Antiarrhythmic drugs in cardiac arrest: should amiodarone be moved up two shocks? Is lidocaine the winner by a slim margin?

This trial, published in NEJM, has been the subject of numerous social media posts. The popular spin is that this is just another study showing that the drugs do not work. But isn’t that simple. Let’s take a look at the paper:

Patients

The trial included patients 18 years of age or older with nontraumatic out-of-hospital cardiac arrest and shock-refractory ventricular fibrillation or pulseless ventricular tachycardia, defined as confirmed persistent (nonterminating) or recurrent (restarting after successful termination) ventricular fibrillation or pulseless ventricular tachycardia after one or more shocks anytime during resuscitation (inclusive of rhythms interpreted as being shockable by an automated external defibrillator.

It is useful to pause here and note the importance of this paragraph. It says that amiodarone was tested in circumstances different from those in which it is recommended in the current resuscitation guidelines. The guidelines call for amiodarone after the third shock as a IIb recommendation. This study looked at antiarrhythmic use as early as after the first shock (more accurately, 2 minutes after the first shock since providers are blind to the rhythm for 2 minutes after shocking). Thus, we are looking at a potential move for antiarrhythmic therapy up two steps in the resuscitation sequence.

From the results and conclusions:

Results

In the per-protocol population, 3026 patients were randomly assigned to amiodarone (974), lidocaine (993), or placebo (1059); of those, 24.4%, 23.7%, and 21.0%, respectively, survived to hospital discharge. The difference in survival rate for amiodarone versus placebo was 3.2 percentage points (95% confidence interval [CI], −0.4 to 7.0; P=0.08); for lidocaine versus placebo, 2.6 percentage points (95% CI, −1.0 to 6.3; P=0.16); and for amiodarone versus lidocaine, 0.7 percentage points (95% CI, −3.2 to 4.7; P=0.70). Neurologic outcome at discharge was similar in the three groups. There was heterogeneity of treatment effect with respect to whether the arrest was witnessed (P=0.05); active drugs were associated with a survival rate that was significantly higher than the rate with placebo among patients with bystander-witnessed arrest but not among those with unwitnessed arrest. More amiodarone recipients required temporary cardiac pacing than did recipients of lidocaine or placebo.

Conclusions

Overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo among patients with out-of-hospital cardiac arrest due to initial shock-refractory ventricular fibrillation or pulseless ventricular tachycardia.

BUT---

In a subgroup analysis of patients whose arrests were witnessed there was a significant improvement in mortality with both drugs. Amiodarone was associated with an increased requirement for temporary pacing.

I disagree with the popular spin on this study, that the drugs were of no benefit. I do not think we should ignore subgroup analysis. I suspect what this means is that these drugs are more effective if used earlier post arrest.