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American Academy of Emergency Medicine

Position Statement on the Use of Amiodarone in Refractory Pulseless VT/VF

AAEM statements are not to be construed as dictating an exclusive course of action nor are they intended to replace the medical judgment of healthcare professionals. The unique circumstances of individual patients and environments are to be taken into account in any diagnosis and treatment plan. AAEM statements reflect clinical and scientific advances as of the date of their publication and are subject to change.

At its May 5, 2001 meeting, the AAEM Board of Directors adopted an official position statement after reviewing the report from the AAEM Amiodarone for Refractory VT/VF Working Group. The full report follows the position statement.

AAEM Position Statement: Use of Amiodarone in Refractory Pulseless VT/VF
"It is the position of the American Academy of Emergency Medicine that the use of amiodarone in refractory pulseless ventricular tachycardia or ventricular fibrillation (VT/VF) should not be considered the current 'standard of care' for this condition. The Academy does not condemn non-research use of amiodarone given the absence of any proven beneficial alternatives, however, there is currently no reason to conclude that its use is mandatory or represents a 'standard of care.' Until ongoing or future research clarifies this issue, emergency physicians should use their own discretion regarding antiarrhythmic therapy in patients with cardiac arrest."

AAEM Working Group Report
Purposes:
At the request of the AAEM Board of Directors, the Working Group examined the question of whether the use of amiodarone for adults with refractory pulseless ventricular tachycardia/ventricular fibrillation (VT/VF) represents a "standard of care" for Emergency Medicine.

Background: Sudden death from life-threatening cardiac arrhythmias occurs in 250,000-350,000 adults in the United States each year (1-3). The most common arrhythmias encountered in cardiac arrest are ventricular tachycardia and ventricular fibrillation. Initial management for pulseless VT/VF involves rapid defibrillation. However, if the arrhythmia persists after three shocks from an external defibrillator, the American Heart Association's Guidelines for Advanced Cardiac Life Support have traditionally recommended the use of "medications of probable benefit [lidocaine, bretylium, magnesium sulfate, and procainamide] in persistent or recurrent ventricular fibrillation" (4). Lidocaine has generally been considered the antiarrhythmic of first choice because of its ease of use, rapid onset, and good side-effect profile. The use of each of these medications, however, including lidocaine, is not well supported by human studies. In fact, none of these antiarrhythmic medications has been shown in any study to improve survival compared to placebo, in cardiac arrest. The most recent edition of AHA's Guidelines notes that "meticulous, systematic review reveals that relevant, valid, and credible evidence to confirm a benefit due to [those] agents simply does not exist" (5).

In 1999, Kudenchuk, et al (3) published the first randomized, double blind, placebo controlled trial of an antiarrhytmic drug, amiodarone, in cardiac arrest. This study forms the basis for a change in the AHA Guidelines, which now classify amiodarone as a Class IIb drug ("acceptable and useful...supported by fair to good evidence"). Lidocaine is currently listed as a Class Indeterminate drug ("no harm but no benefit...evidence insufficient to support final class decision") for patients with VT/VF (5). The AHA does not contend that this means amiodarone is preferred over lidocaine in VT/VF (R. Cummins. personal communication), even though this seems to be suggested by their respective classifications.

Data: Kudenchuk, et al (3) studied the use of amiodarone in more than 500 patients with shock-resistant out-of-hospital cardiac arrest due to VF. Patients received three precordial shocks, intubation, and 1 mg of intravenous epinephrine. They were then randomized to receive a single intravenous dose of either placebo of 300 mg amiodarone. Subsequent treatment was at the discretion of the medics and physicians; it was not standardized. More patients treated with Amiodarone (44%) than with placebo (34%) survived to hospital admission with a spontaneously perfusing rhythm. (Patients who died in the emergency department were not considered to have been admitted.) This difference was statistically significant (p=0.03). However, there was no difference in any clinically important outcome, including survival to hospital discharge (13.4% of amiodarone-treated patients versus 13.2% of placebo-treated patients) and number of patients returning to independent living or to their former employment (7.3% versus 6.6%, respectively).

Discussion: Proponents of amiodarone for refractory pulseless VT/VF stress that use of amiodarone, compared to placebo, was associated with an increase in "successful resuscitations" in the study by Kudenchuk. In this context, "successful resuscitation" refers to survival to hospital admission. This does not, however, equate to survival to hospital discharge or neurologic recovery, for which amiodarone was no better than placebo.

Emergency physicians may remember that the use intermediate dosages, escalating dosages, and high dosages of intravenous epinephrine (HDE) was given a IIb classification in previous editions of the Advanced Cardiac Life Support Guidelines (4,6). This was based on animal studies, anecdotal reports, and small human trials that demonstrated improved return of spontaneous circulation (ROSC) and survival to hospital admission when cardiac arrest patients were treated with higher than standard dosages of epinephrine (7-13). Although it was assumed by some that a medication that is associated with improved ROSC and survival to hospital admission would also be associated with improved survival to hospital discharge and neurologic recovery, this was never the case with HDE. Subsequent studies confirmed that HDE in adult victims of cardiac arrest is not associated with an improvement in patient survival to hospital discharge or neurologic recovery (14-20). As a result, the use of high dosages of epinephrine is no longer recommended in the most recent Guidelines (5).

The study by Kudenchuk suggests that amiodarone, like HDE, is associated with ROSC and short-term survival only. The cost associated with this type of short-term survival should not be ignored, given the expense of an intensive care unit admission. No data exist that use of amiodarone leads to long-term survival or any neurologic recovery; to the contrary, the only available data suggests otherwise.

Studies are now underway to compare amiodarone versus lidocaine in prehospital and in-hospital cardiac arrest. This may facilitate efforts to choose between these two agents, but unless and until there is evidence of benefit of either, compared to placebo, it will be inappropriate to insist on their use.

Conclusion: This Working Group finds that the use of amiodarone in refractory pulseless VT/VF should not be considered "standard of care" for this condition. Indeed, it could be argued that amiodarone should only be used in cardiac arrest (if at all) in the context of further study protocols. Nevertheless, the Working Group believes it would be inappropriate to condemn non-research use of amiodarone, given the absence of any proven beneficial alternatives. On the other hand, there is certainly no reason to conclude that its use is mandatory, or represents a "standard of care." Ongoing and future studies may clarify this issue, but until such time, emergency physicians should use their own discretion regarding antiarrhythmic therapy in patients with cardiac arrest.

References:

1. Gillum RF. Sudden coronary death in the United States: 1980-1985. Circulation 1989;79:756-65.

2. Gonzalez ER, Kannewurf BS, Omato JP. Intravenous amiodarone for ventricular arrhythmias: overview and clinical use. Resuscitation 1998:39:33-42.

3. Kudenchuk PJ, Cobb LA, Copass MK, et al. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med 1999;341:871-8.

4. Cummins RO, ed. Advanced cardiac life support. Dallas; American Heart Association; 1997:1-21.

5. Cummins RO, et al, ed. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Dallas; American Heart Association; 2000:142-150.

6. Cummins RO, ed. Advanced cardiac life support. Dallas: American Heart Association; 1994:1-21.

7. Koscove EM, Paradis NA. Successful resuscitation from cardiac arrest using high dose epinephrine therapy. Report of two cases. JAMA 1988;259:3031-4.

8. Martin D, Werman HA, Brown CG. Four case studies: high-dose epinephrine in cardiac arrest. Ann Emerg Med 1990;19:322-6.

9. Paradis NA, Martin GB, Rosenberg J, et al. The effect of standard- and high-dose epinephrine on coronary perfusion pressure during prolonged cardiopulmonary resuscitation. JAMA 1991;265:1139-44.

10. Cipolotti G, Paccagnella A, Simini G. Successful cardiopulmonary resuscitation using high doses of epinephrine. Int J Cardiol 1991;33:430-1.

11. Barton C, Callaham M. High-dose epinephrine improves the return of spontaneous circulation rates in human victims of cardiac arrest. Ann Emerg Med 1991;20:722-5.

12. Paradis NA, Martin GB, Rosenberg J, et al. The effect of standard- and high-dose epinephrine on coronary perfusion pressure during prolonged cardiopulmonary resuscitation. JAMA 1991;265:1139-44.

13. Wortsman J, Paradis NA, Martin GB, et al. Functional responses to extremely high plasma epinephrine concentrations in cardiac arrest. Crit Care Med 1993;21:692-7.

14. Stiell IG, Hebert PC, Weitzman BN, et al. High-dose epinephrine in adult cardiac arrest. N Engl J Med 1992;327:1045-50.

15. Brown CG, Martin DR, Pepe PE, et al. A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. N Engl J Med 1992;327:1051-5.

16. Lipman J, Wilson W, Kobilski S, et al. High-dose adrenaline in adult in-hospital asystolic cardiopulmonary resuscitation: a double-blind randomised trial. Anaesth Intensive Care 1993;21:192-6.

17. Rivers EP, Wortsman J, Rady MY, et al. The effect of the total cumulative epinephrine dose administered during human CPR on hemodynamic, oxygen transport, and utilization variables in the postresusciation period. Chest 1994;106:1499-507.

18. Sherman BW, Munger MA, Foulke GE, et al. High-dose versus standard-dose epinephrine treatment of cardiac arrest after failure of standard therapy. Pharmacotherapy 1997;17:242-7.

19. Behringer W, Kittler H, Sterz F, et al. Cumulative epinephrine dose during cardiopulmonary resuscitation and neurologic outcome. Ann Intern Med 1998;129:450-6.

20. Gueugniaud PY, Mois P, Goldstein P, et al. A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. N Engl J Med 1998;339:1595-601.

The AAEM Amiodarone for Refractory VT/VF Working Group is comprised of Amal Mattu, MD FAAEM, Carey Chisholm, MD FAAEM, and Jerome R. Hoffman, MA MD FAAEM.