Adrenaline Rush!!! Does early adrenaline make a difference?

We all know that IV adrenaline (along with CPR) is standard of care for patients in cardiac arrest with non-shockable rhythms. But… did you know there really hasn't been any well controlled trials to see if it really makes a difference in endpoints such as improved survival and neurologically intact survival outcomes?  M.W. Donnino and his team in Boston have just published a study that shows it just might.

They did a retrospective review of  25,000 patients at 570 hospitals. Hold on. 570?!? Lets hope that doesn't become the benchmark for 'multi-centered'. Anyways, this review looked at patients who had an in-hospital non-shockable cardiac arrest (asystole or PEA) on the wards. (i.e. not in the ICU or ED). They found about 50% received their fist adrenaline dose at  >3 minutes following the start of resuscitation.

Crunching the numbers showed that delayed administration of adrenaline was associated with significantly lower chance for survival to hospital discharge. (12%, 10%, 8%, and 7% survival, respectively, for patients receiving their first epinephrine dose ≤3 minutes, 4–6 minutes, 7–9 minutes, and >9 minutes after arrest).

Neurologically intact survival at hospital discharge was significantly more likely after earlier adrenaline as well.  Their conclusion: In patients with non-shockable cardiac arrest in hospital, earlier administration of adrenaline is associated with a higher probability of return of spontaneous circulation, survival in hospital, and neurologically intact survival. 

Chip's thoughts:

The first thing that comes to mind is the < 3minutes to adrenaline is from the start of CPR/resuscitation ....not at specific time of arrest. That would appear to be a significant factor in survival at discharge as well as neuro status at discharge. The authors do state this in their limitations; " We performed several sensitivity analyses to assess the robustness of our findings when we considered delays in the initiation of cardiopulmonary resuscitation. We were, however, unable to ascertain the specific reasons for delays in the arrival of advanced resuscitation teams."

The second is the quality of CPR was not factored in and we know this makes a difference as well. The authors conclude "shorter time to administration of 'adrenaline' is associated with better outcomes after in-hospital cardiac arrest with a non-shockable rhythm". I would agree with those findings. However the importance of good CPR and well run code teams cannot be overstated. Without that, I don't think it would make much of a difference

Andy's thoughts: 

My thoughts would be that people who got the adrenaline in < than three minutes died in areas of the hospital that had well run codes. It is likely that promptness of adrenaline is a "marker" for good code teams who provided good CPR and good ALS care.

The question of how much the prompt adrenaline really helps is basically impossible to tease-out using a retrospective registry data. You can do all the multiple regression modeling you want, but it isn't going to really help you get rid of all the confounders.  

But who knows, until some esteemed body (like the NZ resuscitation council) tells me that adrenaline is useless, I'll keep giving it to all my non-traumatic cardiac arrests who have a chance at survival.  

Donnino MW, Salciccioli JD, Howell MD, Cocchi MN, Giberson B, Berg K, Gautam S, Callaway C; American Heart Association’s Get With The Guidelines-Resuscitation Investigators. Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry. BMJ. 2014 May 20;348:g3028.