Abstract 360: Effects of Different Doses of Pralidoxime Administered During Cardiopulmonary Resuscitation and the Role of Alpha-Adrenergic Receptors in its Pressor Action

Introduction: We previously reported that pralidoxime potentiated the pressor effect of epinephrine and improved restoration of spontaneous circulation (ROSC) rate and short-term survival in pigs undergoing cardiopulmonary resuscitation (CPR). We sought to explore the optimal dose of pralidoxime to be used during CPR and to evaluate the involvement of α-adrenoceptors in its pressor action. Methods: In the first substudy, 44 pigs randomly received one of three doses of pralidoxime (40, 80, or 120 mg/kg) or saline placebo during CPR. All animals were given epinephrine every 3 minutes. In the second substudy, 49 rats were divided into 7 groups. In the first 4 groups, the effects of 40 mg/kg pralidoxime on arterial pressure were determined after pretreatment with saline, guanethidine, phenoxybenzamine, or phentolamine. In the other 3 groups, the effects of 200 mg/kg pralidoxime were determined after pretreatment with saline, propranolol, or phentolamine. Results: In the first substudy, 40 mg/kg pralidoxime resulted in the highest coronary perfusion pressure (CPP) among the groups, while 120 mg/kg pralidoxime resulted in the lowest CPP (group effect P <0.001). Sustained ROSC was attained in 4 (36.4%), 11 (100%), 9 (81.8%), and 3 (27.3%) animals in the saline, 40 mg/kg, 80 mg/kg, and 120 mg/kg groups, respectively ( P <0.001). In the second substudy, 40 mg/kg pralidoxime elicited a pressor response. Phenoxybenzamine completely inhibited the pressor response, but guanethidine and phentolamine did not. The pressor response of pralidoxime was even greater after pretreatment with guanethidine or phentolamine. Two-hundred mg/kg pralidoxime produced an initial vasodepressor response followed by a delayed pressor response. Phentolamine eliminated the initial vasodepressor response and reversed it into a pressor response. Conclusions: Forty mg/kg of pralidoxime administered with epinephrine led to a significantly higher ROSC rate by improving CPP in a pig model of cardiac arrest, whereas 120 mg/kg did not improve CPP or the ROSC rate. Our findings suggest that the pressor effect of pralidoxime is unrelated to α-adrenoceptors and that its pressor effect is buffered by its vasodepressor action mediated by the inhibition of the sympathetic nervous system.