Amiodarone in Cardiac Arrest

The administration of 300mg amiodarone (Cordarone) in cardiac arrest patients experiencing ventricular fibrillation, is creating compelling evidence, in the minds of many clinicians, that challenges previously identified antidysrythmics (lidocaine, procainamide, bretylium).

In the most often cited literature, to date, regarding the administration of amiodarone during cardiac arrest, Dr. Peter Kudenchuk, associate professor of medicine and director of arrhythmia services at University of Washington Medical Center, and colleagues performed a study, called ARREST (Amiodarone in the Out-of-Hospital Resuscitation of Refractory Sustained Ventricular Tachyarrhythmias). The results were first presented back in November 1997 at the American Heart Association's 70th Scientific Sessions in Orlando, Florida, and subsequently published. 

ARREST is the first-ever large-scale, placebo-controlled, emergent field-based cardiac arrest investigation. This blinded study focused on out-of-hospital cardiac arrests managed by King County paramedics.

The ARREST study concluded that resuscitation into a stable heart rhythm was increased by 26 percent in people treated with intravenous amiodarone, as compared to those who received all other standard treatments for cardiac arrest. The authors also concluded that among people in whom defibrillation shocks alone could only temporarily maintain a stable heart beat, amiodarone improved their chances of being admitted alive to the hospital by 56 percent. 

The drug was administered to 504 people (more than 75% of them male, and ranging from 20 to 94 years old) in Seattle and King County, Washington that were in cardiac arrest  presenting with ventricular fibrillation. The study ran from November 1994 to February 1997.  

Investigators noted that the main treatment endpoint for the ARREST trial was being admitted alive to a hospital. As lead investigator, Kudenchuk conceded that the trial was not sufficiently large enough to evaluate the effect of treatment on the likelihood of being discharged from the hospital alive. "From a statistical standpoint, proving this would require far more patients and years of study," said Kudenchuk.

Although there was a very slight improvement in survival-to-hospital discharge in those treated with amiodarone, it was not statistically significant. Kudenchuk concedes, "getting patients to the hospital alive is only the first hurdle. Further research is needed to find better ways of protecting the brain and heart from injury during cardiac arrest. That is what determines ultimate survival in those we are fortunate enough to resuscitate successfully." 

Additional notes:

While amiodarone was well-tolerated in this critically ill population, there was a higher incidence of hypotension and of bradycardia requiring therapy in the amiodarone group. The principle investigator noted that all of these episodes were clinically manageable. As Advanced Cardiac Life Support guidelines are currently under review, some are speculating that amiodarone adminstration may be recommended shortly after an initial dose of  epinephrine, or more alpha-specific agonist such as vasopressin to counteract these affects.

Reviewing ARREST results and their applicability elsewhere, some have noted that Seattle's MedicOne EMS service has a shorter than average response time, comparing it to other areas of the country. Speculation has also centered on the average time-to-administration of the amiodarone (in ARREST it was 20 minutes) and the likely effect of both earlier and later administration on outcomes. 

Amiodarone is primarily a class III antiarrythmic that prolongs duration of action potential and effective refractory period, also providing noncompetitive alpha and beta adrenergic inhibition. It decreases AV conduction velocity and sinus node function. 

Packaged in 50mg/ml and given as a 300mg bolus, the drug does have to reconstituted. In cardiac arrest, a single 300 mg IV dose seems to be the most common approach. 

Intravenous amiodarone was approved for use in the U.S. in 1996 and is marketed as 
Cordarone I.V. by Wyeth-Ayerst Laboratories. 

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