The prehospital game has always been muddy, particularly when it comes to the various pharmacologic interventions fixed in the constellation of Advanced Life Support. You could – and some have – go as far as to say virtually nothing in the armamentarium of prehospital care has been proven to improve meaningful survival following cardiac arrest.
This latest evidence drop is the ALPS trial from the Resuscitation Outcomes Consortium – amiodarone, lidocaine, or placebo in patients with shock-refractory ventricular fibrillation/ventricular tachycardia. The underlying physiologic theory would be that there’s a period of time between onset of VF/VT and death where drugs are the answer. Early on, an appropriately delivered shock solves the disorganized electrical problem. Later on, after the intracellular rigor sets in, nothing will be reliably beneficial. In some intervening period, there is hope that amiodarone or lidocaine provides a little extra stabilization to help a shock take hold.
These authors performed a prospective, double-blinded, placebo-controlled, randomized trial with three arms to compare each antiarrhythmic therapy to placebo. With a 90% power to detect a 6% survival to hospital discharge between arms, these authors enrolled 3,026 patients. Groups were generally well-balanced for important prognostic features, adjunctive treatments, and post-admission care. But, unfortunately, the survival advantage seen was 3.2% for amiodarone and 2.6% for lidocaine – meaning the confidence intervals each cross unity and the p-values are 0.08 and 0.16, respectively.
So, we have, yet again, a study that provides more to argue about than to inform practice. Delving into the secondary outcomes and the supplementary appendix, it is clear that both antiarrhythmic drugs are doing something. Patients receiving the active arms in the trial required fewer shocks, received fewer doses of alternative antiarrhythmic drugs (e.g., magnesium, procainamide), and had significantly higher rates of hospital admission – 45.7% vs. 47.0% as. 39.7% for amiodarone, lidocaine, and placebo, respectively. However, all these advantages on the front-end decayed into smaller and smaller absolute differences on the back end – where mRS 3 or better discharge status was only 18.8% vs. 17.5% vs. 16.6%.
The glass half-full look at this is: even though it’s not statistically significant, even a couple percentage points of life vs. death represents a couple thousand additional neurologically intact survivors each year. The glass half-empty look at this is: 26.9% of the amiodarone group required immense resource outlay and ICU care and was still ultimately dead or disabled, along with 29.5% of the lidocaine group, but only 23.1% of the placebo group.
These data suggest many reasonable choices may be made. The signal may not be strong enough, and the downstream costs high enough, that a case could be made to dramatically curtail use of both active drugs. Or, specific instances of use or delivery improvements could be proposed, based on other survival signals hidden in the secondary data. Finally, costs, ease of use, and other secondary signals could make dueling cases to discontinue use of one of the two active drugs.
I think these drugs probably have value – but, their value won’t be maximized until in-hospital care produces either a better yield of neurologically intact survivors or better prognosticates resuscitation to reduce ultimate resource utilization.
“Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest”
https://www.ncbi.nlm.nih.gov/pubmed/27043165
HMMM.
Thanks for the breakdown Ryan. I find you last two paragraphs really resonate for me as a practitioner of the dark arts of prehospital care. It seems to me that there are likely patients who may benefit from these drugs, as well (possibly) as a raft of other unproven interventions (maybe even mechanical CPR, despite my usual scathing response to these expensive toys)
The key is surely finding those patients who may benefit: sorting the chafe from the wheat. It seems intuitive (although we know how badly intuition usually works out) that the 42 year old with chest pain who drops in front of bystanders and gets CPR and/or Public Access Defibrillation will be more likely to be a survivor than the 87 year old with a 2 page long list of comorbidities, found down after who knows how long.
Unfortunately, we continue to treat these patients the as the same population for the purposes of cardiac arrest care/research in the field, which seems to me to be utter madness, and potentially to wash out any benefit an intervention may have to survivors from the research.
Identification of survivors/non-survivors before we start the resus ball rolling (beyond the obvious shockable/non-shockable rhythm) must surely afford better utilisation of scarce resources, and perhaps lead to more applicable research into what actually may make a difference to good neurological function post cardiac arrest.
Robbie (@AmboFOAM)
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