Epinephrine needs some epinephrine, stat!

The Journal of the American College of Cardiology recently published a paper on the use of epinephrine for out of hospital cardiac arrest. The results are about as encouraging as the development of a wide-complex pulseless electrical rhythm!

Over 1500 patients were eligible for inclusion into this study. The study involved a European EMS system in which physicians staffed ambulances. Outcomes of interest included (1) survival to discharge and a (2) neurologically favorable outcome. Neurologically favorable outcomes were reported as Cerebral Performance Category (CPC) scores of 1 or 2. Not surprisingly, the administration of epinephrine was associated with a worsened neurological outcomes. The authors performed a multivariate logistic regression analysis in an attempt to control for patient and situation specific factors. Simply stated, the negative association of epinephrine persisted across various patient subgroups (older patients, patients with witnessed arrest, etc).


CPC Score Description: 

Some other interesting observations:

• Favorable neurologic outcome became less likely with an increased duration of arrest
• The delay in epinephrine administration was "linearly" associated with worsened outcomes
• Worsened neurological outcomes occurred in patients receiving "state of the art" in hospital care such as hypothermia and PCI

So, is the use of epinephrine beyond resuscitation? 

Not quite. As the authors state, it is difficult to establish a cause and effect relationship in the absence of a randomized controlled trial. Even then, out of hospital cardiac arrest does not always lend itself to an orderly collection of data. The timing of epinephrine is something that is not completely understood- epinephrine probably has no role during the "metabolic" phase of cardiac arrest. During this phase, which occurs very late into the event, epinephrine may only potentiate an already acidotic and cytotoxic environment. On the other hand, should epi be routinely administered to patients in the "electrical" phase of the arrest? In the first few minutes following collapse, defibrillation should probably take priority over IV/IO access and catecholamine administration. Perhaps epinephrine administration needs to be tailored to the individual patient presentation as opposed to routinely given every 3-5 minutes. There's actually quite a bit of conversation around a "goal directed" protocol. Epinephrine should be titrated to achieve a minimum diastolic blood pressure.

Prehospital bottom line:

• Timing of epinephrine administration may be important (the earlier, the better) 
• Continue to focus on time-tested interventions linked to improved neurologic survival
• Minimally interrupted, high performance CPR is key to maintaining adequate coronary perfusion
• Epinephrine may be linked to an increased incidence of prehospital ROSC but does not appear to confer longer term survival or neurologic benefits following out of hospital cardiac arrest

Article abstract in PubMed

J Am Coll Cardiol. 2014 Dec 9;64(22):2360-7. doi: 10.1016/j.jacc.2014.09.036. Epub 2014 Dec 1.

Is epinephrine during cardiac arrest associated with worse outcomes in resuscitated patients?

Dumas F1, Bougouin W2, Geri G2, Lamhaut L3, Bougle A4, Daviaud F4, Morichau-Beauchant T4, Rosencher J5, Marijon E6, Carli P7, Jouven X6, Rea TD8,Cariou A2.

Author information

Abstract

BACKGROUND:

Although epinephrine is essential for successful return of spontaneous circulation (ROSC), the influence of this drug on recovery during the post-cardiac arrest phase is debatable.

OBJECTIVES:

This study sought to investigate the relationship between pre-hospital use of epinephrine and functional survival among patients without-of-hospital cardiac arrest (OHCA) who achieved successful ROSC.

METHODS:

We included all patients with OHCA who achieved successful ROSC admitted to a cardiac arrest center from January 2000 to August 2012. Use of epinephrine was coded as yes/no and by dose (none, 1 mg, 2 to 5 mg, >5 mg). A favorable discharge outcome was coded using a Cerebral Performance Category 1 or 2. Analyses incorporated multivariable logistic regression, propensity scoring, and matching methods.

RESULTS:

Of the 1,556 eligible patients, 1,134 (73%) received epinephrine; 194 (17%) of these patients had a good outcome versus 255 of 422 patients (63%) in the nontreated group (p < 0.001). This adverse association of epinephrine was observed regardless of length of resuscitation or in-hospital interventions performed. Compared with patients who did not receive epinephrine, the adjusted odds ratio of intact survival was 0.48 (95% confidence interval [CI]: 0.27 to 0.84) for 1 mg of epinephrine, 0.30 (95% CI: 0.20 to 0.47) for 2 to 5 mg of epinephrine, and 0.23 (95% CI: 0.14 to 0.37) for >5 mg of epinephrine. Delayed administration of epinephrine was associated with worse outcome.

CONCLUSIONS:

In this large cohort of patients who achieved ROSC, pre-hospital use of epinephrine was consistently associated with a lower chance of survival, an association that showed a dose effect and persisted despite post-resuscitation interventions. These findings suggest that additional studies to determine if and how epinephrine may provide long-term functional survival benefit are needed.

Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

cardiac arrest; hypothermia; percutaneous coronary intervention