Using epinephrine during resuscitation for out-of-hospital cardiac arrest may lower neurologically intact survival, according to an observational study published online Dec. 1 in the Journal of the American College of Cardiology.
This negative effect was dose related and unaffected by postresuscitation interventions such as percutaneous coronary intervention or therapeutic hypothermia in a single-center observational cohort study, said Dr. Florence Dumas of the Parisian Cardiovascular Research Center, Paris Descartes University, and her associates.
In this study, as in some previous studies, epinephrine was associated with an improved rate of return of spontaneous circulation. But that benefit didn’t translate into higher long-term survival, possibly because of an as-yet unidentified harmful effect during the postresuscitation phase of treatment, the investigators noted.
International resuscitation guidelines recommend giving epinephrine every 3-5 minutes during cardiac arrest resuscitation efforts, regardless of the initial cardiac rhythm. This approach has been shown to enhance the return of spontaneous circulation. However it is unclear how the treatment affects long-term survival, with some studies reporting no effect or even deleterious effects on that outcome. To examine the issue, Dr. Dumas and her associates assessed outcomes for 1,556 patients who had nontraumatic out-of-hospital cardiac arrest, achieved return of spontaneous circulation, and were then admitted to a large specialized medical center during a 12-year period.
The average patient age was 60 years, and 71% were men. Nearly 75% of the participants received epinephrine during resuscitation. As expected, those who were given epinephrine had less favorable prognostic characteristics than patients who were not given the drug; they were older, less likely to have had a witnessed cardiac arrest, and less likely to have had a shockable rhythm when paramedics arrived, and they had longer durations of resuscitation.
A total of 449 patients (29%) survived to hospital discharge with a good neurologic status, defined as a Cerebral Performance Category of 1 or 2. Patients who received epinephrine during resuscitation were markedly less likely to do so (17%) than patients who didn’t receive epinephrine (60%).
To control for the baseline differences between the two study groups that may have contributed to this discrepancy in survival, the investigators performed several adjusted analyses of the data, including propensity scoring, cross matching, and numerous sensitivity analyses. The negative effect associated with epinephrine “was robust to a variety of different methodological approaches designed to limit confounding,” Dr. Dumas and her associates said (J. Am. Coll. Cardiol. 2014 Dec. 1 [doi:10.1016/j.jacc.2014.09.036]).
There was a stepwise association between increasing dose of epinephrine and decreasing odds of surviving neurologically intact, with an odds ratio of 0.48 for 1 mg epinephrine, 0.30 for 2-5 mg, and 0.23 for more than 5 mg. The timing of administration also showed a linear association with survival odds. Patients who received epinephrine within 9 minutes of cardiac arrest had an odds ratio of neurologically intact survival of 0.54, those who received it at 10-15 minutes had an OR of 0.33, those who received it at 16-22 minutes had an OR of 0.23, and those who received it after 22 minutes had an OR of 0.17.
“Before incriminating the drug itself, our findings probably should provoke further discussion on the most appropriate scheme of treatment and its interaction regarding the resuscitation phases,” the researchers said, referring to the “electrical phase” within the first few minutes after cardiac arrest, when epinephrine isn’t required; the subsequent “circulatory phase” when both epinephrine and chest compressions enhance reperfusion; and the later “metabolic phase” when epinephrine might be detrimental.
“It is highly probable that patients receiving late or repeated doses of epinephrine have little or no chance of survival. Altogether, the scheme and timing of administration may be crucial to provide the appropriate effect of epinephrine,” they said.
Dr. Dumas and her associates emphasized that an observational study such as theirs cannot determine causality, so it cannot be said that epinephrine caused the negative effect on intact survival. They also noted that findings from their single-center study may not be generalizable to all communities.
Dr. Dumas and her associates reported having no relevant financial disclosures.