Background

  • ACLS protocols for cardiac arrest have long recommended epinephrine administration, dosed at 1mg via intravenous or intraosseous push every 3-5 minutes. While there is considerable data that epinephrine administration improves return of spontaneous circulation (ROSC) and survival to hospital admissions, studies have failed to show that epinephrine administration has impact on functional outcomes (1,2).
  • This group of authors recently conducted a trial (3) comparing the usual multi-dose epinephrine protocol (MDEP) to a single-dose epinephrine protocol (SDEP). In this trial, they found higher rates of ROSC in the MDEP group, but no changes in survival to hospital admission between the two groups.
  • At high doses, epinephrine can cause increased myocardial oxygen demand and dysrhythmias. This group hypothesized that older adults in cardiac arrest are more susceptible to these adverse events, so they conducted a subgroup analysis of their original trial to test this hypothesis.

Clinical Question

  • In adults aged 65 and older with cardiac arrest, does single-dose epinephrine, when compared to traditional multi-dose epinephrine, increase odds of survival to hospital discharge?

Population

  • 1690 patients who suffered out of hospital cardiac arrest in five counties in North Carolina.
    • 864 aged 65 and older (Older)
    • 538 aged 46-64 (Middle Age)
    • 288 aged 18-45 (Young)
  • Patients with both shockable and non-shockable initial cardiac rhythms were included.

Intervention

  • A pre-hospital protocol that advised only a single (1mg) dose of intravenous or intraosseous epinephrine.

Outcomes

  • The primary outcome was survival to hospital discharge, defined as leaving the hospital alive regardless of neurologic function.
  • Secondary outcomes included ROSC (defined as pulse being present for 20 minutes without need for chest compressions) and favorable neurologic outcome (Cerebral Performance Category 1 or 2).

Design

  • This was a pre- and post-implementation study, not a randomized trial. Data on cardiac arrest outcomes were collected from a CPR outcomes database (the CARES database) for one year prior to SDEP implementation and one year after SDEP implementation.
  • They adjusted for covariates including race, sex, witnessed arrests, bystander CPR and/or AED use, initial rhythm, EMS response time, and arrest location type.

Excluded

  • Patients with traumatic arrest, DNR order, or missing outcomes data were excluded.

Primary Results

  • After implementation of SDEP protocol, there was a 5.6% absolute increase in survival among older adults (OR 1.95, statistically significant). There was also an absolute increase in survival with good neurologic outcome in this group (OR 1.61, statistically significant). These associations remained significant even when adjusting for covariates (AOR 1.87).
  • However, there was also an absolute decrease in ROSC (roughly 10-15%) in older and middle-aged adults after implementation of the SDEP protocol (also statistically significant). After adjusting for covariates, ROSC rates were lower in all cohorts post-implementation.

Strengths

  • It was impressive that the authors managed to capture a difference in survival (and survival with good neurologic outcome) with this study. These findings tend to be rare in resuscitation studies, because absolute differences in survival are often small.

Limitations

  • This was not a randomized trial, and while the authors tried to control for potential confounders, they were limited in these efforts by the scope of the database from where they pulled the data.
  • The database that the authors used was rather limited. It did not allow them to track adherence to the SDEP protocol or measure and adjust for patient comorbidities.
  • Since this was a pre-hospital trial, after arrival to the hospital, there was no restriction on further epinephrine doses.

Author's Conclusions

  • Implementation of a single-dose epinephrine EMS protocol was associated with a modest increase in survival rates among older adults, but was also associated with a decrease in rates of ROSC among all patients.

Our Conclusions

  • This study is hypothesis-generating only and is not rigorous enough to inform changes in clinical practice. My biggest concern, other than the lack of randomization, is that there are no measurements of adherence to SDEP/MDEP protocols or total epinephrine given.
  • With that being said, the findings are meaningful and do warrant further study. The single-dose epinephrine protocol nearly doubled rates of survival in the older adults cohort; this makes a pretty strong argument that there may be some harm associated with the high doses of epinephrine we often give to these patients. We’ve seen a randomized trial that found benefit of epinephrine over placebo (3), but a trial that compares “low-dose epinephrine” to traditional “high-dose epinephrine” specifically in older adults might favor lower doses of epinephrine and have the potential to be practice-changing.
  • Even as we do get more data, I would personally have a high threshold to individualize protocols for the early phases of resuscitation. Particularly in the prehospital environment where personnel and resources are often limited, we don’t want to detract focus from what matters most in these patients: good quality CPR and early defibrillation.

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References

  1. Fernando SM, Matthew R, Sadeghirad B, et al. Epinephrine in Out-of-Hospital Cardiac Arrest: A Network Meta-Analysis and Subgroup Analysis of Shockable and Non-Shockable Rhythms. Chest. 2023; 164 (2): 381-393.
  2. Perman SM, Elmer J, Maciel CB, et al. 2023 American Heart Association Focused Update on Adult Advanced Cardiovascular Life Support: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2024; 149 (5): e254-e273
  3. Perkins GD, Ji C, Deakin CD, et al. A randomized Trial of Epinephrine in Out of Hospital Cardiac Arrest. New England Journal of Medicine. 2018; 379:711-721.