EPI for Cardiac Arrest: Time to Step Away?
Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Link MS, Berkow LC, Kudenchuk PJ, et al.
Every 5 years, the American Heart Association (AHA) releases its update on Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. The 2015 Guidelines were released in October without much fanfare or groundbreaking changes. The latter point is unfortunate, as many of us who follow the emergency resuscitation literature were expecting...hoping...that the AHA would take a step away from its longstanding recommendation regarding routine use of epinephrine (EPI) in patients with cardiac arrest.
The following is a brief summary of the 2015 guidelines as they pertain to the use of EPI:
Standard-dose EPI (1 mg every 3-5 minutes) may be reasonable for patients in cardiac arrest (class IIb -- possibly helpful).
High-dose EPI (HDE) is not recommended for routine use in cardiac arrest (class III -- harmful).
Vasopressin in combination with EPI offers no advantage as a substitute for standard-dose EPI (class IIb).
It may be reasonable to administer EPI as soon as feasible after the onset of cardiac arrest due to an initial nonshockable rhythm (class IIb).
Although the strength of recommendation for use of EPI by the AHA seems to be weak, the continued endorsement of EPI in patients with cardiac arrest reminds me of the routine use of backboards for spinal immobilization by prehospital providers.
Backboards were introduced into prehospital-care protocols in the 1980s based on virtually no evidence. Nevertheless, they became a dogmatic practice in prehospital medicine. Evidence eventually began to accumulate that the backboards didn't, in fact, produce better outcomes for patients who are victims of trauma. On the contrary, the evidence began to show that the routine use of backboards was associated with pain, discomfort, pressure sores, respiratory compromise, airway difficulties,[2,3] and occasional neurologic complications.
Despite significant literature published over the past 2+ decades showing that the harm exceeded any benefit for routine use of backboards, it has only been in the past few years that the use of backboards is being discouraged for routine use in prehospital protocols. The use of backboards in selected patients seems reasonable, but routine use just doesn't make sense. However, as this backboard protocol demonstrates, once a recommendation finds its way into a formal protocol or guideline, no matter how little evidence there was to start, it becomes extremely difficult to remove it from protocols and standard practice.
Such appears to be the case with the use of EPI in cardiac arrest. This and other advanced life support drugs were first introduced into resuscitation protocols in the 1960s based on poorly controlled case series involving asphyxiated healthy young dogs in which a standard 1-mg dose was defined without any weight adjustments or consideration of interspecies variation.
The presumed benefits of EPI were based on the alpha-adrenergic effects that produce increased coronary perfusion pressure, and some benefits in terms of survival were noted in these early dog studies. Soon thereafter, assumptions were made that HDE would be even better. In fact, I was taught to use HDE in the late 1980s and early 1990s. Subsequent studies[7,8,9,10,11] demonstrated that although larger dosages of EPI, whether given in bolus form or cumulative, were associated with an increase in return of spontaneous circulation (ROSC) and survival to hospital admission, they did not produce an increase in survival to discharge or neurologic recovery.
In fact, evidence suggested worse discharge and neurologic outcomes with these higher dosages, presumably related to the beta-adrenergic effect of EPI. The AHA responded by removing HDE from its recommendations, but the guidelines continued to ignore the concerns of cumulative dosing of standard-dose EPI. The recommendation for EPI continued to be 1 mg every 3-5 minutes and ... apparently ... will continue indefinitely. Cardiac arrest victims were continuing to be placed on "backboards" despite mounting concerns and lack of quality evidence of benefit of EPI.
Since the publication of the 2010 Guidelines, further studies have questioned the dogma of repeated dosages of EPI in cardiac arrest.[12,13] These studies again support an increase in early ROSC but demonstrate worse neurologic and functional outcomes, especially with increasing cumulative dosages of EPI. An in-hospital study of cardiac arrest also showed that outcomes were improved with less frequent dosing of EPI than generally recommended in the guidelines. The most optimistic study of EPI was by Jacobs and colleagues in 2011, a randomized, double-blind, placebo-controlled study evaluating EPI vs placebo in cardiac arrest. This study showed at best a trend toward a better outcome with EPI, but the investigators did not find a statistically significant benefit. The investigators also did not evaluate the outcomes associated with cumulative dosages of EPI.
The recent study by Dumas and colleagues and accompanying editorial has proposed what I believe is the most cogent argument to when and how EPI should be used in cardiac arrest. During the first minutes of cardiac arrest, referred to as the "electrical phase," prompt defibrillation and continuous chest compressions should be the priority. It is during the second or "circulatory" phase of cardiac arrest that vasopressors appear to have the best chance of improving outcomes by improving coronary perfusion generated by chest compressions. During the third or "metabolic" phase of cardiac arrest, continuing dosages of EPI appear to be associated with a worse neurologic outcome in survivors. Continued accumulating dosages of EPI produce impaired oxygen utilization, increased myocardial oxygen demand, myocardial and cerebral ischemia, dysrhythmias, impaired lactate clearance, and a prothrombotic state.
In summary, the data suggest that the benefits of EPI are likely to be optimal in the first 10 minutes after cardiac arrest, and EPI may be detrimental beyond that timeframe.
Perhaps it is about time for us to rethink our continued use of the indefinite "every 3-5 minute" dosing of EPI in victims of cardiac arrest. There is possible benefit to the early use of EPI but evidence of harm to the later continued use. It's time to put the "backboard of cardiac arrest" aside. It's time to start making more intelligent decisions about how to care for victims of cardiac arrest and use EPI in a more sensible way instead of being strapped to dogmatic longstanding protocols that are bereft of good evidence.
Medscape Emergency Medicine © 2015 WebMD, LLC
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Amal Mattu. Epinephrine: The 'Backboard' of Cardiac Arrest? - Medscape - Oct 30, 2015.