Rethinking Priorities in Out-of-Hospital Cardiac Arrest – Which Comes First Epi or Airway?

Cardiac arrest remains one of the most challenging emergencies prehospital care providers face, with survival rates that hinge on the actions taken in the first few minutes. Understanding which interventions truly make a difference is crucial. In this post we look at a recent article published in JAMA Network Open entitled “Sequence of Epinephrine and Advanced Airway Placement After Out-of-Hospital Cardiac Arrest” which sought to understand the impact of the sequence in which epinephrine and advanced airway management are administered, on patient outcomes.

The Essentials of Early Response

Lets begin with a stark reminder of the well-established pillars of cardiac arrest management: early and high-quality CPR, minimal interruptions in chest compressions, and prompt defibrillation. These fundamentals are the backbone of successful resuscitation efforts, significantly increasing the chances of survival.

Advanced Interventions: A Closer Look

While advanced tools and techniques are available to paramedics, we need to take a critical evaluation of their impact. This article looks at advanced airway management and the administration of epinephrine, two areas under scrutiny for their timing and effectiveness in cardiac arrest scenarios.

Study Design and Population

This was a retrospective cohort analysis leveraging the nationwide, population-based out-of-hospital cardiac arrest registry in Japan. This registry is comprehensive, capturing a wide range of data points on OHCA incidents across the country. The researchers focused on adults aged 18 and older who experienced an OHCA and were treated by EMS personnel who administered epinephrine and/or performed advanced airway management between January 1, 2014, and December 31, 2019. This period provided a substantial dataset for analysis, encompassing a total of 259,237 patients.

Interventions and Comparison

A key aspect of this study was its examination of the sequence of interventions—specifically, whether epinephrine was administered before or after the placement of an advanced airway. In Japan, advanced airway management typically involves the use of supraglottic airway devices but may also include endotracheal intubation. It’s important to note that in this study, intravenous (IV) access was used for epinephrine administration, as intraosseous (IO) access is not commonly practiced by EMS in Japan. This detail is crucial, as it impacts the timing of epinephrine administration and could influence the study’s applicability to systems where IO access is prevalent.

Findings and Implications

The study’s findings revealed that early administration of epinephrine, prior to advanced airway management, was associated with better outcomes in both shockable and non-shockable rhythms. Specifically, epinephrine administration earlier was associated with improved rates of one-month survival, survival with favorable neurological outcomes, and prehospital return of spontaneous circulation (ROSC).

The authors suggest that in the sequence of interventions for OHCA, prioritizing early epinephrine administration could have a significant impact on patient survival and neurological recovery. It’s a finding that challenges some existing literature surrounding outcomes in OHCA with epinephrine use.

Considerations and Context

It’s important to consider the study’s context when interpreting its findings. The retrospective nature means it can identify associations but not causation. Additionally, the absence of intraosseous (IO) access in the Japanese EMS system is a notable difference from practices in countries like the United States and Canada.

While this study suggested potential benefits of early epinephrine administration, other research has not shown the same benefit and has presented a more complex picture, particularly regarding long-term outcomes and neurological recovery.

Paramedic 2 Trial: One of the most recent pivotal studies was the PARAMEDIC2 trial, a well-executed randomized controlled trial that directly compared the administration of epinephrine to placebo in cardiac arrest cases. The trial’s findings revealed a nuanced outcome: while the use of epinephrine did indeed increase the overall survival rates at one month compared to placebo, this increase was largely attributed to survivors with poor neurological outcomes. This result raises ethical and practical questions about the value of survival at the expense of quality of life. Is there a fate worse than death?

Systematic Review and Meta-Analysis: Further complicating the narrative, a systematic review and meta-analysis published in the journal Chest last year, entitled “Epinephrine and Out-of-Hospital Cardiac Arrest,” synthesized data from several studies, including randomized controlled trials comparing epinephrine to placebo. The analysis concluded that while epinephrine might increase the chances of survival to hospital admission, it does not significantly impact survival to hospital discharge or survival with favorable neurological outcomes. This comprehensive review further underscores the ongoing debate about the role of epinephrine in OHCA management, suggesting that its benefits may be limited to short-term survival gains without necessarily improving the chances of a good quality of life post-resuscitation.

So how do we reconcile these conflicting results?

Conclusion: Back to Basics

In my mind, does earlier epinephrine improve outcomes? Maybe. Maybe not. What do I feel the true implication of this study is? The basics matter. For me, this result continues to de-emphasize our advanced tools such as advanced airway management in the setting of OHCA. While the quest for improvement and innovation in cardiac arrest care continues, the message is clear: mastering the basics remains the most crucial step in saving lives. On my next resuscitation I will prioritize making sure high quality continuous CPR is being preformed, a monitor is available and hooked up, IV or IO access is obtained quickly, and a good history of events is understood. Only after assuring the basics are covered, will I consider moving on to my advanced airway management.

As prehospital care evolves, so too will the strategies to combat one of medicine’s greatest challenges, but the cornerstone of cardiac arrest management will always be early, quality CPR and defibrillation.


Sequence of Epinephrine and Advanced Airway Placement After Out-of-Hospital Cardiac Arrest. JAMA Netw Open. 2024 Feb 5;7(2):e2356863. doi: 10.1001/jamanetworkopen.2023.56863.

Association of timing of epinephrine administration with outcomes in adults with out-of-hospital cardiac arrest.  JAMA Netw Open. 2021;4(8):e2120176. doi:10.1001/jamanetworkopen.2021.20176

Epinephrine in Out of Hospital Cardiac Arrest: A Network Meta-analysis and Subgroup Analyses of Shockable and Nonshockable Rhythms. Chest. 2023 Aug;164(2):381-393. DOI: 10.1016/j.chest.2023.01.033

A Randomized Trial of Epinephrine in Out of Hospital Cardiac Arrest. (PARAMEDIC2) New Eng J Med. DOI: 10.1056/NEJMoa1806842

The influence of time to adrenaline administration in the Paramedic 2 randomised controlled trial.  Intensive Care Med. 2020;46(3):426-436. doi:10.1007/s00134-019-05836-2

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