Timely epinephrine for pediatric in-hospital cardiac arrest

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Current guidelines upheld

The findings by Dr. Andersen and his associates provide fairly strong evidence that following current guidelines for epinephrine timing is best practice, supporting an AHA class I strength of recommendation.

The investigators are correct to note that observational data cannot establish causality. Almost all of these cardiac arrests were witnessed; approximately two-thirds occurred in the pediatric intensive care unit, operating room, or postanesthesia setting; and half of the patients were receiving mechanical ventilation. So it is possible that the link between timing of epinephrine and outcomes may simply reflect factors such as the circumstances of the cardiac arrest, the presence of an airway and intravenous access, or the quality of chest compressions.

Dr. Robert C. Tasker and Dr. Adriennne G. Randolph are with the division of critical care medicine, department of anesthesia, perioperative, and pain medicine at Boston Children’s Hospital and the department of anesthesia at Harvard Medical School. Dr. Tasker is also with the department of neurology at both institutions and Dr. Randolph is also with the department of pediatrics at Harvard. Both authors reported having no relevant financial conflicts of interest. Dr. Tasker and Dr. Randolph made these remarks in an accompanying editorial (JAMA. 2015;314:776-7. doi: 10.1001/jama.2015.9527).




Delay in administering epinephrine is associated with significantly poorer outcomes among pediatric patients who have in-hospital cardiac arrest with an nonshockable rhythm, according to a report published online Aug. 25 in JAMA.

For the approximately 16,000 U.S. children and adolescents in this patient population each year, epinephrine is the recommended first-line pharmacologic therapy, even though no randomized placebo-controlled trials have ever been performed to support this practice.

It is highly unlikely that any such study will ever be done, given the ethical considerations, so to examine the effect of the timing of epinephrine therapy, investigators analyzed data from the Get With the Guidelines-Resuscitation registry concerning 1,558 patients aged 0-18 years who were treated during a 15-year period, said Dr. Lars W. Andersen of the department of emergency medicine at Beth Israel Deaconess Medical Center, Boston, and the department of anesthesiology at Aarhus (Denmark) University and his associates.

All the patients received chest compressions and at least one epinephrine bolus while pulseless with a documented nonshockable initial rhythm. The median age was 9 months, and the median time to first epinephrine dose was 1 minute (range, 0-20 minutes). A total of 37% of these patients received their first dose of epinephrine within 1 minute after loss of pulse was noted, and 15% received their first dose more than 5 minutes afterward.

Delay in epinephrine treatment was significantly associated with a lower chance of survival to hospital discharge (relative risk, 0.95 per minute of delay), the primary outcome measure of the study. In addition, longer time to epinephrine delivery was significantly associated with a decreased chance of return to spontaneous circulation (RR, 0.97 per minute of delay), for survival at 24 hours (RR, 0.97 per minute of delay), and for survival with favorable neurologic outcome (RR, 0.95 per minute of delay).


In a further analysis of the data, patients were divided into two groups according to the length of time before epinephrine administration. The 1,325 patients who received epinephrine within 5 minutes had a 33.1% rate of survival to hospital discharge, while the 233 who received epinephrine after 5 minutes had elapsed had a significantly lower 21.0% rate of survival to hospital discharge, Dr. Andersen and his associates said (JAMA. 2015 Aug 25. doi: 10.1001/jama.2015.9678).

These findings suggest, but cannot establish, that treatment delay causes poorer outcomes because an observational study cannot determine causality. Even though the data were adjusted to account for numerous patient and hospital characteristics, and even though the results remained robust through multiple sensitivity analyses, it remains possible that time to epinephrine administration is not a causal mediator but a marker of other aspects of the resuscitation process, the researchers added.

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