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There’s a big difference between patients who are mostly dead and all dead. Mostly dead is, by logical extension, slightly alive. Slightly alive we can work with.
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ACEP Now: Vol 37 – No 10 – October 2018However, this leads to a question: Which application of the medical sciences is best for the slightly alive?
Two important questions have remained controversial for decades: the use of epinephrine in cardiac arrest and the type of advanced airway management provided. This year has brought to light several new studies concerning these topics, but they seem to provide only minimal illumination.
Epinephrine Research
ARAMEDIC2, a randomized, double-blinded, placebo-controlled trial of epinephrine in adults with out-of-hospital cardiac arrest (OHCA), was conducted in the United Kingdom’s prehospital system.1 This study used the contemporary dose of 1 mg intravenously repeated every three to five minutes as indicated by advanced cardiac life support protocols. The primary outcome? Survival at 30 days.
So the unqualified answer favors epinephrine, but the details are a little more complicated. Of the 8,014 patients randomized into this trial, survival at 30 days was 3.2 percent in the epinephrine group versus 2.4 percent in the placebo group. Dismal numbers, but incrementally less dismal when treated with epinephrine.
The catch—and there’s always a catch—is the entirety of excess patients surviving to 30 days in the epinephrine cohort were all gravely disabled. In these small cohorts of survivors, 31 percent of those randomized to epinephrine were gravely disabled at follow-up compared with only 17.8 percent of those randomized to placebo. In short, as we parse these results down to the most important patient-oriented outcomes, the differences disappear.
But wait: When we dig into these results more closely, the differences are actually magnified. A full 36.3 percent of patients in the epinephrine cohort had some return of spontaneous circulation during prehospital transport compared with only 11.7 percent of those randomized to placebo. Initial treatment in the hospital sheared another chunk off the top of each group, but still nearly three times as many patients survived to hospital admission in the epinephrine cohort as compared to the placebo group.
We can interpret this as either an advantage or a disadvantage. When no reliable difference appears regarding favorable neurological outcomes, short-term survival can be seen as a substantial cost and burden to the health system absent long-term benefit. However, the survival advantage associated with epinephrine is still massive.
Potential interventions such as early coronary angiography, targeted temperature management, and other potential physiologic and neuroprotective interventions may yet generate clear separation between the two groups with regard to neurologically intact survival. In sum, the decisions we make today regarding the use of epinephrine may be quite different than those a few years from now.
Airway Management Studies
Two trials, AIRWAYS-2 and PART, compared endotracheal intubation (ETI) with the placement of a supraglottic airway (SGA).2,3 The larger trial, AIRWAYS-2, was conducted in England, enrolling 9,296 people in its intention-to-treat population. In this trial, individual paramedics at four emergency medical services (EMS) were randomized to use ETI or SGA as their initial method of securing the airway. For SGA, they used the i-gel device (chosen because it is the most commonly used device in England), and all intubation attempts utilized direct laryngoscopy. Their primary outcome was a good outcome on the modified Rankin Scale, measured as a score ≤3 at hospital discharge or 30 days.
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2 Responses to “Studies Test Common Cardiac-Arrest Advanced Life Support Practices”
October 28, 2018
William ReedRegarding the PARAMEDIC2 trial reviewed by Dr. Radecki.
First, love the Princess Bride reference.
Second, I would respectively offer another interpretation of the study.
The study shows that epinephrine in OHCA will likely not improve “neuro-intact” survival if:
1. Your EMS agency does not give the drug earlier than a median of 14.8 minutes after arrival.
And,
2. Your EMS agency has a very low overall survival rate for OHCA (1/5th that of the great state of Oregon’s – 2017 CARES data).
Close, but no cigar.
Repeating this study in the US with EMS agencies with a CPR fraction greater than 90% and who give Epi early (less than 10 minutes after EMS arrival) would help better define the utility of this drug in OHCA.
Respectfully submitted “as you wish.”
WJR
November 1, 2018
Ryan RadeckiThanks for the comment, William.
I agree with all your points.
Generalizability of a study is always of concern – if a study’s population and practices do not reflect your own, it limits the applicability to your setting. It blurs the line between practice-defining and hypothesis-generating, as you note, where either a subgroup analysis may be more informative, or another type of trial altogether.
Cheers,
Ryan