Doubt cast on epinephrine benefits in cardiac arrest
MedWire News: Use of epinephrine may worsen outcomes in patients with out-of-hospital cardiac arrest, despite increasing their chances for return of spontaneous circulation, show findings published in JAMA.
The Japanese study was observational, but was very large, including more than 400,000 patients. Recent randomized controlled trials of epinephrine (adrenaline) have met with recruitment problems because of ethical objections to withholding epinephrine from cardiac arrest patients.
The current study covers the period 2005-2008. Japanese ambulance crews have been allowed to administer epinephrine since April 2006, so the rate of epinephrine use rose from 1.3% in 2005 to 54.4% in 2008.
"Despite the limitations to the study, the associations between epinephrine use before hospital arrival and short- and long-term outcomes were strong and consistent," say Akihito Hagihara (Kyushu University Graduate School of Medicine, Fukuoka, Japan) and colleagues.
In the entire cohort, spontaneous return of circulation occurred in significantly more patients given epinephrine than controls, at 18.5% of 15,030 versus 5.7% of 402,158.
There was a similar pattern in a cohort of 13,401 epinephrine patients and controls matched by a propensity score representing the likelihood for receipt of epinephrine before hospital arrival, at 18.3% and 10.5%, respectively.
In the whole cohort, slightly but significantly more patients given epinephrine than controls survived for at least 1 month, at 5.4% versus 4.7%. But the reverse was true in the propensity-matched cohort, at corresponding rates of 5.0% and 7.0%.
Moreover, significantly fewer patients given epinephrine than controls survived with good or moderate cerebral outcomes (Cerebral Performance Category 1 or 2), at 1.4% versus 2.2% in the entire cohort and 1.3% versus 3.1% in the propensity-matched cohort. The same was true for survival with good or moderate overall outcome.
The positive effect of epinephrine on return of spontaneous circulation remained after adjustment for confounders, but so did its negative effect on outcomes at 1 month.
In an accompanying editorial, Clifton Callaway (University of Pittsburgh, Pennsylvania) says: "If these observations are true, prehospital epinephrine use must increase morbidity and mortality after restoration of pulses to a degree that more than offsets its short-term benefits."
He suggests that this may relate to epinephrine's mechanism of action, noting that it "increases coronary perfusion pressure by decreasing blood flow to all other organs, an effect that may persist after restoration of pulses."
This suggests that epinephrine saves the heart at the expense of the body and brain, says Callaway, which could account for the poor outcomes in surviving patients given the drug.
"Properly evaluating this traditional therapy now seems necessary and timely and should consist of a rigorously conducted and adequately powered clinical trial comparing epinephrine with placebo during cardiac arrest," he concludes.
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By Eleanor McDermid