We attempted to determine the effect of extreme alkalemia induced by high-dose sodium bicarbonate on the vasopressor effects of epinephrine during cardiopulmonary resuscitation (CPR). Subjects in this randomized, blinded study performed in a controlled laboratory environment were 12 mongrel dogs that had had a previous episode of CPR. Each dog underwent 3 minutes of ventricular fibrillation (VF) followed by 7 minutes of closed-chest CPR. Animals were assigned to receive either sodium bicarbonate 3 mEq/kg and epinephrine 0.1 mg/kg, or normal saline 3 ml/kg and epinephrine 0.1 mg/kg. The sodium bicarbonate or normal saline was infused over 2 minutes beginning at 4 minutes of VF (1 min of CPR) followed by bolus epinephrine. Arterial pH in the sodium bicarbonate group was significantly higher at each sampling point (7.7 ± 0.1 vs 7.29 ± 0.06 at 1 min after drug, p<0.001). However, there were no statistically or clinically significant differences in coronary perfusion pressure between the groups at any time: 29 ± 13 versus 32 ± 21 mm Hg 1 minute, and 22 ± 12 versus 26 ± 19 mm Hg 4 minutes after epinephrine for sodium bicarbonate and normal saline, respectively (p>0.7). Increased arterial pH (alkalemia) induced by high-dose sodium bicarbonate administration did not improve the vasopressor effects of epinephrine during CPR in this canine model. These results suggest the limited value of administering sodium bicarbonate during CPR to improve the responsiveness to epinephrine.