When you take vacation, the relentless march of the medical literature does not. Even though this blog is a week late to this party – an eternity in the world of rapid post-publication peer review – I would be remiss not to here briefly mention PARAMEDIC2.
This is, by far, the largest prospective, randomized, controlled trial of epinephrine in out-of-hospital cardiac arrest. Effectively the mainstay of resuscitation for many decades now, smaller trials and other post-hoc analyses have found inconsistent survival advantages associated with its use. Epinephrine, it has seemed, will flog the heart back into some level of cardiac output compatible with “life”. However, the other deleterious effects of epinephrine – or the context of the peri-arrest physiology – fails to produce an advantage with regard to neurologically-intact survival.
And that’s what we see, again, here.
This trial enrolled 8,014 patients with OHCA with the primary outcome being survival at 30 days. The intervention arm administered 1mg intravenous or intraosseous doses of epinephrine every 3 to 5 minutes during resuscitation or saline placebo. Secondary outcomes were survival to hospital admission, length-of-stay in the intensive care unit, and neurologic outcomes at hospital discharge and at 3 months. A “favorable” neurologic outcome was defined as a score of 3 or less on the modified Rankin scale, which is a little bit different than other trials using Cerebral Performance Category.
Both cohorts were fairly evenly matched with regard to prognostic features, which is to say, they were basically terrible. Nearly 80% of the cohort had a non-shockable rhythm, although over 60% were witnessed arrest and had bystander CPR. Response times by ambulance to the scene were around 7 minutes, and 21 minutes elapsed between call and first use of trial medication.
Just as in the previous evidence, epinephrine functions as advertised – the return of spontaneous circulation in the prehospital setting was 36.3% with epinephrine, compared with 11.7% without. However, with every advancing time point, the gap between the arms narrowed. At hospital admission, epinephrine was favored 23.8% to 8.0%. Survival to hospital discharge favored epinephrine 3.2% to 2.3%, and then 3.0% to 2.0% at three months. Finally, neurologic outcomes were even more narrowly in favor of epinephrine at three months, 2.1% to 1.6%. Further splicing out the outcomes with regard to mRS, the small excess favoring epinephrine were those with mRS 3, whereas the small numbers with mRS 0,1 or 2 were effectively identical. Of note, from these 8,000 starting with cardiac arrest, only 27 survived with an mRS of 0. Bleak.
So, we’re effectively back where we started – but with the best evidence to date regarding the limitations of epinephrine. Giving epinephrine up-front is a rewarding, “life-saving!” experience for the initial treating providers. Unfortunately, the ultimate outcomes are effectively just as dismal – only vastly more costly in terms of real currency and resource utilization when epinephrine is featured. Until substantial advances can be made with regard to improving post-arrest functional outcomes, it is entirely reasonable to consider omitting epinephrine from resuscitation from out-of-hospital arrest.
“A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest”