Correspondence

Amiodarone in Out-of-Hospital Cardiac Arrest

N Engl J Med 2000; 342:216-217January 20, 2000

Article

To the Editor:

Kudenchuk and colleagues (Sept. 16 issue)1 report that in patients with refractory out-of-hospital cardiac arrest, a single dose of intravenous amiodarone improves survival to hospital admission (44 percent of patients in the amiodarone group survived to admission, as compared with 34 percent of those in the placebo group). However, the best measure of the benefit of an intervention for cardiac arrest is whether it improves survival to hospital discharge. Although we acknowledge that the study by Kudenchuk and colleagues was not designed to show such a benefit, we are concerned that there was not even a trend toward improved survival to discharge in the amiodarone group (13.4 percent survival, as compared with 13.2 percent survival in the placebo group). Because 29 percent more patients in the amiodarone group were admitted to the hospital, amiodarone significantly increased costs without providing a long-term benefit to patients.

In addition, this study was conducted in the Seattle area, where emergency response times are much shorter and, consequently, survival after cardiopulmonary resuscitation is much higher, than in most areas. However, an average of more than 20 minutes elapsed before the patients received amiodarone. Replication of this study in areas with longer response times and lower survival rates would be even less likely to show any long-term benefit from amiodarone.

These results are similar to those with the use of high-dose epinephrine for cardiac arrest; epinephrine, like amiodarone, was shown to improve immediate survival after cardiopulmonary resuscitation. Enthusiasm for this treatment waned when subsequent studies showed that high-dose epinephrine did not improve long-term survival.2 There has also been research showing that the advanced cardiac life support provided by paramedics contributes little to neurologically meaningful survival after out-of-hospital cardiac arrest.3

Survival in patients with out-of-hospital cardiac arrest is directly related to how quickly defibrillation is provided. For example, automatic external defibrillators clearly improve out-of-hospital survival after cardiopulmonary resuscitation.4 Improving survival in patients with refractory cardiac arrest appears to be very difficult. Perhaps the most important lesson we can learn from this study is that more time and money should be used to find ways to decrease the time to defibrillation.

Kenneth A. Ballew, M.D.
John T. Philbrick, M.D.
University of Virginia, Charlottesville, VA 22903

4 References

1
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 | Medline

2
Stiell IG, Hebert PC, Weitzman BN, et al. High-dose epinephrine in adult cardiac arrest. N Engl J Med 1992;327:1045-1050
Full Text | Web of Science | Medline

3
Callaham M, Madsen CD. Relationship of timeliness of paramedic advanced life support interventions to outcome in out-of-hospital cardiac arrest treated by first responders with defibrillators. Ann Emerg Med 1996;27:638-648
CrossRef | Web of Science | Medline

4
Weaver WD, Hill D, Fahrenbruch CE, et al. Use of the automatic external defibrillator in the management of out-of-hospital cardiac arrest. N Engl J Med 1988;319:661-666
Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Drs. Ballew and Philbrick state a point of view with which we completely agree. Short-term outcomes after resuscitation in patients with cardiac arrest (such as the return of spontaneous circulation) are not replacements for the principal relevant outcome: survival with intact neurologic function.

However, we also believe it is reasonable to consider that intermediate outcomes may guide us to new approaches for improving long-term survival after cardiac arrest. The unprecedented observation that a pharmacologic intervention increased the proportion of patients admitted alive to the hospital should not be dismissed because of failure to demonstrate improved survival after admission. In our study, treatment was given only after multiple shocks, intubation, and epinephrine had failed to restore circulation in patients in whom resuscitative efforts had been made for an average of more than 20 minutes. Amiodarone appeared to promote the stabilization of cardiac rhythm and facilitate the return of spontaneous circulation, a finding that could lead to improved long-term survival if it, or similar therapies, are administered earlier in the course of resuscitation.

With respect to early defibrillation: there is no doubt that delivering shocks promptly after the development of ventricular fibrillation is highly effective. However, strategies to “shock fast” and to provide public-access defibrillation, as appealing as they seem, may or may not prove to have a substantial public health benefit. Most cardiac arrests occur at home rather than in public places, where automated defibrillators are more likely to be made available.1 Furthermore, the addition of early defibrillation (by first-arriving emergency medical technicians) to emergency-medical-service programs staffed by paramedics has not been shown to improve survival when assessed within entire communities.2,3 Unless defibrillation can be applied within two to three minutes after collapse, it is not evident that sole reliance on such treatment will have a major effect on long-term outcomes. Finally, the question remains of how to treat the substantial proportion of patients with cardiac arrest in whom initial defibrillator shocks fail to restore or maintain circulation.4

We believe that adjunctive measures such as the use of effective antifibrillatory agents and interventions to prevent or minimize myocardial and cerebral ischemia are likely to have an important role in the management of cardiac arrest. Randomized, controlled clinical trials are sorely needed to address these issues. Unfortunately, since the initiation of our study, federal regulations regarding the waiver of informed consent have made it extremely difficult to perform such trials in the United States. Unless some of these regulatory barriers to clinical research are eased, advances in resuscitation are likely to be made slowly, if at all.

Peter J. Kudenchuk, M.D.
Leonard A. Cobb, M.D.
Michael K. Copass, M.D.
University of Washington, Seattle, WA 98195-6422

4 References

1
Becker L, Eisenberg M, Fahrenbruch C, Cobb L. Public locations of cardiac arrest: implications for public access defibrillation. Circulation 1998;97:2106-2109
Web of Science | Medline

2
Kellermann AL, Hackman BB, Somes G, Kreth TK, Nail L, Dobyns P. Impact of first-responder defibrillation in an urban emergency medical services system. JAMA 1993;270:1708-1713
CrossRef | Web of Science | Medline

3
Cobb LA, Fahrenbruch CE, Walsh TR, et al. Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation. JAMA 1999;281:1182-1188
CrossRef | Web of Science | Medline

4
Cox SV, Woodhouse SP, Weber M, Boyd P, Case C. Rhythm changes during resuscitation from ventricular fibrillation. Resuscitation 1993;26:53-61
CrossRef | Web of Science | Medline

Citing Articles (4)

Citing Articles

1
David C. Cone, Roger J. Lewis. (2003) Should This Study Change My Practice?. Academic Emergency Medicine 10:5, 417-422
CrossRef
2
John M. Field. (2003) Update on cardiac resuscitation for sudden death: International Guidelines 2000 on Resuscitation and Emergency Cardiac Care. Current Opinion in Cardiology 18:1, 14-25
CrossRef
3
Jerry P. Nolan, Francisco J. de Latorre, Petter A. Steen, Douglas A. Chamberlain, Leo L. Bossaert. (2002) Advanced life support drugs: do they really work?. Current Opinion in Critical Care 8:3, 212-218
CrossRef
4
(2000) Current Awareness. Pharmacoepidemiology and Drug Safety 9:4, 341-356
CrossRef