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.

However, 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.

Again, as expected with cardiac arrest not seen on television, overall outcomes were dismal. Survival in the first 72 hours was 13.1 percent in the ETI cohort and 13.6 percent with SGA, and a good outcome was observed in 6.8 percent and 6.4 percent, respectively. Unlike the epinephrine trial, however, outcomes remained essentially parallel at all time points in the study.

This study featured several interesting quirks. Patients treated by paramedics randomized to the ETI cohort were far less likely to have any advanced airway attempted, with almost 25 percent of those in the ETI cohort simply receiving no airway attempt compared with 14 percent of those in the SGA group. These patients were managed with bag-valve-mask ventilation as indicated, and the overall rate of good outcome in these patients measured approximately 17 percent. Only 2.3 percent of those in whom an ETI was attempted had a good outcome compared with only 3.2 percent of those in whom SGA was attempted.

Caution: Beware imagining a causal relationship between attempting an advanced airway and poorer outcomes. It is far more likely individual patient factors associated with a better prognosis led to the difference in management strategies, but these data cannot definitively answer questions regarding the necessity of an advanced airway.

The PART study, conducted in the United States and enrolling 3,004 patients, was similar, although with minor differences in design. Rather than randomizing at the individual paramedic level, randomization occurred at the EMS agency level and included crossover periods for each. Additionally, the SGA device used was a laryngeal tube, the most commonly used SGA in the United States.

These authors observed outcomes similar to AIRWAYS-2, with a 72-hour survival of 15.4 percent in the ETI cohort compared to 18.3 percent with SGA. Neurological survival also favored SGA, with good outcomes occurring in only 5 percent of those randomized to ETI compared with 7.1 percent for SGA.

This study is also full of quirks relating to the individual agencies and the devices used. A handful of agencies were made up of EMS providers with only basic life support training. Patients randomized to ETI enrolled by these cohorts received noninvasive ventilation while awaiting the arrival of an advanced life support provider. Additionally, the overall rate of initial airway success was only 51.6 percent with ETI compared to 90.3 percent with SGA. Only one attempt was mandated, but any potential delay or interruption of resuscitative efforts may be interpreted to have deleterious effects on outcomes for the ETI cohort.

So what should we do for the airway based on the results from these 12,000 total patients? Although there is more than enough room for debate, it seems the least favorable position would be to support prehospital ETI. ETI cannot conclusively be shown to result in harm compared to SGA, but it is challenging to consider it the best strategy.

A better question may be whether any advanced airway is routinely necessary. A small trial in France could not reach a conclusion regarding the utility of ETI compared to bag-valve-mask ventilation even though that trial utilized physicians for airway procedures in the prehospital setting.⁴

I believe the current evidence favors conserving limited health care resources by omitting epinephrine and using primarily SGA, if any airway is even needed. However, it would be just as reasonable for a medical director to draw up protocols using both epinephrine and ETI as it would be to omit both. At the end of the day, we are a little closer to definitive answers, but we have many new questions.

References

1. Perkins GD, Ji C, Deakin CD, et al. A randomized trial of epinephrine in out-of-hospital cardiac arrest. N Engl J Med. 2018;379(8):711-721.
2. Benger JR, Kirby K, Black S, et al. Effect of a strategy of a supraglottic airway device vs tracheal intubation during out-of-hospital cardiac arrest on functional outcome: the AIRWAYS-2 randomized clinical trial. JAMA. 2018;320(8):779-791.
3. Wang HE, Schmicker RH, Daya MR, et al. Effect of a strategy of initial laryngeal tube insertion vs endotracheal intubation on 72-hour survival in adults with out-of-hospital cardiac arrest: a randomized clinical trial. JAMA. 2018;320(8):769-778.
4. Jabre P, Penaloza A, Pinero D, et al. Effect of bag-mask ventilation vs endotracheal intubation during cardiopulmonary resuscitation on neurological outcome after out-of-hospital cardiorespiratory arrest: a randomized clinical trial. JAMA. 2018;319(8):779-787.