Correspondence
Amiodarone versus Lidocaine for Shock-Resistant Ventricular Fibrillation
N Engl J Med 2002; 347:368-370August 1, 2002
- Article
To the Editor:
Dorian and colleagues (March 21 issue)1 report increased rates of survival to hospital admission among patients treated with amiodarone for out-of-hospital ventricular fibrillation. Although their conclusion is consistent with their data and is in accordance with those reported previously by Kudenchuk and coworkers,2 the questions of cost versus benefit and of reasonable outcome measures are raised. The results presented by Dorian et al. suggest that treatment of 100 patients could result in 10 additional hospital admissions but survival to discharge from the hospital for only 1 additional patient, without proven neurologic recovery.
In both studies, the use of amiodarone was associated with an increase in the percentage of admitted patients who died or who had adverse neurologic outcomes: the increase was 8.8 percentage points (32 of 180 patients treated with amiodarone vs. 15 of 167 treated with lidocaine) in the current study1 and 9.2 percentage points (75 of 246 patients who received amiodarone vs. 55 of 258 who received placebo, respectively) in the study by Kudenchuk et al.2 Kudenchuk et al. reported that the rate of survival with good neurologic recovery with amiodarone was similar to that without amiodarone (7.3 percent vs. 6.5 percent). If this difference were significant, the number needed to treat would be 125. If all the discharged patients in the study by Dorian et al. had good neurologic outcomes, the combined data would yield an absolute reduction in the rate of death or an unfavorable neurologic outcome of 1.0 percent (5.3 percent with amiodarone vs. 6.3 percent with lidocaine or placebo). Since approximately 650,000 out-of-hospital cardiac arrests occur in the United States3 and Europe4 annually, with 10 percent meeting the inclusion criteria of these two studies,1,2 the use of amiodarone in 65,000 patients would result in an additional 650 patients surviving to discharge from the hospital, at the price of 5850 additional nonsurvivors.
In the light of considerable suffering, limited intensive-care-unit resources, and additional hospital costs, we agree that the use of amiodarone in persons who have an out-of-hospital cardiac arrest should be thoroughly investigated. We hope that the use of mild therapeutic hypothermia (with a combined number needed to treat of six for survival with a good neurologic outcome, without increased in-hospital mortality, in two recent studies4,5) will also benefit patients resuscitated with the use of amiodarone.
5 ReferencesTom Silfvast, M.D., Ph.D.
Ville Pettilä, M.D., Ph.D.
Helsinki University Hospital, 00029 Helsinki, Finland
tom.silfvast@hus. fi 1
Dorian P ,Cass D ,Schwartz B ,Cooper R ,Gelaznikas R ,Barr A . Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation. N Engl J Med 2002;346:884-890
Full Text | Web of Science | Medline2
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;341:871-878
Full Text | Web of Science | Medline3
Bigger JT . Expanding indications for implantable cardiac defibrillators. N Engl J Med 2002;346:931-933
Full Text | Web of Science | Medline4
The Hypothermia after Cardiac Arrest Study Group
Full Text | Web of Science | Medline5
Bernard SA ,Gray TW ,Buist MD , et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557-563
Full Text | Web of Science | Medline
To the Editor:
Although an increase in the rate of survival to admission is a laudable intermediate outcome, there are many potential harms if the rate of survival to discharge is not also improved. In the study by Dorian and colleagues, because there was no improvement in long-term survival, the 90 percent relative improvement in survival to hospitalization substantially increased costs and prolonged the suffering of patients and families, without any long-term benefit. Can the authors provide information on the length and costs of hospitalization among short-term survivors?
On average, 24 minutes elapsed from the time of dispatch to the time of administration of the study drug. With an interval this long, even though amiodarone improves the restoration of spontaneous circulation, there is frequently permanent neurologic damage as a result of prolonged hypoxia, making the potential for an improvement in long-term survival remote. The authors did find that the rate of short-term survival was higher among patients treated less than 24 minutes after the time of dispatch than in those treated after 24 minutes. We would be interested to know whether there was a trend toward improved long-term survival in the patients who were treated after the shorter interval. If so, future studies could focus on the use of amiodarone in such patients; these studies should be designed to demonstrate improvement in both short-term and long-term rates of survival.
Kenneth A. Ballew, M.D.
John T. Philbrick, M.D.
University of Virginia, Charlottesville, VA 22903To the Editor:
Dorian et al. believe that their research proves that amiodarone is the drug of choice for shock-resistant ventricular fibrillation. The focus of their research is patients who survive to hospital admission. However, only nine of the patients in the amiodarone-treated group survived to discharge, as compared with five of those in the lidocaine-treated group. Two extremely important questions are not addressed by their article. First, what was the neurologic outcome in the survivors? If the patients were discharged alive but without clinically significant neurologic recovery, then I believe the outcome would be worse for society than the patients' deaths. Second, if the total number of patients discharged without neurologic deficits was no higher with amiodarone than with lidocaine, then surely the survival of many more patients to hospital admission, with the subsequent costly yet futile hospital stay, is once again a bad outcome for society as a whole.
William Tomkiewicz, M.D.
Kaiser Hospital, San Francisco, CA 94115
wrtomcat@hotmail.com To the Editor:
We are concerned about the use of polysorbate 80 in the lidocaine group in the study by Dorian et al. Polysorbate 80 (the diluent of intravenous amiodarone) is considered to have hypotensive effects and to cause a decrease in the heart rate and atrioventricular conduction disturbances.1,2 All the patients in the lidocaine group received lidocaine combined with polysorbate 80 as a so-called matching placebo. This cannot be considered an inactive placebo. The mixture of polysorbate 80 and lidocaine was used in order to have identical-looking drug containers, as part of the double-blind study design (Dorian P: personal communication). This design followed that of the Amiodarone in Out-of-Hospital Resuscitation of Refractory Sustained Ventricular Tachycardia study, in which amiodarone was compared with polysorbate 80 (as placebo)3 and the results of which contributed to the recommended use of amiodarone in the guidelines for advanced cardiac life support.4
4 ReferencesDirk Grosse Meininghaus, M.D.
Klaus Langes, M.D.
Juergen Spehn, M.D.
Zentralkrankenhaus Links der Weser, D-28277 Bremen, Germany
d.grosse-meininghaus@online. de 1
Kowey PR ,Marinchak RA ,Rials SJ ,Filart RA . Intravenous amiodarone. J Am Coll Cardiol 1997;29:1190-1198
CrossRef | Web of Science | Medline2
Späth G. Herzrhythmusstörungen — Aktuelle Bedeutung von Amiodaron. 2. Auflage. Weinheim, Germany: Beltz-Verlag, 1992:43-5.
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;341:871-878
Full Text | Web of Science | Medline4
The American Heart Association, International Liaison Committee on Resuscitation (ILCOR)
Author/Editor Response
The authors reply:
To the Editor: Silfvast and Pettilä, Ballew and Philbrick, and Tomkiewicz all comment on the important question of the benefits versus the cost of attempting to resuscitate patients after out-of-hospital cardiac arrest. The design of our study does not permit definitive conclusions about the potential for treatment with intravenous amiodarone to improve long-term outcomes in patients resuscitated after shock-resistant ventricular fibrillation. However, the in-hospital rates of death in the amiodarone and lidocaine groups in our study were 78 percent and 75 percent, respectively — similar to in-hospital death rates reported previously.1 In our study, 64 percent of the patients discharged alive had a favorable neurologic outcome (a Glasgow–Pittsburgh Scale score of at least 4 on a scale from 1 to 5, where higher scores indicate a better outcome). The number of survivors who were treated early (less than 24 minutes after dispatch) as compared with late (24 minutes or more after dispatch) was too small to allow meaningful conclusions about the effect the time to treatment had on rates of discharge from the hospital. We agree with Ballew and Philbrick that it is reasonable to suppose that earlier treatment, and thus earlier restoration of effective circulation, may be expected to result in better ultimate neurologic outcomes and believe that this should be investigated in future clinical trials. With respect to overall costs and effectiveness of advanced care before hospital admission, it is important to remember that other commonly used therapies, such as intravenous epinephrine or defibrillation with automated devices by first responders, have not been shown in randomized trials to improve survival to hospital discharge.2
With respect to our use of polysorbate 80 in the lidocaine-treated group, since the diluent used in the preparation of amiodarone foams and is highly viscous, it would not have been possible to blind the study adequately by using some other compound (e.g., 5 percent dextrose in water). In addition, bolus administration of the diluent alone results in transient increases in the heart rate and decreases in blood pressure lasting four minutes but does not result in a significant decrease in indexes of contractility.3 A comparison of the effects of amiodarone with polysorbate 80 as a diluent and without it showed similar results. It is thus unlikely that the diluent was responsible for the observed differences between the amiodarone and lidocaine groups.4
Finally, as Silfvast and Pettilä point out, one can hope that the sequential administration of therapies that may be effective in early resuscitation and improved subsequent care of patients who have had a cardiac arrest will result in measurable and useful improvements in long-term survival.1,2 Much research needs to be done to optimize advanced cardiac life support.
4 ReferencesPaul Dorian, M.D.
St. Michael's Hospital, Toronto, ON M5B 1W8, Canada
dorianp@smh.toronto. on. ca Brian Schwartz, M.D.
Sunnybrook and Women's College Health Sciences Centre, Toronto, ON M3J 3H7, CanadaRichard Cooper, M.D.
University Health Network, Toronto, ON M5G 2N2, Canada1
Bernard SA ,Gray TW ,Buist MD , et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557-563
Full Text | Web of Science | Medline2
Eisenberg MS ,Mengert TJ . Cardiac resuscitation. N Engl J Med 2001;344:1304-1313
Full Text | Web of Science | Medline3
Sicart M ,Besse P ,Choussat A ,Bricaud H . Action hémodynamique de l'amiodarone intra-veineuse chez l'homme. Arch Mal Coeur Vaiss 1977;70:219-227
Medline4
Munoz A ,Karila P ,Gallay P , et al. A randomized hemodynamic comparison of intravenous amiodarone with and without Tween 80. Eur Heart J 1988;9:142-148
Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Rhonda S. Rea, Sandra L. Kane-Gill, Maria I. Rudis, Amy L. Seybert, Lance J. Oyen, Narith N. Ou, Julie L. Stauss, Levent Kirisci, Umbreen Idrees, Sean O. Henderson. (2006) Comparing intravenous amiodarone or lidocaine, or both, outcomes for inpatients with pulseless ventricular arrhythmias*. Critical Care Medicine 34:6, 1617-1623
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