BACKGROUND Epinephrine is administered to increase coronary perfusion pressure during advanced life support and promote short-term survival. Recent cardiopulmonary resuscitation (CPR) guidelines recommend an epinephrine dosing interval of 3 to 5 minutes during resuscitation; however, scientific evidence supporting this recommendation is lacking. Therefore, we aimed to investigate the hemodynamic effects of repeated epinephrine doses during CPR by monitoring augmented blood pressure after its administration in a swine model of cardiac arrest. RESULTS A secondary analysis of data from a published study was performed using a swine cardiac arrest model. The epinephrine dose was fixed at 1 mg, and the first dose of epinephrine was administered after no-flow and low-flow times of 2 minutes and 8 minutes, respectively, and subsequently administered every 4 minutes. Four cycles of dosing intervals were defined because a previous study was terminated 26 minutes after the induction of ventricular fibrillation. Augmented blood pressures and corresponding timelines were determined. Augmented blood pressure trends following cycles and the epinephrine effect duration were also monitored. Among the 140 CPR cycles, the augmented blood pressure after epinephrine administration was the highest during the first cycle of CPR and decreased gradually with further cycle repetitions. The epinephrine effect duration did not differ between repeated cycles. The maximum blood pressure was achieved 78 to 97 seconds after epinephrine administration. CONCLUSIONS Hemodynamic augmentation with repeated epinephrine administration during CPR decreased with cycle progression. Further studies are required to develop an epinephrine administration strategy to maintain its hemodynamic effects during prolonged resuscitation.