Epinephrine Timing Key in In-Hospital Pediatric Cardiac Arrest

Troy Brown, RN

August 27, 2015

Timing of epinephrine administration matters in children who experience in-hospital cardiac arrest with initial nonshockable rhythm, according to a recent study. Delayed epinephrine administration was linked to decreased chance of survival to hospital discharge, return of spontaneous circulation (ROSC), 24-hour survival, and survival to hospital discharge with a favorable neurological outcome.

Lars W. Andersen, MD, from the Beth Israel Deaconess Medical Center, Boston, Massachusetts, and Aarhus University Hospital in Denmark, and colleagues report their findings in an article published in the August 25 issue of JAMA.

"There are notable differences between pediatric and adult cardiac arrest in etiology, epidemiology, and treatment, including that more children have a nonshockable rhythm," the authors write. "Despite this, the current findings in the pediatric population are in line with those previously reported for adults."

The researchers analyzed data from the Get With the Guidelines–Resuscitation registry. They included US pediatric patients younger than 18 years with an in-hospital cardiac arrest and an initial nonshockable rhythm who received at least one dose of epinephrine. The final cohort included a total of 1558 patients (median age, 9 months; interquartile range [IQR], 13 days - 5 years).

The researchers defined time to epinephrine as the time in minutes from recognition of pulselessness to the first epinephrine dose.

Less than one third (31.3%; n = 487) of the 1558 patients survived to hospital discharge, which was the primary study endpoint. The median time to first dose of epinephrine was 1 minute (IQR, 0 - 4 minutes; range, 0 - 20 minutes; mean [standard deviation], 2.6 [3.4] minutes).

Longer time to administration of epinephrine was associated with lower risk for survival to discharge (multivariable-adjusted risk ratio [RR] per minute delay, 0.95; 95% confidence interval [CI], 0.93 - 0.98).

In addition, longer time to epinephrine administration was linked to decreased risk for ROSC (multivariable-adjusted RR per minute delay, 0.97; 95% CI, 0.96 - 0.99) and decreased risk for survival at 24 hours (multivariable-adjusted RR per minute delay, 0.97; 95% CI, 0.95 - 0.99). Longer time to administration was also linked to decreased risk for survival with favorable neurological outcome (multivariable-adjusted RR per minute delay, 0.95; 95% CI, 0.91 - 0.99), which was defined as a score of 1 to 2 on the Pediatric Cerebral Performance Category scale.

The 233 patients whose time to epinephrine administration was longer than 5 minutes had a lower risk for in-hospital survival to discharge compared with those whose time to epinephrine administration was 5 minutes or less (21.0% vs 33.1%; multivariable-adjusted RR, 0.75 [95% CI, 0.60 - 0.93]; P = .01).

"The current study included only patients who initially had a nonshockable rhythm. We decided to analyze data only from this patient population to avoid confounding by defibrillation, which has previously been found to be a time-sensitive component of cardiac arrest resuscitation in adult patients with a shockable rhythm," the authors conclude. "As such, the findings should not be extrapolated to patients with a shockable rhythm; neither should they be extrapolated to out-of-hospital cardiac arrest, for which the time to initiation of therapy is often much longer."

The study "presents an interesting conundrum," Robert C. Tasker, MBBS, MD, and Adrienne G. Randolph, MD, both from Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, write in an accompanying editorial.

Evaluation of drug efficacy typically "requires rigorous testing in a randomized clinical trial" (RCT), but this study is an observational study, they point out. They note that this is a difficult setting in which to conduct an RCT, so evidence from an RCT is unlikely to be available for this patient population any time soon.

"Given there will never be an RCT and that epinephrine is listed in the [Pediatric Advanced Life Support] guidelines as the next step after [cardiopulmonary resuscitation] for nonshockable rhythms, these new data provide fairly strong evidence that following the guidelines with regards to epinephrine dosing and timing is best practice, with this study likely providing an [American Heart Association] Class I strength of recommendation," the editorialists write. "The data support what is currently recommended and show some benefit in the first 5 minutes. It is not known if epinephrine should be given within 2 minutes, as a good number of patients did not receive the drug at all and had ROSC in that time."

One author reports being a paid consultant for the American Heart Association. The remaining authors and editorialists have disclosed no relevant financial relationships.

JAMA. 2015;314:802-810. Article abstract, Editorial extract

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