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Thursday, March 22, 2012

Epinephrine Bad for Long-Term Arrest Survival

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For out-of-hospital cardiac arrest, administration of epinephrine on the way to the hospital initially improves the chances of resuscitation but hurts survival and function longer term, Japanese researchers found.
Circulation returned before arrival at the hospital for 18.5% of those given the adrenaline drug intravenously by paramedics, compared with 5.7% who didn't receive it (P<0.001) in a registry study by Akihito Hagihara, DMSc, MPH, of Kyushu University in Fukuoka, Japan, and colleagues.
However, survival to one month was 54% less likely and survival without severe neurological disability was 68% less likely with prehospital administration of epinephrine, the group reported in the March 21 issue of the Journal of the American Medical Association.
The results remained significant after propensity matching and in sensitivity analyses accounting for inhospital epinephrine use and cardiopulmonary resuscitation (CPR) duration.
"We believe that the present findings are important both theoretically and practically," the group concluded.
Epinephrine has been a cornerstone of cardiac resuscitation since the 1960s, despite little evidence for patient outcome benefits from either epidemiologic or randomized trials, Clifton W. Callaway, MD, PhD, of the University of Pittsburgh, noted in an accompanying editorial.
The new results provide the equipoise needed to really test epinephrine for out-of-hospital cardiac arrest in an adequately powered placebo-controlled trial, he suggested.
Meanwhile, "physicians and other practitioners involved in cardiac resuscitation must consider carefully whether continued use of epinephrine is justified," Callaway wrote, pointing out that the association "with worse meaningful outcomes appears to be real and robust."
The explanation may be that epinephrine boosts coronary perfusion pressure needed for resumption of a pulse by decreasing blood flow to all other organs, resulting in greater problems with myocardial dysfunction, cerebral microcirculation, and ventricular arrhythmias after resuscitation.
It appears that "epinephrine provides a short-term gain for the heart by incurring a metabolic debt from the body and brain," Callaway wrote. "This debt may be too great for many patients."
Hagihara's group looked at a national registry of emergency services in Japan during a period when a policy change made epinephrine standard therapy for prehospital administration in out-of-hospital cardiac arrest -- a database that Callaway called one of the largest ever observational databases of CPR.
Of the more than 417,000 out-of-hospital cardiac arrest cases analyzed, the number of patients who received epinephrine before arrival at the hospital rose from 190 in 2005 to 8,124 in 2008.
After propensity matching, epinephrine still held the advantage for return of spontaneous circulation prior to hospital arrival (18.3% versus 10.5%, P<0.001). The adjusted propensity matched odds were 2.51-fold higher with epinephrine (both P<0.001).
Survival rates at one month, though, went the other direction.
Raw one-month survival rates were 5.4% versus 4.7% without prehospital epinephrine, for an odds ratio of 0.46. The corresponding propensity-matched rates were 5.1% versus 7% for an odds ratio of 0.54 (all P<0.001).
Survival with good or moderate cerebral performance, determined by a Cerebral Performance Category of 1 or 2, occurred in 1.3% of epinephrine-treated patients compared with 3.1% treated without prehospital epinephrine in the propensity-matched analysis, for an odds ratio of 0.21 (P<0.001).
Survival with no more than moderate neurological disability, determined by an Overall Performance Category score of 1 or 2, likewise favored no prehospital use of epinephrine. Propensity-matched rates were again 1.3% with epinephrine versus 3.1% without it, for an odds ratio of 0.23 (P<0.001).
All the results persisted across the four different models used.
A major confounder may have been receipt of epinephrine after hospital arrival, but a sensitivity analysis in only the patients who resumed spontaneous circulation before arrival at the hospital and who thus wouldn't have had an indication for epinephrine at the hospital, showed the same disadvantages for survival and disability with prehospital epinephrine.
Time from the call to emergency services to their arrival on-scene or to arrival at the hospital didn't differ by epinephrine use.
The researchers acknowledged that their study may have been affected by residual confounding and the lack of data on inhospital CPR after arrival.
The researchers reported having no conflicts of interest to disclose.
Callaway reported receiving support from the American Heart Association as worksheet editor during development of the 2010 Emergency Cardiovascular Care Guidelines and is an investigator for the Resuscitation Outcomes Consortium, which performs clinical trials in cardiac arrest. He has received consulting fees or honoraria from Take Heart Austin, the Post Cardiac Arrest Symposium, the Sudden Cardiac Arrest Association, and the Society for Critical Care Medicine; a study section stipend from the National Institutes of Health; an equipment loan for laboratory studies from Medivance; and royalties on patents related to defibrillation from Medtronic ERS.
From the American Heart Association:
Primary source: Journal of the American Medical Association
Source reference:
Hagihara A, et al "Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest" JAMA 2012; 307: 1161-1168.
Additional source: Journal of the American Medical Association
Source reference:
Callaway CW "Questioning the use of epinephrine to treat cardiac arrest" JAMA 2012; 307: 1198-1200.

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