Despite advanced life support protocols, there is little evidence that drugs do very much to improve meaningful outcomes after cardiac arrest.
Along with this comes a tremendous effort and trial published in the New England Journal of Medicine. Unfortunately it may not help us too much but, it does provide us with some interesting data to ponder.
This was a randomized, double blind placebo controlled trial in adults with shock refractory VF or VT that took place in 10 sites in the USA and Canada. (Ian Stiell is one of the authors of course. One cannot conduct a large trial in Canada without his approval.)
The primary outcome was survival to hospital discharge. It was powered to find a 6.3% absolute difference. This was done by a per-protocol analysis rather than intention-to-treat which was fine in this case. They also looked at more important secondary outcomes. You could probably guess what they are…
Results? 37,889 patients were screened for eligibility (holy smokes) and about 3000 patients ultimately randomized to amiodarone, lidocaine or placebo. 70% of the arrests were witnessed and the time to EMS arrival was just over five minutes.
Between the groups, there was no difference in the primary outcome. The absolute difference between amiodarone and placebo was 3.2% (95% CI 0.4 to 7.0.) p=0.08. Nevertheless, this is quite an eyebrow raising trend.
In the pre-specified subgroup of witnessed arrest, the drugs seem to work. At least it was statistically significant with a 5% increase in survival to hospital discharge.
As expected, the conclusion as printed in the NEJM is very measured and reported as a negative trial. However, I’m sure this study will be interpreted in many different ways.
We know that the best predictors of successful outcomes in out-of-hospital cardiac arrest are; witnessed arrest, bystander CPR, and an initial shockable rhythm. It makes sense that an intervention will be more successful in this particular group. So perhaps we should be aggressive.
I don’t think we should be throwing away our drugs quite yet. In fact, I interpret this trial as supporting the existing protocols and use of amiodarone in selected patients. The press release from the NIH seems to agree. However, we could ultimately be proven wrong.
Kudenchuk, PF, Bron SP, Daya M, et al. Amiodarone,Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med2016;374:1711-22.