TORONTO—Although lidocaine is the drug traditionally used to treat ventricular fibrillation (VF) after out-of-hospital cardiac arrest, there is little evidence demonstrating its efficacy in this situation. A new study has shown that intravenous amiodarone is superior to lidocaine as an adjunct to defibrillation for patients who arrested outside the hospital with “shock-resistant” VF (ie, VF that persists after three unsuccessful defibrillation attempts).

Results of the study, known as the Amiodarone Versus Lidocaine in Prehospital Ventricular Fibrillation Evaluation (ALIVE) trial, demonstrated that 23% of the patients given amiodarone by paramedics for shock-resistant VF survived to hospital admission, compared with 12% of those treated with lidocaine.[1] “That difference was not just statistically significant but also clinically meaningful,” lead investigator Paul Dorian, MD, told PULMONARY REVIEWS.

This study complements the Amiodarone in Out-of-Hospital Resuscitation of Refractory Sustained Ventricular Tachycardia (ARREST) trial of antiarrhythmic therapy for VF or pulseless ventricular tachycardia.[2] In that trial, 44% of the amiodarone group and 34% of the placebo group survived to hospital admission.

MOUNTING EVIDENCE

The ALIVE and ARREST trials were planned simultaneously but independently; as a result, they nearly ended up being redundant. “We considered comparing amiodarone to placebo but fortunately decided that it would be more useful for clinicians if we compared it to lidocaine,” said Dr. Dorian, a Professor of Cardiology at the University of Toronto and St. Michael’s Hospital.

The ALIVE trial included 347 adults with electrocardiographically confirmed out-of-hospital VF not caused by trauma or with other cardiac rhythms that converted to VF. In all patients, VF had recurred after successful initial defibrillation or continued after three shocks with an external defibrillator followed by at least one dose of intravenous (IV) epinephrine and a fourth shock.

The patients were randomized in double-blind fashion to IV amiodarone (5 mg/kg of estimated body weight) or to IV lidocaine (1.5 mg/kg). Both groups were given further defibrillator shocks and advanced cardiac life support as necessary. If another shock was administered and VF persisted, the protocol required a second dose of the study drug (2.5 mg/kg of amiodarone or 1.5 mg/kg of lidocaine).

SURVIVAL VARIABLES

Except for antiarrhythmic drug assignment, there were no significant differences between the two groups in baseline characteristics or in treatments or procedures administered. Forty-one amiodarone-treated patients and 20 lidocaine recipients survived to hospital admission. Compared with the lidocaine group, the amiodarone group had an adjusted odds ratio for survival to hospital admission of 2.49.

After adjustment for potential confounders, the only significant influences on survival were the study drug assignment, time to administration of the study drug, and whether a transient return of spontaneous circulation occurred before administration. The median time from paramedic dispatch to study drug administration was 24 minutes. Among patients treated at or before that time, the rate of survival to hospital admission was 28% in the amiodarone group and 15% in the lidocaine group. For patients treated after that time, 18% survived to admission in the amiodarone group, compared with 6% in the lidocaine group. Thus, survival rates were significantly higher in the amiodarone group regardless of how long it was until the drug was administered.

A transient return of spontaneous circulation before treatment was observed in only 24 patients randomized to amiodarone and in 11 of those assigned to lidocaine; among these patients, 42% of the amiodarone-treated patients but only 27% of the lidocaine recipients survived to hospital admission. Among those who did not exhibit a spontaneous return of circulation, survival to hospital admission was 20% versus 11%, respectively.

Of course, the “ultimate proof” of amiodarone’s efficacy would be data indicating that it increases survival to hospital discharge, remarked Dr. Dorian, but the trial had too few patients to conclusively show this, he said. The results did associate amiodarone administration with a nonsignificant increase in survival to discharge, however.

“Amiodarone is an effective antiarrhythmic in the cardiac arrest situation, and it is superior to lidocaine,” Dr. Dorian asserted. “It seems fairly clear to me that it should be the drug of choice if an antiarrhythmic is to be used.”

Whether amiodarone’s manufacturer will seek FDA approval for the drug’s use in the treatment of shock-resistant VF remains to be seen. However, clinical practice guidelines already permit physicians to choose it over lidocaine, Dr. Dorian said. “But when the guidelines committee meets again, I suspect that it may make an even stronger recommendation for the use of amiodarone based on the ALIVE trial,” he speculated.

—Timothy Begany

References
1. Dorian P, Cass D, Schwartz B, et al. Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation. N Engl J Med. 2002;346:884-890.

2. 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.

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