and refractory period. The efficacy American Heart AIn the setting of cardiac of amiodarone in the treatment of ventricular arrhythmias emergency (eg, ventricular tachycardia with a palpable is thought to be due to suppression of premature ventricular pulse), the recommended dose of intravenous amiodarone depolarization and the occurrence of further arrhythmias.
is 150 mg. In cardiac arrest (eg, ventricular fibrillation),the recommended dose of amiodarone is 300 mg adminis- Amiodarone: Administration and Adverse Events tered intravenously, followed by a subsequent dose of 150mg as needed for sustained arrhythmia. In the 2005 Amer- In the clinical trials that have evaluated the use of amiodarone ican Heart Association guidelines, the recommendation for for the treatment of ventricular arrhythmias, there has beena wide range of variability in the dose, rate of administra-tion, and dilution of amiodarone.1-14,18,19 The range of Heather D. Eppert is Clinical Specialist, Emergency Medicine, Blount Me- amiodarone doses reported has ranged from 18.75 mg to morial Hospital, Department of Pharmacy, Maryville, TN, and Assistant 600 mg. Similarly, the rate of administration has varied Professor, University of Tennessee College of Pharmacy, Department of Clin- widely, from rapid intravenous administration to infusion of up to 30 minutes. Based on all of the available literature to Kara B. Goddard is Doctor of Pharmacy Candidate, 4th Professional Year, date, only 3 studies have reported rapid intravenous infusion University of Tennessee College of Pharmacy, Knoxville, TN.
of amiodarone.14,15,18 Each of these 3 protocols varied in the For correspondence, write: Heather D. Eppert, PharmD, BCPS, 1924 Alcoa dilution of amiodarone, ranging from undiluted solution to Highway, Box 117, Knoxville, TN 37920; E-mail: dilution in either 20 or 30 mL of 5% dextrose in water.
Concerns have been raised regarding the rapid adminis- Available online 25 June 2009.
0099-1767/$36.00 tration of intravenous amiodarone. This concern results fromreports of numerous adverse events associated with the admin- Copyright 2010 Emergency Nurses Association. Published by Elsevier Inc.
All rights reserved.
istration of amiodarone, the most notable of these adverse events being hypotension, bradycardia, and phlebitiIn clinical studies reported to date, the incidence of these adverse be administered in a central vein; if central venous access events has been highly variable, with the incidence of hypo- is not available, administration should occur through the tension ranging from 7% to 59%, bradycardia ranging from 0% to 41%, and phlebitis ranging from 0% to 27%.1-15,18,19However, an in-depth evaluation of the clinical studies that have evaluated the use of amiodarone for the treatment of Recent literature has found amiodarone to be the anti- ventricular arrhythmias reveals that the incidence of adverse arrhythmic of choice in the resuscitation of cardiac emer- events from administration of amiodarone appears to be rela- gencies due to ventricular arrhythmias. As a result, the use tively varied, regardless of the rate of administration or dilu- of intravenous amiodarone has steadily increased. How- ever, amiodarone has been associated with multiple adverse It is difficult to define the occurrence of adverse drug events, raising concerns regarding the appropriate adminis- events in resuscitation trials and even more difficult to deter- tration of amiodarone in this setting. When administrating mine an association of adverse events with a specific drug intravenous amiodarone, the need for rapid administration, therapy. For example, several clinical studies resorted to the risk for adverse events, and the clinical condition of the the definition of hypotension in the clinical trial as the need patient must be considered. In the case of life-threatening for vasopressor therapy (eg, dopamine) after the resuscita- ventricular arrhythmias, rapid achievement of therapeutic tion.1-11,14 This definition is tenuous, because vasopressor drug concentrations and the suppression of further arrhyth- supportive therapy of blood pressure is commonly required mia is a high priority. Therefore, in the setting of cardiac in post-cardiac arrest victims.The protective effect of emergency (eg, hemodynamic instability with a palpable simultaneous administration of potent vasoconstrictive drugs pulse), a recommended dose of intravenous amiodarone, commonly used during resuscitation, such as epinephrine or 150 mg administered over 10 minutes with continuous car- dopamine, against the development of hypotension and bra- diac monitoring, is appropriate. In the setting of cardiac dycardia in this setting has been debated.3,15,18 Therefore, it arrest (eg, ventricular fibrillation), rapid intravenous would be difficult to deduce whether the hypotension, bra- administration of amiodarone, 300 mg, is reasonable. This dycardia, or proarrhythmia observed in the clinical trials of method of administration can be accomplished in 1 of amiodarone during cardiac arrest are in fact due to the pri- 2 ways: either via direct injection of the undiluted drug, mary cause of the arrest (eg, myocardial infarction), the loss followed by a minimum of 10-mL flush, or by minimally of cardiac output during the arrest, or as the result of an diluting each of two 150-mg doses within two 10-mL adverse effect from amiodarone therapy.
0.9% sodium chloride–filled syringes.
Recommendations for Amiodarone Administration Based on the results of recent research, amiodarone is the Scheinman MM, Levine JH, Cannom DS, et al. Dose-ranging study of intravenous antiarrhythmic drug of choice for the resuscita- intravenous amiodarone in patients with life-threatening ventricular tion of patients with ventricular arrhythmias.Amiodarone tachyarrhythmias. Circulation. 1995;92:3264-72.
is commercially available as a 150-mg, 3-mL vial.In the Levine JH, Massumi A, Scheinman MM, et al. Intravenous amiodarone urgent treatment setting (eg, ventricular tachycardia with for recurrent sustained hypotensive ventricular tachyarrhythmias. J Am palpable pulses), a loading dose of amiodarone, 150 mg, is preferably administered in 100 mL of 5% dextrose in Helmy I, Herre JM, Gee G, et al. Use of intravenous amiodarone foremergency treatment of life-threatening ventricular arrhythmias. J Am Coll water over 10 minutes, as per the manufacturer’s recom- mendations.In the setting of cardiac arrest, some refer- Morady F, Scheinman MM, Shen E, Shapiro W, Sung RJ, DiCarlo L.
ences have recommended rapid administration of undiluted Intravenous amiodarone in the acute treatment of recurrent sympto- amiodarone, followed immediately by a 10-mL flush with matic ventricular tachycardia. Am J Cardiol. 1983;51:156-9.
either 5% dextrose in water or 0.9% normal saline solu- Mostow ND, Rakita L, Vrobel TR, et al. Amiodarone: intravenous load- tion.18,20 Anecdotally, one practical method for rapid admin- ing for rapid suppression of complex ventricular arrhythmias. J Am Coll istration of amiodarone during cardiac arrest (eg, ventricular fibrillation) is to withdraw the contents of one 150-mg vial Leak D. Intravenous amiodarone in the treatment of refractory life-threatening cardiac arrhythmias in the critically ill patient. Am Heart into each of two 10-mL syringes filled with 0.9% sodium chloride. These 2 syringes, for a total of 300 mg, could Klein RC, Machell C, Rushforth N, Standefur J. Efficacy of intravenous be administered via rapid intravenous infusion in the set- amiodarone as short-term treatment for refractory ventricular tachycar- ting of cardiac emergency. Amiodarone should preferably Schutzenberger W, Leisch F, Kerschner K, et al. Clinical efficacy of in- 14. Dorian P, Cass D, Schwartz B, Cooper R, Gelaznikas R, Barr A. Amio- travenous amiodarone in the short term treatment of recurrent sustained darone as compared with lidocaine for shock-resistant ventricular fibrilla- ventricular tachycardia and ventricular fibrillation. Br Heart J.
tion. N Engl J Med. 2002;346:884-90.
15. Kudenchuk PJ, Cobb LA, Copass MK, et al. Amiodarone for resusci- Williams ML, Woelfel A, Cascio W, et al. Intravenous amiodarone dur- tation after out-of-hospital cardiac arrest due to ventricular fibrillation.
ing prolonged resuscitation from cardiac arrest. Ann Intern Med.
16. Emergency Cardiovascular Care Committee, Subcommittees, and Task 10. Ochi RP, Goldenberg IF, Almquist A, et al. Intravenous amiodarone for Forces of the American Heart Association. 2005 Guidelines for cardiopul- the rapid treatment of life-threatening ventricular arrhythmias in criti- monary resuscitation and emergency cardiovascular care. Circulation.
cally ill patients with coronary artery disease. Am J Cardiol. 1989;64: 17. Cordarone (amiodarone hydrochloride) [product information]. Philadel- 11. Mooss AN, Mohiuddin SM, Hee TT, et al. Efficacy and tolerance of phia, PA: Wyeth-Ayerst Company; 2001.
high-dose intravenous amiodarone for recurrent, refractory ventricular 18. Skrifvars MB, Kuisma M, Boyd J, et al. The use of undiluted amiodar- tachycardia. Am J Cardiol. 1990;65:609-14.
one in the management of out-of-hospital cardiac arrest. Acta Anesthesiol 12. Nalos PC, Ismail Y, Pappas JM, et al. Intravenous amiodarone for short- term treatment of refractory ventricular tachycardia or fibrillation. Am 19. Remme WJ, Kruyssen HACM, Look MP, et al. Hemodynamic effects and tolerability of intravenous amiodarone in patients with impaired left ventri- 13. Kowey PR, Levine JG, Herre JM, et al. Randomized, double-blind cular function. Am Heart J. 1991;122: 96-103.
comparison of intravenous amiodarone and bretylium in the treatment 20. Gonzalez ER, Kannewurf BS, Ornato JP. Intravenous amiodarone for of patients with recurrent, hemodynamically destabilizing ventricular ventricular arrhythmias: overview and clinical use. Resuscitation.
tachycardia or fibrillation. Circulation. 1995;92:3255-63.

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