Abstract 10437: Epinephrine in Cardiac Arrest: A Randomized, Multicenter, Double-blinded, Placebo-Controlled Experimental Trial

Introduction: Epinephrine is universally used in cardiac arrest primarily to increase coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR). The effect of different modes of epinephrine administration and the persistence of effect with repeated doses are not known. Methods: We conducted a preclinical, randomized, multicenter, double-blinded, placebo-controlled experimental trial of 45 swine from five different laboratories (Ann Arbor, MI; Baltimore, MD; Los Angeles, CA; Pittsburgh, PA; Toronto, ON) using a standard treatment protocol. Ventricular fibrillation was induced and left untreated for 6 min before starting continuous CPR, which included mechanical chest compressions (100/min) and manual ventilations using a bag-valve-mask with 100% O2 (10 breaths/min). After 2 min of CPR onset, nine animals from each lab were centrally randomized to one of three treatment arms: 1) Continuous IV epinephrine infusion (0.00375mg/kg/min) for 12 min and placebo IV normal saline (NS) boluses every 4 min, 2) Three IV epinephrine boluses (0.015mg/kg) every 4 min and placebo IV NS infusion, or 3) Placebo NS infusion and boluses. The primary outcome was mean CPP during the drug therapy period (2-14 minutes after CPR onset). Differences in CPP were analyzed using repeated measures regression modeling. Results: There was no statistical difference in mean minute CPP (mmHg) between the three groups: 14.4±6.8 (infusion), 16.9±5.9 (bolus), and 14.4±5.5 (placebo) (p=NS). Repeated bolus doses of epinephrine caused transient increases in CPP that tended to peak at ~2 min after drug administration (Figure). Conclusion: Standard dose epinephrine, whether given by infusion or repeated boluses during CPR, did not significantly improve average CPP over time compared to placebo. Tachyphylaxis to epinephrine may occur regardless of mode of administration. This study raises important questions about optimal epinephrine dosing and administration strategy.