Epinephrine use in out-of-hospital cardiac arrest associated with greater mortality

Patients who received epinephrine for out-of-hospital cardiac arrest were more likely to die or have debilitating brain damage, a new study found.

French researchers analyzed medical records of 1,556 patients who experienced nontraumatic out-of-hospital cardiac arrest (OHCA), had return of spontaneous circulation, and were then admitted to a Parisian hospital between January 2000 and August 2012. They determined whether the patients received epinephrine and the dose (none, 1 mg, 2 to 5 mg, or >5 mg). The main outcome was favorable neurological outcome at discharge, defined as a Cerebral Performance Category score of 1 or 2. Results were published Dec. 9 by the Journal of the American College of Cardiology.

Seventy-three percent (n=1,134) of the 1,556 eligible patients received epinephrine. These patients were older, were less likely to have a witnessed event, were less likely to present with a shockable rhythm, and had a longer duration of resuscitation than patients who didn't get epinephrine.

After adjustment for confounders like these, epinephrine use overall was negatively associated with good neurological outcome (adjusted odds ratio [AOR], 0.32; 95% CI, 0.22 to 0.47; P<0.001). Seventeen percent of patients who were treated with epinephrine survived with good neurological outcome compared to 63% of patients in the nontreated group (P<0.001).

Outcome data based on the dose of epinephrine showed an AOR for intact survival of 0.48 (95% CI, 0.27 to 0.84) for 1 mg of epinephrine, 0.30 (95% CI, 0.20 to 0.47) for 2 to 5 mg, and 0.23 (95% CI, 0.14 to 0.37) for >5 mg of epinephrine—i.e., outcomes were worse at higher doses. Patients who received epinephrine in the first 9 minutes after cardiac arrest had better outcomes. The association of epinephrine with poorer outcomes didn't vary by length of resuscitation attempt or by presence or type of in-hospital interventions.

International guidelines recommend administering 1 mg of epinephrine every 3 to 5 minutes during resuscitation. In a press release, lead study author Florence Dumas, MD, PhD, noted that the current study's results don't indicate an urgent need to change guidelines. “It's very difficult, because epinephrine at a low dose seems to have a good impact in the first few minutes, but appears more harmful if used later,” Dr. Dumas said. “It would be dangerous to completely incriminate this drug, because it may well be helpful for certain patients under certain circumstances. This is one more study that points strongly to the need to study epinephrine further in animals and in randomized trials.”