A randomized, blinded trial of high-dose epinephrine versus standard- dose epinephrine in a swine model of pediatric asphyxial cardiac arrest

Objective: To determine whether high-dose epinephrine administration during cardiopulmonary resuscitation (CPR) in a swine pediatric asphyxial cardiac arrest model improves outcome (i.e., resuscitation rate, survival rate, and neurologic function) compared with standard-dose epinephrine. Design: A randomized, blinded study. Setting: A large animal cardiovascular laboratory at a university. Subjects: Thirty domestic piglets (3 to 4 months of age) were randomized to receive standard-dose epinephrine (0.02 mg/kg) or high-dose epinephrine (0.2 mg/kg) during CPR after 10 mins of cardiac standstill with loss of aortic pulsation after endotracheal tube clamping. Interventions: Two minutes of CPR were provided, followed by advanced pediatric life support. Successfully resuscitated animals were supported in an intensive care unit (ICU) setting for 2 hrs and then observed for 24 hrs. Measurements and Main Results: Electrocardiogram, thoracic aortic blood pressure, and right atrial blood pressure were monitored continuously until the intensive care period ended. Survival rate and neurologic outcome were determined. Return of spontaneous circulation was obtained in 13 of 15 high- dose epinephrine piglets vs. ten of 15 standard-dose epinephrine piglets (p < .20). Four of 13 high-dose piglets died in the ICU period after initial resuscitation vs. 0 of ten standard-dose piglets (p ≤ .05). Nine high-dose piglets survived 2 hrs vs. ten standard-dose piglets. Three piglets in each group survived for 24 hrs, but all were severely neurologically impaired. Two minutes after resuscitation, piglets treated with high-dose epinephrine had higher heart rates (210 ± 24 vs. 189 ± 40 beats/min, p < .05) and higher aortic diastolic pressures (121 ± 39 vs. 74 ± 40 mm Hg, p < .01). Within 10 mins of return of spontaneous circulation, severe tachycardia (>240 beats/min) was more frequently noted in the high-dose group than in the standard-dose group (p < .05). All four high-dose piglets that died in the ICU period experienced ventricular fibrillation within 10 mins of return of spontaneous circulation. Conclusions: High-dose epinephrine did not improve 2-hr survival rate, 24-hr survival rate, or neurologic outcome. High-dose epinephrine resulted in severe tachycardia and hypertension immediately after resuscitation and in a higher mortality rate immediately after resuscitation.