Earlier Epinephrine in Cardiac Arrest Tied to Better Outcomes

Marlene Busko

November 14, 2021

Patients with out-of-hospital cardiac arrest (OHCA) with shockable rhythm who received epinephrine within 4 minutes of a first defibrillator shock had better outcomes than those who received epinephrine later, in a large observational study.

Specifically, in more than 6000 adults in North America who had a shockable OHCA from 2011 to 2015, those who received earlier vs later epinephrine were more likely to have prehospital return of spontaneous circulation (ROSC), survive until hospital discharge, and be discharged with favorable neurologic outcomes.

Shengyuan Luo, MD, MHS, presented the study at the American Heart Association (AHA) Resuscitation Science Symposium (ReSS) 2021, which is being held in conjunction with AHA's Scientific Sessions 2021.

"The data suggests that in OHCA with a shockable rhythm, prioritizing early epinephrine treatment following an electric shock may be advisable," Luo, an internal medicine resident physician at Rush University Medical Center in Chicago, told theheart.org | Medscape Cardiology in an email.

Asked to comment, Amal Mattu, MD, who was not involved with the study, noted that the authors looked at the dosing of epinephrine soon after the first shock, "but in reality, the key thing is to look at how soon after onset of [cardiac] arrest is epinephrine given."

"Early epinephrine after onset of [cardiac] arrest is the key," Mattu, professor and vice chair, Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, stressed.

Study limitations, he added, include that it was retrospective and that "we don't know how long the patients were in cardiac arrest before the first shocks were given," he noted. "For example, if the patient had been in cardiac arrest for 10 minutes before the first shock, we expect a better outcome than if the patient had been in cardiac arrest for 20 minutes."

Nevertheless, finding better outcomes after earlier administration of epinephrine "makes sense," and the findings "do align with guidelines and most of the opinion of experts," according to Mattu.

Defibrillation "should be done ASAP," he told theheart.org | Medscape Cardiology. "After that, if epinephrine is given early, e.g. in the first approximately 15 minutes of cardiac arrest, it seems to have its best benefit, but epinephrine given beyond 20 minutes after the onset of cardiac arrest doesn't help much, and continued dosing of epinephrine after that is associated with poor outcome."

Luo clarified that patients in the earlier and later epinephrine treatment groups had matched propensity scores for emergency medical services (EMS) response time and time from EMS dispatch until the first electric shock.

He did concede that other factors may be at play. "In our opinion, the prognosis associated with epinephrine may be dependent on many factors, such as its total dose, route of administration, frequency of doses, et cetera," he said.

"Studying the timing of epinephrine is only part of our effort to comprehensively evaluate the effects of the treatment in cardiac arrest." Therefore, further research is needed.

Each Minute Delay Reduced Optimal Outcome by 8%

Previous research suggested that epinephrine should be given after 3 unsuccessful electric shocks with an automated external defibrillator, but it was unclear whether giving epinephrine even earlier, such as after the first electric shock, would be better.

To examine the merits of earlier vs later epinephrine treatment in cardiac arrest, the researchers identified 6416 patients who had a shockable OHCA and received epinephrine.

The patients had a median age of 64 years, and 80% were men. Roughly a third of the patients (35%) had received epinephrine within 4 minutes after a first defibrillation.

Most patients (80%) had prehospital ROSC, roughly 1 in 5 (19%) survived until hospital discharge, and somewhat fewer (16%) were discharged with a favorable neurologic outcome.

After adjustment for confounders, for each additional minute of delay in receiving epinephrine after the first shock was given, prehospital ROSC decreased by 5% (odds ratio [OR], 0.95; 95% CI, 0.94 - 0.96), survival to hospital discharge decreased by 9% (OR, 0.91; 95% CI, 0.89 - 0.92), and being discharged with a favorable neurologic outcome decreased by 8% (OR, 0.92; 95% CI, 0.90 - 0.93) (P < .001 for all).

Compared with patients who received epinephrine within 4 minutes of the first defibrillation attempt, those who received it later were close to or half as likely to have prehospital ROSC (OR, 0.58; 95% CI, 0.51 - 0.68), survive until hospital discharge (OR, 0.50; 95% CI, 0.43 - 0.58), or be discharged with good neurologic function (OR, 0.51; 95% CI, 0.43 - 0.59) (P < .001 for all).

The associations remained significant in a well-balanced propensity score–matched cohort and subgroup analyses based on witnessed cardiac arrests, EMS response times, and total epinephrine dose.

"It is crucial that whenever a cardiac arrest event is suspected, the emergency medical system be notified and activated immediately, so that people with cardiac arrest receive timely, life-saving medical care," Luo said in an AHA press release.

The findings support the latest AHA cardiopulmonary resuscitation and emergency cardiovascular care guidelines issued in October 2020, which recommend  administering epinephrine as early as possible to maximize the chance of good resuscitation outcomes, based on observational data.

Luo and Mattu have no relevant financial disclosures.

Resuscitation Science Symposium (ReSS) 2021 held in conjunction with the American Heart Association (AHA) 2021 Scientific Sessions. Presented November 13, 2021. Abstract R07

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